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    Drug Interactions

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    This document discusses drug interactions, which occur when two or more drugs are administered together and one drug modifies the effect of the other. It defines types of interactions such as pharmacokinetic and pharmacodynamic. It provides examples of interactions that can occur during absorption, distribution, metabolism and excretion of drugs. It also discusses interactions between drugs and food, laboratory tests, and herbal products. Vulnerable patient populations are identified. The document emphasizes the importance of being aware of potential drug interactions to avoid adverse effects or reduce therapeutic effectiveness.

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    Drug Interactions

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    This document discusses drug interactions, which occur when two or more drugs are administered together and one drug modifies the effect of the other. It defines types of interactions such as pharmacokinetic and pharmacodynamic. It provides examples of interactions that can occur during absorption, distribution, metabolism and excretion of drugs. It also discusses interactions between drugs and food, laboratory tests, and herbal products. Vulnerable patient populations are identified. The document emphasizes the importance of being aware of potential drug interactions to avoid adverse effects or reduce therapeutic effectiveness.

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    This document discusses drug interactions, which occur when two or more drugs are administered together and one drug modifies the effect of the other. It defines types of interactions such as pharmacokinetic and pharmacodynamic. It provides examples of interactions that can occur during absorption, distribution, metabolism and excretion of drugs. It also discusses interactions between drugs and food, laboratory tests, and herbal products. Vulnerable patient populations are identified. The document emphasizes the importance of being aware of potential drug interactions to avoid adverse effects or reduce therapeutic effectiveness.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    524 views33 pages

    Drug Interactions

    Uploaded by

    88AKK
    This document discusses drug interactions, which occur when two or more drugs are administered together and one drug modifies the effect of the other. It defines types of interactions such as pharmacokinetic and pharmacodynamic. It provides examples of interactions that can occur during absorption, distribution, metabolism and excretion of drugs. It also discusses interactions between drugs and food, laboratory tests, and herbal products. Vulnerable patient populations are identified. The document emphasizes the importance of being aware of potential drug interactions to avoid adverse effects or reduce therapeutic effectiveness.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
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    The key takeaways are that drug interactions can result in beneficial or adverse effects and occur when two or more drugs are administered simultaneously or in quick succession. Drug interactions are likely in situations involving self-medication, treatment by unqualified practitioners, drugs with steep dose-response curves and low safety margins, and drugs that induce or inhibit drug-metabolizing enzymes.

    Drug interactions are likely in the following situations: self-medication, treatment by semi-qualified paramedics/quacks, drugs having steep dose-response curves with low safety margins, drugs having enzyme-inducing/inhibiting effects, drugs having zero-order or mixed-order kinetics, and drugs that are used for a prolonged period requiring precise maintenance of plasma concentration.

    Regular medication drugs that are likely to be involved in drug interactions include antidiabetics, antihypertensives, antianginal drugs, antiepileptics, antiparkinsonian drugs, oral contraceptives, antiasthmatic drugs, corticosteroids, psychopharmacological agents, and anti-TB and anti-HIV drugs.

    DRUG INTERACTIONS

    06/03/2013

    Dr Rajesh Basavaraj, PG, Dept. of Pharmacology.

    DRUG INTERACTIONS
    Def: Modification of response to one drug by another drug when they are administered simultaneously or in quick succession It may result into beneficial effects or into adverse effects

    KD Tripathi, 6th ed.

    Drug interactionslikely in following situations


    Self medication
    Treatment by semi qualified paramedics / quacks Drugs having steep DRC with low safety of margins

    Drugs having enzyme inducing/inhibiting effects


    Drugs having zero order/mixed order kinetics Drugs that are used for prolonged period with precise maintenance of plasma concentration

    Regular medication drugs (likely to be involved in drug interactions)


    Antidiabetics
    Antihypertensives Antianginal drugs Antiepileptic drugs Antiparkinsonian drugs

    Oral contraceptives
    Antiasthamtic drugs Corticosteroids Psychopharmacological agents Anti-TB & anti-HIV drugs

    Risky drugs
    o affect vital processes - Warfarin, CPZ, morphine o saturable kinetics - phenytoin theophylline salicylates o steep DRC - verapamil, L-Dopa, chlorpropamide

    o demonstrate dose dependent toxicity - digoxin, Mtx, lithium aminoglycosides


    o prophylactic action - OCPs, cyclosporine

    o high PPB ability - NSAIDs oral anticoagulants sulfonylureas

    Vulnerable patients
    Elderly pts. receiving many drugs Pts. with hepatic / renal disease Pts. with unstable disease
    epilepsy, diabetes mellitus, cardiac disease

    Pts. dependent on drug therapy for survival


    transplant recipients, Addisons disease

    Pts with more than one prescribing doctor

    Adverse drug-drug interactions


    A. In vitro drug interactions B. In vivo drug interactions

    In vitro drug-drug interactions


    Drugs
    Thiopentone sodium + SCh/ morphine

    Mixed into
    In the same syringe

    Result
    Precipitation / activation
    Inactivation of heparin

    Hydrocortisone/gentamicin In the same syringe + Heparin

    Hydrocortisone + Penicillin In the same syringe


    Penicillin + Gentamicin Noradrenaline In the same syringe In i.v infusion fluid NS or BT

