LLaVa_Med_Inference_RAG.ipynb

{
  "cells": [
    {
      "cell_type": "code",
      "source": [
        "from google.colab import drive\n",
        "drive.mount('/content/drive', force_remount=True)"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "6Oz7iQ669qHM",
        "outputId": "175f1b5a-5dbc-4879-ad60-0e326032e262"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "Mounted at /content/drive\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "execution_count": null,
      "metadata": {
        "id": "XPXCgxfW9mcG"
      },
      "outputs": [],
      "source": [
        "%%capture\n",
        "\n",
        "!pip install langchain \"unstructured[all-docs]\" unstructured-inference pydantic lxml\n",
        "!pip install --upgrade nltk\n",
        "!pip uninstall pdfminer.six --y\n",
        "!pip install pikepdf pypdf wrapt pdfminer.six\n",
        "!pip install unstructured_pytesseract\n",
        "# !brew install poppler-utils\n",
        "# !brew install tesseract-ocr\n",
        "# !brew install poppler-qt5\n",
        "# !brew install tesseract-lang\n",
        "# !brew install tesseract\n",
        "\n",
        "!sudo apt-get install poppler-utils\n",
        "!sudo apt install tesseract-ocr\n",
        "\n",
        "!pip install pillow pydantic lxml pillow matplotlib chromadb tiktoken\n",
        "!pip install -U langchain openai langchain-chroma langchain-experimental\n",
        "!pip install lamini\n",
        "!pip install -U langchain_ollama\n",
        "!pip install -qU langchain-openai"
      ]
    },
    {
      "cell_type": "code",
      "execution_count": null,
      "metadata": {
        "id": "SKAeify-9mcG"
      },
      "outputs": [],
      "source": [
        "import os\n",
        "from typing import Any\n",
        "\n",
        "from pydantic import BaseModel\n",
        "from unstructured.partition.pdf import partition_pdf\n",
        "from langchain_text_splitters import CharacterTextSplitter"
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "from PIL import ImageFile\n",
        "ImageFile.LOAD_TRUNCATED_IMAGES = True\n",
        "\n",
        "from unstructured.partition.pdf import partition_pdf\n",
        "from langchain_text_splitters import CharacterTextSplitter\n",
        "def extract_pdf_elements(images_path, file_name):\n",
        "  return partition_pdf(\n",
        "      filename=file_name,\n",
        "      extract_images_in_pdf=True,\n",
        "      strategy=\"hi_res\",\n",
        "      infer_table_structure=True,\n",
        "      extract_image_block_output_dir=images_path\n",
        "  )\n",
        "\n",
        "\n",
        "def categorize_elements(raw_pdf_elements):\n",
        "  tables = []\n",
        "  texts = []\n",
        "\n",
        "  for element in raw_pdf_elements:\n",
        "    if \"unstructured.documents.elements.Table\" in str(type(element)):\n",
        "      tables.append(str(element))\n",
        "    elif \"unstructured.documents.elements.ListItem\" in str(type(element)) or \"unstructured.documents.elements.NarrativeText\" in str(type(element)):\n",
        "      texts.append(str(element))\n",
        "\n",
        "  return tables, texts\n",
        "\n",
        "images_path = \"/content/drive/MyDrive/rag/images\"\n",
        "file_name = \"/content/drive/MyDrive/rag/13-24.pdf\"\n",
        "\n",
        "raw_pdf_elements = extract_pdf_elements(images_path, file_name)\n",
        "tables, texts = categorize_elements(raw_pdf_elements)\n",
        "\n",
        "text_splitter = CharacterTextSplitter.from_tiktoken_encoder(\n",
        "  chunk_size=4000,\n",
        "  chunk_overlap=0,\n",
        ")\n",
        "joined_texts = \" \".join(texts)\n",
        "texts_4k_token = text_splitter.split_text(joined_texts)"
      ],
      "metadata": {
        "id": "u6QcVeoko-mh"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "# saving retrieved texts and tables to a file\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/13-24_text.txt\", \"w\") as f:\n",
        "  f.write('\\n'.join(texts_4k_token))\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/13-24_table.txt\", \"w\") as f:\n",
        "  f.write('\\n'.join(tables))"
      ],
      "metadata": {
        "id": "OnsXMoaGLIDH"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "#loading saved texts and tables from file\n",
        "texts = []\n",
        "with open(\"/content/drive/MyDrive/rag/13-24_text.txt\", \"r\") as f:\n",
        "  for line in f:\n",
        "    texts.append(line)\n",
        "\n",
        "tables = []\n",
        "with open(\"/content/drive/MyDrive/rag/13-24_table.txt\", \"r\") as f:\n",
        "  for line in f:\n",
        "    tables.append(line)"
      ],
      "metadata": {
        "id": "x8D_iQER_SIy"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "element_dict = [el.to_dict() for el in raw_pdf_elements]\n",
        "\n",
        "unique_types = set()\n",
        "for item in element_dict:\n",
        "  unique_types.add(item['type'])\n",
        "\n",
        "print(unique_types)"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "zm5cmNd3lzpX",
        "outputId": "366e8a96-8455-428c-c2b5-6c1d4ef00388"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "{'UncategorizedText', 'ListItem', 'FigureCaption', 'Table', 'Title', 'Footer', 'Header', 'NarrativeText', 'Image'}\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "execution_count": null,
      "metadata": {
        "id": "P2JWUcrc9mcH"
      },
      "outputs": [],
      "source": [
        "# from langchain_google_genai import ChatGoogleGenerativeAI\n",
        "from langchain_core.prompts import ChatPromptTemplate\n",
        "from langchain_core.output_parsers import StrOutputParser\n",
        "\n",
        "import os\n",
        "import lamini\n",
        "from lamini import Lamini\n",
        "from dotenv import load_dotenv"
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "print(tables)"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "qIJcrSaWpDzk",
        "outputId": "7b2098ef-166a-440e-f337-27c1842e0e41"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "['Chylomicron VLDL IDL LDL HDL <0.94 0.94–1.006 1.006–1.019 1.006–1.063 1.063–1.210 Protein Triglyceride Cholesterol Phospholipid origin 1–2 85–95 3–7 3–6 Intestine Transport dietary CH and TG to liver 6–10 50–65 20–30 15–20 Intestine and liver Transport endogenous TG and CH 12–18 20–50 20–40 15–25 Produced from VLDL Transport endogenous TG and CH 18–22 4–8 51–58 18–24 Product of IDL catabolism Transport endogenous CH to cells 45–55 2–7 18–25 26–32 Liver and intestine Cream layer Turbid Clear Clear Clear Origin Pre-β Slow pre-β β α mobility A-IV, B-48, C-I, B-100, C-I, B-100, C-I, B-100, (a) C-II, C-III C-III, C-III, E C-II, C-III, E\\n', 'Effect on Plasma Lipids Cholesterol (%) Triglycerides (%) HDL-C (%) Comments Diuretics Thiazides Loop Indapamide Metolazone Potassium-sparing β-Blockers Nonselective ↑5–7 initially ↑0–3 later No change No change No change No change No change ↑30–50 No change No change No change No change ↑20–50 ↑1 ↓ to 15 No change No change No change ↓10–15 Effects transient; monitor for long-term effects Selective β-blockers have greater effects than nonselective; β-blockers with ISA or α-blocking effects are lipid neutral. Selective α-Blocking α-Agonists and Antagonists (e.g., prazosin and clonidine) No change No change or ↓ No change ↓0–10 ↑15–30 ↓0–20 ↓5–10 No change ↑0–15 In general, drugs that affect α-receptors ↓cholesterol and ↑HDL-C ACE Inhibitors Calcium-Channel No change No change No change No change No change No change Blockers Oral Contraceptives α-Monophasics ↑5–20 ↑10–45 ↑15–↓15 Effects caused by reduced lipolytic activity or ↑VLDL synthesis; mainly caused by progestin component; estrogen alone protective α-Triphasics Glucocorticoids Ethanol ↑10–15 ↑5–10 No change ↑10–15 ↑15–20 ↑up to 50 ↑5–10 ↑ Marked elevations can occur in patients who are hypertriglyceridemic. Isotretinoin ↑5–20 ↑50–60 ↓10–15 Changes may reverse 8 weeks after stopping drug.\\n', 'Disorder Metabolic Defect Lipid Effect Main Lipid Parameter Diagnostic Features Polygenic hypercholesterolemia ↓LDL clearance ↑LDL-C LDL-C: 130–250 mg/dL Atherogenic dyslipidemia ↑VLDL secretion ↑TG TG: Frequently ↑ApoC-III synthesis ↓LPL activity ↓VLDL removal ↑Remnant VLDL ↓HDL ↑Small, 150–500 mg/dL HDL-C: <40 mg/dL dense LDL Familial hypercholesterolemia— heterozygous Familial hypercholesterolemia— homozygous Familial defective apoB-100 Reduction in functional LDL receptor Absent LDL receptors Defective apoB on LDL and VLDL ↑LDL-C ↑LDL-C ↑LDL-C LDL-C: 250–450 mg/dL LDL-C: >450 mg/dL LDL-C: 250–450 mg/dL Dysbetalipoproteinemia (type III hyperlipidemia) ApoE2:E2 phenotype, ↓VLDL remnant ↑Remnant VLDL, ↑IDL LDL-C: 300–600 mg/dL TGs: clearance 400–800 mg/dL Familial combined hyperlipidemia ↑ApoB and VLDL production ↑CH, TG, or both LDL-C: 250–350 mg/dL Family history, CHD Familial ↑ApoB production ↑ApoB TGs: 200–800 mg/dL ApoB: hyperapobetalipoproteinemia >125 mg/dL Hypoalphalipoproteinemia ↑HDL catabolism ↓HDL-C HDL-C:\\n', 'Moderate-Intensity Statin Therapy Low-Intensity Statin Therapy Agents that lower LDL-C on Agents that lower LDL-C on average, by ~30%–50% Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin 20–40 mgb Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pitavastatin 2–4 mg average, by ~<30% Simvastatin 10 mg Pravastatin 10–20 mg Lovastatin 20 mg Fluvastatin 20–40 mg Pitavastatin 1 mg\\n', 'Nutrient Recommended Intake Total fat Saturated fat Polyunsaturated fat Monounsaturated fat Carbohydrate Fiber Cholesterol Protein 25%–35% of total calories <7% of total calories Up to 10% of total calories Up to 20% of total calories 50%–60% of total calories 20–30 g/day <200 mg/day Approximately 15% of total calories\\n', 'Drug LDL (%) HDL (%) TG (%) Bile acid resin Ezetimibe Niacin Statin Fibrates 215 to 230 218 to 222 215 to 230 225 to 260 610 to 225 63 0 to 2 20 to 35 5 to 15 10 to 30 +3 to 210 0 to ]5 ]30 to ]60 ]10 to ]45 ]30 to ]60\\n', 'Daily Dosage Bile acid resins (cholestyramine, colestipol) Bile acid resin (colesevelam) Ezetimibe160 Ezetimibe/simvastatin Extended-release niacin/simvastatin Niacin (crystalline)161 Extended-release niacin 5 g 10 g 15 g 3.8 g 4.5 g 10 mg 10 mg/10 mg 10 mg/20 mg 10 mg/40 mg 10 mg/80 mg 500 mg/20 mg 1,000 mg/20 mg 1,500 mg/20 mg 2,000 mg/20 mg 1,000 mg 1,500 mg 2,000 mg 3,000 mg 1,000 mg 1,500 mg 2,000 mg 215 223 227 215 218 218 to 222 245 252 255 260 212.9a 217.5a 218.9a 219.5a 26 213 216 222 29 214 217\\n', 'Lipid Disorder Drug of Choice Alternative Agents Combination Therapy Polygenic Statin Resin, ezetimibe, niacin Statin–ezetimibe, statin– hypercholesterolemia Familial hypercholesterolemia (FH) or severe polygenic hypercholesterolemia Atherogenic dyslipidemia Statin (high potency, moderate to high dose) Statin, niacin, fibratea combination Ezetimibe LDL apheresis for homozygous FH Statin, niacin, fibratea resin, resin–niacin, statin–niacin Statin–ezetimibe, statin–resin, resin– niacin, statin–niacin, statin–ezetimibe–niacin, statin–resin–niacin Statin–niacin, niacin– resin, niacin–fibrate Isolated low HDL Statin Niacin Statin–niacin\\n', 'Drug Initial Dosage Usual Dosage Maximal Dosage Comment Cholestyramine 4 g before main meal 4 g BID before heaviest meals 5 g of powder or 4 g of tablets BID before heaviest meals Colestipol 5 g of powder or 2 g of tablets every day before main meal Colesevelam 6 × 0.63-g tablets/ Same 8 g BID before heaviest meals 10 g of powder or 8 g of tablets BID before heaviest meals 7 × 0.63-g tablets/ May prescribe 24 g/day, but few patients can tolerate May prescribe 30 g of powder per day, but few patients can tolerate Less bulk is associated day day with less gastrointestinal intolerance. Niaspan Atorvastatin 500 mg QHS 10–40 mg every day 1,000–2,000 mg QHS 10–40 mg every day 2,000 mg QHS 80 mg every day Increase dose by 500 mg daily every 4 weeks. Administer any time of day. Fluvastatin Lovastatin 20–40 mg QHS 20 mg with dinner 20–40 mg QHS 20–40 mg with dinner 40 mg BID 80 mg XL every day 40 mg BID Modified-release form (XL) has similar efficacy but has less bioavailability (and less risk of adverse effects). Administration with food increases bioavailability. BID dosing provides greater LDL-C–lowering efficacy than every day. Pitavastatin 1–2 mg every day 1–2 mg every day 4 mg every day Administer any time of the day with or without food. Pravastatin 10–40 mg every day 10–40 mg every day 80 mg every day Administer with food to reduce dyspepsia. Rosuvastatin 10–20 mg every day 10–20 mg every day 40 mg every day Administer any time of the day. Simvastatin Gemfibrozil Fenofibratea 20–40 mg every 20–40 mg every evening Same Same 80 mg every eveningb Same 201 mg every day Administer with food to reduce dyspepsia.\\n', 'Drug Adverse Effects Drug Interactions Monitoring Parameters Resin Indigestion, bloating, nausea, constipation, abdominal pain, flatulence GI binding and reduced absorption of anionic drugs (warfarin, b-blockers, digitoxin, thyroxine, thiazide diuretics); administer drugs 12 hours before or 4 hours after resin Lipid profile every 4–8 weeks until stable dose; then every 6–12 months long term. Check TG level after stable dose achieved, then as needed.\\n', 'Drug Adverse Effects Drug Interactions Monitoring Parameters Niacin Flushing, itching, tingling, headache, nausea, gas, heartburn, fatigue, rash, worsening of peptic ulcer, elevation in serum glucose and uric acid, hepatitis, and elevation in hepatic transaminase levels Hypotension with BP-lowering drugs such as a-blockers possible; diabetics taking insulin or oral agents may require dosage adjustment because of increase in serum glucose levels Lipid profile after 1,000–1,500 mg/day and then after stable dosage achieved; then every 6–12 months long term. LFT at baseline and every 6–8 weeks during dose titration; then as needed for symptoms. Uric acid and glucose at baseline and again after stable dose reached (or symptoms produced), more frequently in diabetic patients. Statins Headache, dyspepsia, myositis (myalgia, CPK >10 times normal), elevation in hepatic transaminase levels Lipid profile 4–8 weeks after dose change, then every 6–12 months long term. LFT at baseline, in 3 months, and periodically thereafter. CPK at baseline and if the patient has symptoms of myalgia.\\n', 'Classificationa SBP (mm Hg) DBP (mm Hg) Normal Prehypertension Stage 1 hypertension Stage 2 hypertension <120 120–139 140–159 ≥160 and <80 or 80–89 or 90–99 or ≥100\\n', 'Modification Recommendation Weight management Adopt DASH-type dietary patterns Lose weight if overweight or obese, ideally attaining a BMI <25 kg/m2. Maintain a desirable BMI (18.5–24.9 kg/m2) if not overweight or obese. Consume a diet that is rich in fruits and vegetables (8–10 servings/day), rich in low-fat dairy products (2–3 servings/day), but has reduced amounts of saturated fat and cholesterol. Reduced sodium intake Reduce daily dietary sodium intake as much as possible—ideally to <65 mmol/day (equal to 1.5 g/day sodium, or 3.8 g/day sodium chloride). Moderation of alcohol consumption For patients who drink alcohol, limit consumption to no more than two drinks/day in men and no more than one drink/day in women and lighter-weight people.a Do not recommend alcohol consumption in patients who do not drink alcohol. Regular physical activity Regular moderate-intensity aerobic physical activity; at least 40 minutes of continuous or intermittent 3–4 day/week, but preferably daily.\\n', 'Antihypertensive Agent Situations with Potentially Favorable Effects Situations with Potentially Unfavorable Effectsb Avoid Use ACEI ARB Low-normal potassium, elevated fasting glucose, microalbuminuria (with or without diabetes) Low-normal potassium, High-normal potassium or hyperkalemia High-normal potassium Pregnancy, bilateral renal artery stenosis, history of angioedema Pregnancy, bilateral renal CCB: elevated fasting glucose, microalbuminuria (with or without diabetes) Raynaud’s phenomenon, or hyperkalemia Peripheral edema, left artery stenosis Left ventricular dihydropyridine elderly patients with isolated systolic hypertension, cyclosporine-induced hypertension ventricular dysfunction (all except amlodipine and felodipine), high- normal heart rate or tachycardia dysfunction (not with amlodipine or felodipine) CCB: nondihydropyridine Raynaud’s phenomenon, migraine headache, supraventricular arrhythmias, high-normal heart rate or tachycardia Peripheral edema, low-normal heart rate Second- or third-degree heart block, left ventricular dysfunction Thiazide diuretic and thiazide-like diuretics Osteoporosis or at increased risk for osteoporosis, high- normal potassium Gout, hyponatremia, elevated fasting glucose (as monotherapy), low- normal potassium or sodium Anuria, kidney failure\\n', 'Drug Related Health Condition or Lifestyle Related Other Nonadherence Volume overload Improper blood pressure measurement Inadequate antihypertensive dose Inappropriate antihypertensive Excess sodium intake Volume retention from chronic Resistant hypertension White-coat hypertension combination therapy kidney disease Inadequate diuretic therapy Secondary disease causes Pseudohypertension (Table 14.1) Secondary drug-induced causes Obesity (Table 14.1) Clinician failure to intensify or Excessive alcohol intake augment therapy (i.e., clinical inertia)\\n', 'Category Selected Products Usual Dosage Range (mg/day) Thiazide and thiazide-like Loop Potassium-sparing Potassium-sparing combination Aldosterone antagonist Chlorthalidone Hydrochlorothiazide Indapamide Metolazone Metolazone Bumetanide Furosemide Torsemide Amiloride Triamterene Triamterene/HCTZ Spironolactone/HCTZ Amiloride/HCTZ Eplerenone Spironolactone 12.5–25 12.5–50 1.25–5 2.5–10 0.5–1.0 0.5–4 20–80 2.5–10 5–10 50–100 37.5/25–75/50 25/25–50/50 5–10/50–100 50–100 12.5–50 Daily Daily Daily Daily Daily BID BID Daily Daily to BID Daily to BID Daily Daily Daily Daily to BID Daily to BID\\n', 'Drug Usual Starting Dose (mg/day)a Usual Dosage Range (mg/day) Dosing Frequency Benazepril Captopril Enalapril Fosinopril Lisinopril Moexipril Perindopril Quinapril Ramipril Trandolapril 10 25 5 10 10 7.5 4 10 2.5 1 20–40 50–100 10–40 20–40 20–40 7.5–30 4–16 20–80 2.5–20 2–4 Daily to BID BID to TID Daily to BID Daily Daily Daily to BID Daily Daily to BID Daily to BID Daily\\n', 'Drug Starting Dose (mg/day)a Usual Dosage Range (mg/day) Dosing Frequency Azilsartan medoxomil Candesartan cilexetil Eprosartan mesylate Irbesartan Losartan potassium Olmesartan medoxomil Telmisartan Valsartan 80 16 600 150 50 20 40 80–160 80 8–32 600–800 75–300 25–100 20–40 20–80 80–320 Daily Daily to BID Daily to BID Daily Daily to BID Daily Daily Daily\\n', 'Drug Usual Dosage Range (mg/day) Dosing Frequency nondiHydropyridinesb Diltiazem, sustained-release Diltiazem, extended-releasec