DRUG INTERACTIONS

Nur Permatasari

To obtain a desired therapeutics obyective/ to treat coexisting disease multiple drugs therapy

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DRUG INTERACTIONS

DRUG INTERACTIONS
A MEASURABLE MODIFICATION OF THE ACTION OF ONE DRUG BY PRIOR OR CONCOMITANT ADMINISTRATION OF ANOTHER SUBSTANCES ( drugs, food, alcohol)
The effects desirable, adverse, inconsequentials

Estimates of the incidence of clinical drug-drug interactions:

- > 10 drugs 3-5 % - 10-20 drugs 20%

Estimates the adverse reaction rate in patients receiving:

- > 5 drugs 4% - 6-10 drugs 10% - 11-15 28% - 16-20 drugs 54%

Mechanism of drug interactions

pharmacokinetics pharmacodynamics

Decrease/increase in the magnitude or duration of one/more effects of drug

Mechanism of drug interactions

Pharmacokinetics: Chemical/pharmace Pharmacodynamics: Receptor

utics interactions Absorption Distribution Metabolism Elimination

interactions Pharmacodynamics interactions

Chemical/pharmaceutic interactions
Drugs can react physically/chemically

with each other before administration ~ drugs are mixed prior to parenteral administration Chemical interaction in GI tract ( tetracycline and calcium, aluminium etc)

 Gastric emptying ~ rate of absorption

~ bioavaibility (>> empty stomach, volume of water at least 200 ml, upright position, drug: metoclopramide,domperidone << food, heavy exercise, drug:antacids, anticholinergic) Alter GI microorganism
Damage the intestinal absortive surface

(oral neomysin, antineoplastic)

flow, liver metabolism)

Presystemic elimination (~ liver blood

Systemic Availability

Therapeutics window

~ reduced liver blood flow

(propanolol, cimetidine) increase bioavaibility high hepatic ER drugs ~ liver metabolism/ gut wall (MAOI) decrease tyramine metabolism

Routes of Administration

BIOAVAIBILITY

Plasma protein binding

Metabolic enzyme induction or inhibition

GI absorption

 Drug distribution, is dependent on: - ionic composition - lipid solubility - protein binding competitive

displacement clinically significant effect if the index drug has a small Vd and narrow TI

Enzymes Inhibitors Chloramphenicol Cimetidine Isoniazid Erythromycin Oral

contraceptives Phenylbutazone Sulfonamide etc

Enzyme inducers Phenobarbital Carbamazepine Phenobarbital Phenytoin Ethanol(chronic) Rifampin Tobacco smoke etc

Liver metabolism:

Enhance via induction ( phenobarbital, policyclic hydrocarbon, steroid, alcohol type) efficacy decrease, adverse/toxicity effect increase

Inhibit directly accumulation to toxic concentration

Renal excretion: Water soluble drugs ~ GFR Tubular active secretion

(probenicid + penicillin advantage, salicylate + metotrexate toxicity)

Renal tubular secretion

Inhibit secretion of weak acids, bases (penicillin,salicylate)~ acid, cimetidine ~ bases)

Tubular reabsorbtion
(lithium + thiazide/loop diuretic)

DRUG ELIMINATION

PHARMACODYNAMIC Receptor interaction:

- antagonism on the receptor level ( Beta bluker ~ beta agonist, L-dopa ~ Dopamine bloker, tricyclic ` clonidine) - inhibit on the transport process (tricyclic antidepresant~E/NE) - sinergism on the receptor w/ mild effect (antiH , tricyclic antidepresant~ atropine)

Pharmacodynamic interactions

- additive on the pharmacological effects

(benzodiazepine ~ alcohol sedative action, warfarin~aspirin anticoagulant action)

- additive on undesirable effects

(hydrocortizone~thiazide hyperglycemia, potasiun sparring diuretics~ACEinhibitor hyperkalemia)

- potentiate on risk of toxicity

(digoxin~diuretic induce hypokalemia digitalis toxicity, amynoglycoside~furoseemide ototoxicity, nephrotoxicity)

Should the physician remember all

the potensial drug interaction?

NO

Being aware of clinical setting

High-risk clinical setting

Drugs with a narrow therapeutic index Multiple-drugs therapy Critically ill patient Passive patient Age ~ elderly patient Drug abusers

Principle of preventions adverse drug interaction

Document and record all drugs that your

patient consuming Learn about the pharmacodynamics and pharmacokinetics of drugs you prescribe Minimize the number of drugs given Be aware with patients taking index drugs Be cautions in high-risk clinical setting Look carefully for the possibility of an adverse drug interactions Look for undescribed interaction for new drugs

Index drugs with low therapeutic indices

Oral anticoagulants Anti cancer and immunosuppressive drugs Lithium carbonate Oral hypoglycemic drugs Anticonvulsants Theophilline Digoxin Aminoglycosides