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

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

1963 propranolol – Beta-adrenoceptor blocking drugs – hypertension, angina pectoris 1972 cimetidine – H 2 -receptor-antagonists – Ulcer-healing drugs Sir James W. Black Nobel price 1988 DISCOVERY OF NEW DRUGS

THE AIM OF TEACHING PHARMACOLOGY 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 mechanism of action, evidence of effect, adverse reactions,, fate in the body (absorption, distribution, elimination), course of effect …

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 INTRODUCTION TO PHARMACOKINETICS 4. Plasma concentration-effect relationship

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

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

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

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

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

BIOEQUIVALENCE...

- 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 1.2 DISTRIBUTION Depends on:

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