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Unit-3 Pharmacokinetics of Drug Interaction.pptx

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Unit-3 Pharmacokinetics of Drug Interaction.pptx

  1. 1. Dr Shivaraj D R Assistant Professor & Clinical Pharmacist Department of Pharmacy Practice Sree Siddaganga College of Pharmacy and SMCRI Tumakuru 2021-2022
  2. 2. Unit-3 Pharmacokinetics of drug interaction
  3. 3. DEFINITION Drug interaction is defined as the pharmacological activity of one drug is altered by the concomitant use of another drug or by the presence of some other substance. • The drug whose activity is effected by such an interaction is called as a “Object drug.” • The agent which precipitates such an interaction is referred to as the “Precipitant.”
  4. 4. 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
  5. 5. The net effect of 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 effects.
  6. 6. Drug Interactions are thus-  Mostly undesirable  Rarely desirable (beneficial): for example,. Enhancement of activity of penicillin's when administered with probenecid.
  7. 7. 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
  8. 8. Multiple drug therapy • This is very common in most acute and chronic care settings. • Example: Patient suffering from hypertension and congestive heart failure includes antihypertensive as well as digitalis which together may lead to abnormal heart rhythms. • Over 50% of drug interactions occur, when a patient receiving 5 medications and probability increases 100% when 7 drugs are used.
  9. 9. Multiple Prescribers • Patient to be treated by one or more specialists, it is very difficult for one prescriber to become aware of all the medications that have been prescribed by others. • Example: one doctor may prescribe an Anxiolytic for a patient while another prescribes an Antihistamine having sedative properties with the possible consequence of an excessive depressant effect.
  10. 10. Multiple pharmacological effects of drug • Most drugs used in current therapy exhibit more than one type of pharmacological action and have the capacity to influence many physiological systems. • Therefore, 2 concomitantly administered drugs will often affect some of the same systems. • Example: Combining antipsychotics, antidepressants and anti- parkinsonism drugs causing unanticipated additive anticholinergic effect.
  11. 11. Multiple diseases/predisposing illness • Some patients take several drugs due to their suffering from more than one disease. • Example: patient with both DM & HTN; therapies like oral hypoglycemics and beta blockers can result in decreased response to anti-diabetic drug resulting in elevated blood sugar levels.
  12. 12. Poor patient compliance • Patient does not take medication in the manner intended by the doctor, which may be due to inadequate instructions from the doctor or pharmacist, confusion regarding taking several medicines. • All of which may lead to either under dosing or overdosing and a consequent drug interaction.
  13. 13. Advancing age of patient • Increased tendency of drug interaction episodes in elderly due to decrease in liver function. Drug related factors  Clinically significant interactions are most likely to occur between drugs that have potent effects, a narrow therapeutic index and a steep dose-response curve.  Example: cytotoxic, anti-hypertensive and hypoglycemic drugs, digoxin, warfarin etc..
  14. 14. Mechanisms of Drug Interactions: The 3 mechanisms by which an interaction can develop are: 1. Pharmaceutical interactions. 2. Pharmacokinetic interactions. 3. Pharmacodynamic interactions.
  15. 15. Pharmaceutical Interactions • 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 dextran in solutions and are broken down or from chemical compounds.
  16. 16. 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
  17. 17. Absorption Interaction: 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 Major mechanisms of absorption drug 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.
  18. 18. Object drug Precipitant drug Influence on object drug Complexation and adsorption Tetracycline, Fluoroquinolones like ciprofloxacin, penicillamine Antacids, food and mineral supplements containing Al, Mg, Fe, Zn, Bi, and Ca ions Formation of poorly soluble and unabsorbable complex with such heavy metal ions. Cephalexin, Sulfamethoxazole, Trimethoprim, Warfarin and Thyroxin Cholestyramine Reduced absorption due to adsorption and binding Alteration of GI pH Sulphonamides, aspirin Antacids Enhancement dissolution and absorption rate. Ferrous sulphate Sodium bicarbonate, calcium carbonate Decreased dissolution Ketoconazole, tetracycline, alcohol Antacids Decreased dissolution and bioavailability
  19. 19. Object drug Precipitant drug Influence on object drug Alteration of Gut Motility Aspirin, diazepam, levodopa, lithium carbonate, Paracetamol, mexilitetine Metoclopramide Rapid gastric emptying; increased rate of absorption levodopa, lithium carbonate, Mexilitetine Anticholinergic’s (Atropine) Delayed gastric emptying; decreased rate of absorption Alteration of GI Microflora Digoxin Antibiotics (Erythromycin, Tetracycline) Increased bioavailability due to destruction of bacterial flora that inactivates digoxin ion lower intestine. Oral contraceptives Antibiotics (Ampicillin Decreased reabsorption of drugs secreted as conjugates via bile in the intestine.