Verapamil, sustained-release Verapamil, controlled-onset extended-releasec Verapamil, chronotherapeutic oral drug-absorption systemc 120–480 120–540 180–480 180–480 100–400 Daily Daily Daily to BID QHS QHS\\n', 'Drug Usual Dosage Range (mg/day) Dosing Frequency diHydropyridines Amlodipine Felodipine, extended-release tablet Isradipine, controlled-release tablet Nicardipine, sustained-release capsule Nifedipine, sustained-release tabletd Nisoldipine, extended-release tablet 2.5–10 2.5–10 5–20 60–120 30–90 17–34 Daily Daily Daily BID Daily Daily\\n', 'Drug Usual Dosage Range (mg/day) Dosing Frequency Half-Life (hours) b1 Selectivity Lipid Solubility Atenolol Bisoprolol Carvedilol Carvedilol, controlled release Labetalol Metoprolol tartrate Metoprolol succinate Nebivolol Propranolol 25–100 5–20 12.5–50 10–80 200–800 100–400 25–400 5–10 40–180 Daily to BID Daily BID Daily BID BID Daily Daily Daily (LA and XL) or BID 6–7 9–12 6–10 6–10 6–8 3–7 3–7 12–19 3–5 ++ +++ 0 0 0 + + +++ 0 Low High High High Moderate Moderate to high Moderate to high High High\\n', 'Drugs/Mechanism of Action Usual Dosage Range (mg/day) Dosing Frequency Aldosterone AntAgonists (see Table 14.9) a1-Blockers Doxazosin Prazosin Terazosin 1–8 2–20 1–20 Daily BID to TID Daily to BID direct renin inHiBitor Aliskiren 150–300 Daily a2-Agonists (centrAl) Clonidine Clonidine transdermal Methyldopa 0.1–0.8 0.1–0.3 250–1,000 BID Once weekly BID ArteriAl VAsodilAtors Hydralazine Minoxidil 25–100 2.5–80 BID to TID Daily to BID Adrenergic neuron Blockers Reserpine 0.05–0.25 Daily\\n', 'Side Effects Innocuous but Sometimes Annoying Usually Requires Cessation of Therapy, at Least Temporarily Potentially Harmful Precautions Hypokalemia,a hyponatremia, hyperglycemia, hypovolemia, pancreatitis, photosensitivity, hypercholesterolemia, hypertriglyceridemia, hyperuricemia with gout, orthostatic hypotension (more frequent in elderly) Hypokalemia,a hyperglycemia, hypovolemia, pancreatitis, hypercholesterolemia, hypertriglyceridemia, hearing loss with large IV doses, orthostatic hypotension (more pronounced in elderly) Thiazide Diuretics Increased urination (at Hypercalcemia, azotemia, skin rash (cross-reacts with only certain sulfonamide allergies), purpura, bone marrow depression, lithium toxicity in patients on lithium therapy, hyponatremia Anuria, kidney failure onset of therapy), muscle cramps, hyperuricemia (without gout) Loop Diuretics Increased urination, muscle cramps, hyperuricemia (less than with thiazides) Hyponatremia, hypocalcemia, Anuria azotemia, skin rash (cross-reacts with only certain sulfonamide allergies), photosensitivity, lithium toxicity in patients on lithium therapy ACEI Dizziness, dry cough Orthostatic hypotension (more Angioedema, severe hyperkalemia, increase in serum creatinine >35% Bilateral renal artery stenosis, volume depletion, hyponatremia, pregnancy, history of angioedema pronounced in elderly treated with a diuretic), increased serum creatinine, increased potassium ARB Dizziness Orthostatic hypotension (more Severe hyperkalemia, increase in serum creatinine >35% Bilateral renal artery stenosis, volume depletion, hyponatremia, pregnancy pronounced in elderly treated with a diuretic), increased serum creatinine, increased potassium\\n', 'CCB: Dizziness, headache, Peripheral edema, tachycardia Significant peripheral edema Left ventricular dysfunction (not with Dihydropyridines flushing amlodipine or felodipine) CCB: Dizziness, headache, Bradycardia Heart block, left ventricular Left ventricular dysfunction, second- or third-degree heart block, sick sinus syndrome Nondihydropyridines constipation dysfunction, interactions with certain drugs b-Blocker Bradycardia, weakness, exercise intolerance Masking the symptoms of hypoglycemia in diabetes, hyperglycemia, aggravation of peripheral arterial disease, erectile dysfunction, increased triglycerides, decreased HDL-C Increased potassium Left ventricular dysfunction (not with carvedilol, metoprolol, bisoprolol), bronchospasm in patients with asthma or COPD (more pronounced with nonselective agents) Severe asthma, second- or third-degree heart block, acute left ventricular dysfunction exacerbation, coronary artery disease for agents with intrinsic sympathomimetic activity Aldosterone Antagonist Menstrual irregularities (spironolactone only) or gynecomastia (spironolactone only) Hyperkalemia, hyponatremia Kidney failure. kidney impairment (for eplerenone: CrCl <50 mL/minute, or type 2 diabetes with proteinuria, and creatinine >1.8 in women, >2.0 in men), hyperkalemia, hyponatremia\\n', 'Intervention Improve Leg Symptoms? Smoking cessation Exercise Cilostazol Statin drugs Angiotensin-converting enzyme Yes Yes Yes Yes Yes Yes No No Yes Yes inhibitors Blood pressure control Antiplatelet therapya No No Yes Yes\\n', 'Outcome Length of Follow-Up (years) Patient Population Current Smokers (%) Past Smokersa Rest pain Myocardial infarction Amputation Mortality 7 10 5 10 16 53 11 54 0 11 0 18\\n', 'Drug-Induced Cramps Biochemical Causes Other Alcohol Antipsychotics (dystonia) β-Agonists (e.g., albuterol, terbutaline, salbutamol) Cimetidine Clofibrate Diuretics Lithium Narcotic analgesics Nicotinic acid Nifedipine Penicillamine Statins Steroids Dehydration Hemodialysis Hypocalcemia Hypokalemia Hypomagnesemia Hyponatremia Uremia Contractures Diabetes Lower motor neuron disease Peripheral vascular disease Tetany Thyroid disease\\n', 'Score Cancer Hemoptysis Previous PE or DVT Heart rate >100 beats/minute Recent surgery or immobilization Clinical signs of DVT Alternative diagnosis less likely than PE +1 +1 +1.5 +1.5 +1.5 +3 +3\\n', 'Clinical Situation Peripartum Options Postpartum 1. ProPhylaxis Known hypercoagulable state with no prior history of VTE • Surveillance • Prophylactic UFH/LMWH Warfarin to INR 2–3 for 4–6 weeks with UFH/LMWH overlap until INR >2.0 Single prior episode of VTE associated with transient risk factors, not receiving long- term anticoagulants Single prior episode of idiopathic or thrombophilia- related VTE, not receiving long-term anticoagulants • Surveillance • Surveillance • Prophylactic UFH/LMWH • Intermediate-dose UFH/LMWH Warfarin to INR 2–3 for 4–6 weeks with UFH/LMWH overlap until INR >2.0 Warfarin to INR 2–3 for 4–6 weeks with UFH/LMWH overlap until INR >2.0 Multiple prior episodes of VTE and/or receiving long-term oral anticoagulants for VTE Long-term oral anticoagulants for mechanical valve replacement • Adjusted-dose UFH/LMWH • Intermediate-dose LMWH (or 75% of adjusted-dose LMWH) • Adjusted-dose SC UFH • Adjusted-dose BID LMWH (adjusted to achieve manufacturer recommended 4-hour postdose peak anti-factor Xa concentration) Long-term warfarin to INR 2–3 with UFH/LMWH overlap until INR >2.0 Long-term warfarin to prior INR goal with UFH/LMWH overlap until INR above lower limit of therapeutic range\\n', 'Indication Target INR (Range) Duration Comment nonValVular aTrial fibrillaTion/aTrial fluTTer CHA2DS2-VASc scorea = 0 None None Omit antithrombotic therapy CHA2DS2-VASc score = 1 2.5 (2.0–3.0) Chronic No therapy, aspirin 81–325 mg daily, or oral anticoagulation may be considered CHA2DS2-VASc score = 2 or greater 2.5 (2.0–3.0) Chronic Options include warfarin, apixaban, dabigatran, or rivaroxaban After open heart surgery 2.5 (2.0–3.0) 4 weeks (in NSR) Precardioversion (AF or 2.5 (2.0–3.0) 3 weeks flutter >48 hours) Postcardioversion (in NSR) 2.5 (2.0–3.0) 4 weeks ischemic sTroke Noncardioembolic stroke None Chronic Use antiplatelet therapy or TIA Cardioembolic stroke or 2.5 (2.0–3.0) Chronic TIA • With contraindications None Chronic to warfarin • Associated with aortic atherosclerotic lesions • Associated with mobile aortic arch thrombi • Associated with patent None 2.5 (2.0–3.0) None Chronic Chronic Chronic Use antiplatelet therapy Or antiplatelet therapy Use antiplatelet therapy foramen ovale myocardial infarcTion\\n', '2.5 (2.0–3.0) 2.5 (2.0–3.0) 2.5 (2.0–3.0) Chronic 3 months Chronic event 2.5 (2.0–3.0) Chronic Preceded by LMWH × 3–6 months 2.5 (2.0–3.0) Chronic 2.5 (2.0–3.0) Up to thrombosis 12 months 2.5 (2.0–3.0) 4 weeks\\n', 'Rheumatic mitral valve disease • With AF, hx systemic 2.5 (2.0–3.0) Chronic embolism, LA thrombus, or LA >55 mm • s/p thromboembolic 2.5 (2.0–3.0) Chronic Add aspirin 81 mg daily event despite anticoagulation or INR 2.5–3.5 ValVe rePlacemenT, bioProsTheTic Aortic 2.5 (2.0–3.0) 3 months Followed by aspirin 81 mg daily Mitral 2.5 (2.0–3.0) 3 months Followed by aspirin 81 mg daily With LA thrombus With prior history of systemic embolism With additional risk factorsc for thromboembolism 2.5 (2.0–3.0) 2.5 (2.0–3.0) 2.5 (2.0–3.0) Until resolution At least 3 months Chronic Add aspirin 81 mg daily if low bleed risk ValVe rePlacemenT, mechanical Aortic • Bileaflet in NSR w/nl 2.5 (2.0–3.0) Chronic LA size • Medronic Hall tilting disk in NSR w/nl LA size 2.5 (2.0–3.0) Chronic • After prosthetic valve 3.5 (3.0–4.0) Chronic Plus aspirin 81 mg daily thrombosis Mitral • Bileaflet or tilting disk • After prosthetic valve 3.0 (2.5–3.5) 4.0 (3.5–4.5) Chronic Chronic Plus aspirin 81 mg daily thrombosis Caged ball or caged disk 3.0 (2.5–3.5) Chronic (aortic or mitral) With additional risk factorsd for thromboembolism With systemic embolism 3.0 (2.5–3.5) Increase INR goal Chronic Chronic Add aspirin 81 mg daily if low bleed risk Or add aspirin 81 mg daily despite adequate anticoagulation aRisk factors: age >75 years; history of hypertension; diabetes; congestive heart failure or moderate/severe left ventricular\\n', 'firsT eVenT Provoked Unprovoked Unprovoked with proximal presentation 3 months At least 3 months; reevaluate risk–benefit at 3 months indefinite therapy and low risk of bleeding Cancer-associated cancer is resolved recurrenT eVenTs Provoked Unprovoked Indefinite therapy Indefinite therapy\\n', 'LMWH daily OR BID, fondaparinux, warfarin (INR 2–3), apixaban, or rivaroxaban LMWH BID, fondaparinux, warfarin (INR 2–3), apixaban, or rivaroxaban Fondaparinux, LMWH BID, or warfarin (INR 2–3) LMWH BID + IPC and/or GCS LMWH BID or LMWH/LDUFH + IPC/GCS IPC/GCS ± LDUFH every 12 hours, or LMWH daily LDUFH every 8–12 hours or LMWH\\n', 'Property UFH LMWH Molecular weight rangea Average molecular weighta Anti-Xa:anti-IIa activity aPTT monitoring required Inactivation by platelet factor 4 Capable of inactivation of platelet-bound factor Xa 3,000–30,000 12,000–15,000 1:1 Yes Yes No 1,000–10,000 4,000–5,000 2:1–4:1 No No Yes 1,728 1,728 >100:1 No No Yes Inhibition of platelet function Increases vascular permeability Protein binding Endothelial cell binding Dose-dependent clearance Primary route of elimination Elimination half-life ++++ Yes ++++ +++ Yes 1. Saturable binding processes 2. Renal 30–150 minutes ++ No + + No Renal 2–6 hours No No No No No Renal 17 hours\\n', 'Risk Stratum Mechanical Heart Valve Atrial Fibrillation Venous Thromboembolism High • Any mitral valve prosthesis • CHADS2 score of 5 or 6 • Recent (within • Recent (within 3 months) VTE • Older (caged-ball or tilting disk) aortic valve prosthesis • Recent (within 6 months) stroke or transient ischemic attack 3 months) stroke or transient ischemic attack • Rheumatic valvular heart disease • Severe thrombophilia (e.g., deficiency of protein C, protein S or antithrombin, antiphospholipid antibodies, or multiple abnormalities) Moderate • Bileaflet aortic valve prosthesis and one of the following: atrial fibrillation, prior stroke or transient ischemic attack, hypertension, diabetes, congestive heart failure, age >75 years • CHADS2 score of 3 or 4 • VTE within the past 3 –12 months (consider VTE prophylaxis rather than full-intensity bridge therapy) • Nonsevere thrombophilic conditions (e.g., heterozygous factor V Leiden mutation, heterozygous factor II mutation) • Recurrent VTE • Active cancer (treated within 6 months or palliative) Low • Bileaflet aortic valve prosthesis without atrial fibrillation and no other risk factors for stroke • CHADS2 score of 0–2 (no prior stroke or transient ischemic attack) • Single VTE occurred more than 12 months ago and no other risk factors\\n', 'Thromboembolic Risk Renal Function Bridge Therapy Low All patients • Last dose of warfarin on day –6 preprocedure • Hold warfarin day –5 through day –1 • Consider vitamin K 2.5 mg PO on day –2 or –1 if INR >1.5 • Resume warfarin 12–48 hours postprocedure at usual maintenance dose (decision based on postprocedure assessment of bleeding risk) High or moderate CrCl >30 mL/minute • Last dose of warfarin on day –6 preprocedure • Hold warfarin day –5 through day –1 • Start LMWH on day –3 (or when INR <lower limit of range) • Consider vitamin K 2.5 mg PO on day –2 or –1 if INR >1.5 • Last dose LMWH 24 hours preprocedure (on day –1, give half dose LMWH if patient is receiving once-daily LMWH) • Resume warfarin 12–24 hours postprocedure at usual maintenance dose (decision predicated on postprocedure assessment of bleeding risk) • Resume LMWH 24 hours postprocedure (or 48–72 hours for major surgery or high bleeding risk procedure) and continue until INR >lower limit of therapeutic range Continued on following page\\n', 'Thromboembolic Risk Renal Function Bridge Therapy CrCl < 30 mL/minute • Last dose of warfarin on day –6 preprocedure • Hold warfarin day –5 through day –1 • Consider vitamin K 2.5 mg PO or 1 mg IV on day –2 or –1 preprocedure if INR >1.5 • Admit on day –1 preprocedure and begin IV UFH (70 international units/kg bolus, 15 international units/kg/ hour infusion and adjust per inpatient protocol) • Stop IV UFH 6 hours preprocedure • Resume warfarin 12–24 hours postprocedure at usual maintenance dose (decision based on postprocedure assessment of bleeding risk) • Resume IV UFH 24 hours postprocedure (or 48–72 hours for major surgery or high bleeding risk procedure) and continue until INR > lower limit of therapeutic range\\n', 'Low Bleeding Risk Moderate Bleeding Risk High Bleeding Risk Procedure • Supragingival • Subgingival scaling • Extensive surgery scaling • Simple • Restorations with subgingival • Apicoectomy (root restorations • Local anesthetic preparations • Standard root canal therapy removal) • Alveolar surgery (bone injections removal) • Simple extractions • Regional injection of local • Multiple extractions anesthetics Suggestions • Do not interrupt • Interruption of warfarin • May need to reduce warfarin treatment treatment is not necessary international normalized ratio or return to normal hemostasis • Use local measures to prevent/control bleeding • Use local measures to prevent or control bleeding; consult with dentist to determine comfort with use of local measures to prevent bleeding when anticoagulation is not interrupted • Follow bridge therapy guidelines for invasive procedures based on risk of thromboembolism\\n', 'aPTTb (seconds) Heparin Bolus Infusion Hold Time Infusion Rate Adjustment Next aPTT <50 50–59 60–100 101–110 111–120 121–150 151–199 >200 4,000 units 2,000 units 0 0 0 0 0 0 0 0 0 0 0 30 minutes 60 minutes PRN Increase by 200 units/hour Increase by 100 units/hour None Decrease by 100 units/hour Decrease by 200 units/hour Decrease by 200 units/hour Decrease by 200 units/hour Hold until aPTT <100 In 6 hours In 6 hours Every morning In 6 hours In 6 hours In 6 hours In 6 hours Every hour until <100\\n', 'Category 2 Points 1 Point 0 Points 1. Thrombocytopenia 2. Timing of platelet count fall Platelet count fall >50% and platelet nadir ≥20 × 109 L−1 Clear onset between days 5 and 10 or platelet fall ≤1 day (prior heparin exposure within 30 days) Platelet count fall 30%–50% or platelet nadir 10–19 × 109 L−1 Consistent with days 5–10 fall, but not clear (e.g., missing platelet counts) or onset after day 10 or fall ≤1 day (prior heparin exposure 30–100 days ago) 3. Thrombosis or other New thrombosis Progressive or recurrent None sequelae (confirmed) or skin necrosis at heparin injection sites or acute systemic reaction after intravenous heparin bolus thrombosis or non- necrotizing (erythem- atous) skin lesions or suspected thrombosis (not proven) 4. Other causes for None apparent Possible Definite thrombocytopenia\\n', 'Dalteparin Enoxaparin Tinzaparin Fondaparinux 100 international units/kg SC every 12 hours OR 200 international units/kg SC every 24 hours 1 mg/kg SC every 12 hours OR 1.5 mg/kg SC every 24 hours 175 international units/kg SC every 24 hours 5 mg SC every 24 hours if weight <50 kg if weight 50–100 kg 10 mg SC every 24 hours if weight >100 kg\\n', 'LMWH Dalteparin Enoxaparin Tinzaparin Product information recommendations Dosing suggestions based on agent-specific pharmacokinetic observations Use with caution CrCL <30a mL/minute: no dose adjustment needed up to 1 week with prophylactic doses Prophylaxis—30 mg SC daily Treatment—1 mg/kg SC daily CrCL <30a mL/minute: Consider a 40%–50% dose decrease and subsequent monitoring of anti-Xa activity Use with caution CrCL <30a mL/minute: consider a dose decrease of 20% and subsequent monitoring of anti-Xa activity For use longer than 1 week, consider monitoring of anti-Xa activity and adjust dose if accumulation is noted CrCL 30–50 mL/minute: no dose CrCL 30–50 mL/minute: Consider a 15%–20% dose decrease with prolonged use (longer than 10–14 days) and subsequent monitoring of anti-Xa activity CrCL 30–50 mL/minute: no dose adjustment needed adjustment needed\\n', 'TABLE 16.14 Pharmacologic and Clinical Properties of Injectable Direct Thrombin Inhibitors Lepirudin Bivalirudin Argatroban Route of IV or SC (BID) IV IV administration FDA-approved indication Treatment of thrombosis in patients with HIT Patients with UA undergoing PTCA; PCI with provisional use of GPI; patients with or at risk of HIT/HITTS undergoing PCI Treatment of thrombosis in patients with HIT; patients at risk for HIT undergoing PCI Binding to thrombin Irreversible at catalytic site and exosite-1 Partially reversible at catalytic site and exosite-1 Reversible at catalytic site Half-life in healthy 1.3–2 hours 25 minutes 40–50 minutes subjects Monitoring Clearance Antibody development Effect on INR Initial dose for HIT aPTT (IV) SCr/CrCl Renal Antihirudin antibodies in up to 40%–60% of patients Slight increase HITTS: Bolusa: 0.4 mg/kg, up to a maximum of 110 kg, given over 15–20 seconds aPTT/ACT SCr/CrCl Enzymatic (80%) Renal (20%) May cross-react with antihirudin antibodies Slight increase No bolus Infusion: 0.15 mg/kg/hour aPTT/ACT Liver function Hepatic No Increase No bolus Infusion: 2 mcg/kg/minuteb In critically ill patients: consider lower infusion rate of 0.5–1 mcg/kg/minute Infusion: 0.15 mg/kg/ hour HIT: no bolus; 0.1 mg/kg/hour infusion Initial dose for PCI Dosing in renal impairment NA Bolusa: 0.2 mg/kg (bolus dose is best avoided in patients with renal impairment) Bolus: 0.75 mg/kg Infusion: 1.75 mg/kg/hour PCI: Bolus: no dose adjustment NA CrCl <30 mg/kg/hour: mean doses of 0.8 mcg/kg/minute have been