drug interaction

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DRUG INTERACTION:

DRUG INTERACTION NAVEEN KUMAR.M M.PHARMACY(PHARMACEUTICS). 10Y81SO310.

DEFINITION Drug interaction is the pharmacological activity of a drug is altered by the concominant use of another drug or by the presence of some other substance.:

DEFINITION Drug interaction is the pharmacological activity of a drug is altered by the concominant use of another drug or by the presence of some other substance .

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The Drug whose Activity is effected by such an Interaction is called as a “ Object drug .” The agent which precipitates such an interaction is refered to as the “ Precipitant ”.

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Types of drug Interactions 1.Drug-drug interactions. 2.Drug-food interactions. 3.Chemical-drug interactions. 4.Drug-laboratory test interactions. 5.Drug-disease interactions.

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The Net effect of a Drug Interaction is: Generally quantitative i.e.increased or decreased effect. Seldom qualitative i.e.rapid or slower effect. Precipitation of newer or increased adverse effect.

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Factors contributing to drug interactions: 1.Multiple drug therapy. 2.Multiple prescribers. 3.Multiple pharmacological effects of drug. 4.Multiple diseases/predisposing illness. 5.Poor patient compliance. 6.Advancing age of patient. 7.Drug-related factors.

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Mechanisms of drug interactions: 1.Pharmaceutical interactions. 2.pharmacokinetic interactions. 3.Pharmacodynamic interactions.

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Pharmaceutical interactions: Also called as incompatibility.it is a physicochemical interaction that occous when drugs are mixed in i.v . Infusions causing precipitation or inactivation of active principles . Example:- Ampicillin ,chlorpromazine &barbituates interact with dextran in solutions and are broken down or from chemical compounds .

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Pharmacokinetic Interactions: “These interactions are those in which adme properties of the object drug is altered by the precipitant and hence such interactions are also called as ADME interactions”. The resultant effect is altered plasma concentration of the object drug. These are classified as: 1.Absorption interactions 2.Distribution interactions 3.Metabolism interactions 4.Excretion interactions.

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Absorption interactions Are those where the absorption of the object drug is altered the net effect of such an interaction is: Faster or slower drug absorption. More or less complete drug absorption.

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Major mechanisms of absorption interactions are: 1.Complexation and adsorption. 2.Alteration in GI pH. 3.Alteration in gut motility. 4.Inhibition of GI enzymes. 5.Alteration of GI micro flora. 6.Malabsorption syndrome.

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OBJECT DRUG CEPHROFLOXACINE, PENCILLAMINE SULPHONAMIDES, ASPIRIN FERROUS SULPHATE PRECIPITANT DRUGS ANTACIDS,FOOD & MINERALS SUPPLEMENTS CONTAINING AL,Mg,Fe,Zn & Ca IONS ANTACIDS SODIUM BICARBONATE,CALCIUM CARBONATE INFLUENCE ON OBJECT DRUG FORMATION OF POORELY SOLUBLE AND UNABSOBABLE COMPLEX WITH SUCH HEAVY METAL IONS. ENHANCED DISSOLUTION AND ABSORPTION RATE. DECREASED DISOLLUTION AND HENCE ABSORPTION. ABSORPTION INTERACTION 1.COMPLEXATION & ADSORPTION 2.ALTERATION OF GI PH

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ASPIRIN DIAZEPAM,LEVODOPA, MEXILETINE LEVODOPA,LITHIUM CARBONATE, MEXILETINE DIGOXIN METOCLOPRAMIDE ANTI CHOLINERGICS ANTI BIOTICS RAPID GASTRIC EMPTYING,INCREASED RATE OF ABSORPION . DELAYED GASTRIC EMPTYING;DECREASED RATE OF ABSORPTION. INCREASED BIOAVAILABILITY DUE TO DESTRUCTION OF BACTERIAL FLORA THAT INACTIVATES DIGOXIN IN LOWER INTESTINE. 3.ALTERATION OF GUT MOTILITY 4.ALTERATION OF GI MICROFLORA

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VITAMIN A,B 12 ,DIGOXIN NEOMYCIN INHIBITION OF ABSORPTION DUE TO MAL. 5.MALABSORPTION SNDROME

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Distribution interactions Are those where the distribution pattern of the object drug is altered : The major mechanism for distribution interaction is alteration in protein-drug binding. Anti coagulant s Tolbutamide Phenylbutazone,chloral hydrate Sulphonamides Increased clotting tme.increased risk of hemorrhage. Increased hypoglycemic effect. Displaced drug Displacer Competitive displacement interactions

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METABOLISM INTERACTIONS: Mechanisms of metabolism interactions include: 1.Enzyme induction: Increased rate of metabolism. 2.Enzyme inhibition: Decreased rate of metabolism. Are those where the metabolism of the object drug is altered .

