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Factors That Modify Drug Actionsand Drug Interactions

Prof. Dr. Öner SüzerCerrahpaşa Medical Faculty

Department of Pharmacology and Clinical Pharmacologywww.onersuzer.com

Last updated: 08.06.2011

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Contents

Factors modifying drug actionsDrug interactions

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Factors modifying drug actionsApplication routeApplication time (chronopharmacology)Body weightAge Disorders of eliminating organsSex Genetic factors Tolerance Presence of other drugs in human body …

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Factors that modify gastrointestinalabsorption

Factors dealing pharmaceutical preparation:

Absorption of a solution is faster than a suspension.Solid pharmaceutical should disintegrate and dissolutebefore absorption.The rate of these events affect on absorption rate. Disintegration and dissolution can be tested in vitro.

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Factors delaying stomach emptyingSolid, fatty, hot food, ulcer, exercise, excitement, standing, some drugs (anticolinergics, ganglion blockers, nicotine, morfine, β-adrenergic agonists).

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Factors accelerating stomach emptyingCold, liquid food, drinking high amount of water, fasting, light exercise, laying position, cigarette smoking, somedrugs (e.g. metoclopramide).

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Factors altering intestinal absorption of drugs

Stomach pH, and emptying, intestinal movement, particul size, foods, posture, exercise, disorders reducing absorbtion area (e.g. Crohn disease), intestinal microflora, drugs causingvasoconstriction decrease intestinal absorption.Shock, hipotension, congestive heart failure, mixedema andarteral occlusion decreases perfusion and thus decreasesabsorbtion rate.Bile secretion can increase the absorption of some sparely watersoluble drugs such as, diazepam, griseofulvin, spironolactonSome drugs should be taken on an empty stomach to increaseabsorption (e.g. ampicilline, tetracyclines, levodopa, methotrexate, penisilamine, isoniazide).Concomittant drinking a glass of water can can increaseabsorption.

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First pass effectIt can occur in intestine, liver or lungs.

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Enterohepatic circulationSome drugs are eliminated via bile after conjugation.They can be hydrolized (e.g. by β-glucuronidase orsulfatase) in the intestine and reabsorbed.

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Membrane transportersFor drugs that cannot pass membranes freely there aretransport systems in intestine, blood brain barrier, andkidney tubules.These systems play role in pharmacokinetics and even in the actions of drugs.P-glicoprotein system is one of the most important on drugaction.

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Protein binding and other factors thataffect on transport of drugs in blood

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Ion trappingIon trapping effects on distribution of weak acids andbases.If there is an application/exposure of an overdose of a weak acid, alkalization the urine with bicarbonate, acetazolamide, citrate or acetate increases elimination viakidneys.If there is an application/exposure of an overdose of a weak base, acidifying the urine with NH4Cl, ascorbic ormandelic acid increases elimination via kidneys.

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Pharmacokinetic interactionsDrugs can interact at absorption, distribution, metabolismand elimination.These interactions can alter plasma concentration.This is particularly important for drugs having narrowtherapeutic index.There are vast number of examples of drug interactions.In modern era these interactions are controlled withcomputer software.

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