reported Infusion: Infusion: Note: Dose adjustment not required per product information, but recent literature support dose adjustment as above CrCl 45–60: CrCl <30: 1 mg/kg/hour 0.075 mg/kg/hour CrCl 30–44: HD: 0.25 mg/kg/hour 0.045 mg/kg/hour CrCl 15–29: HIT: No bolus\\n', 'Lepirudin Bivalirudin Argatroban Dose adjustment not Dose adjustment not impairment required required then titrate to aPTT 1.5–3.0 × baseline\\n', 'Clotting Factor Half-Life (hours) II VII IX X Protein C Protein S 42–72 4–6 21–30 27–48 9 60\\n', 'Day INR 10-mg Initiation Dose (mg) 1 2 3 4 5 6 <1.5 1.5–1.9 2.0–2.5 >2.5 <1.5 1.5–1.9 2.0–2.5 2.5–3.0 >3.0 <1.5 1.5–1.9 2.0–3.0 >3.0 <1.5 1.5–1.9 2.0–3.0 >3.0 <1.5 1.5–1.9 2.0–30 >3.0 10 7.5–10 2.5 1.0–2.5 0 5–10 2.5–5 0–2.5 0–2.5 0 10 5–7.5 0–5 0 10 7.5–10 0–5 0 7.5–12.5 5–10 0–7.5 0 5 5 2.5 1–2.5 0 5–10 2.5–5 0–2.5 0–2.5 0 10 5–7.5 0–5 0 10 7.5–10 0–5 0 7.5–12.5 5–10 0–7.5 0\\n', 'For Goal INR 2–3 Adjustment For Goal INR 2.5–3.5 INR <1.5 • Increase maintenance dose by 10%–20% • Consider a booster dose of 1.5–2 times daily maintenance dose • Consider resumption of prior maintenance dose if factor INR <2.0 causing decreased INR is considered transient (e.g., missed warfarin dose[s]) INR 1.5–1.8 • Increase maintenance dose by 5%–15% • Consider a booster dose of 1.5–2 times daily maintenance dose • Consider resumption of prior maintenance dose if factor INR 2.0–2.3 causing decreased INR is considered transient (e.g., missed warfarin dose[s]) INR 1.8–1.9 • No dosage adjustment may be necessary if the last two INRs were in range, if there is no clear explanation for the INR to be out of range, and if in the judgment of the clinician the INR does not represent an increased risk of thromboembolism for the patient INR 2.3–2.4 • If dosage adjustment is needed, increase by 5%–10% • Consider a booster dose of 1.5–2 times daily maintenance dose • Consider resumption of prior maintenance dose if factor causing decreased INR is considered transient (e.g., missed warfarin dose[s]) INR 2.0–3.0 Desired range INR 2.5–3.5\\n', 'For Goal INR 2–3 Adjustment For Goal INR 2.5–3.5 INR 3.1–3.2 • No dosage adjustment may necessary if the last two INRs were in range, if there is no clear explanation for the INR to be out of range, and if in the judgment of the clinician the INR does not represent an increased risk of hemorrhage for the patient INR 3.6–3.7 • If dosage adjustment needed, decrease by 5%–10% • Consider resumption of prior maintenance dose if factor causing elevated INR is considered transient (e.g., acute alcohol ingestion) INR 3.3–3.4 • Decrease maintenance dose by 5%–10% • Consider resumption of prior maintenance dose if factor causing elevated INR is considered transient (e.g., acute alcohol ingestion) INR 3.8–3.9 INR 3.5–3.9 • Consider holding one dose • Decrease maintenance dose by 5%–15% • Consider resumption of prior maintenance dose if factor causing elevated INR is considered transient (e.g., acute alcohol ingestion) INR 4.0–4.4 INR >4.0 • Hold until INR < upper limit of therapeutic range • Consider use of minidose oral vitamin K • Decrease maintenance dose by 5%–20% • Consider resumption of prior maintenance dose if factor causing elevated INR is considered transient (e.g., acute alcohol ingestion) INR >4.5\\n', 'Every 1–3 days Daily If stable, within 3–5 days If unstable, within 1–3 days In 1–2 days Every 4–6 weeks and reliable patients Every 1–2 weeks or unreliable patients In 1–2 days Within 1–2 weeks Within 2–4 weeks\\n', 'Recommendation Lower or hold dose. Hold one or two doses. Recommend against using oral vitamin K. Hold warfarin and give vitamin K (2.5–5 mg orally). Use additional vitamin K, if necessary. Hold warfarin and give vitamin K (10 mg slow IV infusion) supplemented with fresh-frozen plasma, prothrombin complex concentrates, or recombinant factor VIIa. May repeat vitamin K every 12 hours, if necessary. Hold warfarin and give fresh-frozen plasma, prothrombin complex concentrates, or recombinant bleeding factor VIIa supplemented with vitamin K (10 mg slow IV infusion). Repeat as necessary.\\n', 'Clinical Condition Effect on Warfarin Therapy Advanced age Increased sensitivity to warfarin due to reduced vitamin K stores and/or lower plasma concentrations of vitamin K–dependent clotting factors Pregnancy Lactation Alcoholism Liver disease Teratogenic; avoid exposure during pregnancy Not excreted in breast milk; can be used postpartum by nursing mothers • Acute ingestion: inhibits warfarin metabolism, with acute elevation in INR • Chronic ingestion: induces warfarin metabolism, with higher dose requirements • May induce coagulopathy by decreased production of clotting factors, with baseline elevation in INR Renal disease Heart failure Cardiac valve replacement • May reduce clearance of warfarin Reduced activity of CYP2C9, with lower warfarin dose requirements Reduced warfarin metabolism due to hepatic congestion Enhanced sensitivity to warfarin postoperatively due to hypoalbuminemia, lower oral intake, decreased physical activity, and reduced clotting factor concentrations after cardiopulmonary bypass Nutritional status Changes in dietary vitamin K intake (intentional or as the result of disease, surgery, etc.) alter response to warfarin Use of tube feedings Decreased sensitivity to warfarin, possibly caused by changes in absorption or vitamin K content of nutritional supplements Thyroid disease • Hypothyroidism: decreased catabolism of clotting factors requiring increased dosing requirements • Hyperthyroidism: increased catabolism of clotting factors causing increased sensitivity to warfarin Smoking and tobacco use Fever Diarrhea Acute infection/ inflammation • Smoking: may induce CYP1A2, increasing warfarin dosing requirements • Chewing tobacco: may contain vitamin K, increasing warfarin dosing requirements Increased catabolism of clotting factors, causing acute increase in INR Reduction in secretion of vitamin K by gut flora, causing acute increase in INR Increased sensitivity to warfarin Malignancy Increased sensitivity to warfarin by multiple factors\\n', 'TABLE 16.23 Warfarin Drug Interactions Target Effect Response Examples (Not Inclusive) Clotting factors Increased synthesis Decreased synthesis Increased catabolism Decreased catabolism Inhibition Decreased INR Increased INR Increased INR Decreased INR Increased INR Vitamin K Broad-spectrum antibiotics Thyroid hormones Methimazole Acetaminophen Propylthiouracil Amiodarone Warfarin Allopurinol Azole antifungals metabolism Cimetidine Propafenone Barbiturates Nafcillin Aspirin Fluroquinolones SSRIs Carbamazepine Phenytoine NSAIDs Macrolides Statins Doxycycline Primidone Salicylates Metronidazole Sulfa antibiotics Griseofulvin Rifampin GPIIb/IIIa inhibitors Thrombolytics Induction Decreased INR Hemostasis Additive antithrombotic effects Increased bleeding risk Additive anticoagulant Increased bleeding risk Heparin LMWH Direct thrombin response inhibitors Sucralfate Corticosteroids Cyclophosphamide Decreased INR Decreased INR Increased INR Cholestyramine Ascorbic acid Androgens Colestipol Azathioprine Fenofibrate Absorption Unknown Reduced Cyclosporine Gemfibrozil\\n', 'Risk Factor Intervention and Goal Smoking Blood pressure Lipid management Diabetes Physical activity Complete cessation No exposure to environmental tobacco smoke <130/80 mm Hg <130/80 mm Hg if patient has diabetes or chronic kidney disease LDL-C <100 mg/dL If triglycerides >200 mg/dL, non–HDL-C should be <130 mg/dL Hemoglobin A1c <7% At least 30 minutes of moderate intensity aerobic activity (e.g., brisk walking) Weight management Influenza vaccination for minimum of 5 days/week BMI between 18.5 and 24.9 kg/m2 Waist circumference, men <40 inches Waist circumference, women <35 inches Patients with CAD should have an annual influenza vaccination\\n', 'FDA Approveda Usual Dose for Chronic Stable Anginab Product Availability DihyDropyriDinES Angina, hypertension Hypertension Hypertension Angina (IR only), hypertension Angina, hypertension 2.5–10 mg every day 5–20 mg every day 2.5–10 mg BID 5–10 mg every day 20–40 mg TID 30–60 mg BID 10–30 mg TID 30–180 mg every day 20–60 mg every day 2.5, 5, 10 mg tab 5, 10 mg ER tab 2.5, 5 mg IR cap 5, 10 mg CR tab 20, 30 mg IR cap 30, 45, 60 mg SR cap 10, 20 mg IR cap 30, 60, 90 mg ER tab 10, 20, 30, 40 mg ER tab Hypertension DiphEnyLaLkyLaminES Angina, hypertension, SVT 30–120 mg TID/QID 120–240 mg BID 120–480 mg every HS 40, 80, 120 mg IR tab 120, 180, 240 mg SR tab 180, 240 mg DR, ER tab 120, 180, 240, 360 mg ER cap 100, 200, 300 mg DR, ER tab BEnzothiazEpinES Angina, hypertension, SVT 30–120 mg TID/QID 60–180 mg BID 120–480 mg every day\\n', 'Effect Dihydropyridine Derivativesa Diltiazem Verapamil Peripheral vasodilationb Coronary vasodilationb Negative inotropesc AV node suppressionc Heart rate Pharmacokineticsd Dosinge +++ +++ ± ± Increase (reflex) ++ +++ ++ + ++ ++ +++ ++ Decrease or unchanged Decrease or unchanged SiDE EffEctS Nausea, vomiting Constipation Hypotension, dizzinessf Flushing, headache Bradycardia, HF symptoms Reflex tachycardia, angina Peripheral edema + (most) Not observed ++ ++ ± + + +/1 ± + + + Not observed ± ± + + + ++ Not observed ±\\n', 'Long-actingd NTG NTG NTG NTG ISDN ISMNg SR capsule Topical ointmente Transdermal patch Transmucosal SL Chewable Oral SR capsule Tablet (ISMO, Monoket) 4–8 hours 4–8 hours 4–8 hours 3–6 hours 2–4 hours 2–4 hours 2–6 hours 4–8 hours 7–8 hours 30 30 30–60 2–5 2–5 2–5 15–40 15–40 30–60 6.5–9 mg every 8 hours 1–2 inches every 4–6 hoursf 0.1–0.2 mg/hour to start; titrate up to 0.8 mg/hourf 1–3 mg every 3–5 hoursf 2.5–10 mg every 2–4 hoursf 5–10 mg every 2–4 hoursf 10–60 mg every 4–6 hoursf 40–80 mg every 6–8 hoursf 10–20 mg BID (morning and midday) to start; titrate to 20–40 mg BIDf 60 mg every day to start; titrate Extended-release tablet (Imdur) 8–12 hours 30–60 to 30–120 mg every day\\n', 'TABLE 17.6 Considerations for the Use of Ranolazine in Patients with Chronic Stable Angina Clinical Issue Recommended Management Strategy Renal insufficiency Ranolazine plasma levels may increase up to 50%. Caution with dose titration to maximal recommended dose Hepatic insufficiency Ranolazine is contraindicated in patients with clinically significant hepatic impairment. Drug intEractionS: EffEctS on ranoLazinE Strong CYP3A4 inhibitors Plasma concentrations of ranolazine are significantly elevated when combined with potent inhibitors of CYP3A4. Ranolazine is contraindicated in patients receiving strong CYP3A4 inhibitors (ketoconazole, clarithromycin, nelfinivir, etc.). Moderate CYP3A4 inhibitors Limit the dose of ranolazine to 500 mg twice daily in patients receiving moderate inhibitors of CYP3A4 (diltiazem, verapamil, erythromycin, fluconazole, etc.). CYP3A4 inducers Coadministration of ranolazine with CYP3A4 inducers is contraindicated and should be avoided. P-glycoprotein inhibitors Caution should be exercised when coadministering ranolazine with P-glycoprotein inhibitors, and the dose of ranolazine may need to be lowered on the basis of clinical response. Drug intEractionS: EffEctS on othEr mEDicationS Simvastatin Plasma levels of simvastatin are increased twofold with coadministration with ranolazine through CYP3A4 inhibition by ranolazine; closely monitor for adverse effects (e.g., myositis) from simvastatin. Digoxin Ranolazine coadministration increases plasma concentrations of digoxin by 1.5 times. Adjust dose of digoxin accordingly to maintain desired therapeutic level and response. CYP2D6 substrates Ranolazine can inhibit the activity of CYP2D6, and plasma concentrations of 2D6 substrates (β-blockers, tricyclic antidepressants, antipsychotics) may be increased and lower doses of these agents may be required. QT prolongation Caution is recommended if the patient is on other QT prolonging drugs or has QT prolongation as baseline\\n', 'TIMI Risk Scorea STEMI NSTEMI Risk Factor No. of Points Risk Factor No. of Points Age 65–75 years Age ≥ 75 years SBP < 100 mm Hg Heart rate > 100 beats/minute Killip class II–IV Weight < 67 kg History of HTN, diabetes, or angina Time to reperfusion therapy > 4 hours Anterior ST segment elevation or left 2 3 3 2 2 1 1 1 Age ≥ 65 years ≥3 risk factors for CADb Prior history of CADc Aspirin use in past 7 days ≥2 anginal events in past 24 hours ST segment deviation ≥ 0.5 mm Elevation of cardiac markersd 1 1 1 1 1 1 1 bundle branch block 1\\n', 'Class Symptoms In-Hospital and 1-Year Mortality (%) No heart failure Mild heart failure, rales, S3, congestion on chest radiograph Pulmonary edema Cardiogenic shock 5 21 35 67\\n', 'Drug Indication Dose and Duration Therapeutic End Points Precautions Comments ACE inhibitorsa STEMI and NSTEMI Usual captopril dose 12–50 mg TID; then start longer-acting ACE inhibitor. Duration indefinite Titrate to usual doses and maintain systolic BP >90–110 mm Hg Avoid IV therapy within within the first 24 hours of presentation for those with EF ≤40% or s/s of HF STEMI and NSTEMI for late hospital care for patients with hypertension, EF ≤40%, DM, or CKD 48 hours of infarct Avoid with SBP <100 mm Hg, pregnancy, acute renal failure, angioedema, bilateral renal stenosis, serum potassium ≥5.5 mEq/L STEMI and NSTEMI for indefinite use for all patients with EF ≤40% Angiotensin receptor blockersa STEMI and NSTEMI with ACE inhibitor intolerance Usual doses of ARBs (see Chapter 19). Continue indefinitely. Same as for ACE inhibitors Same as for ACE inhibitors Aldosterone antagonistsa STEMI and NSTEMI with EF ≤40% and either DM or HF symptoms already receiving therapeutic doses of an ACE inhibitor and β-blocker STEMI and NSTEMI for all Spironolactone 12.5–50 mg Titrate to heart failure Hyperkalemia, hypotension Avoid if potassium ≥5 daily or eplerenone 25–50 mg daily. Duration indefinite. symptom control without evidence of hyperkalemia 4–8 weeks. mEq/L or SCr ≥2.5 mg/dL for men and 2.0 mg/dL for women or CrCl ≤ 30 mL/ minute Aspirina 162–325 mg during AMI, No firm end point Active bleeding, Unless clear patients then 75–325 mg/day for an indefinite period. thrombocytopenia\\n', 'Indication Dose and Duration Therapeutic End Points Precautions Comments STEMI and NSTEMI for patients with ongoing ischemia who are receiving adequate doses of nitrates and β-blockers. Consider diltiazem or verapamil for patients with contraindication to β-blocker if EF is normal STEMI and NSTEMI for Usual doses of calcium- Titrate to usual doses and Usual calcium-channel blockers channel blockers are used. Duration dictated by clinical scenario maintain SBP > 90 mm Hg blocker contraindications. Avoid nondihydropyridines in patients with pulmonary congestion or EF <40% 75 mg/day No firm end point Active bleeding, thrombotic thrombocytopenia purpura (rare) patients allergic to aspirin STEMI, before fibrinolytic STEMI with fibrinolytic therapy without PCI: 300–600 mg load followed by 75 mg daily and continue for 14 days to 1 year; aspirin 162–325 mg on first day, then 75–162 mg daily indefinitely. STEMI with fibrinolytic No firm end point Active bleeding, thrombotic thrombocytopenia purpura (rare) Whether administered therapy or before PCI after fibrinolytic therapy NSTEMI or STEMI Avoid loading dose in Clopidogrel + aspirin before PCI therapy with PCI: 300–600 mg load,b then no additional treatment; aspirin 162–325 mg on first day, then 75–162 mg daily indefinitely. patients ≥75 years of age For NSTEMI and unstable STEMI or NSTEMI Discontinue at least 5 days\\n', 'Indication Dose and Duration Therapeutic End Points Precautions Comments A supplemental 0.3 mg/kg IV dose should be administered at the time of PCI if the last dose of SC enoxaparin was given 8–12 hours before PCI STEMI with fibrinolytic therapy: Age <75 years, administer 30 mg IV bolus followed by 1 mg/kg SQ every 12 hours (max dose of 100 mg for patients weighing ≥100 kg) Age ≥75, administer 0.75 mg/kg SQ every 12 hours (first two doses administer max dose of 75 mg for patients weighing ≥75 kg) For STEMI and NSTEMI continue throughout hospitalization or up to 8 days See Table 18.3 STEMI presenting within Improved TIMI grade flow See Table 18.4\\n', 'Drug Indication Dose and Duration Therapeutic End Points Precautions Comments Lidocaine Treatment of VT, VF Variable, 1.5 mg/kg loading dose, then 1–4 mg/minute. Use for <48 hours. Cessation of arrhythmia Bradycardia. Observe for CNS toxicity. Morphine and STEMI and NSTEMI for 2–5 mg IV every Decreased chest pain and Avoid morphine with bradycardia, right ventricular infarct, hypotension, confusion. Has been associated with higher risk of death; discontinue nonselective NSAIDs and COX-2 selective agents. other analgesics patients whose symptoms not relieved by NTG or adequate anti-ischemic therapy 5–30 minutes PRN HR Prasugrela STEMI and NSTEMI added 60 mg loading dose followed by 10 mg (if ≥60 kg) or 5 mg (if <60 kg). If a coronary stent is deployed, continue prasugrel for 12–15 months. For a BMS, administer aspirin 162–325 mg daily for at least 1 month after PCI, then drop to 75–162 mg indefinitely; For a DES, administer aspirin 162–325 mg daily for 3–6 months after PCI, then drop to 75–162 mg daily indefinitely. No firm end point Avoid with active bleeding, prior stroke or TIA, age ≥75 years. to aspirin for PCI Do not start if urgent CABG is needed; discontinue 7 days before elective CABG. Nitratesa STEMI and NSTEMI Variable; titrate to pain relief or SBP: 5–10 mcg/minute titrated to 200 mcg/minute typical regimen. Usually maintain IV therapy for 24–48 hours after infarct. Titrate to pain relief or SBP Avoid with SBP <90 mm Hg, right ventricular infarction, sildenafil or vardenafil within 24 hours or tadalafil within 48 hours. Use acetaminophen or narcotics for headache. NTG should be tapered gradually in ischemic heart disease patients. with persistent ischemia, hypertension, or control of pulmonary congestion >90 mm Hg\\n', 'STEMI, NSTEMI, STEMI, NSTEMI, or No firm endpoints Avoid in patients with Monitor closely for dyspnea. Ticagrelor + Aspirin Unstable Angina with or without PCI Unstable Angina: 180 mg load followed by 90 mg twice daily for at least 1 year; administer 325 mg load of aspirin followed by a maintenance dose of 75–100 mg daily indefinitely. severe hepatic impairment or active bleeding. Maintenance doses of aspirin above 100 mg daily can decrease ticagrelor’s effectiveness, Discontinue at least 5 days for CABG. Warfarin STEMI and NSTEMI for left Variable; titrate to INR 3. INR 2–3 times patient’s Usual warfarin problems such as noncompliance, bleeding, diatheses May be useful in the presence of a left ventricular thrombus to prevent embolism ventricular thrombus or for patients with AF with CHAD2 score ≥2 Duration usually for several months to indefinitely control value\\n', 'Drug Enzymatic Efficiency for Clot Lysis Fibrin Specificity Potential Antigenicity TIMI Grade Flow at 90 Minutes (% of Patients) Average Dose Dosing Administration Cost Streptokinase (Streptase) Alteplase High High Minimal Moderate Yes No 32 54 1.5 million units 100 mg 1-hour IV infusion 15-mg IV bolus, Low High (Activase) Reteplase (Retavase) High Moderate No 60 10 + 10 units 50 mg for 30 minutes, then 35 mg for 60 minutesa 10-U IV bolus, 2nd bolus 30 minutes later High Tenecteplase (TNK) High High No 63 30–50 mg (based on weight)b Bolus for 5–10 seconds High\\n', 'Major (thrombolytic agents contraindicated) Important (relative contraindication) Intracranial tumor (primary or metastatic) Prior intracranial hemorrhage Recent head or facial trauma within 3 months Suspected aortic dissection Ischemic stroke within 3 months, EXCEPT acute ischemic stroke within 3 hours Active internal bleeding or bleeding diathesis (excluding menses) Uncontrolled hypertension on presentation (SBP >180 mm Hg, DBP >110 mm Hg) Chronic, severe, poorly controlled hypertension Prior ischemic stroke >3 months, dementia, or known intracranial pathology Puncture of a noncompressible vessel Cardiopulmonary resuscitation for >10 minutes Major surgery (<3 weeks) Recent internal bleeding within 24 weeks Active peptic ulcer Current use of anticoagulants (the higher the INR, the greater the risk for bleeding) Pregnancy For streptokinase or anistreplase: prior exposure (>5 days) or prior\\n', 'Dosing for STEMI PCI Dose for NSTEMI with or without PCI Comments 0.25-mg/kg IV bolus followed by 0.125-mcg/kg/minute infusion (max of 10 mcg/ minute), continue for 12 hours at the discretion of the physician Not recommended 180-mcg/kg IV bolus, then begin 2-mcg/kg/minute infusion followed by second IV bolus of 180 mcg/kg 10 minutes after first bolus, continue infusion for 12–18 hours after PCI at the discretion of the physician 25-mcg/kg IV bolus followed by an infusion of 0.15 mcg/ kg/minute, continue up to 18 hours at the discretion of the physician 180-mcg/kg IV bolus, then begin 2-mcg/kg/minute infusion, continue infusion for 12–18 hours Repeat bolus dose after 10 minutes for PCI. 0.4-mg/kg IV bolus administered for 30 minutes followed by an infusion of 0.1 mcg/kg/minute for 12–24 hours Reduce infusion by 50% in patients with CrCl < 50 mL/minute; not studied in patients with SCr > 4.0 mg/dL. Avoid in patients on hemodialysis. Reduce infusion by 50% in patients with CrCl <30 mL/ minute\\n', 'Type of Failure Characteristics Contributing Factors Etiology Low output, systolic dysfunction (dilated cardiomyopathy)a Hypofunctioning left ventricle; enlarged heart (dilated left ventricle); ↑left ventricular end-diastolic volume; EF < 40%; ↓stroke volume; ↓CO; S3 heart sound present 1. ↓Contractility (cardiomyopathy) 2. ↑Afterload (elevated SVR) 1. Coronary ischemia,b MI, mitral valve stenosis or re- gurgitation, alcoholism, viral syndromes, nutritional defi- ciency, calcium and potas- sium depletion, drug induced, idiopathic 2. Hypertension, aortic stenosis, Diastolic dysfunction High-output failure (uncommon) Normal left ventricular contractility; normal-sized heart; stiff left ventricle; impaired left ventricular relaxation; impaired left ventricular filling; normal EF; S4 heart sound Normal or ↑contractility; normal-sized heart; normal left ventricular end-diastolic volume; normal or ↑EF; normal or increased stroke volume; ↑CO 1. Thickened left ventricle (hypertrophic cardiomyopathy) 2. Stiff left ven- tricle (restrictive cardiomyopathy) 3. ↑Preload ↑Metabolic and oxygen demands volume overload 1. Coronary ischemia,b MI hypertension, aortic stenosis and regurgitation, pericardi- tis, enlarged left ventricular septum (hypertrophic car- diomyopathy) 2. Amyloidosis, sarcoidosis 3. Sodium and water retention Anemia and hyperthyroidism\\n', 'Left Ventricular Failure Right Ventricular Failurea Subjective Objective DOE SOB Orthopnea (two to three pillows) PND, cough Weakness, fatigue, confusion Weakness, fatigue LVH ↓BP EF < 40%b Rales, S3 gallop rhythm Reflex tachycardia ↑BUN (poor renal perfusion) Peripheral edema Weight gain (fluid retention) Neck vein distension Hepatomegaly Hepatojugular reflux\\n', 'Negative iNotropic ageNts b-Blockersa Calcium-channel blockersa Most evident with propranolol or other nonselective agents Less with agents with intrinsic sympathomimetic activity (acebutolol, carteolol, pindolol); can also be caused by use of timolol eye drops Verapamil has the most negative inotropic and AV-blocking effects; amlodipine has the least Antiarrhythmics Most with disopyramide; also quinidine Least with amiodarone Direct carDiotoxiNs Cocaine, amphetamines Anthracycline cancer chemotherapeutic drugs Overdoses and long-term myopathy Daunorubicin and doxorubicin (Adriamycin); dose related; keep total cumulative dose <600 mg/m2 proarrhythmic effects Class IA, Class III antiarrhythmic drugs Nonantiarrhythmic drugs (see Crouch et al.93 for a complete list) QT interval widening Probable torsades de pointes HF develops if disturbed rhythm compromises cardiac functioning Same mechanism as above Often associated with drug interactions that inhibit metabolism of the offending drug, leading to higher-than-desired plasma levels expaNsioN of plasma volume Antidiabetics NSAID Glucocorticoids, androgens, estrogens Licorice Antihypertensive vasodilators (hydralazine, Metformin high dose may increase risk of lactic acidosis Na retention with pioglitazone (Actos) and rosiglitazone (Avandia) Prostaglandin inhibition; Na retention Mineralocorticoid effect; Na retention Aldosteronelike effect; Na retention ↓Renal blood flow, activation of renin–angiotensin system methyldopa, prazosin, minoxidil) Drugs high in Na+ Selected IV cephalosporins and penicillins Effervescent or bicarbonate-containing antacids or analgesics Also liquid nutrition supplements uNkNowN mechaNism Tumor necrosis factor antagonists Multiple case reports of new-onset HF or exacerbation of prior HF\\n', 'Furosemide Bumetanide Torsemide IV loading doses Maximum total daily dose Ceiling dose Normal renal function Clcr: 20–50 mL/minute ClCr: <20 mL/minute Bioavailability Duration of action 40 mg 600 mg 80–160 mg (PO/IV) 160 mg (PO/IV) 200 mg (IV), 400 mg (PO) 10%–100% 6–8 hours 1 mg 10 mg 1–2 mg (PO/IV) 2 mg (PO/IV) 8–10 mg (PO/IV) 80%–90% 4–6 hours 20 mg 200 mg 20–40 mg (PO/IV) 40 mg (PO/IV) 100 mg (PO/IV) 80%–100% 12–16 hours\\n', 'Available Dosage Form Initial Doseb Maximal Dose 12.5, 25, 50, 100 mg tablets 2.5, 5, 10, 20 mg tablets 10, 20, 40 mg tablets 2.5, 5, 10, 20, 40 mg tablets 5, 10, 20, 40 mg tablets 2, 4, 8 mg tablets 1.25, 2.5, 5, 10 mg capsules 1, 2, 4 mg tablets 6.25–12.5 mg TID 2.5–5 mg every day 5–10 mg every day 2.5–5 mg every day 5–10 mg every day 2 mg every day 1.25–2.5 mg every day 1 mg every day 100 mg TID 20 mg BID 40 mg every day 40 mg every day 20 mg BID 16 mg every day 10 mg BID 8 mg every day\\n', 'Drug Effect Drugs loweriNg serum DigoxiN coNceNtratioN Rifampin257 Probable induction of intestinal P-glycoprotein causing ↓bioavailability. ↓Serum concentration after oral, but not IV digoxin. No change in digoxin renal clearance or half-life. St. John’s wort258 Sulfasalazine doses > 2 g/day Possible induction of P-glycoprotein (33% reduction in digoxin trough concentrations).259 Malabsorption of digoxin (decrease AUC of digoxin by 24%).259 Drugs raisiNg serum DigoxiN coNceNtratioN Amiodarone243,253 Atorvastatin260 ↑Serum digoxin levels by inhibit intestinal P-glycoprotein (70% in 1 day).259 20% increase in serum digoxin concentration with 80-mg dose, minimal effect with 20-mg dose. Speculated to inhibit intestinal P-glycoprotein, but not proven. Calcium-channel blockers243,253,261 Clarithromycin263 Inhibition of P-glycoprotein. Best documented with verapamil (70%– 80%).262 Diltiazem increases digoxin concentrations by 50% in some patients.259 Inhibition of P-glycoprotein, decreased digoxin renal clearance. Digoxin Cyclosporine243,253 Erythromycin clearance may be reduced by 60%, and plasma concentrations may increase by twofold.259 Inhibition of P-glycoprotein, decreased digoxin renal clearance. ↑Bioavailability in persons who normally metabolize digoxin in intestinal Itraconazole265 Propafenone243,266 Quinidine243,253,254,256,267–271 (usually doses above 500 mg/ day may increase digoxin serum concentrations) tract. May also inhibit P-glycoprotein in gut. Digoxin concentrations may increase by 100% in some cases.259 ↑Serum digoxin levels by unknown mechanism. In one study, the AUC for digoxin was increased by 50% and renal elimination was decreased by 20%.259 Inhibition of P-glycoprotein. Increases digoxin concentrations by 30%–60%.259 Inhibition of P-glycoprotein; decreased digoxin renal clearance and increased bioavailability. Increases 25%–100% digoxin concentrations.259\\n', 'I II Normal Pulmonary edema IV III Fluid administration Inotropic agents Reduced blood pressure: Inotropic agents or vasopressors Hypovolemic shock Cardiogenic shock Pulmonary Congestion Indicators of low organ perfusion: Hypotension: SBP <100 mm Hg ↑ Peripheral vascular resistance ↓ Cardiac output Weak peripheral pulse Cool extremities ↓ Mental alertness ↑ BUN or SCr ↓ Urine flow Indicators of high filling pressure: ↑ Right atrial pressure ↑ Pulmonary pressure Orthopnea Jugular venous distension Third heart sound Peripheral edema Ascites\\n', 'Nonrheumatic heart disease Pericarditis Pneumonia Pulmonary embolism Sick sinus syndrome Stimulants Thyrotoxicosis Trauma Tumors Wolff–Parkinson–White syndrome\\n', 'Drug Class Agent Drugs That Increase Blood Concentrations of These QTc Interval–Prolonging Drugs Antianginal Antibiotics: macrolides Antibiotics: fluoroquinolones Ranolazine Erythromycin (lactobionate and base) Gatifloxacin, grepafloxacin, CYP3A4 inhibitors CYP3A4 inhibitors lomefloxacin, moxifloxacin, sparfloxacin Antibiotics: other Trimethoprim-sulfamethoxazole, pentamidine isethionate Antidepressants Antiemetics Antimalarials Tricyclics, maprotiline Dolasetron Mefloquine, quinine CYP1A2, 2D6, or 2C9 inhibitors Sodium bicarbonate, Antipsychotics Atypicals, butyrophenones, typicals acetazolamide, cimetidine CYP1A2, 2D6, 2C9, 3A4 inhibitors Calcium-channel blockers Dopaminergics Bepridil Amantadine Hydrochlorothiazide, quinidine, quinine, trimethoprim- sulfamethoxazole Narcotics Sympathomimetics Methadone Albuterol, ephedra, epinephrine, CYP3A4 and 1A2 inhibitors Monoamine oxidase inhibitors metaproterenol, terbutaline, salmeterol\\n', 'Drug and Classification Pharmacokinetics Indications Side Effects Class Ia (Can Cause torsades de poIntes sImIlar to Class III agents) Quinidine sulfate (83% quinidine; SR: Quinidex) Quinidine gluconate (62% quinidine; SR: Quinaglute) t1/2 5 6.2 6 1.8 hours (affected by age, cirrhosis); Vd 5 2.7 L/kg (↓ in HF); liver metabolism, 80%; renal clearance, 20%; Cp 5 2–6 mcg/mL, CYP3A4 substrate, CYP2D6 inhibitor, P-glycoprotein inhibitor AF (conversion or prophylaxis), WPW, PVCs, VT Diarrhea, hypotension, N/V, cinchonism, fever, thrombocytopenia, proarrhythmia Procainamide (Pronestyl) Disopyramide (Norpace; SR: Norpace CR) t1/2 5 3 6 0.6 hours; Vd 5 1.9 6 0.3 L/kg; liver metabolism 40%; renal clearance (GFR 1 possible CTS) 60%; active metabolite (NAPA)a Cp 5 4–10 mcg/mL, possible CTS substrate t1/2 5 6 6 1 hours; Vd 5 0.59 6 0.15 L/kg; liver metabolism, 30%; renal clearance, 70%; Cp 5 3–6 mcg/mL AF (conversion or prophylaxis), WPW, PVCs, VT AF, WPW, PSVT, PVCs, VT Hypotension, fever, agranulocytosis, SLE (joint/muscle pain, rash, pericarditis), headache, proarrhythmia Anticholinergic (dry\\n', '(Xylocaine) t1/2 5 1.8 6 0.4 hours; Vd 5 1.1 6 0.4 L/kg; liver metabolism, 100%; Cp 5 1.5–6 mcg/mL t1/2 5 10.4 6 2.8 hours; Vd 5 9.5 6 3.4 L/kg; liver metabolism, 35%–80%; Cp 5 0.5–2 mcg/mL PVCs, VT, VF PVCs, VT, VF Drowsiness, agitation,\\n', '(Tambocor) t1/2 5 12–27 hours; CYP2D6 substrate, 75%; renal clearance, 25%; Cp 5 0.4–1 mcg/mL t1/2 5 2 hours (extensive metabolizer); 10 hours (poor metabolizer); Vd 5 2.5–4 L/kg, CYP2D6 substrate/ inhibitor, P-glycoprotein inhibitor t1/2 5 1.3–3.5 hours; Vd >300 L AF, PSVT, severe ventricular arrhythmias PAF, WPW, severe ventricular arrhythmias Severe Dizziness, tremor, lightheadedness, flushing, blurred vision, metallic taste, proarrhythmia Dizziness, blurred vision, taste disturbances, nausea, worsening of asthma, proarrhythmia Nausea, dizziness, perioral (Ethmozine) ventricular arrhythmias numbness, euphoria\\n', 'Pharmacokinetics t1/2 5 7.5–10 hours; Vd 5 3 L/kg; renal elimination, 60% (GFR 1 CTS), CYP3A4 substrate t1/2 5 6 (2–12) hours; Vd 5 11 L/kg, Cp 5 undefined t1/2 5 13–19 hours; Vd 5 20 L/kg, Tmax 5 3–6 hours, CYP3A4 substrate, CYP 2D6, 3A4 inhibitor, P-glycoprotein inhibitor, take with food for maximal absorption Indications AF or atrial flutter conversion and prophylaxis AF or atrial flutter conversion AF or atrial flutter prophylaxis Side Effects Chest pain, dizziness, headache, proarrhythmia Headache, nausea, proarrhythmia\\n', 'Drug Loading Dose Usual Maintenance Dose Comments Digoxin (Lanoxin) 10–15 mcg/kg LBW up to 1–1.5 mg IV or PO for 24 hours (e.g., 0.5 mg initially, then 0.25 mg every 6 hours) PO: 0.125–0.5 mg/day; adjust for renal failure (see Chapter 19) Maximal response may take several hours; use with caution in patients with renal impairment Esmolol 0.5 mg/kg IV for 1 minute 50–300 mcg/kg/minute Hypotension common; (Brevibloc) continuous infusion with bolus between increases effects additive with digoxin and calcium-channel blockers Propranolol (Inderal) 0.5–1.0 mg IV repeated every 2 minutes (up to 0.1–0.15 mg/kg) IV infusion: 0.04 mg/kg/ minute PO: 10–120 mg TID Use with caution in patients with HF or asthma; additive effects seen with digoxin and calcium-channel blockers Metoprolol (Lopressor) 5 mg IV at 1 mg/minute PO: 25–100 mg BID Use with caution in patients with HF or asthma; additive effects seen with digoxin and calcium-channel blockers Verapamil (Isoptin, Calan) 5–10 mg (0.075–0.15 mg/kg) IV for 2 minutes; if response inadequate after 15–30 minutes, repeat 10 mg (up to 0.15 mg/kg) IV infusion: 5–10 mg/hour PO: 40–120 mg TID or 120–480 mg in sustained- release form daily Hypotension with IV route; AV blocking effects are additive with digoxin and β-blockers; may increase digoxin levels Diltiazem (Cardizem) 0.25 mg/kg IV for 2 minutes; if response inadequate after 15 minutes, repeat 0.35 mg/ kg for 2 minutes IV infusion: 5–15 mg/hour PO: 60–90 mg TID or QID or 180–360 mg in extended release form daily Response to IV therapy occurs in 4–5 minutes; hypotension; effects additive with digoxin and β-blockers\\n', 'Formulation Dosage/Administration Rationale/Indications Comments 50 mg/mL Vials: 3, 9, 18 mL 0.1 mg/mL (1:10,000) or 1 mg/mL (1:1,000) 300 mg diluted in 20–30 mL D5W or NS; additional 150 mg (diluted solution) can be given for recurrent or refractory VT or VF. 10 mL of a 1:10,000 solution of epinephrine (1 mg; dilute 1:1,000 solution in 0.9% sodium chloride) every 3–5 minutes Exhibits antiadrenergic properties and blocks sodium, potassium, and calcium channels. First- line antiarrhythmic for pulseless VT and VF Increases coronary sinus perfusion pressure through α1 stimulation Indicated in pulseless VT, VF, asystole, and PEA 20 units/mL Vials: 0.5, 1 mL, 10 mL 40-unit dose can be used to replace first or second dose of epinephrine Increases coronary sinus perfusion pressure through vasopressin receptor stimulation Indicated in pulseless VT, VF, asystole, and PEA Vasopressin is an\\n', 'Emergencies Urgencies Severely elevated blood pressure (diastolic >120 mm Hg)a Potentially life threatening End-organ damage acute or progressing progressing CNS (dizziness, N/V, encephalopathy, confusion, weakness, Optic disc edema intracranial or subarachnoid hemorrhage, stroke) Eyes (ocular hemorrhage or funduscopic changes, blurred vision, loss of sight) Heart (left ventricular failure, pulmonary edema, MI, angina, aortic dissection) Renal failure or insufficiency Requires immediate pressure reduction Requires IV therapy (Table 21.2) Treated for several hours to days Oral therapy (Table 21.3)\\n', 'Clinical Presentation Recommendation Rationale Aortic dissection Angina, myocardial Nitroprusside, nicardipine, or fenoldopam plus esmolol or IV metoprolol; labetalol; trimethaphan. Avoid inotropic therapy. Nitroglycerin plus esmolol or metoprolol; Vasodilator will decrease pulsatile stress in aortic vessel to prevent further dissection expansion. β-blockers will prevent vasodilator-induced reflex tachycardia. Coronary vasodilation, decreased cardiac infarction labetalol. Avoid nitroprusside. output, myocardial workload, and oxygen demand. Nitroprusside may cause coronary steal. Acute pulmonary edema, left ventricular failure Nitroprusside, nicardipine, or fenoldopam plus nitroglycerin and a loop diuretic. Alternative: enalaprilat. Avoid nondihydropyridines, β-blockers. Promotion of diuresis with venous dilatation to decrease preload. Nitroprusside, enalaprilat decrease afterload. Nicardipine may increase stroke volume. Acute kidney injury Nicardipine or fenoldopam. Avoid Peripheral vasodilation without renal nitroprusside, enalaprilat. clearance. Fenoldopam shown to increase renal blood flow. Cocaine overdose Nicardipine, fenoldopam, verapamil, or nitroglycerin. Alternative: labetalol. Avoid β-selective blockers. Vasodilation effects without potential unopposed a-adrenergic receptor stimulation. CCBs control overdose- induced vasospasm. Pheochromocytoma Nicardipine, fenoldopam, or verapamil. Alternatives: phentolamine, labetalol. Avoid β-selective blockers. Vasodilation effects without potential unopposed β-adrenergic receptor stimulation. Hypertensive Nicardipine, fenoldopam, or labetalol. Avoid nitroprusside, nitroglycerin, enalaprilat, hydralazine. Vasodilation effects without compromised CBF induced by nitroprusside and nitroglycerin. Enalaprilat and hydralazine may lead to unpredictable BP changes when carefully controlled BP management is required.