Drug - Drug Interaction of pulmonary concern
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Drug - Drug Interaction of pulmonary concern
- 1. DRUG-DRUG INTERACTION OF PULMONARY CONCERN By Mahmoud E. Abou El-Magd
- 2. INTRODUCTION • An interaction occurs when the effects of one drug are changed by another drug, food, drink or exposure to an environmental chemical. • A drug interaction occurs when two or more drugs interact in such a way that the effectiveness or toxicity of one or more of the drugs is altered. • Interactions can be harmful, either by increasing the toxicity of a drug or by reducing its efficacy. However, some drug interactions can also be beneficial . DRUG - DRUG INTERACTIONS 2
- 3. RISK FACTORS • Genetic make up . • Multiple prescribers . • Multiple pharmacies . • Specific population like e.g, females , elderly, obese, criticaly ill patient , trasplant recipient . • Specific illness E.g. Hepatic disease, Renal dysfunction . • Narrow therapeutic index drugs as warfarin , digoxin , theophyllin . DRUG - DRUG INTERACTIONS 3
- 4. OUTCOMES OF DRUG INTERACTIONS 1) Loss of therapeutic effect . 2) Toxicity . 3) Beneficial effects e.g additive & potentiation (intended) or antagonism (unintended). 4) Chemical or physical interaction e.g I.V incompatibility in fluid or syringes mixture . DRUG - DRUG INTERACTIONS 4
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- 6. Mechanisms DRUG - DRUG INTERACTIONS 6
- 7. TYPES OF PHARMACOKINETIC INTERACTION. DRUG - DRUG INTERACTIONS 7
- 8. ALTERED GIT ABSORPTION. •Altered pH •Altered bacterial flora • formation of drug chelates or complexes • drug induced mucosal damage • altered GIT motility. DRUG - DRUG INTERACTIONS 8
- 9. TYPES OF PHARMACOKINETIC INTERACTION. DRUG - DRUG INTERACTIONS 9
- 10. CYP450 ISOENZYMES • Present in lipid layer of the endoplasmic reticulum of hepatocytes . • Major enzymes involved in metabolism and bioactivation . • About 75% of reactions . DRUG - DRUG INTERACTIONS 10
- 11. CYTOCHROME P450 (CYP450) • Inducer • Speeds up metabolism • Decreases substrate level (lack of efficacy is concern) • Gradual onset/offset • Inhibitor • Slows metabolism • Increases substrate level (toxicity is concern) • Quick onset/offset DRUG - DRUG INTERACTIONS 11
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- 14. PHARMACODYNEMIC INTERACTION It means alteration of the dug action without change in its serum concentration by pharmacokinetic factors. These are of two types 1.direct pharmacodynamic interactions. 2.Indirect pharmacodynamic interactions DRUG - DRUG INTERACTIONS 14
- 15. 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. DRUG - DRUG INTERACTIONS 15
- 16. INDIRECT PHARMACODYNAMIC INTERACTION: 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: salicylatesdecrease the ability of the platelets to aggregate thus impairing the Homeostasis if warfarin indused bleeding occurs. DRUG - DRUG INTERACTIONS 16
- 17. 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 . DRUG - DRUG INTERACTIONS 17
- 18. Examples DRUG - DRUG INTERACTIONS 18
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- 26. MISCELLANEOUS ANTIBACTERIAL ANTIBIOTICS DRUG - DRUG INTERACTIONS 26
- 27. ANTIMYCOBACTERIAL AGENTS DRUG - DRUG INTERACTIONS 27
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- 29. ANTICOAGULANTS/THROMBOLYTIC AGENTS DRUG - DRUG INTERACTIONS 29
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- 33. ANTICONVULSANTS DRUG - DRUG INTERACTIONS 33
- 34. ANTINEOPLASTIC AGENTS DRUG - DRUG INTERACTIONS 34
- 35. BRONCHODILATORS DRUG - DRUG INTERACTIONS 35
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- 38. CORTICOSTEROIDS DRUG - DRUG INTERACTIONS 38
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- 45. FOOD-DRUG INTERACTIONS… • -Advise patients to take medication with a full glass of water. • -Do not take vitamin pills at the same time you take medication (i.e, take medication 1 hour after taking vitamins). • -Not mix medication into hot drinks, because the heat from the drink may destroy the effectiveness of the drug. • -Never take medication with alcoholic drinks. DRUG - DRUG INTERACTIONS 45
- 46. 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. Diet also may influence urinary pH values. Lime juice is most acidic Milk products alter pH DRUG - DRUG INTERACTIONS 46
- 47. DRUG INDUCED NUTRITIONAL EFICIENCIES DRUG ANTIEPILECTIC DRUGS (phenytion , phenobarbitone, primidone, valproic acid) AFFECTED NUTRIENTS POSSIBLE MECHANISM EFFECT Folate Vitamin D Vitamin E Zinc Decreased absorption Enzyme induction Excess utilization ? Chelation Selenium Vitamin K Peroxide damage ? Megaloblastic anemia Osteomalacia Haemolysis Anorexia , celebellar dysfunction Hepatotoxicity Hemorrhage ANTIFOLATE DRUGS (e.g. methotrexate, pyrimethamine, trimethamine, trimethoprim) Folate Dihydrofolate reductase inhibition Megaloblastic anemia, cytopenia CEPHALOSPORINS (Cefamendole, cefoperazone, latamoxef) Vitamin K Decreased prothrombin synthesis Bleeding episodes DRUG - DRUG INTERACTIONS 47
