Pharmacology Flashcards
What is phase I of drug metabolism?
Occurs in the endoplasmic reticulum, driven by cytochrome p450 enzymes
Includes oxidation, reduction and hydrolysis
What is phase II of drug metabolism
Involves conjugation (eg glucuronidation, acetylation)
What is first pass metabolism?
Extent to which drug concentration is reduced after its first passage
through an organ prior to reaching systemic circulation
Mainly refers to PO drugs passing via the liver
Which CYP enzyme is the most important liver enzyme for drug metabolism?
CYP3A4
Examples of CYP450 Inducers?
Phenytoin
Phenobarb
Carbamazepine
Rifampicin
What effect do CYP450 inducers have on other drugs?
Can increase other drugs metabolism, making them less effective (unless they are a prodrug)
Examples of CYP450 inhibitors?
Sodium valproate
Fluconazole/ azoles
Erythromycin
Clarithromycin
Doxycylcin
Metronidazole
Isoniazid
Grapefruit, pomegranate
Nifedipine, diltiazem, verapamil
What effect do CYP450 inhibitors have on drug metabolism?
They inhibit other drug metabolism -> higher concentrations/more toxicity
How to calculate drug clearance?
(volume of distribution x 0.7)/ half life
How to calculate half life?
(Volume of distribution x 0.7)/ clearance
Formula for volume of distribution?
Total amount of drug in body (mg) / blood concentration (mg/L)
What effect do lipid soluble drugs have on volume of distribution
Lipid soluble drugs increase vd
What effect do water soluble drug have on volume of distribution?
Water soluble drugs decrease vd
HLA B5701 carriers have increased risk of toxicity with which 2 drugs?
Flucloxacillin and abacivir (cause liver injury)
2 loss of function alleles for CYP2D6 can result in what?
Poor codeine metabolism (and hence no analgesic effect)