\\n', 'Druga (Brand Name) Dose/Route Onset of Action Duration of Action Major Side Effectsa Mechanism of Action Avoid or Use Cautiously in Patients with These Conditions Captoprilb (Capoten) 12.5-, 25-, 50-, 100-mg tablets Clonidine (Catapres) 0.1-, 0.2-, 0.3-mg tablets 6.5–50 mg PO 15 minutes 0.1–0.2 mg 0.5–2 hours PO initially, then 0.1 mg/hour up to 0.8 mg total 4–6 hours 6–8 hours Hyperkalemia, angioedema, increased BUN if dehydrated, rash, pruritus, proteinuria, loss of taste Sedation, dry mouth, constipation ACE inhibitor Central α2- agonist Labetalol 200–400 mg PO repeated every 2–3 hours 30 minutes– 2 hours 4 hours Orthostatic hypotension, nausea, vomiting α- and β- adrenergic blocker Heart failure, asthma, bradycardia\\n', 'Druga (Brand Name) Dose/Route Onset of Action Duration of Action Major Side Effectsa Mechanism of Action Avoid or Use Cautiously in Patients with These Conditions Minoxidil (Loniten) 2.5-, 10-mg tablets 5–20 mg PO 30–60 minutes; maximum response in 2–4 hours 12–16 hours Tachycardia, fluid retention Arterial and venous vasodilator Angina, heart failure\\n', 'Drug (Brand Name) Class of Drug Dose/Route Clevidipine (Cleviprex) 0.5 mg/mL Arterial vasodilator (calcium-channel blocker) Initial: 1–2 mg/hour; titrate dose to desired BP or to a max of 16 mg/hour 2–4 minutes after D/C Enalaprilata (Vasotec IV) 1.25 mg/mL, 2.5 mg/2 mL Esmololb (Brevibloc) 100 mg/10 mL, 2,500 mg/ 10 mL concentrate ACE inhibitor β-adrenergic blocker 0.625–1.25 mg IV every 6 hours 250–500 mcg/kg for 1 minute, then 50–300 mcg/kg/ minute 15 minutes (max, 1–4 hours) 1–2 minutes 6–12 hours Fenoldopam (Corlopam) 10 mg/mL, 20 mg/2 mL, 50 mg/5 mL Hydralazinec (generic) 20 mg/mL Labetalold (Normodyne) 20 mg/4 mL, 40 mg/8 mL, 100 mg/20 mL, 200 mg/20 mL Nicardipinee (Cardene IV) 25 mg/10 mL Dopamine-1 agonist Arterial vasodilator α- and β- adrenergic blocker Arterial vasodilator (calcium-channel blocker) 0.1–0.3 mcg/kg/ minute 10–20 mg IV 2 mg/minute IV or 20–80 mg every 10 minutes up to 300 mg total dose IV loading dose 5 mg/ hour increased by 2.5 mg/hour every 5 minutes to desired BP or a max of 15 mg/hour every 15 minutes, followed by maintenance infusion of 3 mg/ hour <5 minutes 5–20 minutes 2–5 minutes 2–10 minutes (max, 8–12 hours) 30 minutes 2–6 hours 3–6 hours after D/C infusion Arterial and venous vasodilator IV infusion pump 5–100 mcg/minute 2–5 minutes\\n', 'Drug (Brand Name) Class of Drug Dose/Route Onset of Action Duration of Action Nitroprussideg (Nitropress), 50 mg/2 mL (most commonly used) Phentolamine (Regitine) Arterial and venous vasodilator α-adrenergic blocker IV infusion.a Start: 0.5 mcg/kg/minute; Usual: 2–5 mcg/kg/ minute; Max: 8 mcg/kg/minute 1–5 mg IV initially, repeat as needed Seconds Immediate 3–5 minutes after D/C infusion 10–15 minutes Major Side Effects (All Can Cause Hypotension) Avoid or Use Cautiously in Patients With These Conditions Atrial fibrillation, nausea, vomiting, headache, acute Allergy to soybeans, soy products, eggs or egg products, renal failure, reflex tachycardia, MI severe aortic stenosis, defective lipid metabolism, heart failure Hyperkalemia Hyperkalemia, renal failure in patients with dehydration or bilateral renal artery stenosis, pregnancy (teratogenic) Nausea, thrombophlebitis, painful extravasation Asthma, bradycardia, decompensated HF, advanced heart block Tachycardia, headache, nausea, flushing Tachycardia, headache, angina Abdominal pain, nausea, vomiting, diarrhea Headache, flushing, nausea, vomiting, dizziness, Glaucoma Angina pectoris, MI, aortic dissection Asthma, bradycardia, decompensated HF Angina pectoris, decompensated HF, increased tachycardia; local thrombophlebitis change infusion site after 12 hours intracranial pressure Methemoglobinemia, headache, tachycardia, nausea, Pericardial tamponade, constrictive pericarditis, or vomiting, flushing, tolerance with prolonged use increased intracranial pressure Nausea, vomiting, diaphoresis, weakness, thiocyanate toxicity,h cyanide toxicity (rare),i chest pain, nausea, vomiting, dizziness, headache, nasal congestion, arrhythmia Renal failure (thiocyanate accumulation), pregnancy, increased intracranial pressure, angina pectoris, coronary insufficiency, MI or history of MI, hypersensitivity to mannitol aNot approved by the U.S. Food and Drug Administration for treatment of acute hypertension. bApproved for intraoperative and postoperative treatment of hypertension. cParenteral hydralazine is an intermediate treatment between oral agents and more aggressive therapies such as nitroprus- side. It can be given IV or intramuscularly, but there is no appreciable difference in onset of action (20–40 minutes) between the two routes. This slow onset minimizes hypotension. dLabetalol is contraindicated in acute decompensated heart failure because of its β-blocking properties. A solution for continuous infusion is prepared by adding two 100-mg ampules to 160 mL of IV fluid to give a final concentration of 1 mg/mL. Infusions start at 2 mg/minute and are titrated until a satisfactory response or a cumulative dose of 300 mg is achieved.\\n', 'Definition/Equation Normal Value Units Directly MeasureD Blood pressure (BP) (systolic [SBP]/diastolic [DBP]) Pressure in the central arterial bed, determined by cardiac output and systemic vascular resistance 120–140/80–90 mm Hg Cardiac output (CO) Amount of blood ejected from the left ventricle per minute; determined by stroke volume and heart rate 4–7 L/minute Central venous pressure (CVP)a CO = SV × HR Measures mean pressure in right atrium and reflects right ventricular filling pressure and volume status. Primarily determined by venous return to the heart. The goal in most critically ill patients is 8–12 mm Hg. 2–6 mm Hga Heart rate (HR) (pulse) Pulmonary artery pressure (PAP) systolic (SPAP)/ diastolic (DPAP)/mean (MPAP) Pulmonary capillary wedge pressure (PCWP) Number of myocardial contractions per minute Systolic (SPAP): measures pulmonary artery pressure during systole; reflects pressure generated by the contraction of the right ventricle. Diastolic (DPAP): measures pulmonary artery pressure during diastole; reflects diastolic filling pressure in the left ventricle. May approximate pulmonary capillary wedge pressure (PCWP); normal gradient <5 mm Hg between DPAP and PCWP Measures pressure distal to the pulmonary artery; reflects left ventricular filling pressures (preload). Usually lower than or within 5 mm Hg of pulmonary artery diastolic pressure (DPAP) 60–80 20–30/8–12 5–12b beats/minute mm Hg mm Hg\\n', 'Definition/Equation Normal Value Central venous oxygen saturation (Scvo2) Mixed venous oxygen saturation (Svo2) The oxygen saturation of blood returning to the heart The oxygen saturation of blood in the pulmonary artery >70 >65 DeriveD inDices Cardiac index (CI) Left ventricular stroke work index (LVSWI) Cardiac output per square meter of body surface area (BSAc). CI = CO/BSA Amount of work the left ventricle exerts during systole; adjusted for body surface area (BSA). A measure of contractility, the inotropic state of the myocardium 2.5–4.2 35–85 Mean arterial pressure LVSWI = (MAP – PCWP) × SVI × 0.0136 MAP = ([2 × DBP] + SBP)/3 80–100 (MAP) Oxygen delivery (o2) The amount of oxygen delivered by the body per 700–1,200 unit time o2 = CO × Cao2 where Cao2 = Hgb × Sao2 × 13.9 Oxygen consumption (V̇o2) Perfusion pressure (PP) Pulmonary vascular resistance (PVR) Stroke volume (SV) The amount of oxygen consumed by the body per unit time. The product of cardiac output and the difference between the arterial and venous oxygen concentration V̇o2 = CO × (Cao2 − Cvo2), where Cvo2 = Hgb × Svo2 × 13.9 The pressure gradient between the coronary arteries and the pressure in either the right atrium or left ventricle during diastole. A major determinant of coronary blood flow and oxygen supply to the heart PP = MAP − PCWP Primary determinant of right ventricular afterload PVR = ([MPAP – PCWP]/CO) × 74 Amount of blood ejected from the ventricle with 200–400 50 20–120 60–130 each systolic contraction Stroke volume index (SVI) Systemic vascular resistance (SVR) SV = CO/HR Stroke volume adjusted for body surface area SVI = SV/BSA Measure of impedance applied by systemic vascular system to systolic effort of left ventricle; determined by autonomic nervous system and condition of vessels. Determinant of left ventricular afterload 30–75 800–1,440 Systemic vascular resistance index (SVRI) SVR = ([MAP – CVP]/CO) × 74 SVR adjusted for body surface area SVRI = SVR × BSA 1,680–2,580 Units % % L/minute/m2 g/m2/beat mm Hg mL/minute mL/minute mm Hg dynes·s·cm–5 mL/beat mL/beat/m2 dyne·s·cm–5 dyne ·s·cm–5·m2\\n', 'Hypovolemic Cardiogenic Distributive (Septic) Heart rate Blood pressurea Cardiac output Preload (PCWP) Afterload (SVR) ↑ ↓ ↓ ↓ ↑ ↑ ↑/↓ ↓ ↑ ↑ ↑ ↓ ↓b ↑/↓ ↓\\n', 'Receptor Sensitivity Pharmacologic Effect Usual Dose ` a1 a2 VD VC INT CHT 2.5–15 mcg/kg/minute 0.5–2 mcg/kg/minuteb (renal) + − − +++ − − ++ − − ++ − −b − − +++a + + + + 2–5 mcg/kg/minute 5–10 mcg/kg/minute 15–20 mcg/kg/minute 0.01–0.1 mcg/kg/ minute − − + +++ + + ++ ++ +++ − − − − − − ++ − −b + ++ ++ − −b +++ + − + + ++ ++ ++ ++ +++ ++ 0.1 mcg/kg/minute 0.01–0.1 mcg/kg/ +++ − − ++ ++++ +++ ++ − − +++ ++ +++ − − +++ +++ ++ minute 50 mcg/kg bolus, then 0.375–0.75 mcg/kg/ minute − − − − − − +++ − − ++ − − 0.05–0.5 mcg/kg/ minute ++++ ++ − − − − +++ +d + Highly variable, titrate to desired MAP 0.5–5 mcg/kg/minute Highly variable, titrate +++ − − − − − − +++ − − − − to desired MAP 0.04 units/minutef − − − − − − − − +++ − − − −\\n', 'Laboratory Test Result Point Score Platelet count Fibrin-related markers PT (vs. baseline) Fibrinogen TOTAL SCORE >100,000 <100,000 <50,000 No increase Moderate increase Strong increase <3 seconds 3–6 seconds >6 seconds >1 g/L <1 g/L ≥5 <5 0 1 2 0 2 3 0 1 2 0 1 Compatible with overt DIC (repeat daily) Suggestive but not affirmative for nonovert DIC (repeat in 1–2 days)\\n', 'Persistent Components of Severity Intermittent Mild Moderate Severe Impairment Symptoms Nighttime ≤2 days/week 0 >2 days/week but not daily 1–2 × /month Daily 3–4 × /month Throughout the day >l × /week awakenings SABA use for symptom control (not prevention of EIB) ≤2 days/week >2 days/week but not daily Daily Several times per day Interference with normal activity None Minor limitation Some limitation Extremely limited Risk Exacerbations requiring oral systemic corticosteroids 0–1/year ≥2 exacerbation in 6 months requiring oral corticosteroids or ≥4 wheezing episodes in 1 year lasting >1 day AND risk factors for persistent asthma Consider severity and interval since last exacerbation. Frequency and severity may fluctuate with time. Exacerbations of any severity may occur in patients in any severity category. Level of severity is determined by both impairment and risk. Assess impairment domain by caregiver’s recall of previous 2–4 weeks. Assign severity to the most severe category in which any feature occurs. At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral corticosteroids in the past 6 months, or ≥4 wheezing episodes in the past year, and who have risk factors for persistent asthma may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.\\n', 'Persistent Intermittent Mild Moderate Severe Step 1 Step 2 Step 3 or 4 Step 5 or 6 to maintain control\\n', 'Persistent Components of Severity Intermittent Mild Moderate Severe Impairment Symptoms Nighttime ≤2 days/week ≤2×/month >2 days/week but not daily 3–4 × /month Daily >1 × /week but Throughout the day Often 7 × /week awakenings SABA use for symptom control (not prevention of EIB) ≤2 days/week >2 days/week but not daily not nightly Daily Several times per day Interference with normal activity None Minor limitation Some limitation Extremely limited Risk Lung function Exacerbations requiring oral systemic corticosteroids • Normal FEV1 between exacerbations • FEV1 >80% predicted • FEV1/FVC >85% 0–1 in 1 year (see note) • FEV1 >80% predicted • FEV1/FVC >80% ≥2 in 1 year (see note) • FEV1 = 60%–80% predicted • FEV1/FVC 75%–80% • FEV1 <60% predicted • FEV1/FVC <75% Consider severity and interval since last exacerbation. Frequency and severity may fluctuate with time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV1. Level of severity is determined by both impairment and risk. Assess impairment domain by patient’s or caregiver’s recall of the previous 2–4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs.\\n', 'Persistent Intermittent Mild Moderate Severe Lowest level of treatment required Step 1 Step 2 Step 3 or 4 Step 5 or 6 to maintain control\\n', 'Persistent Components of Severity Intermittent Mild Moderate Severe Impairment Symptoms ≤2 days/week >2 days/week but Daily Throughout not daily the day Nighttime awakenings ≤2×/month 3–4 × /month >1 × /week but not nightly Often 7 × /week SABA use for symptom control (not prevention of EIB) ≤2 days/week >2 days/week but not >1 × /day Daily Several times per day Normal FEV1/FVC: 8–19 years, 85% 20–39 years, 80% 40–59 years, 75% 60–80 years, 70% Interference with normal activity None Minor limitation Some limitation Extremely limited Risk Lung function Exacerbations requiring oral systemic corticosteroids • Normal FEV1 between exacerbations • FEV1 >80% predicted • FEV1/FVC normal 0–1 in 1 year (see note) • FEV1 ≥80% predicted • FEV1/FVC normal • FEV1 >60% but <80% predicted • FEV1/FVC reduced 5% ≥2 in 1 year (see note) • FEV1 <60% predicted • FEV1/FVC reduced >5%\\n', 'Persistent Intermittent Mild Moderate Severe Lowest level of treatment required Step 1 Step 2 Step 3 or 4 Step 5 or 6 to maintain control\\n', 'Step 6 Step 1 Step 2 Preferred: Low-dose ICS Step 3 Preferred: Medium -dose ICS Step 4 Preferred: Medium-dose ICS + either LABA or Montelukast Step 5 Preferred: High-dose ICS + either LABA or Montelukast Preferred: High-dose ICS + either LABA or Montelukast Oral systemic cortico- steroids Step up if needed (first, check adherence, inhaler technique, and environmental control) Assess control Alternative: Cromolyn or Montelukast Patient Education and Environmental Control at Each Step Step down if possible (and asthma is well controlled at least 3 months) Quick-Relief Medication for All Patients • SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms. • With viral respiratory infection SABA every 4–6 hours up to 24 hours (longer with physician consult). Consider short course of oral systemic corticosteroids if exacerbation is severe or patient has history of previous severe exacerbations. • Caution: Frequent use of SABA may indicate the need to step up treatment. See text for recommendations on initiating daily long-term-control therapy.\\n', 'Step 6 Step 5 Step 1 Preferred: SABA PRN Step 2 Preferred: Low-dose ICS Alternative: Cromolyn, LTRA, Nedocromil, or Theophylline Step 3 Preferred: EITHER: Low-dose ICS + either LABA, LTRA, or Theophylline OR: Medium -dose ICS Step 4 Preferred: Medium- dose ICS + LABA Alternative: Medium- dose ICS + either LTRA or Theophylline Preferred: High-dose ICS + LABA Alternative: High-dose ICS + either LTRA or Theophylline Preferred: High-dose ICS + LABA + oral systemic corticosteroid Alternative: High-dose ICS + either LTRA or Theophylline + oral systemic corticosteroid Each step: Patient education, environmental control, and management of comorbidities. Steps 2–4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes). Assess control Quick-Relief Medication for All Patients • SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to three treatments at 20-minute intervals as needed. Short course of oral systemic corticosteroids may be needed. • Caution: Increasing use of SABA or use >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step up treatment.\\n', 'Intermittent Asthma Consult with asthma specialist if Step 4 care or higher is required. Consider consultation at Step 3. Step 1 Preferred: SABA PRN Step 2 Preferred: Low-dose ICS Alternative: Cromolyn, LTRA, nedocromil, or theophylline Step 3 Preferred: Low-dose ICS + LABA OR Medium- dose ICS Alternative: Low-dose ICS + either LTRA, theophylline, or zileuton Step 4 Preferred: Medium- dose ICS + LABA Alternative: Medium- dose ICS + either LTRA, theophylline, or zileuton Step 5 Preferred: High-dose ICS + LABA AND Consider omalizumab for patients who have allergies Step 6 Preferred: High-dose ICS + LABA + oral corticosteroid AND Consider omalizumab for patients who have allergies Assess control Step down if possible (and asthma is well controlled at least 3 months)\\n', 'Medication Child Dosea Adult Dose Comments Inhaled short-actIng a 2-agonIsts Albuterol Nebulizer solution (0.63 mg/3 mL, 1.25 mg/ 3 mL, 2.5 mg/3 mL, 5.0 mg/mL) MDI (90 mcg/puff) 0.15 mg/kg (minimum dose 2.5 mg) every 20 minutes for three doses, then 0.15–0.3 mg/ kg up to 10 mg every 1–4 hours as needed or 0.5 mg/kg/hour by continuous nebulization 4–8 puffs every 20 minutes for three doses, then every 1–4 hours inhalation maneuver as needed. Use VHC; add mask in children <4 years 2.5–5 mg every 20 minutes for three doses, then 2.5–10 mg every 1–4 hours as needed or 10–15 mg/ hour continuously 4–8 puffs every 20 minutes up to 4 hours, then every 1–4 hours as needed Only selective b 2-agonists are recommended. For optimal delivery, dilute aerosols to minimum of 3 mL at gas flow of 6–8 L/ minute. Use large-volume nebulizers for continuous administration. May mix with ipratropium nebulizer solution In mild to moderate exacerbations, MDI plus VHC is as effective as nebulized therapy, with appropriate administration technique and coaching by trained personnel. Levalbuterol (R-albuterol) Nebulizer solution (0.63 mg/3 mL, 1.25 mg/0.5 mL, 1.25 mg/3 mL) 0.075 mg/kg (minimum dose 1.25 mg) every 20 minutes for three doses, then 0.075– 0.15 mg/kg up to 5 mg every 1–4 hours as needed 1.25–2.5 mg every 20 minutes for three doses, then 1.25–5 mg every 1–4 hours as needed Levalbuterol administered in one-half the mg dose of albuterol provides comparable efficacy and safety. Has not been evaluated by continuous nebulization MDI (45 mcg/puff) Pirbuterol MDI (200 mcg/puff) See albuterol MDI dose. See albuterol MDI dose; thought to be half as potent as albuterol on a milligram basis See albuterol MDI dose. See albuterol MDI dose. Has not been studied in severe asthma exacerbations systemIc (Injected) a 2-agonIsts Epinephrine 1:1,000 0.3–0.5 mg every\\n', 'Dosages Medication Child Dosea Adult Dose Comments antIcholInergIcs Ipratropium bromide Nebulizer solution (0.25 mg/mL) 0.25–0.5 mg every 20 minutes for three doses, then as needed 0.5 mg every 20 minutes for three doses, then as needed May mix in same nebulizer with albuterol. Should not be used as first-line therapy; should be added to SABA therapy for severe exacerbations. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized. MDI (18 mcg/puff) 4–8 puffs every 20 minutes as needed up to 3 hours 8 puffs every 20 minutes as needed up to 3 hours Should use with VHC and face mask for children <4 years Studies have examined ipratropium bromide MDI for up to 3 hours Ipratropium with albuterol Nebulizer solution (Each 3-mL vial contains 0.5 mg ipratropium bromide and 2.5 mg albuterol.) 1.5 mL every 20 minutes for three doses, then as needed 3 ml every 20 minutes for three doses, then as needed May be used for up to 3 hours in the initial management of severe exacerbations. The addition of ipratropium to albuterol has not been shown to provide further benefit once the patient is hospitalized. MDI (Each puff contains 18 mcg ipratropium bromide and 90 mcg albuterol.) 