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    Liver Disease

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    GANESH KUMAR JELLA
    The liver plays a key role in metabolizing many medications. In liver disease, the liver's ability to break down drugs is reduced, which can cause drug levels to rise to toxic levels. Many drugs require dosage adjustments or should be avoided in patients with liver disease to prevent adverse effects. Common issues in liver disease include reduced protein binding of drugs, impaired blood clotting, and fluid retention, which medications may exacerbate. Drugs that are highly metabolized by the liver or have potential side effects like fluid retention require especially close monitoring and potential dosage adjustments.

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    Liver Disease

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    GANESH KUMAR JELLA
    3K views17 pages
    The liver plays a key role in metabolizing many medications. In liver disease, the liver's ability to break down drugs is reduced, which can cause drug levels to rise to toxic levels. Many drugs require dosage adjustments or should be avoided in patients with liver disease to prevent adverse effects. Common issues in liver disease include reduced protein binding of drugs, impaired blood clotting, and fluid retention, which medications may exacerbate. Drugs that are highly metabolized by the liver or have potential side effects like fluid retention require especially close monitoring and potential dosage adjustments.

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    The liver plays a key role in metabolizing many medications. In liver disease, the liver's ability to break down drugs is reduced, which can cause drug levels to rise to toxic levels. Many drugs require dosage adjustments or should be avoided in patients with liver disease to prevent adverse effects. Common issues in liver disease include reduced protein binding of drugs, impaired blood clotting, and fluid retention, which medications may exacerbate. Drugs that are highly metabolized by the liver or have potential side effects like fluid retention require especially close monitoring and potential dosage adjustments.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    3K views17 pages

    Liver Disease

    Uploaded by

    GANESH KUMAR JELLA
    The liver plays a key role in metabolizing many medications. In liver disease, the liver's ability to break down drugs is reduced, which can cause drug levels to rise to toxic levels. Many drugs require dosage adjustments or should be avoided in patients with liver disease to prevent adverse effects. Common issues in liver disease include reduced protein binding of drugs, impaired blood clotting, and fluid retention, which medications may exacerbate. Drugs that are highly metabolized by the liver or have potential side effects like fluid retention require especially close monitoring and potential dosage adjustments.

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    LIVER DISEASE

     

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    Medications requiring dosage adjustments in hepatic disease


    Liver is the principal organ responsible for processing and providing major pathways for the biotransformation of many ingested medications.

    METABOLIC PROCESS INVOLVED IN THE HEPATIC EXCRETION OF DRUGS


     

      

    PHASE I Enzymes cyt p 450 ,hydrolysis, oxidation, dealkylation and Reduction of drug molecules. PHASE II Involve conjugation of drug molecules E.g.: Glucorinic acid , sulphates , Amino acids, acetates
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    LIVER DISORDERS
    

           

    HYPOPROTEINAEMIA -reduced protein binding & increased toxicity of some highly protein-bound drugs such as phenytoin & prednisolone. REDUCED CLOTTING Indicated by a prolonged prothrombin time, increases the sensitivity to oral anticoagulants such as warfarin& phenindione. HEPATIC ENCEPHALOPATHY many drugs can further impair cerebral function & drugs may precipitate These include all sedative drugs, opioid analgesics, those diuretics that produce hypokalaemia, & drugs that cause constipation. FLUID OVERLOAD Edema & ascites in chronic liver disease may be exacerbated by drugs that give rise to fluid retention, e.g. NSAIDs, corticosteroids, & carbenoxolone.
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    RELIABLE AND SENSITIVE TEST OF LIVER INJURY


    Measurement: Direct and total serum albumin Direct and total serum bilurubin Serum alanine Amino transferase Alkaline phosphates. Assessment of: Protrombin time Protrombin Ratio  hepatic function  increasing INR, PTT, GGT,  A Systematic Review of the Performance Characteristics of Clinical Event Monitor Signals Used to Detect Adverse Drug Events in the Hospital Setting.

