Drug Interactions

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DRUG INTERACTIONS

DRUG INTERACTIONS (DI):

DRUG INTERACTIONS (DI) Drug interaction is a consequence in which effect of one drug are altered by prior or concomitant administration of another drug. CLASSES OF DI Adverse Drug-Drug Interactions (undesirable) Beneficial (desired): To effectiveness/ toxicity Drug- Laboratory Test Interactions Drug-Food Interactions Drug- Herbal Interactions

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ADVERSE DRUG-DRUG INTERACTIONS (UNDESIRABLE) In Vitro Adverse Drug Interactions Occurs outside the body No PK/PD principles are involved Examples Thiopental+ Succinylcholine--- Same Syringe– Pptn/inactivation Hydrocortison+ Heparin-- Same Syringe—Inactivation of Heparin Penicillin + Gentamicin -- ---do----Mutual inactivation NA--- In IV infusion fluid---- Oxidized Aminophyllin IV solution----IV Epinephrine, Erythromycin, Cephalothin– Decomposed at alkaline pH of Aminophyllin In Vivo Adverse Drug Interactions Pharmacokinetics Pharmacodynamics

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Pharmacokinetic Absorption : Atropine delays gastric emptying and thus reduces intestinal absorption of other drugs Metoclopramide , Cisapride , Domperidone increases Gastric emptying and increases absorption of drugs Milk, antacids (Ca, Al, Mg) and iron preparations forms chelates with TTC FQs forms divalent cations of antacids and decreases bioavail Erythromycin/TTC inhibit intestinal bacterial flora and thus prevent inactivation of digoxin to increase its biavailability . ADR with LA slows systemic absorption of LA Distribution Sulfonamides displace bilirubin in neonates causing kernicterus Salicylates and Sulfonamides displace tolbutamide – Hypoglycemia Salicylates and Sulfonamides displace Warfarin - Bleeding Quinidine , Verapamil ,, and Amidarone displaces digoxin from tissue binding to increase its toxicity.

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Metabolism Enzyme Induction Oral anti coagulants+ Phenobarbital– Decreased anti-coagulant effect Oral Contraceptives+ Rifampicin/Phenytoin- Unwanted Pregnancy Levodopa+ Pyridoxine--- Decreased L-Dopa effect in PD Quinidine + Phenytoin ------ Decreased Quinidine effect BBT+BBT--------------- Decreased effect Enzyme Inhibition Theophyllin, Warfarin, Carbamazepine+ Erythromycin (- CYT P450)--- Impairs metabolism and potentiates their effects. Theophyllin + FQ (- CYT-P450) – Impair metabolism Ethanol+ Disulfiram ----- Inhibit metabolism of Alcohol Tolbutamide + Chloramphenicol ---- Hypoglycaemia. Azathioprine + Allopurinol ------ Potentiated Toxicity

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Excretion Caffiene increases renal blood flow and GFR--- increases excretion Probenecid blocks tubular secretion of Penicillins , Cephalosporins , Zidovudine --- prolongs their actions Quinidine decreases tubular secretion of digoxin and potentiates its toxicity Loop and Thiazide Diuretics increases reabsorption of Lithium --- Lithium Toxicity Pharmacodynamics Interaction between drugs with similar or Opposite effects CNS stimulants and CNS depressants mutually antagonise . Thiazide Diuretics increases BSL---- may decreases Oral hypoglycemics NSAID’s decreases anti hypertensive effect of Beta Blockers Use of two CNS depressant drugs--- potentiates sedation AG + NM Blocking effect of d- tubocurarine TCA+ Atropine--- potentiates anticholinegic activity of Atropine. Metoclopramide aggravates extrapyramidal side effects Sildenafil + Nitrates----- Severe Hypotension/ Myocardial infarction

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B. Interference with Neuronal uptake or NT release TCA inhibit uptake of Guanethidine ---- reduced antihypertensive effect TCA reverse antihypertensive effect of Clonidine SSRI with MAO inhibitors --- elevated levels of 5-HT--- Serotonin Syndrome C. Interactions due to changes in fluid and electrolyte balance Thiazides/ Loop diuretics cause hypokalemia---- Heart become more sensitive for Digitalis effects Hypokalaemia can reduce antiarrythmic effect of Lignocaine , Quinidine , Procainamide ACE inhibitors + Potassium sparing Diuretics ----Severe hyperkalemia Sodium depletion----- increases Lithium toxicity.

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BENEFICIAL DRUG-DRUG INTERACTIONS Interactions leading to increased therapeutic effect Cotrimoxazole L- Dopa + Carbidopa Nitrates with Beta blockers Nitrates with CCB Thiazides with Potassium Supplements + Beta Blockers--- For HT Thiazides with Potassium Supplements + Alpha methyldopa-- For HT Probenecid + Penicillin/ Cephalosporin--- increases serum conc Amoxicillin + Beta Lactamase inhibitor--- to prevent degradation of amox Hydroclorthiazide + Triamterene ----- HT,minimising K + loss B. Interactions providing advantages in mgt of poisoning and drug overdose Naloxane for morphine poisoning and morphine addiction Protamine SO4 for Heparin toxicity Physostigmine for Atropine toxicity Neostigmine for reversal effect of d- tubocurarine Ethanol for Methanol poisoning Deferoxamine for Iron Poisoning.

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DRUG-LABORATORY TEST INTERACTIONS False positive test for Urinary Glucose Diuretics affect electrolyte (Na+, K +) test result Alcohol increases gamma- glutamyl transpeptidase values Salicylates , nalidixic acid and Vit -C—false positive test of urine sugar Spironolactone decreases real values of digoxin by RIA Estrogen causes increase in serum thyroxine values MAOIs decreases level of VMA DRUG- FOOD INTERACTIONS Tyramine containing food with MAOIs Spinach and Brocoli antagonize effect of Warfarin TTC forms complex with Milk Food increases bioavailability of griseofulvin , metoprolol , propranolol , phenytoin Food delays bioavailability of NSAIDs, TTC, ethanol, and didanosine Grape fruit or Oranges inhibit CYP3A4 isoenzyme increasing bioavailability of indinavir , midazolam , nimodipine , nifedipine , lovastatin Rich protein diet in acidic urine increases promotes xcretion of basic drugs

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Charcoal broiled beef can increase metabolism of theophyllin Food, Orange juice, cofffee /tea reduces bioavailability of alendronate Acarbose to be taken at the start of meal DRUG- HERBAL INTERACTIONS Aloe Vera has laxative and lowers BSL --- avoid concomitant laxatives and hypoglycemic drugs Asian/ Chinese ginseng potentiates effects of anticoagulants, antiplatelets, MAOIs and CNS stimulants Gingko biloba increases bleeding with anti-platelets and anticoagulants Kava-kava potentiates BZD and other CNS depressant activity Ginger and Garlic with anticoagulants and anti-platelet drugs increases risk of bleeding

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