22 MAY 2006

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• 22 MAY 2006
• By Tina Yap

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MECHANISM OF DRUG ACTION

• Absorption
• Distribution
• Metabolism
• Excretion

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ABSORPTION

• Movement of a drug from site of
• application to the systemic
• circulation

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ABSORPTION

• Factors that affect absorption
• Concentration
• Physical State
• Dissolution Rate
• Blood Flow
• Gastric Emptying

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DISTRIBUTION

• Factors that affect distribution of a drug
• Lipophilic drugs vs. hydrophilic drugs
• Protein Binding

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METABOLISM

• Mainly takes place in the liver
• Biotransformation
• conversion of drugs by microsomal
  enzymes to metabolites
• Types of Biotransformation
• Oxidation, reduction, conjugation,
• hydrolysis

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EXCRETION

• Mainly takes place in the KIDNEYS
• Dosage adjustment is required if renal
• function is impaied
• Other routes of excretion include
• Bile, skin thru sweat, lung, milk in
  
• lactating mothers.

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PHARMACOKINETIC PROFILE
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DRUG-DRUG INTERACTIONS

• Absorption Interactions
• Example
• Paracetamol Metocopramide or
• Cisapride
• ? Paracetamol absorption due to
• ? gut motility

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ABSORPTION INTERACTION

• Example
• Ciprofloxacin antacids containing
• (Mg)Cl2
• ? Ciprofloxacin absorption due to
• chelation by Mg2

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ABSORPTION INTERACTION

• Example
• Ketoconazole Omeprazole
• ? Ketoconazole absorption due to
• inhibition of acid secretion

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DRUG-DRUG INTERACTIONS

• Drug Displacement (Protein-binding)
• interactions
• Example
• Warfarin (99 bound) Tobultamide
• (96 bound)

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DRUG-DRUG INTERACTIONS

• Drug Metabolism Interactions
• Drugs that induce activity of microsomal
• enzymes Carbamazepine, Rifampin
• Drugs/Foods that inhibit activity of
• microsomal enzymes Chloramphenichol,
• grapefruit juice

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DRUG METABOLISM INTERACTIONS

• Example
• Warfarin Lovastatin
• Metabolism of Warfarin is inhibited
• ? anticoagulant effect
• ? bleeding

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INTERACTION DUE TO CHANGES IN EXCRETION

• Example
• Probenacid Indomethacin / Nalidixic acid
• Probenacid reduces excretion of
• Indomethacin / Nalidixic Acid ????
• ?Indomethacin / Nalidixic Acid serum level

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INTERACTION DUE TO CHANGES IN EXCRETION

• Example
• Contraceptives Tetracycline (TC)
• TC destroys gut flora which metabolize
• estrogen conjugate to parent drug ??
• Effectiveness of contraceptive is cut down

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DRUG-DRUG INTERACTIONS

• Pharmacodynamic Interactions
• When 2 drugs have the same effects or
• side effects, when given together, their
• combines effects may be additive.

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PHARMACODYNAMIC INTERACTIONS

• Examples
• Alcohol Zopiclone
• ?? drowsiness
• Prednisolone Naproxen (NSAIDs)
• ?? GI bleeding

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PHARMACODYNAMIC INTERACTIONS

• Example
• Frusemide Hydrochlorthiazide (HCTZ)
• ?? Potassium (K) loss

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Source of Reference

• CLINICAL PHARMACOLOGY
• By Sirtori, Kuhlmann, TillementVrhovac
• Published by
• McGraw-Hill Intl (UK) Ltd.

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MIMS CLASSIFICATION

• 1. GI Hepatobiliary System
• 2. Cardiovascular Hematopoietic System
• 3. Respiratory System
• 4. Neuro-muscular System
• 5. Hormones
• 6. Contraceptive Agents
• 7. Antibiotics

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MIMS CLASSIFICATION (contd)

• 8. Other Chemotherapeutics
• 9. Genito-urinary System
• 10. Endocrine Metabolic System
• 11. Vitamins Minerals
• 12. Nutrition
• 13. Eye, ear, mouth throat
• 14. Dermatologicals

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MIMS CLASSIFICATION (contd)

• 15. Anaesthetics Local General
• 16. Diagnostic Agents
• 17. Allergy Immune System
• 18. Antidotes, Detoxifying Agents Drug
• Used in Substance Dependence
• 19. IV other sterile solutions
• 20. Miscellaneous

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MIMS DRUG MONOGRAPH

• Trade name eg. Avandia, Norvasc
• Manufacturer eg. GSK, Teva
• Forensic classification
• NP non-poison
• P1 part I poison
• P1S1 part 1 schedule 2 poison
• P1S1S3 Part 1 Schedule 3 poison

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MIMS DRUG MONOGRAPH

• P2 Part 2 poison
• DD Dangerous Drug
• local agent
• C Composition
• generic name

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MIMS DRUG MONOGRAPH

• I Indications
• eg. Duodenal ulcer, Essential HTN
• D Dosage
• eg. 40mg once daily
• SP Special Precaution
• eg. Prolonged Use Pregnancy Lactation
  Should not be used in
  children
• AR Adverse Reaction
• eg. Nausea vomiting, diarrhea, headache,
  rash, restlessness

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MIMS DRUG MONOGRAPH

• CI Contraindications
• eg. Hypersensitivity Kidney failure
• DI Drug Interactions
• P/P Presentations
• eg. Tab 500s, Susp 200ml
• US FDA Preg Cat Drug Safety in Pregnancy

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DRUG SAFETY IN PREGNANCY

• Category A possibility of foetal harms
• remains remote
• Category B animal studies show safety
• (or no adverse effect ) but no controlled
• studies in women

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DRUG SAFETY IN PREGNANCY

• Category C (a) Studies in animals show
• teratogenic or embryocidal, and no
• controlled studies in women (b) no
• controlled studies in both women and
• animals

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DRUG SAFETY IN PREGNANCY

• Category D Evidence of human foetal
• risk, but benefits from use in pregnant
• women may be acceptable despite the
• risk (eg. In life-threatening situation)
• Category X contraindicated in women
• who are or may become pregnant.

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DRUG SAFETY IN PREGNANCY

• Examples
• Paracetamol ? B
• Morphine ? C
• Fluvastatin ? X
• Isotretinoin ? X

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• THE END