BIOL 2048/9 Pharmacokinetics Lecture 1 PDF

BIOL 2048/9 Pharmacology PHARMACOKINETICS The link between dose and response MyEngagement: Dr. Charles Birts Join: vevox.app ID: 125-820-690 [email protected] Organisation of lectures 5 Lectures Biological Basis of...

BIOL 2048/9 Pharmacology PHARMACOKINETICS The link between dose and response MyEngagement: Dr. Charles Birts Join: vevox.app ID: 125-820-690 [email protected] Organisation of lectures 5 Lectures Biological Basis of Pharmacokinetics Mathematical Basis of Pharmacokinetics Learning Outcomes Explain the pharmacokinetic processes of absorption, distribution, metabolism and excretion (ADME). Apply mathematical principles to the pharmacokinetic processes of absorption, distribution and elimination. Recommended Text Chapter 9: Absorption and distribution of drugs Chapter 10: Drug metabolism and elimination Chapter 11: Pharmacokinetics Jove summary videos Pharmacology PHARMACODYNAMICS PHARMACOKINETICS Effect of the drug Effect of the body In the body on drug delivery to site of action DR interactions Generally the same for Processes specific to most drugs (ADME) each class of drug irrespective of their therapeutic activity Pharmacology PHARMACOKINETICS PHARMACODYNAMICS Dosage Regimes COMPOUND AT THERAPEUTIC How much? How often? SITE OF ACTION RESPONSE DOCTOR PATIENT DRUG ACTIVITY In-vivo therapeutic response PHARMACOKINETICS PHARMACODYNAMICS ADMINISTERED COMPOUND AT THERAPEUTIC DOSE SITE OF ACTION RESPONSE Absorption Receptor binding Distribution Cellular changes Metabolism Therapeutic effect Excretion Pharmacokinetics An understanding of pharmacokinetics is important for each of the following processes: 1. Time of onset of action 2. Intensity and duration of effect 3. Accumulation 4. Inter-individual differences 5. Intra-individual differences 6. Drug interactions 7. Inter-species differences Key pharmacokinetic processes ABSORPTION RATE The speed DISTRIBUTION METABOLISM EXTENT Eliminat The amount ion EXCRETION  BODY TISSUES Drugs go PERIPHERAL COMPARTMENT everywher e! GENERAL SITE CIRCULATION OF LIVER ACTION CENTRAL COMPARTMENT EFFECT KIDNEYS LUNGS Cross-section of a mouse given an oral dose of the b-adrenoceptor antagonist propranolol Brain Lung Intestine s Hear Liver Urinary t bladder The light areas are areas of high radioactivity  Increasing physiological response The relationship between the plasma concentration of the b- adrenoceptor antagonist propranolol and the reduction in exercise-induced tachycardia in different individuals Increasing concentration in the plasma Key Messages: As the plasma concentration of the drug  the response  The concentration of the drug in the plasma is proportional to the therapeutic effect There are different routes of drug administration BODY TISSUES INTRAMUSCULAR INTRAVENOUS PERIPHERAL DOSE DOSE COMPARTMENT GENERAL CIRCULATION SITE ORAL LIVER OF DOSE CENTRAL ACTION COMPARTMENT EFFECT METABOLISM BILE INHALED KIDNEYS LUNGS FAECES DOSE EXCRETION EXCRETION EXCRETION Drugs have a variety of different chemical structures N2O Nitrous oxide Halothane Aspirin Amphetamine Diazepam Morphine Tubocurarine …..our bodies need to be able to ‘deal with’ this vast variety of structures! (Do not try to memorise all of these drug In the food we eat there is a range of chemical structures that our bodies need to process 2mg/g Tyramine HO CH2CH2NH2 cheese HO CH2CH2NH2 3mg/100g 5-HT N bananas H Combustion Benzo[a]pyrene products  COFFEE CONTAINS OVER 200 LOW MOLECULAR WEIGHT COMPONENTS! HO CH=CHCOO Chlorogenic Acid COOH 300mg per cup HO OH O OH CH3 CH3 N Caffeine N 5% of powder N N O CH3 1. ABSORPTION Processes that take place between the site of administration and the site of measurement  Drug Drug Drug Drug Drug Drug Drug MEMBRANE PORES – Low molecular weights (