    Inactivation of penicillin
    Mutual inactivation Oxidized

    IN VITRO DRUG-DRUG INTERACTIONS


    Aminophylline i.v soln. i.v epinephrine, erythromycin or cephalothin In i.v infusion fluid 5% dextrose Into blood / plasma, amino acid soln., mannitol soln., NaHCO3 soln., heparin i.v These drugs get decomposed at alkaline PH of aminophylline Drugs are precipitated in the acidic PH of dextrose soln. Get inactivated or precipitated

    Na+ salts of phenytoin, barbiturates, heparin, penicillin & sulfonamides Almost all drugs (as a rule)

    IN VIVO DRUG-DRUG INTERACTIONS


    A. Pharmacokinetic interactions B. Pharmacodynamic interactions

    Pharmacokinetic interactions
    o Alteration of the concentration of object drug that reaches its site of action o consequently the intensity of response will be altered

    Pharmacokinetic interactions
    Drug absorption: Due to formation of insoluble or poorly absorbable complexes in gut
    atropine and its substitutesdelay gastric emptying intestinal absorption of other drugs

    prokinetic drugs- hasten gastric emptying- intestinal absorption of other drugs


    milk, antacids containing Ca2+, Mg2+, Al3+ and iron absorption of tetracyclines erythromycin/ tetracyclines- bioavailability of digoxin adrenaline + LA Systemic antacids + Omeprazole

    Pharmacokinetic interactions
    Drug distribution: Mainly due to displacement of one drug by another from its binding site on plasma proteins
    sulfonamides displace bilirubin in neonates- kernicterus

    salicylates and sulfonamidestolbutamide and Mtx

    displace

    warfarin,

    quinidine, verapamil and amiodarone- displace digoxin and also its excretion (by inhibiting P-glycoprotein) direct curtailment of drug distribution protamine sulfate heparin desferrioxamine - iron

    Pharmacokinetic interactions
    Drug metabolism: Enzyme induction: 1-2 wks to develop
    Enzyme inducer Phenobarbitone Phenytoin, CBZ Glucocorticoids Pioglitazone Rifampicin Phenobarbitone Enzyme induced CYP3A4 Drugs affected Midazolam, alprozolam Barbiturates Ritonavir, CCBs Macrolides OCPs, Warfarin, Losartan Ibuprofen, Tamoxifen

    CYP3A4 CYP2C9

    Smoking Omeprazole
    INH Chronic alcohol intake

    CYP1A2
    CYP2E1

    Theophylline, Warfarin Imipramine, PCT


    Halothane, PCT Ethanol

    Effect of rifampicin on the metabolism and anticoagulant action of warfarin

    Pharmacokinetic interactions
    Microsomal enzymes- liver, but also in lungs CYP1A2 in smokers Clinical significance of enzyme induction: Consequences of drug metabolism plasma levels therapeutic effect of coadministered drug Inactive metabolite Active metabolite

    Enzyme induction- toxicity


    Therapeutic benefits

    Pharmacokinetic interactions
    Enzyme inhibition: Hepatic microsomal mixed function oxidase (MFDs), MAO, xanthine oxidase, aldehyde dehydrogenase
    Inhibitors Cimetidine Enzyme inhibited Hepatic microsomal MFDs Drugs affected Phenytoin, warfarin Antidepressants, Diazepam Theophylline, quinidine Phenytoin, Primidone Phenobarbitone Theophylline, CBZ Warfarin, Cyclosporine Theophylline

    Sodium valproate Erythromycin Fluoroquinolones except ofloxacin

    Hepatic microsomal MFDs Hepatic microsomal MFDs Hepatic microsomal MFDs

    Pharmacokinetic interactions
    Chloramphenicol Verapamil, diltiazem Allopurinol Hepatic microsomal MFDs Terfenadine Phenytoin, warfarin Hepatic microsomal MFDs Theophylline, CBZ Cyclosporine Xanthine oxidase 6-MP, azathioprine

    MAO-Is
    Disulfiram Metronidazole Chlorpropamide Cefoperazone Carbidopa Ecothiophate

    MAO
    Aldehyde dehydrogenase

    Morphine, pethidine
    Alcohol, phenytoin Warfarin

    Peripheral dopa decarboxylase AChE

    L-Dopa Suxamethonium

    Pharmacokinetic interactions
    Clinical significance of enzyme inhibition: Potentially adverse consequences Cimetidine + dicumarol- enhanced bleeding MAO-Is + Morphine - severe respiratory depression Dicumarol/ chloramphenicol + Phenytoin - severe ataxia, drowsiness Chloramphenicol/ ketoconazole + Terfenadine precipitate cardiac arrhythmias

    Therapeutically beneficial consequences L-Dopa + carbidopa


    d-TC + neostigmine Alcohol + disulfiram

    Pharmacokinetic interactions
    Drug excretion

    Altering protein binding, and hence filtration


    Inhibiting tubular secretion Altering urine flow &/or urine pH

    Inhibition renal tubular secretion:


    Drug(s) causing inhibition Probenicid, Phenlybutazone Sulfonamides, Aspirin Thiazide diuretics Verapamil Quinidine Amiodarone Indomethacin Aspirin NSAIDs Drug(s) affected Penicillin Indomethacin

    Digoxin Furosemide Methotrexate

    Pharmacokinetic interactions
    Alteration of urine flow and pH:

    Alkalinization of urine by NaHCO3 excretion of acidic drugs


    Acidification of urine by ammonium chloride/ ascorbic acid- excretion of basic drugs Loop and thiazide diuretics- proximal tubular reabsorption of lithium

    Pharmacodynamic interactions
    Modification of the pharmacological effect of a drug without altering its concentration in tissue fluid May result in Synergism

    Antagonism
    Abnormal response

    o Abnormal response
    Propranolol + Insulin / oral hypoglycemic drugsmasks symptoms of hypoglycemia predispose to hypoglycemic coma

    Pharmacodynamic interactions
    Synergism
    Aspirin + Warfarin
    BZDs + Antihistaminics+ CPZ + Morphine+ Alcohol d-TC + Aminoglycosides

    Antagonism
    CNS stimulants + Depressants
    Thiazides + Oral hypoglycemic drugs NSAIDs + -blockers/ ACE-Is Atropine + ACh / Anti-ChEs d-TC + Ach ACE-Is + Spironolactone L-dopa + Antipsychotics Bacteriostatic + Bactericidal (tetracycline + penicillin)

    TCAs + Atropine
    Metoclopramide + Phenothiazines Halothane + Adrenaline Sildenafil + Organic nitrates 2 bactericidal agents (penicillin + gentamicin) Bacteriostatic + Bactericidal (Rifampicin + Dapsone)

    Interactions due to change in fluid and electrolyte balance


    Hypokalaemia (Thiazide / Loop diuretics) + Digoxin/d-TC Hypokalaemia + Lignocaine, quinidine, procainamide

    ACE-Is + K+ sparing diuretics


    Sodium depletion lithium toxicity

    Beneficial drug-drug interactions


    Interactions leading to therapeutic effects

    Sulfamethoxazole + Trimethoprim (Cotrimoxazole)


    L-Dopa + Carbidopa Nitrates + blockers angina

    Nitrates + CCBs angina


    Thiazides + K+ sparing diuretics + blockers HTN Probenicid + penicillin / cephalosporins Amoxicillin + -Lactamase inhibitor ACE-Is + SGLT-2 cotransporter inhibitors

    Beneficial drug-drug interactions


    Interactions providing advantage in management of poisoning and drug overdose Naloxone- morphine poisoning / addiction Protamine sulfate heparin toxicity

    Physostigmine- atropine poisoning


    Neostigmine- reversal of muscle relaxation due to d-TC Ethanol- methanol poisoning Desferrioxamine / deferiprone- iron poisoning

    Drug-laboratory test interactions


    Cephalosporins- false + ve urine glucose test Cephalosporins- spurious serum creatinine levels Diuretics- serum electrolyte tests, blood sugar levels ACE-Is hypokalaemia MAO-Is- urinary VMA levels

    Drug-food interactions
    Tyramine containing food items + MAO-Is Cheese reaction Spinach, broccoli- rich in Vit K antagonize effects of warfarin Food- bioavailability of griseofulvin, metoprolol, propranolol, phenytoin, dicumarol Food- bioavailability didanosine of NSAIDs, tetracyclines,

    Protein rich diet- acidic urine- promotes excretion of basic drugs and vice-versa

    Drug-food interactions
    Grape, orange, garlic inhibit CYP3A4 bioavailability of indinavir, saquinavir, nimodipine, nifedipine, simvastatin, lovastatin Acarbose - inhibits -glucosidase- taken at the start of each meal- delays carbohydrate absorption Tetracyclines complex with milk Ca2+ Milk iron absorption

    Drug-herbal products interactions


    Ginger, Garlic & Ginkgo biloba- risk of bleedinganticoagulants and antiplatelet drugs St. Johns wort phototoxicity when sulfonamides and PPIs used with tetracyclines,

    summation effects with CNS depressants plasma concentration of digoxin, cyclosporine, warfarin and protease inhibitors

    Drug-herbal products interactions


    Chinese ginseng potentiates effects of caffeine, anticoagulants, antiplatelets, MAO-I and CNS stimulants effects of antihypertensives, cardiac glycoside

    Aloeveras latex laxative properties, blood sugar- concurrent use of laxatives and hypoglycemics should be avoided intestinal absorption of Vit K

    REFERENCES:
    Essentials of medical pharmacology; KD Tripathi, 6th edition Pharmacology and pharmacotherapeutics; RS Satoskar, SD Bhandarkar, Nirmala N Rege, 21st edition

    Rang and Dales pharmacology; HP Rang, MM Dale, JM Ritter, RJ Flower, 6th edition
    Basic and clinical pharmacology; Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor, 11th edition Principles of pharmacology; HL Sharma, KK Sharma, 2nd edition

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