Pharmacology Flashcards
Which 2 classes of commonly used medications are strong inhibitors of CYP 3A4 enzymes?
Non-dihydropyridine CCBs -> Verapamil / diltiazem
Antifungals -> itraconazole, posa
Name 3 medications which are strong inducers of CYP3A4
Carbamazepine
Phenytoin
Rifampicin
Which drugs are substrates of p-glycoprotein pathway?
Digoxin
Cyclosporin
Loperamide
What is the target of digoxin conc in HFrEF?
0.5-0.8 ng/ml
Most effective drug for maintaining sinus rhythm post AF cardioversion?
Amiodarone
Mainstay of treatment for TCA overdose with cardiac toxicity?
IV sodium bicarb
Gene that encodes Ikr channel which is blocked in QT prolongation?
hERG (human ether a go go gene)
CYP 2D6 - relevance of codeine and Nortriptyline
Both codeine and nortriptyline are metabolized by CYP2D6; however, codeine is a prodrug and its analgesic properties are not manifest until it is metabolized by CYP2D6, primarily to morphine and codeine-6-glucuronide. In contrast, nortriptyline is the active moiety and its metabolism results in inactivation of the drug to its primary metabolite.
At conventional doses, subjects who are poor metabolizers based upon CYP2D6 genotype will derive no therapeutic benefit from codeine (because it will not be converted to its active moiety), but they may be “overdosed” with nortriptyline, and at increased risk of side effect
What is the issue with combining anti-epileptics and COCP?
Carbamazepine and Phenytoin are CYP 3A4 inducers
COCP is CYP 3A4 substrate
Thus these can decrease effectiveness of contraception
What is the role of p-glycoprotein?
Works as efflux pump in gut, to pump drug out back into lumen to be excreted
Key p-gp substrates
Dabigatran
Digoxin
Loperamide
Cyclosporin
Key p-gp inhibitors? (3)
Verapamil
Diltiazem
Amiodarone
What are the key CYP3A4 inhibitors?
DR KEG Diltiazem and Verapamil Ritonavir and protease inhibitors Ketoconazole Erythromycin / clarithromycin Grapefruit juice
Nature of interaction between smoking and clozapine?
Smoking induces CYP1A2 , thus reducing levels of clozapine. Quitting can thus increase level ++
Nature of interaction between codeine and CYP2D6?
Needs enzyme to convert to active form. Thus problem with enzyme causes it to not work
Nature of interaction between paroxetine and tamoxifen?
Paroxetine inhibits CYP2D6
Tamoxifen needs this to convert from pro-drug to active form, thus with enzyme inhibition, anti-cancer effect is reduced
What is the equation for half life?
t1/2 = 0.7 x Vd / Cl
What is equation for steady state concentration?
Cpss (for IV drugs) = Dose rate / Clearance
What is the equation for loading dose?
Vd x target plasma conc / bioavailability
Describe what drug clearance means
The rate of active drug removed from the body
Measured as volume of blood cleared per unit of time
Describe what steady state means
rate of drug admin = rate of drug elimination
What happens to weak acids with alkalinasation of urin?
Becomes more ionised, thus increases the elimination
What type of reaction is glutathione conjugation in liver/
Phase 2
What type of reaction is ADH’s role in ETOH metabolism?
Phase 1
What is the cause of a clockwise hysteresis curve?
Tolerance / tachyphylaxis
What is the cause of an anti-clockwise hysteresis curve?
Delayed distribution, response delay
e.g. digoxin
What is the most important parameter to show efficacy of Abx -> beta lactams?
Time above MIC
What is the most important parameter to show efficacy of Abx -> aminoglycosides?
Cmax
What is the most important parameter to show efficacy of Abx -> vancomycin?
Area under the curve