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    Hepatic drug Clearance


          

    Liver blood flow Intrinsic enzyme metabolism capacity of liver to that drug. Hepatic excretion Ratio IN LIVER DISEASE Decrease metabolism Decreased liver blood flow Alteration of intra extra hepatic shunting
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    Hepatic drug Clearance


             

    High clearance Drugs Lidocaine Propronolol Morphine Antipsychotic Beta blockers Ca channel blockers Nitrates Opoids Tricycles anti depressants

                  

    Low clearance Drugs Phenytoin Warfarin Theophyllin Aminodarone Anti convalcents Anti Parkinson Anti thyroids Benzodiazepines Quinidine Retinoids Rifamcin Spiranolactone Sulfonylureas Proton pump inhibitors

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    DRUG DOSING IN LIVER DISEASE


    

    Abnormal function of the liver can result in alterations of drug metabolism. For example, diazepam, a commonly used medication for anxiety, sedation, and muscle spasticity, has a half-life halfthat is doubled in patients with chronic liver failure.
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    Dosage adjustments in hepatic disease


         

    In hepatic disease, great potential exists. For use in a hospital system, the rules should: 1) Detect current and potential adverse drug events. 2) Avoid alert fatigue. 3) Incorporate future pharmacogenetic data into clinical decision alerts. 4) Create well defined standards by consensus guidelines for defining rules. 5) Evaluate sensitivity, specificity, and PPV of rules.
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    Increased risk of gastrointestinal bleeding and may aggravate fluid retention. Avoid NSAIDs in severe liver disease
            

    NSAIDs Celecoxib Diclofenac Etodolac Ibuprofen Indometacin Ketoprofen Ketorolac Mefenamic acid

            

    Meloxicam Nabumetone Naproxen Phenylbutazone Piroxicam Rofecoxib Sulindac Tenoxicam Tiaprofenic Acid
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    Anesthetics and muscle relaxants


             

    Halothane Avoid if history pyrexia or jaundice Thiopental Reduce dose for induction in severe liver disease Suxamethonium chloride Prolonged apnoea may occur in severe liver disease due to reduced hepatic synthesis of Pseudocholinesterase Desflurane - reduce dose Tizanidine - Avoid in severe liver disease
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    Opioid analgesics  Codeine  Morphine  Dextropropoxyphene  Diphenoxylate  Fentanyl  Methadone  Nalbuphine  Pethidine  Tramadol Avoid or reduce dose. May precipitate coma.
    

          

    ACE inhibitors: Captopril Enalapril Fosinopril Quinapril Ramipril Trandolapril

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    ALIMENTARY TRACT AND METABOLISM


     

          

    Antacids Avoid those containing large amounts of sodium(magnesium trisilicate) and those containing calcium compounds which cause constipationasthis may aggravate encephalopath Carbenoxolone -Produce sodium & water retention andhypokalaemia Cimetidine & Ranitidine - Increased risk of confusion, reduce dose. Lansoprazol - In severe liver disease dose should not exceed 30mg daily Omeprazol - In liver disease not more than 20mg daily needed Pentoprazol - Max 20mg daily in severe hepatic impairment &cirrhosis- monitor liver function Sulphonylureas, Chlorpropamide, Glibenclamide, Gliclazide, Tolbutamide, Glipizide Increased risk of hypoglycemia in severe liver disease, Avoid or use small dose, can produce jaundice
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    Reduced dose
      

        

    Leflunomide -active metabolite may accumulate Gold salts- Hepatotoxicity may occur ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS Quinolones Norfloxacin Nalidixic acid Ofloxacin Neomycin -Absorbed from gastro-intestinal tract in liver disease- increased risk of ototoxicity
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    Reduce Dose
              

    Antigout agents-Antigout agents Loop diuretic Thiazides Bumetanide Chlortalidone Furosemide Hydrochlorothiazide Oral contraceptives Avoid in active liver disease & if history of pruritis or cholestasis during pregnancy Oestrogens Estradiol Norethisterone

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    Antimigraine agents Ergotamine and Naratripan - Max 2.5mg in 24 hours in moderate hepatic impairment avoid if severe

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