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