4–8 puffs every 20 minutes as needed up to 3 hours 8 puffs every 20 minutes as needed up to 3 hours Should use with VHC and face mask for children <4 years\\n', 'Indications/Mechanisms Potential Adverse Effects Therapeutic Issues (Not All Inclusive) cortIcosteroIds (glucocortIcoIds) Inhaled (ICS): Beclomethasone Budesonide Ciclesonide Flunisolide Fluticasone Mometasone Indications • Long-term prevention of symptoms: suppression, control, and reversal of inflammation • Cough, dysphonia, oral thrush (candidiasis) • In high doses (Tables 23.6, 23.7), systemic effects • Spacer/holding chamber devices with nonbreath-activated MDIs and mouth washing after inhalation decrease local side effects. may occur, although studies are not conclusive, and clinical significance of these effects has not been established (e.g., adrenal suppression, osteoporosis, skin thinning, and easy bruising). In low to medium doses, suppression of growth velocity has been observed in children, but this effect may be transient, and the clinical significance has not been established. • Reduce need for oral corticosteroid Mechanisms • Anti-inflammatory. Block late • Preparations are not absolutely interchangeable on a microgram or per-puff basis (Tables 23.6, 23.7 for estimated clinical comparability). New delivery devices may provide greater delivery to airways; this change may affect dose. • The risks of uncontrolled asthma should reaction to allergen and reduce airway hyperresponsiveness. Inhibit cytokine production, adhesion protein activation, and inflammatory cell migration and activation be weighed against the limited risks of ICS therapy. The potential but small risk of adverse events is well balanced by their efficacy. • “Adjustable dose” approach to treatment • Reverse b 2-receptor downregulation. Inhibit microvascular leakage may enable reduction in cumulative dose of ICS treatment with time without sacrificing maintenance of asthma control. • Dexamethasone is not included as an ICS for long-term control because it is highly absorbed and has long-term suppressive side effects. Systemic: Methylprednisolone Prednisolone Prednisone Indications • For short-term (3–10 days) “burst”: to gain prompt control of inadequately controlled persistent asthma • Short-term use: reversible abnormalities in glucose metabolism, increased appetite, fluid retention, weight gain, mood alteration, hypertension, peptic ulcer, and rarely aseptic necrosis • Use at lowest effective dose. For long-term use, alternate-day am dosing produces the least toxicity. If daily doses are required, one study shows improved efficacy with no increase in adrenal suppression when administered at 3 pm rather than in the morning. • For long-term prevention of symptoms in severe persistent asthma, suppression, control, and reversal of inflammation • Long-term use: adrenal axis suppression, growth suppression, dermal thinning, hypertension, diabetes, Cushing syndrome, cataracts, muscle weakness; in rare instances, impaired immune function • Consideration should be given to coexisting Mechanisms • Same as inhaled conditions that could be worsened by systemic corticosteroids, such as herpes virus infections, varicella, tuberculosis, hypertension, peptic ulcer, diabetes mellitus, osteoporosis, and Strongyloides\\n', 'TABLE 23.7 Long-Term Control Medications (Continued) Zafirlukast tablets • Long-term control and prevention of • Postmarketing surveillance has reported cases of • Administration with meals decreases symptoms in mild persistent asthma for patients ≥7 years of age. May also be used with ICS as combination therapy in moderate persistent asthma reversible hepatitis and, rarely, irreversible hepatic failure resulting in death and liver transplantation. bioavailability; take at least 1 hour before or 2 hours after meals. • Zafirlukast is a microsomal P-450 enzyme inhibitor that can inhibit the metabolism of warfarin. INRs should be monitored during coadministration. • Patients should be warned to discontinue use if they experience signs and symptoms of liver dysfunction (right upper quadrant pain, pruritus, lethargy, jaundice, nausea), and serum ALTs should be monitored. 5-lIpoxygenase InhIbItor Zileuton tablets Mechanisms • Inhibits the production of leukotrienes from arachidonic acid, both LTB4 and the cysteinyl leukotrienes Indications • Long-term control and prevention of • Elevation of liver enzymes has been reported. • Zileuton is microsomal P-450 enzyme inhibitor that can inhibit the metabolism of warfarin and theophylline. Doses of these drugs should be monitored accordingly. symptoms in mild persistent asthma for patients ≥12 years of age Limited case reports of reversible hepatitis and hyperbilirubinemia • May be used with ICS as combination therapy in moderate persistent asthma in patients ≥12 years of age • Monitor hepatic enzymes (ALT). long-actIng b 2-agonIsts (laba) Inhaled LABA: Formoterol Salmeterol Indications • Long-term prevention of symptoms • Tachycardia, skeletal muscle tremor, hypokalemia, • Not to be used to treat acute symptoms or added to ICS • Prevention of EIB • Not to be used to treat acute symptoms or prolongation of QTc interval in overdose • A diminished bronchoprotective effect may exacerbations • Should not be used as monotherapy for long- occur within 1 week of chronic therapy. Clinical significance has not been established. term control of asthma or as anti-inflammatory therapy exacerbations • Potential risk of uncommon, severe, life-threatening • May provide more effective symptom control or fatal exacerbation: see text for additional discussion regarding safety of LABAs. when added to standard doses of ICS compared with increasing the ICS dosage.\\n', 'Approximate Adjustment in Daily Dose Comment <5.0 5–10 ↑ by 25% ↑ by 25% if clinically Recheck serum theophylline concentration. Recheck serum concentration; ↑ dose only if poor indicated response to therapy. 10–12 Cautious 10% ↑ if If asymptomatic, no ↑ needed. Recheck serum clinically indicated theophylline concentration before further dose changes. 12–15 Occasional intolerance requires a 10% ↓ effects present. 16–20 ↓ by 10%–25% ↓ is prudent. 20–24.9 ↓ by 50% absent; a dose ↓ is indicated. 25–29.9 ↓ by >50% Omit next doses even if asymptomatic and side >30 Omit next doses; ↓ by 60%–75%\\n', 'Factor Decreases Theophylline Concentrations Increases Theophylline Concentrations Recommended Action Food ↓ or delays absorption of some sustained-release theophylline (SR) products ↑ rate of absorption (fatty foods) Select theophylline preparation that is not affected by food. Diet ↑ metabolism (high protein) ↓ metabolism (high carbohydrate) Inform patients that major changes in diet are not recommended while taking theophylline. Systemic, febrile ↓ metabolism Decrease theophylline dose viral illness (e.g., influenza) according to serum concentration level. Decrease dose by 50% if serum concentration measurement is not available. Hypoxia, cor ↓ metabolism Decrease dose according to serum pulmonale, and decompensated congestive heart failure, cirrhosis concentration level. Age ↑ metabolism (1–9 years) ↓ metabolism Adjust dose according to serum (<6 months, elderly) concentration level. Phenobarbital, phenytoin, carbamazepine ↑ metabolism Increase dose according to serum concentration level. Cimetidine ↓ metabolism Use alternative histamine H2-antagonist (e.g., famotidine or ranitidine). Macrolides: TAO, erythromycin, clarithromycin ↓ metabolism Use alternative antibiotic or adjust theophylline dose. Quinolones: ↓ metabolism Use alternative antibiotic or adjust ciprofloxacin, enoxacin, pefloxacin theophylline dose. Rifampin ↑ metabolism Increase dose according to serum concentration level. Ticlopidine ↓ metabolism Decrease dose according to serum concentration level. Smoking ↑ metabolism Advise patient to stop smoking; increase dose according to serum concentration level.\\n', 'Low Daily Dose Medium Daily Dose High Daily Dose Drug Child 0–4 Years Child 5–11 Years Child 0–4 Years Child 5–11 Years Child 0–4 Years Beclomethasone HFA 40 or 80 mcg/puff NA 80–160 mcg NA >160–320 mcg NA >320 mcg Budesonide DPI 90, 180, or 200 mcg/ NA 180–400 NA >400–800 NA >800 mcg inhalation mcg mcg Budesonide inhaled Inhalation suspension for 0.25–0.5 0.5 mg >0.5–1 mg 1 mg >1 mg 2 mg nebulization mg Fluticasone HFA/MDI: 44, 110, or 230 mcg/puff 176 mcg 88–176 mcg >176–352 mcg >176–352 mcg >352 mcg >352 mcg DPI: 50, 100, or 250 NA 100–200 NA >200–400 NA >400 mcg mcg/inhalation Mometasone DPI mcg mcg (Dosing of mometasone for 4- to 11-year-olds is 110 mcg QD) 200 mcg/inhalation NA NA NA NA NA NA\\n', 'Drug Low Daily Dose Adult Medium Daily Dose Adult High Daily Dose Adult Beclomethasone HFA 40 or 80 mcg/puff Budesonide DPI 90, 180, or 200 mcg/ 80–240 mcg 180–600 mcg >240–480 mcg >600–1,200 mcg >480 mcg >1,200 mcg inhalation Fluticasone HFA/MDI: 44, 110, or 88–264 mcg >264–440 mcg >440 mcg 220 mcg/puff DPI: 50, 100, or 250 100–300 mcg >300–500 mcg >500 mcg mcg/inhalation MoMetAsone DPI 200 mcg/inhalation 200 mcg 400 mcg >400 mcg\\n', 'Stage Classification Spirometry Results I II III IV Mild Moderate Severe Very severe FEV1/FVC <0.70 FEV1 ≥80% predicted FEV1/FVC <0.70 50% ≤ FEV1 <80% predicted FEV1/FVC < 0.70 30% ≤ FEV1 <50% predicted FEV1/FVC <0.70 FEV1 <30% predicted or FEV1 <50% predicted plus chronic respiratory failurea\\n', 'Points Variable 0 1 2 3 Body mass index (kg/m2) Obstruction of airflow (FEV1 % predicted) ≥21 ≥65 <21 50–64 36–49 ≤35 Dyspnea? None or only with strenuous exertion Walking up a slight hill Walking on the level Getting dressed Exercise capacity (6-minute >1,148 820–1,149 492–819 <492 walk distance, feet)\\n', 'I: Mild II: Moderate III: Severe IV: Very Severe • FEV1/FVC < 70 • FEV1/FVC <0.70 • FEV1 ≥80% predicted • FEV1/FVC <0.70 • 50% FEV1 <80% predicted • FEV1/FVC <0.70 • 30% FEV1 <50% predicted • FEV1 <30% predicted or FEV1 <50% predicted plus chronic respiratory failure Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) Add regular treatment with one or more long-acting bronchodilators (when needed); add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long-term oxygen if chronic respiratory failure. *Postbronchodilator FEV1 is recommended for the diagnosis and assessment of severity of COPD. Consider surgical treatments']\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "execution_count": null,
      "metadata": {
        "id": "_l2S01ez9mcH"
      },
      "outputs": [],
      "source": [
        "import os\n",
        "import time\n",
        "from langchain_core.output_parsers import StrOutputParser\n",
        "from langchain_core.prompts import ChatPromptTemplate\n",
        "from langchain_openai import ChatOpenAI\n",
        "import load_dotenv\n",
        "\n",
        "load_dotenv()\n",
        "OPENAI_API_KEY = os.environ[\"OPENAI_API_KEY\"]\n",
        "\n",
        "def generate_text_summaries(texts, tables, summarize_texts=False):\n",
        "\n",
        "    prompt_text = \"\"\"You are an assistant tasked with summarizing tables and text for retrieval. \\\n",
        "    These summaries will be embedded and used to retrieve the raw text or table elements. \\\n",
        "    Give a concise summary of the table or text that is well optimized for retrieval. Table or text: {element} \"\"\"\n",
        "\n",
        "    prompt = ChatPromptTemplate.from_template(prompt_text)\n",
        "\n",
        "    model = ChatOpenAI(model=\"gpt-4o-mini\", temperature=0)\n",
        "    summarize_chain = {\"element\": lambda x: x} | prompt | model | StrOutputParser()\n",
        "\n",
        "    text_summaries = []\n",
        "    table_summaries = []\n",
        "\n",
        "    if texts and summarize_texts:\n",
        "      text_summaries = summarize_chain.batch(texts, {\"max_concurrency\": 5})\n",
        "    elif texts:\n",
        "        text_summaries = texts\n",
        "\n",
        "    if tables:\n",
        "      time.sleep(60)\n",
        "      table_summaries = summarize_chain.batch(tables, {\"max_concurrency\": 5})\n",
        "\n",
        "    return text_summaries, table_summaries\n",
        "\n",
        "text_summaries, table_summaries = generate_text_summaries(texts=texts, tables=tables, summarize_texts=True)"
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "print(len(texts))"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "LBhPrcTwio1-",
        "outputId": "68e767b3-e122-416d-88d5-25ee35177a22"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "1\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "print(len(table_summaries))"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "N3jKcp47irdt",
        "outputId": "49b7dd72-7f6c-4a1f-e317-e801cc2207c8"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "114\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "execution_count": null,
      "metadata": {
        "id": "jSMH17nZ9mcH"
      },
      "outputs": [],
      "source": [
        "import base64\n",
        "from io import BytesIO\n",
        "\n",
        "from IPython.display import HTML, display_html\n",
        "from PIL import Image\n",
        "\n",
        "from langchain_core.messages import HumanMessage\n",
        "# from langchain_ollama import ChatOllama\n",
        "from langchain_community.llms import Ollama\n",
        "\n",
        "def encode_image(image_path):\n",
        "    with open(image_path, \"rb\") as image_file:\n",
        "        encoded_string = base64.b64encode(image_file.read()).decode(\"utf-8\")\n",
        "    return encoded_string\n",
        "\n",
        "\n",
        "def image_summarize(img_base64, prompt):\n",
        "\n",
        "    chat = ChatOpenAI(model=\"gpt-4o-mini\", max_tokens=1024)\n",
        "\n",
        "    msg = chat.invoke(\n",
        "        [\n",
        "            HumanMessage(\n",
        "                content=[\n",
        "                    {\"type\": \"text\", \"text\": prompt},\n",
        "                    {\n",
        "                        \"type\": \"image_url\",\n",
        "                        \"image_url\": {\n",
        "                            \"url\": f\"data:image/jpeg;base64, {img_base64}\"\n",
        "                            },\n",
        "                    }\n",
        "                ]\n",
        "            )\n",
        "        ]\n",
        "    )\n",
        "\n",
        "    return msg.content\n",
        "\n",
        "def generate_img_summaries(path):\n",
        "    img_base64_list = []\n",
        "\n",
        "    image_summaries = []\n",
        "\n",
        "    prompt = \"\"\"\"You are an assistant tasked with summarizing these images for retrieval. \\\n",
        "                These summaries will be embedded and used to retrieve the raw image. \\\n",
        "                Give a concise summary of the image that is well optimized for retrieval.\"\"\"\n",
        "\n",
        "    for img_file in sorted(os.listdir(path)):\n",
        "        if img_file.endswith(\".jpg\"):\n",
        "            img_path = os.path.join(path, img_file)\n",
        "            img_base64 = encode_image(img_path)\n",
        "            img_base64_list.append(img_base64)\n",
        "\n",
        "            image_summaries.append(image_summarize(img_base64, prompt))\n",
        "\n",
        "    return img_base64_list, image_summaries\n",
        "\n",
        "# Image summaries\n",
        "images_path = \"/content/drive/MyDrive/rag/images\"\n",
        "img_base64_list, image_summaries = generate_img_summaries(images_path)"
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "# saving generated summaries to a file\n",
        "import pickle\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/text_summaries.txt\", \"wb\") as f:\n",
        "  pickle.dump(text_summaries, f)\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/table_summaries.txt\", \"wb\") as f:\n",
        "  pickle.dump(table_summaries, f)\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/image_summaries.txt\", \"wb\") as f:\n",
        "  pickle.dump(image_summaries, f)\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/img_base64_list.txt\", \"wb\") as f:\n",
        "  pickle.dump(img_base64_list, f)"
      ],
      "metadata": {
        "id": "OpWpTeCcr3_I"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "# loading generated summaries to a file\n",
        "text_summaries = []\n",
        "table_summaries= []\n",
        "image_summaries = []\n",
        "img_base64_list = []\n",
        "\n",
        "import pickle\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/text_summaries.txt\", \"rb\") as f:\n",
        "  text_summaries = pickle.load(f)\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/table_summaries.txt\", \"rb\") as f:\n",
        "  table_summaries = pickle.load(f)\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/image_summaries.txt\", \"rb\") as f:\n",
        "  image_summaries = pickle.load(f)\n",
        "\n",
        "with open(\"/content/drive/MyDrive/rag/img_base64_list.txt\", \"rb\") as f:\n",
        "  img_base64_list= pickle.load(f)"
      ],
      "metadata": {
        "id": "Wa_DcmHzEMzF"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "print(len(tables))"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "TjNtbfeJQljo",
        "outputId": "ca6049d2-4d60-4a4f-c8e1-07d9126b4abf"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "114\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "print(len(table_summaries))"
      ],
      "metadata": {
        "id": "mMKrkFMYPE-_",
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "outputId": "ab21130f-ae28-4e83-d795-f18a1fede0ec"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "114\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "import uuid\n",
        "import os\n",
        "\n",
        "from langchain.retrievers.multi_vector import MultiVectorRetriever\n",
        "from langchain.storage import InMemoryStore\n",
        "from langchain_chroma import Chroma\n",
        "from langchain_core.documents import Document\n",
        "from langchain_openai import OpenAIEmbeddings\n",
        "# from langchain_ollama import OllamaEmbeddings\n",
        "\n",
        "def create_multi_vector_retriever(vectorstore, text_summaries, texts, table_summaries, tables, image_summaries, img_base64_list):\n",
        "\n",
        "  store = InMemoryStore()\n",
        "  id_key = \"doc_id\"\n",
        "\n",
        "  retriever = MultiVectorRetriever(\n",
        "      vectorstore=vectorstore,\n",
        "      docstore=store,\n",
        "      id_key=id_key\n",
        "  )\n",
        "\n",
        "  def add_documents(retriever, doc_summaries, doc_contents):\n",
        "    doc_ids = [str(uuid.uuid4()) for _ in doc_contents]\n",
        "    summary_docs = [\n",
        "        Document(page_content=s, metadata={id_key: doc_ids[i]})\n",
        "        for i, s in enumerate(doc_summaries)\n",
        "    ]\n",
        "    retriever.vectorstore.add_documents(summary_docs)\n",
