Pharmacology of Drugs interactions
- 1. Presented By Dr. Manoj Kumar Assistant Professor Department of Pharmacology Adesh Medical College & Hospital Ambala Can’t
- 2. Drug interaction is defined as the modification of the effect of one drugs (i.e. the object drugs) pharmacological activity is altered by the concominant use of another drug (i.e. the precipitant drug) or by the presence of some other substance. Drug interactions may either Enhance or Diminish the intended effect of one drugs. The interaction may modify the diagnostic, preventive or therapeutic activity of either drug. E.g. several hemorrhage may occur if warfarin and salicylates are combined.
- 3. 1. Drug-drug interactions. 2. Drug-food interactions. 3. Chemical-drug interactions. 4. Drug-laboratory test interactions. 5. Drug-disease interactions.
- 4. Generally quantitative i.e. increased or decreased effect. Seldom qualitative i.e. rapid or slower effect. Precipitation of newer or increased adverse effect.
- 5. Mostly undesirable. Rarely desirable(beneficial): for e.g. enhancement of activity of penicillin's when administered with probenecid.
- 6. 1. Multiple drug therapy. 2. Administration of two or more drugs simultaneously. 3. Multiple prescribers. 4. Multiple pharmacological effects of drug. 5. Multiple diseases/predisposing illness. 6. Poor patient compliance. 7. Advancing age of patient. 8. Drug-related factors.
- 7. 1. Insufficient knowledge 2. Dietary factors 3. Physiology of the individual 4. Presence of disease states
- 8. The three mechanisms by which an interaction can develop are- In Vitro 1. Pharmaceutical interactions. Physical interactions Chemical interactions In - Vivo 1. pharmacokinetic interactions. 2. Pharmacodynamic interactions.
- 9. Also called as incompatibility. it is a physicochemical interaction that occurs when drugs are mixed in i.v Infusions causing precipitation or inactivation of active principles . Example:- Ampicillin ,chlorpromazine & barbiturates interact with dextrin in solutions and are broken down or from chemical compounds.
- 10. “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.
- 11. 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.
- 12. 1. Complication 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.
- 13. Ciprofloxacin, Pencillamine, Antacids, Food & Minerals supplements CONTAINING AL, Mg, Fe, Zn & Ca IONS FORMATION OF POORELY SOLUBLE AND UNABSOBABLE COMPLEX WITH SUCH HEAVY METAL IONS. 2.ALTERATION OF GI PH SULPHONAMIDES, ASPIRIN FERROUS SULPHATE ANTACIDS SODIUM BICARBONATE,CALCIUM CARBONATE, ENHANCED DISSOLUTION AND ABSORPTION RATE. DECREASED DISOLLUTION AND HENCE ABSORPTION.
- 14. 3.ALTERATION OF GUT MOTILITY ASPIRIN DIAZEPAM, LEVODOPA, MEXILETINE METOCLOPRAMIDE RAPID GASTRIC EMPTYING,INCREASED RATE OF ABSORPION. LEVODOPA, LITHIUM CARBONATE, MEXILETINE ANTI CHOLINERGICS DELAYED GASTRIC EMPTYING;DECREASED RATE OF ABSORPTION. 4.ALTERATION OF GI MICROFLORA DIGOXIN ANTI BIOTICS INCREASED BIOAVAILABILITY DUE TO DESTRUCTION OF BACTERIAL FLORA THAT INACTIVATES DIGOXIN IN LOWER INTESTINE. 5.MALABSORPTION SNDROME VITAMIN A,B12,DIGOXIN NEOMYCIN INHIBITION OF ABSORPTION DUE TO MAL.
- 15. Are those where the distribution pattern of the object drug is altered : The major mechanism for distribution interaction is alteration in protein-drug binding. Competitive displacement interactions Displaced drug Displacer Anti coagulants Phenylbutazone, chloral hydrate Increased clotting time. increased risk of hemorrhage. Tolbutamide Sulphonamides Increased hypoglycemic effect.
- 16. Are those where the metabolism of the object drug is altered. Mechanisms of metabolism interactions include: 1. Enzyme induction: Increased rate of metabolism. 2. Enzyme inhibition: Decreased rate of metabolism. It is the most significant interaction in comparison to other interactions and can be fatal.
- 17. 1. ENZYNE INDUCTION CORTICOSTEROIDS, ORAL CONTRACEPTIVES, COUMARINS, PHENYTOIN BARBITURATES DECREASED PLASMA LEVELS; DECREASED EFFICASY OF OBJECT DRUGS ORAL CONTRACEPTIVES, ORAL HYPOGLYCAEMICS RIFAMICIN DECREASED PLASMA LEVELS 1. ENZYME INHIBITION TYRAMINE RICH FOOD MAO INHIBITORS ENHANCED ABSORPTION OF UN METABOLISED TYRAMINE. COUMARINS METRANIDAZOLE PHENYL BUTAZONE INCREASED ANTI COAGULANT ACTIVITY. ALCOHOL DISULPHIRAM, METRONIDAZOLE INCREASED IN PLASMA ACETALDEHYDE LEVELS
- 18. Are these where the excretion pattern of the object drug is altered. Major mechanisms of excretion interactions are- Alteration in renal blood flow Alteration of urine PH Competition for active secretions Forced diuresis
- 19. 1. CHANGES IN ACTIVE TUBULAR SECRETION Penicillin, cephalosporin's, nalidixic acid ELEVATED PLASMA LEVELS OF ACIDIC DRUGS 1. CHANGES IN URINE PH Amphetamine, antacid & thiazidesa increased passive reabsorbation of basic drugs. INCRESED RISK Of TOXICITY 1. CHANGES IN RENAL BLOOD FLOW Lithium bicarbonate & NSAIDS decrease Renan clearance of lithium. INCREASED RISK OF TOXICITY
- 20. 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.
- 21. 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.
- 22. 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
- 23. It is an enhancement of action of one drug by another Example: Alcohol enhances the analgesics activity of aspirin.
- 24. 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.
- 25. The consequences of drug interactions may be: Major: Life threatening. Moderate: Deteriotion of patients status. Minor: Little effect.
- 26. 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. 5. Avoid complex therapeutic regiments when possible. 6. Educate the patient. 7. Monitor therapy.
- 27. 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.
- 28. 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.
- 29. Food effects the rate and extent of absorption of drugs from the GI tract. Example: Many anti biotics should be given at least 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 Fluoroquinolones derivatives. Diet also may influence urinary pH values.