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PHARMACOLOGY

WHAT IS PHARMACOLOGY ?. Searches for new drugs. pharmacologists are drug hunters. PHARMACOLOGY. Investigates effects of known drugs. mechanism of action, evidence of effect, adverse reactions,, fate in the body (absorption, distribution, elimination), dosage, course of effect ….

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PHARMACOLOGY

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  1. WHAT IS PHARMACOLOGY ? Searches for new drugs pharmacologists are drug hunters PHARMACOLOGY Investigates effects of known drugs mechanism of action, evidence of effect, adverse reactions,, fate in the body (absorption, distribution, elimination), dosage, course of effect …

  2. PHARMACOLOGY x PHARMACY Pharmacology is the study of effects of drugs (chemicals) on the functioning of the body Pharmacy deals with the preparation (compounding, manufacture), distribution and supply of medicines

  3. DISCOVERY OF NEW DRUGS 1963 propranolol – Beta-adrenoceptor blocking drugs– hypertension, angina pectoris 1972 cimetidine – H2-receptor-antagonists – Ulcer-healing drugs Sir James W. Black Nobel price 1988

  4. THE AIM OF TEACHING PHARMACOLOGY mechanism of action, evidence of effect, adverse reactions,, fate in the body (absorption, distribution, elimination), course of effect … PHARMACOLOGY – TEXTBOOKS BASIC TERMS: generic [non-proprietary]names x trade (brand, proprietary) names paracetamol x PARALEN, PANADOL, etc ATC = Anatomical Therapeutic Chemical (ATC) Classification of drugs SPC = Summary of Product Characteristics BNF, AISLP, Micromedex = electronic drug databases

  5. INTRODUCTION TO PHARMACOKINETICS 1. Fate of drugs in the body 1.1 absorption 1.2 distribution 1.3 elimination 2. The half-life and its uses 3. Repeated administration of drugs 4. Plasma concentration-effect relationship

  6. 1. FATE OF DRUGS IN THE BODY WHAT HAPPENS TO DRUGS INSIDE THE BODY ADMINISTERED • ABSORPTIONdepends on • membrane penetration which depends on • lipid solubility • ionization (depends on pH) • routes of administration ABSORBED DISTRIBUTION depends on: „HIDDEN“ FIRST-PASS EFFECT BIOAVAILABILITY - membrane penetration - protein binding ELIMINATED ELIMINATION ONLY A FREE DRUG ACTS! ACTING • metabolic • excretion

  7. 1.1 ABSORPTION • Depends on: • lipid solubility • ionization (depends on pH) • non-ionized (non-polar) local changes in the pH • routes of administration • per os • presystemic elimination FIRST-PASS EFFECT • pharmaceutical technology BIOAVAILABILITY, bioequivalence • parenteral

  8. FIRST-PASS EFFECT: loss of a drug by a metabolism mostly in the liver that occurs en route from the gut lumen to the systemic circulation e.g. in nitroglycerin, morphine

  9. Clinical consequence of the first-pass effect: • limited effect after oral administration • great interindividual differences in dosage

  10. BIOAVAILABILITY: the proportion of drug that reaches the systemic circulation It is usually calculated from the AUC (Area Under the Curve)

  11. BIOEQUIVALENCE ...

  12. 1.2 DISTRIBUTION Depends on: • - membrane penetration • - protein binding • plasma proteins • tissue proteins • ONLY A FREE DRUG ACTS! • The bound drug is inactive. • Free and bound drug are in equilibrium. • Displacement: drug-drug interactions

  13. 1.3 ELIMINATION: • METABOLIC (biotransformation) • mostly in the liver • ENZYME INDUCTION/ INHIBITION • oxidase enzymes - cytochrom P450 (CYP2D6 etc) • GENETIC POLYMORPHISM • EXCRETION • kidneys metabolites or unchanged (almost completely unchanged e.g. digoxin, gentamycin) • GIT... enterohepatic circulation e.g. tetracyclines

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