        "    # doc_contents = doc_contents + [None] * (len(doc_summaries) - len(doc_contents))\n",
        "    retriever.docstore.mset(list(zip(doc_ids, doc_contents)))\n",
        "\n",
        "  if text_summaries:\n",
        "    add_documents(retriever, text_summaries, texts)\n",
        "  if table_summaries:\n",
        "    add_documents(retriever, table_summaries, tables)\n",
        "  if image_summaries:\n",
        "    add_documents(retriever, image_summaries, img_base64_list)\n",
        "\n",
        "  return retriever\n",
        "\n",
        "vectorstore = Chroma(\n",
        "    collection_name=\"rag\",\n",
        "    embedding_function=OpenAIEmbeddings(),\n",
        "    persist_directory=\"/content/drive/MyDrive/rag/db\"\n",
        ")\n",
        "\n",
        "multi_vector_retriever = create_multi_vector_retriever(\n",
        "    vectorstore,\n",
        "    text_summaries,\n",
        "    texts,\n",
        "    table_summaries,\n",
        "    tables,\n",
        "    image_summaries,\n",
        "    img_base64_list)\n"
      ],
      "metadata": {
        "id": "F0VkuocdMfzD"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "import io\n",
        "import re\n",
        "\n",
        "from IPython.display import HTML, display\n",
        "from langchain_core.runnables import RunnableLambda, RunnablePassthrough\n",
        "from PIL import Image\n",
        "\n",
        "from langchain_core.output_parsers import StrOutputParser\n",
        "from langchain_core.prompts import ChatPromptTemplate\n",
        "from langchain_openai import ChatOpenAI\n",
        "from langchain_core.messages import HumanMessage\n",
        "\n",
        "def plt_imge_base64(img_base64):\n",
        "  image_html = f'<img src=\"data:image/jpeg;base64,{img_base64}\" />'\n",
        "  display(HTML(image_html))\n",
        "\n",
        "def looks_like_base64(sb):\n",
        "  return re.match(\"^[A-Za-z0-9+/]+[=]{0,2}$\", sb) is not None\n",
        "\n",
        "def is_image_data(b64data):\n",
        "  image_signatures = {\n",
        "      b\"\\xff\\xd8\\xff\": \"jpg\",\n",
        "      b\"\\x89\\x50\\x4e\\x47\\x0d\\x0a\\x1a\\x0a\": \"png\",\n",
        "      b\"\\x47\\x49\\x46\\x38\": \"gif\",\n",
        "      b\"\\x52\\x49\\x46\\x46\": \"webp\",\n",
        "  }\n",
        "  try:\n",
        "    header = base64.b64decode(b64data)[:8]\n",
        "    for sig, format in image_signatures.items():\n",
        "      if header.startswith(sig):\n",
        "        return True\n",
        "    return False\n",
        "  except Exception:\n",
        "    return False\n",
        "\n",
        "def resize_base64_image(base64_string, size=(128, 128)):\n",
        "  img_data = base64.b64decode(base64_string)\n",
        "  img = Image.open(io.BytesIO(img_data))\n",
        "\n",
        "  resized_img = img.resize(size, Image.LANCZOS)\n",
        "  buffered = io.BytesIO()\n",
        "  resized_img.save(buffered, format=img.format)\n",
        "\n",
        "  return base64.b64encode(buffered.getvalue()).decode(\"utf-8\")\n",
        "\n",
        "def split_image_text_types(docs):\n",
        "    \"\"\"\n",
        "    Split base64-encoded images and texts\n",
        "    \"\"\"\n",
        "    b64_images = []\n",
        "    texts = []\n",
        "    for doc in docs:\n",
        "        # Check if the document is of type Document and extract page_content if so\n",
        "        if isinstance(doc, Document):\n",
        "            doc = doc.page_content\n",
        "        if looks_like_base64(doc) and is_image_data(doc):\n",
        "            try: # Try to resize the image, if it fails, skip it\n",
        "                doc = resize_base64_image(doc, size=(1300, 600))\n",
        "                b64_images.append(doc)\n",
        "            except Exception as e:\n",
        "                pass\n",
        "        else:\n",
        "            texts.append(doc)\n",
        "    return {\"images\": b64_images, \"texts\": texts}\n",
        "\n",
        "\n",
        "def img_prompt_func(data_dict):\n",
        "    \"\"\"\n",
        "    Join the context into a single string\n",
        "    \"\"\"\n",
        "    formatted_texts = \"\\n\".join(data_dict[\"context\"][\"texts\"])\n",
        "    messages = []\n",
        "\n",
        "    # Adding image(s) to the messages if present\n",
        "    if data_dict[\"context\"][\"images\"]:\n",
        "        for image in data_dict[\"context\"][\"images\"]:\n",
        "            image_message = {\n",
        "                \"type\": \"image_url\",\n",
        "                \"image_url\": {\"url\": f\"data:image/jpeg;base64,{image}\"},\n",
        "            }\n",
        "            messages.append(image_message)\n",
        "\n",
        "    # Adding the text for analysis\n",
        "    text_message = {\n",
        "        \"type\": \"text\",\n",
        "        \"text\": (\n",
        "            \"You are medical doctor tasked with providing clinical decisions.\\n\"\n",
        "            \"You will be given a mix of text, tables, and image(s) usually of graphs, inforgraphics, x-rays, CT scans and MRIs.\\n\"\n",
        "            \"Use this information to provide clinical information related to the user question. \\n\"\n",
        "            f\"User-provided question: {data_dict['question']}\\n\\n\"\n",
        "            \"Text and / or tables:\\n\"\n",
        "            f\"{formatted_texts}\"\n",
        "        ),\n",
        "    }\n",
        "    messages.append(text_message)\n",
        "    return [HumanMessage(content=messages)]\n",
        "\n",
        "\n",
        "def multi_modal_rag_chain(retriever):\n",
        "    \"\"\"\n",
        "    Multi-modal RAG chain\n",
        "    \"\"\"\n",
        "\n",
        "    # Multi-modal LLM\n",
        "    model = ChatOpenAI(temperature=0, model=\"gpt-4o-mini\", max_tokens=1024)\n",
        "\n",
        "    # RAG pipeline\n",
        "    chain = (\n",
        "        {\n",
        "            \"context\": retriever | RunnableLambda(split_image_text_types),\n",
        "            \"question\": RunnablePassthrough(),\n",
        "        }\n",
        "        | RunnableLambda(img_prompt_func)\n",
        "        | model\n",
        "        | StrOutputParser()\n",
        "    )\n",
        "\n",
        "    return chain\n",
        "\n",
        "\n",
        "# Create RAG chain\n",
        "chain_multimodal_rag = multi_modal_rag_chain(multi_vector_retriever)"
      ],
      "metadata": {
        "id": "vf71xUWHsa4p"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "markdown",
      "source": [
        "###### Testing the retriever"
      ],
      "metadata": {
        "id": "bbPy_hQI61lV"
      }
    },
    {
      "cell_type": "code",
      "source": [
        "query = \"What triggers platelet aggregation\"\n",
        "result = multi_vector_retriever.invoke(query)\n",
        "plt_imge_base64(result[0])"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/",
          "height": 1000
        },
        "id": "fxlWTOnLyNLG",
        "outputId": "fd0c2202-23ea-4b18-d585-871a769a1b4a"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "display_data",
          "data": {
            "text/plain": [
              "<IPython.core.display.HTML object>"
            ],
            "text/html": [
              "<img 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\" />"
            ]
          },
          "metadata": {}
        }
      ]
    },
    {
      "cell_type": "markdown",
      "source": [
        "###### testing rag"
      ],
      "metadata": {
        "id": "2VLXMRNl7b9_"
      }
    },
    {
      "cell_type": "code",
      "source": [
        "query = \"Tell me about atherosclerosis\"\n",
        "print(chain_multimodal_rag.invoke(query))"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "PNU-7XSm5zH8",
        "outputId": "f19d4ef9-346a-466d-f116-1adecd3d1955"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "### Overview of Atherosclerosis\n",
            "\n",
            "Atherosclerosis is a chronic inflammatory disease characterized by the buildup of plaques within the arterial walls, leading to narrowed arteries and reduced blood flow. It is a significant contributor to cardiovascular diseases, including coronary artery disease (CAD), myocardial infarction (heart attack), and stroke.\n",
            "\n",
            "#### Pathophysiology\n",
            "- **Cholesterol and Lipoproteins**: Cholesterol is essential for various bodily functions, but elevated levels, particularly low-density lipoprotein cholesterol (LDL-C), are directly linked to the development of atherosclerosis. LDL-C accounts for 60% to 70% of total cholesterol and is the primary contributor to plaque formation. Conversely, high-density lipoprotein cholesterol (HDL-C) helps transport cholesterol from peripheral tissues back to the liver, and higher levels are considered protective against atherosclerosis.\n",
            "- **Plaque Formation**: The process begins with endothelial injury, which can be caused by factors such as hypertension, smoking, diabetes, and high cholesterol levels. This injury leads to the accumulation of lipids, inflammatory cells, and smooth muscle cells, forming atherosclerotic plaques. Over time, these plaques can calcify and rupture, leading to acute cardiovascular events.\n",
            "\n",
            "#### Risk Factors\n",
            "- **Modifiable Risk Factors**: These include high LDL-C levels, low HDL-C levels, hypertension, smoking, diabetes, obesity, and physical inactivity.\n",
            "- **Non-Modifiable Risk Factors**: Age, gender (males are at higher risk), and family history of cardiovascular disease.\n",
            "\n",
            "#### Clinical Presentation\n",
            "- Atherosclerosis can be asymptomatic for many years. Symptoms typically arise when significant arterial blockage occurs, leading to conditions such as:\n",
            "  - **Angina**: Chest pain due to reduced blood flow to the heart.\n",
            "  - **Claudication**: Pain in the legs during physical activity due to reduced blood flow.\n",
            "  - **Acute Coronary Syndrome**: Sudden symptoms of reduced blood flow to the heart, including heart attack.\n",
            "\n",
            "#### Diagnosis\n",
            "- **Lipid Profile**: Blood tests to measure cholesterol levels (total cholesterol, LDL-C, HDL-C, and triglycerides).\n",
            "- **Imaging Studies**: Ultrasound, CT scans, or angiography can visualize plaque buildup in arteries.\n",
            "\n",
            "#### Management\n",
            "- **Lifestyle Modifications**: Diet changes (increasing fruits, vegetables, and whole grains while reducing saturated fats), regular exercise, smoking cessation, and weight management.\n",
            "- **Medications**:\n",
            "  - **Statins**: First-line therapy to lower LDL-C and reduce cardiovascular risk.\n",
            "  - **Other Lipid-Lowering Agents**: Ezetimibe, fibrates, and PCSK9 inhibitors may be used in specific cases.\n",
            "  - **Antiplatelet Agents**: Aspirin or clopidogrel may be prescribed to reduce the risk of clot formation.\n",
            "- **Surgical Interventions**: In severe cases, procedures such as angioplasty or bypass surgery may be necessary to restore blood flow.\n",
            "\n",
            "#### Conclusion\n",
            "Atherosclerosis is a complex disease influenced by various risk factors and can lead to serious cardiovascular events. Early detection and management through lifestyle changes and medications are crucial in preventing disease progression and associated complications. Regular monitoring of cholesterol levels and adherence to treatment plans can significantly reduce the risk of atherosclerosis-related events.\n"
          ]
        }
      ]
    },
    {
      "cell_type": "markdown",
      "source": [
        "### Assesing RAG retrieval performance"
      ],
      "metadata": {
        "id": "GiKGorbZa8tw"
      }
    },
    {
      "cell_type": "code",
      "source": [
        "%%capture\n",
        "!pip install trulens trulens-apps-langchain trulens-providers-openai"
      ],
      "metadata": {
        "id": "3gy5q-Dfa_7n"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "from trulens.apps.langchain import TruChain\n",
        "from trulens.core import TruSession\n",
        "\n",
        "session = TruSession()\n",
        "session.reset_database()"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "_pZNhhgWbNXZ",
        "outputId": "22e80f4c-c7ab-4e38-c329-79c7e47a905f"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "🦑 TruSession initialized with db url sqlite:///default.sqlite .\n",
            "🛑 Secret keys may be written to the database. See the `database_redact_keys` option of `TruSession` to prevent this.\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "import numpy as np\n",
        "from trulens.core import Feedback\n",
        "from trulens.providers.openai import OpenAI\n",
        "\n",
        "# Initialize provider class\n",
        "provider = OpenAI()\n",
        "\n",
        "# select context to be used in feedback. the location of context is app specific.\n",
        "context = TruChain.select_context(chain_multimodal_rag)\n",
        "\n",
        "# Define a groundedness feedback function\n",
        "f_groundedness = (\n",
        "    Feedback(\n",
        "        provider.groundedness_measure_with_cot_reasons, name=\"Groundedness\"\n",
        "    )\n",
        "    .on(context.collect())  # collect context chunks into a list\n",
        "    .on_output()\n",
        ")\n",
        "\n",
        "# Question/answer relevance between overall question and answer.\n",
        "f_answer_relevance = Feedback(\n",
        "    provider.relevance_with_cot_reasons, name=\"Answer Relevance\"\n",
        ").on_input_output()\n",
        "# Context relevance between question and each context chunk.\n",
        "f_context_relevance = (\n",
        "    Feedback(\n",
        "        provider.context_relevance_with_cot_reasons, name=\"Context Relevance\"\n",
        "    )\n",
        "    .on_input()\n",
        "    .on(context)\n",
        "    .aggregate(np.mean)\n",
        ")"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "fN4njxxmbato",
        "outputId": "63c34085-c7c3-4b51-8536-1d4b7fc0d3c9"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "✅ In Groundedness, input source will be set to __record__.app.first.steps__.context.first.invoke.rets[:].page_content.collect() .\n",
            "✅ In Groundedness, input statement will be set to __record__.main_output or `Select.RecordOutput` .\n",
            "✅ In Answer Relevance, input prompt will be set to __record__.main_input or `Select.RecordInput` .\n",
            "✅ In Answer Relevance, input response will be set to __record__.main_output or `Select.RecordOutput` .\n",
            "✅ In Context Relevance, input question will be set to __record__.main_input or `Select.RecordInput` .\n",
            "✅ In Context Relevance, input context will be set to __record__.app.first.steps__.context.first.invoke.rets[:].page_content .\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "tru_recorder = TruChain(\n",
        "    chain_multimodal_rag,\n",
        "    app_name=\"ChatApplication\",\n",
        "    app_version=\"Chain1\",\n",
        "    feedbacks=[f_answer_relevance, f_context_relevance, f_groundedness],\n",
        ")"
      ],
      "metadata": {
        "id": "lTVkjsB8bubx"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "with tru_recorder as recording:\n",
        "    llm_response = chain_multimodal_rag.invoke(\"Tell me about atherosclerosis\")\n",
        "\n",
        "display(llm_response)"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/",
          "height": 157
        },
        "id": "T7NXW2Llbq0w",
        "outputId": "d893c98a-447f-4666-e7eb-907b941f0d72"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "display_data",
          "data": {
            "text/plain": [
              "'### Atherosclerosis Overview\\n\\n**Definition**: Atherosclerosis is a chronic inflammatory disease characterized by the buildup of plaques (atheromas) within the arterial walls, leading to narrowed arteries and reduced blood flow.\\n\\n#### Pathophysiology\\n- **Cholesterol and Lipoproteins**: \\n  - **LDL-C (Low-Density Lipoprotein Cholesterol)**: The primary contributor to atherosclerosis, accounting for 60-70% of total cholesterol.\\n  - **HDL-C (High-Density Lipoprotein Cholesterol)**: Helps transport cholesterol from peripheral tissues to the liver; higher levels are protective.\\n  - **VLDL-C (Very-Low-Density Lipoprotein Cholesterol)**: Contributes to total cholesterol but to a lesser extent.\\n\\n- **Inflammation**: Atherosclerosis begins with endothelial injury, leading to inflammation and the accumulation of lipids, immune cells, and fibrous tissue in the arterial wall.\\n\\n#### Risk Factors\\n- **Modifiable**: \\n  - High LDL cholesterol\\n  - Low HDL cholesterol\\n  - Hypertension\\n  - Smoking\\n  - Diabetes\\n  - Sedentary lifestyle\\n  - Obesity\\n\\n- **Non-modifiable**: \\n  - Age\\n  - Gender (higher risk in males)\\n  - Family history of cardiovascular disease\\n\\n#### Clinical Stages\\n- **Stage A**: At risk for atherosclerosis (e.g., presence of risk factors).\\n- **Stage B**: Structural heart disease without symptoms.\\n- **Stage C**: Structural heart disease with previous or current symptoms (e.g., angina, heart failure).\\n- **Stage D**: Advanced structural heart disease with severe symptoms.\\n\\n#### Diagnosis\\n- **Lipid Profile**: Measurement of total cholesterol, LDL, HDL, and triglycerides.\\n- **Imaging**: Ultrasound, CT angiography, or MRI to visualize arterial plaques.\\n- **Stress Testing**: To evaluate the likelihood of coronary artery disease (CAD).\\n\\n#### Management\\n- **Lifestyle Modifications**: \\n  - Diet (low in saturated fats, high in fruits and vegetables)\\n  - Regular exercise\\n  - Smoking cessation\\n\\n- **Medications**: \\n  - **Statins**: First-line therapy to lower LDL cholesterol and reduce cardiovascular risk.\\n  - **Antihypertensives**: To manage blood pressure.\\n  - **Antiplatelet Agents**: Aspirin or clopidogrel to reduce thrombotic events.\\n\\n- **Surgical Interventions**: \\n  - **Angioplasty and Stenting**: To open narrowed arteries.\\n  - **Coronary Artery Bypass Grafting (CABG)**: For severe cases.\\n\\n#### Prognosis\\n- Early detection and management of risk factors can significantly improve outcomes and reduce the risk of cardiovascular events such as heart attacks and strokes. Regular follow-up and monitoring are essential for patients with atherosclerosis.'"
            ],
            "application/vnd.google.colaboratory.intrinsic+json": {
              "type": "string"
            }
          },
          "metadata": {}
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "session.get_leaderboard()"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/",
          "height": 112
        },
        "id": "9wsAhNrCcOgA",
        "outputId": "01d74622-4201-4a2e-ee24-7e1831c9fb50"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "execute_result",
          "data": {
            "text/plain": [
              "                             Answer Relevance  latency  total_cost\n",
              "app_name        app_version                                       \n",
              "ChatApplication Chain1                    1.0     18.0    0.023707"
            ],
            "text/html": [
              "\n",
              "  <div id=\"df-9708f9b3-234b-473b-8a67-44a050927622\" class=\"colab-df-container\">\n",
              "    <div>\n",
              "<style scoped>\n",
              "    .dataframe tbody tr th:only-of-type {\n",
              "        vertical-align: middle;\n",
              "    }\n",
              "\n",
              "    .dataframe tbody tr th {\n",
              "        vertical-align: top;\n",
              "    }\n",
              "\n",
              "    .dataframe thead th {\n",
              "        text-align: right;\n",
              "    }\n",
              "</style>\n",
              "<table border=\"1\" class=\"dataframe\">\n",
              "  <thead>\n",
              "    <tr style=\"text-align: right;\">\n",
              "      <th></th>\n",
              "      <th></th>\n",
              "      <th>Answer Relevance</th>\n",
              "      <th>latency</th>\n",
              "      <th>total_cost</th>\n",
              "    </tr>\n",
              "    <tr>\n",
              "      <th>app_name</th>\n",
              "      <th>app_version</th>\n",
              "      <th></th>\n",
              "      <th></th>\n",
              "      <th></th>\n",
              "    </tr>\n",
              "  </thead>\n",
              "  <tbody>\n",
              "    <tr>\n",
              "      <th>ChatApplication</th>\n",
              "      <th>Chain1</th>\n",
              "      <td>1.0</td>\n",
              "      <td>18.0</td>\n",
              "      <td>0.023707</td>\n",
              "    </tr>\n",
              "  </tbody>\n",
              "</table>\n",
              "</div>\n",
              "    <div class=\"colab-df-buttons\">\n",
              "\n",
              "  <div class=\"colab-df-container\">\n",
              "    <button class=\"colab-df-convert\" onclick=\"convertToInteractive('df-9708f9b3-234b-473b-8a67-44a050927622')\"\n",
              "            title=\"Convert this dataframe to an interactive table.\"\n",
              "            style=\"display:none;\">\n",
              "\n",
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              "  </svg>\n",
              "    </button>\n",
              "\n",
              "  <style>\n",
              "    .colab-df-container {\n",
              "      display:flex;\n",
              "      gap: 12px;\n",
              "    }\n",
              "\n",
              "    .colab-df-convert {\n",
              "      background-color: #E8F0FE;\n",
              "      border: none;\n",
              "      border-radius: 50%;\n",
              "      cursor: pointer;\n",
              "      display: none;\n",
              "      fill: #1967D2;\n",
              "      height: 32px;\n",
              "      padding: 0 0 0 0;\n",
              "      width: 32px;\n",
              "    }\n",
              "\n",
              "    .colab-df-convert:hover {\n",
              "      background-color: #E2EBFA;\n",
              "      box-shadow: 0px 1px 2px rgba(60, 64, 67, 0.3), 0px 1px 3px 1px rgba(60, 64, 67, 0.15);\n",
              "      fill: #174EA6;\n",
              "    }\n",
              "\n",
              "    .colab-df-buttons div {\n",
              "      margin-bottom: 4px;\n",
              "    }\n",
              "\n",
              "    [theme=dark] .colab-df-convert {\n",
              "      background-color: #3B4455;\n",
              "      fill: #D2E3FC;\n",
              "    }\n",
              "\n",
              "    [theme=dark] .colab-df-convert:hover {\n",
              "      background-color: #434B5C;\n",
              "      box-shadow: 0px 1px 3px 1px rgba(0, 0, 0, 0.15);\n",
              "      filter: drop-shadow(0px 1px 2px rgba(0, 0, 0, 0.3));\n",
              "      fill: #FFFFFF;\n",
              "    }\n",
              "  </style>\n",
              "\n",
              "    <script>\n",
              "      const buttonEl =\n",
              "        document.querySelector('#df-9708f9b3-234b-473b-8a67-44a050927622 button.colab-df-convert');\n",
              "      buttonEl.style.display =\n",
              "        google.colab.kernel.accessAllowed ? 'block' : 'none';\n",
              "\n",
              "      async function convertToInteractive(key) {\n",
              "        const element = document.querySelector('#df-9708f9b3-234b-473b-8a67-44a050927622');\n",
              "        const dataTable =\n",
              "          await google.colab.kernel.invokeFunction('convertToInteractive',\n",
              "                                                    [key], {});\n",
              "        if (!dataTable) return;\n",
              "\n",
              "        const docLinkHtml = 'Like what you see? Visit the ' +\n",
              "          '<a target=\"_blank\" href=https://colab.research.google.com/notebooks/data_table.ipynb>data table notebook</a>'\n",
              "          + ' to learn more about interactive tables.';\n",
              "        element.innerHTML = '';\n",
              "        dataTable['output_type'] = 'display_data';\n",
              "        await google.colab.output.renderOutput(dataTable, element);\n",
              "        const docLink = document.createElement('div');\n",
              "        docLink.innerHTML = docLinkHtml;\n",
              "        element.appendChild(docLink);\n",
              "      }\n",
              "    </script>\n",
              "  </div>\n",
              "\n",
              "\n",
              "    </div>\n",
              "  </div>\n"
            ],
            "application/vnd.google.colaboratory.intrinsic+json": {
              "type": "dataframe",
              "summary": "{\n  \"name\": \"session\",\n  \"rows\": 1,\n  \"fields\": [\n    {\n      \"column\": \"Answer Relevance\",\n      \"properties\": {\n        \"dtype\": \"number\",\n        \"std\": null,\n        \"min\": 1.0,\n        \"max\": 1.0,\n        \"num_unique_values\": 1,\n        \"samples\": [\n          1.0\n        ],\n        \"semantic_type\": \"\",\n        \"description\": \"\"\n      }\n    },\n    {\n      \"column\": \"latency\",\n      \"properties\": {\n        \"dtype\": \"number\",\n        \"std\": null,\n        \"min\": 18.0,\n        \"max\": 18.0,\n        \"num_unique_values\": 1,\n        \"samples\": [\n          18.0\n        ],\n        \"semantic_type\": \"\",\n        \"description\": \"\"\n      }\n    },\n    {\n      \"column\": \"total_cost\",\n      \"properties\": {\n        \"dtype\": \"number\",\n        \"std\": null,\n        \"min\": 0.023707499999999996,\n        \"max\": 0.023707499999999996,\n        \"num_unique_values\": 1,\n        \"samples\": [\n          0.023707499999999996\n        ],\n        \"semantic_type\": \"\",\n        \"description\": \"\"\n      }\n    }\n  ]\n}"
            }
          },
          "metadata": {},
          "execution_count": 52
        }
      ]
    },
    {
      "cell_type": "markdown",
      "source": [
        "### RAG_enhanced Inference"
      ],
      "metadata": {
        "id": "LevWOppObOJB"
      }
    },
    {
      "cell_type": "code",
      "source": [
        "!git clone https://github.com/onyekaokonji/LLaVA-Med.git LLaVA_Med"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "Hay3sguq94rf",
        "outputId": "09ff79e7-da55-455c-c926-5e1b9df80b52"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "Cloning into 'LLaVA_Med'...\n",
            "remote: Enumerating objects: 389, done.\u001b[K\n",
            "remote: Counting objects: 100% (83/83), done.\u001b[K\n",
            "remote: Compressing objects: 100% (49/49), done.\u001b[K\n",
            "remote: Total 389 (delta 32), reused 70 (delta 30), pack-reused 306 (from 1)\u001b[K\n",
            "Receiving objects: 100% (389/389), 77.07 MiB | 14.17 MiB/s, done.\n",
            "Resolving deltas: 100% (104/104), done.\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "import warnings\n",
        "warnings.filterwarnings('ignore')\n",
        "\n",
        "import os\n",
        "os.chdir(\"/content/LLaVA_Med\")"
      ],
      "metadata": {
        "id": "q3GUo1LY-DoE"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "%%capture\n",
        "!pip install -q -e ."
      ],
      "metadata": {
        "id": "9n1x1qZ4-J6z"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "from llava.model.builder import load_pretrained_model\n",
        "from llava.mm_utils import get_model_name_from_path\n",
        "\n",
        "model_path_2 = \"onyekaokonji/llava-med-v1.5-mistral-7b-oo\"\n",
        "\n",
        "tokennizer, model, image_processor, context_len = load_pretrained_model(\n",
        "    model_path=model_path_2,\n",
        "    # model_base=model_base,\n",
        "    model_base=None,\n",
        "    # model_name=get_model_name_from_path(model_name),\n",
        "    model_name=get_model_name_from_path(model_path_2)\n",
        ")"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/",
          "height": 569,
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            "- This IS expected if you are initializing LlavaMistralForCausalLM from the checkpoint of a model trained on another task or with another architecture (e.g. initializing a BertForSequenceClassification model from a BertForPreTraining model).\n",
            "- This IS NOT expected if you are initializing LlavaMistralForCausalLM from the checkpoint of a model that you expect to be exactly identical (initializing a BertForSequenceClassification model from a BertForSequenceClassification model).\n"
          ]
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              "generation_config.json:   0%|          | 0.00/111 [00:00<?, ?B/s]"
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              "preprocessor_config.json:   0%|          | 0.00/316 [00:00<?, ?B/s]"
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      "cell_type": "code",
      "source": [
        "%%capture\n",
        "%pip install --force-reinstall pydantic\n",
        "%pip install gradio"
      ],
      "metadata": {
        "id": "VFPnjM55BSIB"
      },
      "execution_count": null,
      "outputs": []
    },
    {
      "cell_type": "code",
      "source": [
        "question = \"what is the modality of this image? is there a disease identifiable in the image and if so, tell me a bit more about it including treatment options\"\n",
        "context = chain_multimodal_rag.invoke(question)\n",
        "print(context)"
      ],
      "metadata": {
        "colab": {
          "base_uri": "https://localhost:8080/"
        },
        "id": "kpB6rMA2C5Wz",
        "outputId": "a4e0c4a7-f08f-4c33-a3ae-d70553896d20"
      },
      "execution_count": null,
      "outputs": [
        {
          "output_type": "stream",
          "name": "stdout",
          "text": [
            "The provided images appear to be a series of medical images, likely X-rays or CT scans, but without visual inspection, I cannot definitively identify the modality. However, based on the context of your question, I will assume that the images are related to a specific disease process.\n",
            "\n",
            "### Identifiable Disease\n",
            "If the images depict a condition such as pneumonia, lung nodules, or other pulmonary diseases, here are some details:\n",
            "\n",
            "1. **Pneumonia**:\n",
            "   - **Description**: Pneumonia is an infection that inflames the air sacs in one or both lungs, which may fill with fluid or pus. Symptoms include cough, fever, chills, and difficulty breathing.\n",
            "   - **Diagnosis**: Typically diagnosed through a combination of physical examination, chest X-ray, and sometimes CT scans.\n",
            "   - **Treatment**: Treatment usually involves antibiotics for bacterial pneumonia, antiviral medications for viral pneumonia, and supportive care such as rest, fluids, and over-the-counter medications to relieve symptoms.\n",
            "\n",
            "2. **Lung Nodules**:\n",
            "   - **Description**: Lung nodules are small masses of tissue in the lung that can be benign or malignant. They are often discovered incidentally on imaging studies.\n",
            "   - **Diagnosis**: Follow-up imaging (CT scans) and sometimes biopsy are used to determine the nature of the nodules.\n",
            "   - **Treatment**: Treatment depends on the underlying cause. Benign nodules may require no treatment, while malignant nodules may necessitate surgery, chemotherapy, or radiation therapy.\n",
            "\n",
            "3. **Chronic Obstructive Pulmonary Disease (COPD)**:\n",
            "   - **Description**: COPD is a progressive lung disease that makes it hard to breathe. It includes emphysema and chronic bronchitis.\n",
            "   - **Diagnosis**: Diagnosed through a combination of medical history, physical examination, and imaging studies (X-ray or CT scan).\n",
            "   - **Treatment**: Treatment includes smoking cessation, bronchodilators, steroids, pulmonary rehabilitation, and oxygen therapy.\n",
            "\n",
            "### Conclusion\n",
            "To provide a more accurate assessment, I would need to see the images directly or have a more detailed description of their contents. If you can specify the findings or symptoms associated with the images, I can offer more tailored information regarding the disease and its treatment options.\n"
          ]
        }
      ]
    },
    {
      "cell_type": "code",
      "source": [
        "import gradio as gr\n",
        "import io\n",
        "from contextlib import redirect_stdout\n",
        "\n",
        "from llava.eval.run_llava import eval_model\n",
        "\n",
        "with gr.Blocks(theme=gr.themes.Monochrome()) as gradio_app:\n",
        "    with gr.Column(scale=1):\n",
        "        gr.Markdown(\"<center><h1>LLaVa-Med + RAG</h1></center>\")\n",
        "\n",
        "        with gr.Row():\n",
        "            image = gr.Image(type=\"filepath\", scale=2)\n",
        "            question = gr.Textbox(placeholder=\"Enter a question\", scale=3)\n",
        "\n",
        "        with gr.Row():\n",
        "            answer = gr.Textbox(placeholder=\"Answer pops up here\", scale=1)\n",
        "\n",
        "        def run_inference(image, question):\n",
        "            # context = chain_multimodal_rag.invoke(question)\n",
        "            # enhanced_query = f\"Question: {question}\\n\\nAdditional Context: {context}\\n\\nPlease analyze the image {image} and answer the question based on the given context.\"\n",
        "            args = type('Args', (), {\n",
        "                \"model_path\": model_path_2,\n",
        "                \"model_base\": None,\n",
        "                \"image_file\": image,\n",
        "                \"query\": question,\n",
        "                \"conv_mode\": None,\n",
        "                \"sep\": \",\",\n",
        "                \"temperature\": 0,\n",
        "                \"top_p\": None,\n",
        "                \"num_beams\": 1,\n",
        "                \"max_new_tokens\": 512\n",
        "                })()\n",
        "\n",
        "            # Capture the printed output of eval_model\n",
        "            f = io.StringIO()\n",
        "            with redirect_stdout(f):\n",
        "                eval_model(args)\n",
        "            output = f.getvalue()\n",
        "\n",
        "            return output\n",
        "\n",
        "        with gr.Row():\n",
        "            btn = gr.Button(\"Run Inference\", scale=1)\n",
        "\n",
        "        btn.click(fn=run_inference, inputs=[image, question], outputs=answer)\n",
        "\n",
        "gradio_app.launch(share=True, debug=True, height=800, width=\"100%\")"
      ],
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          "text": [
            "Colab notebook detected. This cell will run indefinitely so that you can see errors and logs. To turn off, set debug=False in launch().\n",
            "Running on public URL: https://471114e699521e29ca.gradio.live\n",
            "\n",
            "This share link expires in 72 hours. For free permanent hosting and GPU upgrades, run `gradio deploy` from Terminal to deploy to Spaces (https://huggingface.co/spaces)\n"
          ]
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            "Keyboard interruption in main thread... closing server.\n",
            "Killing tunnel 127.0.0.1:7860 <> https://471114e699521e29ca.gradio.live\n"
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