- 48. DRUG AFFECTED NUTRIENTS POSSIBLE MECHANISM EFFECT CORTICOSTEROIDS Calcium Decreased Ca, vitamin D metabolism Bone disorders COUMARIN ANTICOGULANTS Vitamin K ? Hemorrhage DIURETICS Zn , Ca, K, Mg Urinary loss depression Weakness , electrolyte imbalance DRUG AFFECTED NUTRIENTS POSSIBLE MECHANISM EFFECT ISONIAZED (INH) Pyridoxine Complex formation Peripheral neuropathy, Convulsions, psychatric manifestation DRUG - DRUG INTERACTIONS 48
- 49. DRUG AFFECTED NUTRIENTS POSSIBLE MECHANISM EFFECT PARA – AMINO SALICYCLIC (PAS) Vitamin B12 decreased absorption Megaloblastic anaemia POTASSIUM CHLORIDE Vitamin B12 decreased ileal Ph Decreased absorption RIFAMPCIN Vitamin D Enzyme induction Osteomalacia SALICYLATES Vitamin C, Folate Increased excretion, decreased uptake Anemia ,infection DRUG - DRUG INTERACTIONS 49
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- 51. INFLUENCE OF SMOKING ON DRUG INTERACTIONS ?!! DRUG - DRUG INTERACTIONS 51
- 52. INFLUENCE OF ALCOHOL ON DRUG INTERACTION ?!! DRUG - DRUG INTERACTIONS 52
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Notes de l'éditeur
- for example, an additive effect is seen when diuretics and beta-blockers are combined to treat hypertension
- Antacids and binding agents such as cholestyramine may impair absorption of other drugs from the gastrointestinal tract by forming complexes with them.For example, antacids reduce the absorption of quinolones such as ciprofloxacin. Otherdrugs, such as metoclopramide or opiates, may affect gut transit time. This generally influences the rate, rather than the extent, of drug absorption. Most absorption interactions are not clinically significant and can be managed by separating the administration of the drugsDrug displacement interactions occur when two drugs compete for the same protein binding site and one or both is displaced. This results in an increase in the concentration of free (active) drug, but is usually compensated for by an increase in excretion.These interactions usually involve highly protein bound drugs such as phenytoin, warfarin and tolbutamide. However, the effects of displacement interactions are usually minor and transient.Many drugs are metabolised in the liver, mainly by the cytochrome P450 enzyme system. Induction of enzymes by one drug can increase the rate of metabolism of another, resulting in a reduced effect. Conversely, enzyme inhibitors may result in accumulation and increased toxicity of other drugsFinally, drugs that alter renal excretion can affect plasma levels of other drugs. For example, methotrexate and non-steroidalanti-inflammatory drugs compete for renal excretion. Concomitant use of these agents may result inraised methotrexate levels and an increased risk of toxicity, although this combination may be used successfully under specialist supervision. The importance of this type of interaction depends on the extentto which a drug and/or its metabolites are renally excreted.The mechanism of an interaction can also have an effect on its time course.Enzyme inducers stimulate the production of new metabolising enzymes and it often takes between one and three weeks before their effects are at a maximum. In contrast, enzyme inhibitors usually have an effect on hepatic metabolism within 24 hours.
- Antacids and binding agents such as cholestyramine may impair absorption of other drugs from the gastrointestinal tract by forming complexes with them.For example, antacids reduce the absorption of quinolones such as ciprofloxacin. Otherdrugs, such as metoclopramide or opiates, may affect gut transit time. This generally influences the rate, rather than the extent, of drug absorption. Most absorption interactions are not clinically significant and can be managed by separating the administration of the drugsDrug displacement interactions occur when two drugs compete for the same protein binding site and one or both is displaced. This results in an increase in the concentration of free (active) drug, but is usually compensated for by an increase in excretion.These interactions usually involve highly protein bound drugs such as phenytoin, warfarin and tolbutamide. However, the effects of displacement interactions are usually minor and transient.Many drugs are metabolised in the liver, mainly by the cytochrome P450 enzyme system. Induction of enzymes by one drug can increase the rate of metabolism of another, resulting in a reduced effect. Conversely, enzyme inhibitors may result in accumulation and increased toxicity of other drugsFinally, drugs that alter renal excretion can affect plasma levels of other drugs. For example, methotrexate and non-steroidalanti-inflammatory drugs compete for renal excretion. Concomitant use of these agents may result inraised methotrexate levels and an increased risk of toxicity, although this combination may be used successfully under specialist supervision. The importance of this type of interaction depends on the extentto which a drug and/or its metabolites are renally excreted.The mechanism of an interaction can also have an effect on its time course.Enzyme inducers stimulate the production of new metabolising enzymes and it often takes between one and three weeks before their effects are at a maximum. In contrast, enzyme inhibitors usually have an effect on hepatic metabolism within 24 hours.