Intro to clinical pharmacology-1.ppt - Clinical...

This preview shows page 1 - 15 out of 61 pages.

Clinical Pharmacology Dr Wanjala
Definitions Pharmacology The word pharmacology is derived from the Greek words pharmacon, (drug or poison) and logos (science). Clinical Pharmacology Study of drugs in humans Includes drug Discovery Development Use Evaluation
History Only relatively recent emphasis on drug therapy and rational prescribing. ‘a surgeon who uses the wrong side of the scalpel cuts his own fingers and not the patient; if the same applied to drugs they would have been investigated very carefully a long time ago.’ Rudolph Buchheim, 1849 Established first laboratory of experimental pharmacology
PHARMACEUTICAL PROCESS Is the drug getting into the patient?
Is the drug getting to its site of action?
Is the drug producing the required pharmacological effect? THERAPEUTIC PROCESS Is the pharmacological effect being translated into a therapeutic (or toxic) effect?
Pharmacokinetics What your body does to the drug The quantitative analysis of the time course of drug: Absorption Distribution Metabolism Excretion
Pharmacokinetics Improves Drug Dose Selection Traditional: Look up ‘usual’ dose in an official book Memorise ‘usual’ dose Improved: Individualise dosing Apply pharmacokinetics and the ‘target concentration strategy’ Useful when drug has a low therapeutic index and pharmacokinetics account for much of the inter- patient variability in response
Target Concentration Strategy Estimate Initial Dose - Target level - Loading dose - Maintenance dose Begin therapy Assess therapy - Patient response - Drug level Refine dose estimate and Adjust dose Tozer and Rowland, 2006
Absorption Site of administration to plasma Depends on route of administration Administration Cross lipid barriers/ cell walls Distribute Cellular target
Routes of Administration ©2006 Twentieth Century Fox Film Corporation
Oral Absorption Passive non-ionic diffusion Majority of drugs Specialised transporters Large neutral amino acid transporter L-dopa, Methyldopa, Baclofen Oligopeptide transporter Amino beta lactams, ACE inhibitors Monocarboxylic acid transporter Salicylic acid
Oral (enteral): absorption from mouth, stomach and small intestine Stomach: minority Small Intestine: majority Passive > Active Rate ~ 75% in 1-3 hours. Depends on: Motility eg diarrhoea decreases absorption Blood flow Food – enhance or impair Particle size and formulation Physico-chemical factors – Unionised Lipid soluble Rate of gastric emptying rate limiting step
Gastric Emptying Rate Affects Paracetamol Absorption Nimmo et al., Br Med J, 1973 Gastric emptying is: - Delayed by propantheline -Stimulated by metaclopramide
Effects of Food on Oral Drug Absorption Poor acid stability: prolonged gastric exposure → degradation eg erythromycin, azithromycin, isoniazid Require acid environment eg itraconazole, ketoconazole Fat or bile acids enhance absorption

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture