基于COMMONWEALTHOFAUSTRALIACopyrightRegulations.ppt

Barriers to Drug Distribution Blood brain barrier Only lipid soluble drugs can enter brain and CSF ‘Leaky’ in disease – eg penicillin in meningitis Placenta Allows passage of lipid and some water soluble drugs - eg opioids, antiepileptics Enzymes in placenta inactivate some drugs Pharmacokinetics II Quiz Metabolism Excretion Pharmacokinetic drug interaction case * Routes of Administration ?2006 Twentieth Century Fox Film Corporation Topical: Eye Drops Absorption through conjunctival sac epithelium Local effects in eyes with minimal systemic effects Some systemic absorption eg timolol for glaucoma may precipitate bronchospasm in asthma Routes of Administration ?2006 Twentieth Century Fox Film Corporation Topical: Cutaneous Administration Local effect on skin Steroids Slow systemic absorption (patch) Lipid soluble drugs only Oestrogen Opioids – Fentanyl, Buprenorphine 77 year old woman found dead Applied heating pad over fentanyl patch, which was also site of her pain Increased fentanyl absorption due to heat Possible application of 2nd patch without removing 1st First pass metabolism of oral drugs Gut Lilver First Pass Metabolism in Gut Lumen Gastric acid inactivates benzylpenicillin Proteolytic enzymes inactivate insulin First Pass Metabolism in Gut Wall Monoamine oxidase – metabolises monoamines Irreversible MAO inhibitors + amine-containing foods Tyramine not metabolised by MAO in gut wall enters systemic circulation releases NAd from stores in nerve endings causing hypertensive crisis Microsoft Clip Art First Pass Metabolism in Gut Wall CYP 3A4 Blocked by grapefruit juice Many drugs inducers, inhibitors, substrates Plasma Simvastatin Concentration (ng/ml) Water Grapefruit juice Administration of 40mg Simvastatin with Lilja et al., Br J Clin Pharmacology, 1994 First Pass Metabolism in Gut Wall P-glycoprotein (enterocytes to gut lumen) Interactions b/w inhibitors (eg verapamil, macrolides) and substrates (eg digoxin) Administration of 0.75mg digoxin with