mohd ayyub pasha

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Published on March 20, 2014

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SUBMITTED TO : Dr. K. K. PILLAI & Dr. UMA BHANDARI DEPTT.OF PHARMACOLOGY JAMIA HAMDARD, NEW DELHI-110062:  SUBMITTED TO : Dr. K. K. PILLAI & Dr. UMA BHANDARI DEPTT.OF PHARMACOLOGY JAMIA HAMDARD, NEW DELHI-110062 PRESENTED BY MOHD AYYUB M. PHARM(PHARMACOLOGY) 1 ST SEM. DEPTT.OF PHARMACOLOGY, JAMIA HAMDARD DRUG INTERACTION PowerPoint Presentation: Definition: An interaction is said to occur when the effects of one drug are changed by the presence of another drug,food, drink or by some environmental chemical agent PowerPoint Presentation: 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 ”. Risk Factors for Drug Interactions: Risk Factors for Drug Interactions High Risk Patients Elderly, very sick, multiple disease Multiple drug therapy Renal, liver impairment High Risk Drugs Narrow therapeutic index drugs Recognized enzyme inhibitors or inducers Mechanism of Drug Interactions:: Mechanism of Drug Interactions: PHARMACODYNAMIC INTERACTIONS PHARMACEUTICAL INTERACTIONS PHRMACOKINETIC INTERACTIONS PowerPoint Presentation: 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. These are of two types : 1.Direct pharmacodynamic interactions. 2.Indirect pharmacodynamic interactions . PowerPoint Presentation: 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. PowerPoint Presentation: 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. PowerPoint Presentation: 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 effects of the former. Example: salicylates decrease the ability of the platelets to aggregate thus impairing the Homeostasis if warfarin induced bleeding occurs . PowerPoint Presentation:  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 . Pharmacokinetic Drug Interactions: Pharmacokinetic Drug Interactions Altered ADME Interaction during absorption Interaction during distribution Interaction during metabolism Interaction during excretion Altered Absorption (Availability): Altered Absorption (Availability) Change in gastrointestinal pH Ketoconazole needs acidic conditions in gut Drug binding in GI tract E.g. tetracycline and calcium Change in gastrointestinal flora Antibiotics with OCs           Change in gastrointestinal motility Metoclopramide and digoxin Distribution:: Distribution: Displacement of one drug by another from binding sites on plasma proteins is the cause of distribution Eg : Phenylbutazone displaces warfarin from plasma proteins and hence increased anticoagulant effect. Distribution: Distribution Displacement Interaction Strongly bound Phenylbutazone Drug displaced Warfarin Effect of interaction Haemorrhage Metabolism: Metabolism Enzyme inducers : increase metabolism of concomitant drug therefor e increase drug elimination and decrease drug effect . Enzyme inhibitors : decresae metabolism of concomitant drug therefor e decrease drug excretion and increase drug effect Cimetidine, Ketoconazole, Erythromycin, Clarithromycin, Chloramphenicol, CYP 450 System Definitions: CYP 450 System Definitions Substrate: Drug is metabolised by the enzyme system Inducer: Drug that will increase the synthesis of CYP450 enzymes Inhibitor Drug that will decrease the metabolism of a substrate CytochromeP-450: CytochromeP-450 Till now, about 55 human isoforms of CYP450 have been discovered. CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP2E1 CYP3A4 (most abundant) These CYP enzymes are present in the endoplasmic reticulum of hepatocytes and in the small intestine, with smaller quantities in the kidneys, lungs and brain . PowerPoint Presentation: Family CYP 2 D6 Individual gene Sub-family Enzyme Induction : Enzyme Induction increase in the rate of a specific enzyme synthesis from basal to maximum level caused by the presence of a substrate or substrate analogue that acts as an inducer Enzymes that are susceptible to induction are said to be “inducible” Some enzyme Inducers: Some enzyme Inducers Barbiturates (3A) Carbamazepine (2C19, 3A) Phenytoin (3A) Rifampicin (2C19, 2C9, 3A) St Johns Wort (3A) Ethanol (2E1) Troglitazone (3A) Tobacco (1A2) Omeprazole (1A2) Nevirapine (3A) Enzyme Inhibition: Enzyme Inhibition drug metabolism, resulting in ↑ drug activity, prolonging the action of various drugs Often rapid, reversible and relatively short acting. E.g. erythromycin and cyclosporin erythromycin is a substrate and an inhibitor of CYP 3A4 May be prolonged due to long half- life of drug. E.g. amiodarone and Warfarin amiodarone is an inhibitor of CYP2C9 PowerPoint Presentation: Mechanisms of urinary excretion : Simple filtration Active secretion Mechanisms for active secretion Acids Bases Excretion Interactions EXCRETION: EXCRETION PRIMARY DRUG COMPETING DRUG RESULT LITHIUM THIAZIDE Lithium toxicity Digoxin Spironolactone Digoxin toxicity Excretion Interaction Lithium + Thiazides: Excretion Interaction Lithium + Thiazides Probable mechanism: Thiazides cause diuresis and initial sodium loss. Compensatory sodium retention in proximal tubules Proximal tubules do not distinguish sodium from lithium. Lithium also retained and accumulates . Excretion Interaction Change in renal blood flow: Excretion Interaction Change in renal blood flow Methotrexate and NSAIDs NSAIDS can decrease renal blood flow by inhibition of renal prostaglandins. Reduced clearance of MTX and active (toxic) metabolite Other drug interactions:: Other drug interactions: Herb-drug interaction Food-drug interaction PowerPoint Presentation: FOOD DRUG EFFECT Vegetables: boiled/fried onions , cabbage, turnip, warfarin May increase fibrinolytic activity of drug. Vegetables rich in vit.K inhibit the hypoprothrombinemic response of drug. Protein or charcoal meat theophylline Increase plasma half life of drug. Salty food, salt lithium Increase intake of sodium reduces the response to drug. Low salt diet enhances lithium toxicity. liquourice Diuretics (furosemide, thiazide) digoxin Glycyrrhizic acid induces hypokalemia , sodium retention liquorice induced hypokalemia causes digitalis toxicity Beverages (green tea) Anticoagulant theophylline Neuroleptic agents Large intake inhibit the anticoagulant effect Increase intake enhances the drug’s side effects Increased intake results in large variation in plasma drug levels. Grapefruit juice interaction:: Grapefruit juice interaction : Grapefruit juice contains various components known as bioflavonoids, which inhibit CYP450 isoenzymes found in the gut wall. This can impair the oxidative metabolism of some drugs . The max. inhibitory effect occurs within 1 hour, the duration of effect is 24 hrs. The half-life is 12 hrs. Inhibits first pass metabolism of drugs metabolised by CYP3A4 (by selective down regulation of CYP3A4 in the small intestine), CYP1A2, and CYP2D6 . Astemizole, cisapride, carbamazepine, terfenadine, simvastatin should not be given concurrently with grapefruit juice. PowerPoint Presentation: Targeted prescription of medicine: Applied pharmacogenomics Today empirical prescription “ One drug fit all ” Drug A Drug B Drug D Drug C Individual physician experience Cost: time, money & well-being Future Rational prescription “individualized” Patient genetic ’ s profiles Drug A Drug B Drug C Drug D Informed physician diagnosis Saving : time, money & patient ’ s life Management of Drug Interactions:: Management of Drug Interactions: Avoiding the combination entirely Adjusting the dose of the object drug Monitoring for early detection Provide information on patient risk factors that increases the chance of an adverse outcome Improve computerized screening systems PowerPoint Presentation:  REFERENCES Essential of Medical Pharmacology , KD Tripathi , 6 th Edition , Jaypee Brothers Medical Publishers(P)LTD,2008 ,Chapter-4 (Pg 55-58),Chapter-5 (Pg 61-68) , Chapter-69 (Pg 889 – 896). 2. Rang and Dale’s Pharmacology , H.P Rang , M.M.Dale , J.M.Ritter , R.J Flower , 6 th Edition , 2007 ,Churchill Livingstone , Chapter-52 (Pg 739-749). A Textbook of Hospital & Clinical Pharmacy , Theory & Practical , Pratibha Nand , Prof. (Dr.) Roop K. Khar , 6 th Edition, 2008 , Birla Publications Pvt.Ltd , Chapter-5 (Pg 270-278). Goodman & Gilman’s , The Pharmacological Basis of Therapeutics , 12 th Edition , Laurence Brunton , Bruce Chabner , The Mc Graw-Hill companies , Chapter-5 Pg-91 , 101). www.webmed.com www.authorstream

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