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CORTICOSTEROIDS,ORAL CONTRACEPTIVES,COUMARINS,PHENYTOIN ORAL CONTRACEPTIVES, ORAL HYPOGLYCAEMICS TYRAMINE RICH FOOD COUMARINS ALCOHOL BARBITURATES RIFAMICIN MAO INHIBITORS METRANIDAZOLE PHENYL BUTAZONE DISULPHIRAM, METRONIDAZOLE DECREASED PLASMA LEVELS; DECREASED EFFICASY OF OBJECT DRUGS DECREASED PLASMA LEVELS ENHANCED ABSORPTION OF UN METABOLISED TYRAMINE. INCREASED ANTI COAGULANT ACTIVITY. INCREASED IN PLASMA ACETALDEHYDE LEVELS METABOLISM INTERACTIONS 1.ENZYNE INDUCTION 2.ENZYME INHIBITION

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EXCRETION INTERACTIONS ARE THOSE WHERE THE EXCRETION PATTERN OF THE OBJECT DRUG IS ALTERED: MAJOR MECHANISMS ARE: ALTERATION IN RENAL BLOOD FLOW . ALTERATION OF URINE pH. COMPETETION FOR ACTIVE SECRETION.

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PENCILLIN,CEPHALOSPORINS,NALIDIXIC ACID AMPHETAMINE LITHIUM BICARBONATE PROBENICID ANTACIDS,THIAZIDESACETAZOLAMIDE NSAIDS ELEVATED PLASMA LEVELS OF ACIDIC DRUGS INCREASED PASSIVE REABSORPTION OF BASIC DRUGS.INCRESED RISK OF TOXICITY DECREASED RENAL CLEARANCEOF LITHIUM.RISK OF TOXICITY EXCRETION INTERACTIONS 1.CHANGES IN ACTIVE TUBULAR SECRETION 2.CHANGES IN URINE PH 3.CHANGES IN RENAL BLOOD FLOW

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Pharmacodynamic interactions: Are those in which the activity of the object drug at its site of action is altered by the precipitant. Such interactions may be direct or indirect. 1.These are of two types1.direct pharmacodynamic interactions. 2.Indirect pharmacodynamic interactions.

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DIRECT PHARMACODYNAMIC INTERACTIONS: In which drugs having similar or opposing pharmacological effects are used concurrently. The three consequences of direct interactions are 1.Antagonism. 2.Addition or summation. 3.Synergism or potentiation.

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Antagonism : The interacting drugs have opposing actions Example : Acetylcholine and noradrenaline have opposing effects on heart rate . Addition or summation: The interacting drugs have similar actions and the resultant effect is the some of individual drug responses Example: CNS depressants like sedatives and hypnotics,…etc Synergism or potentiation: It is an enhancement of action of one drug by another Example: Alcohol enhances the analgesics activity of aspirin.

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Indirect pharmacodynamic interaction : In which both the object and the precipitant drugs have unrelated effects.but the latter in Some way alerts the effects but latter in some way alerts the effectsof the former. Example: salicylatesdecrease the ability of the platelets to aggregate thus impairing the Homeostasis if warfarin indused bleeding occurs.

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CONSEQUENCES OF DRUG INTERACTIONS: The consequences of drug interactions may be: Major: Life threatening. Moderate: Deteriotion of patients status. Minor: Little effect.

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REDUSING THE RISK OF DRUG INTERACTIONS: 1.Identify the patients risk factors. 2.Take through drug history. 3.Be knowledge about the actions of the drugs being used. 4.Consider therapeutic alternatives. 5Avoid complex therapeutic regiments when possible. 6.Educate the patient. 7.Monitor therapy.

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INFLUENCE OF SMOKING ON DRUG INTERACTIONS: Smoking increases the activity of drug metabolizing enzymes in the liver, With the result that certain therapeutic agents. Example: Diazepam, propoxyphene, theophylline, olanzapine. Are metabolized more rapidly,and their effect is decreased .

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INFLUENCE OF ALCOHOL ON DRUG INTERACTION: Chronic use of alcohol beverages may increases the rate of metabolism Of drugs such as warfarin and phenytoin,probably by increasing the activity of hepatic enzymes. Acute use of alcohol by non alcoholic individuals may cause an inhibition of hepatic enzymes. Use of alcoholic beverages with sedatives and other depressants drugs could result in an excessive depressant response.

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INFLUENCE OF FOOD ON DRUG INTERACTION : Food effects the rate and extent of absorption of drugs from the GI tract. Example: Many anti biotics should be given atleast 1hr before or 2hr after meals to achieve Optimal absorption. The type of food may be important with regard to the absorption of concurrently administered Drugs. Example: Dietary items such as milk and other dairy products that contain calcium may decrease . The absorption of tetracycline and flouroquinolone derivatives. Diet also may influence urinary pH values.

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