  20. 20. Object drug Precipitant drug Influence on object drug Malabsorption syndrome Vitamin A, B12, digoxin Neomycin Inhibition of absorption due to Malabsorption caused by neomycin
  21. 21. Distribution Interaction:  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 Influence Anticoagulants Phenylbutazone, choral hydrate, Salicylates, Increased clotting time; increased risk of hemorrhage Tolbutamide Sulphonamides Increased hypoglycemic effect Methotrexate Sulphonamides, Salicylic acid Increased Methotrexate toxicity Phenytoin Valproic acid Phenytoin toxicity
  22. 22. Metabolism Interaction:  Are those where the metabolism of the object drug is altered.  The mechanism for metabolism interaction includes;  Enzyme induction: increased rate of metabolism.  Enzyme inhibition: decreased rate of metabolism. It is the most significant interaction in comparison to other interactions and can be fatal.
  23. 23. Object drug Precipitant drug Influence on object drug Enzyme Induction Corticosteroids, oral contraceptives, coumarins, tolbutamide, tricyclic antidepressants. Barbiturates Decreased plasma levels; decreased efficacy of object drugs Enzyme Inhibition Tyramine rich food (Cheese, liver, yeast products) MAO inhibitors (Phenelzine, paragyline) Enhanced absorption of unmetabolised Tyramine; increased pressor activity; potentially fatal risk of hypertensive crisis
  24. 24. Excretion Interaction:  Are those where the excretion pattern of the object drug is altered.  Major mechanisms of excretion interactions are; i. Alteration in renal blood flow: example: Ex: NSAID’s with lithium. ii. Alteration of urine pH: antacids with amphetamine. iii. Competition for active excretion: probenecid and penicillin. iv. Forced diuresis.
  25. 25. Object drug Precipitant drug Influence on object drug Changes in active tubular secretion Procainamide, Ranitidine cimetidine Increased plasma levels of basic drugs; risk of toxicity Acetohexamide Phenylbutazone Increased hypoglycemic effect Changes in urine pH Amphetamine, tetracycline, Quinidine Antacids, thiazide, acetazolamide Increased passive reabsorption of passive drugs; increased risk of toxicity Changes in Renal Blood Flow Lithium bicarbonate NSAID’s Decreased renal clearance of lithium; risk of toxicity
  26. 26. Pharmacodynamic Interactions  Are those in which the activity of the object drug at its site of action is altered by the precipitant.  There are 2 types 1. Direct Pharmacodynamic Interaction 2. Indirect Pharmacodynamic Interaction
  27. 27. Direct Pharmacodynamic Interactions In which drugs having similar or opposing pharmacological effects are used concurrently. The 3 consequences of direct interactions are; 1. Antagonism 2. Addition or summation 3. Synergism or potentiation
  28. 28. Antagonism: “The interacting drugs have opposing actions.” Example: Ach and NA having opposite 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.
  29. 29. Indirect Pharmacodynamic Interactions “In which both the object and the precipitant drugs have unrelated effects but the latter in some way alerts the effects of the former.” Example: Salicylates decreases the ability of the platelets to aggregate thus impairing the homeostasis if warfarin induced bleeding occurs.
  30. 30. CONSEQUENCES OF DRUG INTERACTIONS: It may be;  Major: life threatening.  Moderate: Deterioration of patient status.  Minor: little effect.
  31. 31. REDUCING THE RISK OF DRUG INTERACTIONS 1. Reducing the patient risk factors. 2. Take through drug history & maintain complete patient medication records. 3. Keep knowledge about the actions of drugs being used. 4. Consider therapeutic alternatives. 5. Avoid complex therapeutic regimens when possible. 6. Educate the patient. 7. Monitor therapy: Any change in patient behavior should be suspected as drug related until that possibility is excluded.
  32. 32. 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.
  33. 33. INFLUENCE OF ALCOHOL ON DRUG INTERACTIONS:  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 alcohol beverages with sedatives and other depressants drugs could result in an excessive depressant response.