Clinical Pharmacology Flashcards
What must be checked prior to use of abacavir?
HLA-B5701 - risk of hypersensitivity, DRESS.
What HLA subtype increases risk of SJS/TENS in Han Chinese with carbamazepine use?
HLA-B1502. Also avoid phenytoin.
What HLA subtype increases risk of SJS/TENS/DRESS in caucasians/Japanese with carbamazepine use?
HLA-A3101
When should you not use allopurinol in Han Chinese?
HLA-B5801 -> SJS/TENS/DRESS
HLA-B3505 increases risk of SJS with what drug?
Nevirapine (HIV)
What HLA subtype increases risk of liver failure with flucloxacillin?
HLA-B5701
What CYP does tamoxifen require to become activated, and what are clinical implications?
CYP2D6 - Fluoxetine and paroxetine inhibit this, therefore lower activity of tamoxifen
What are some P-glycoprotein inhibitors?
Verapamil, macrolides, amiodarone, CNIs, ketoconazole
What are some P-glycoprotein inducers?
St John’s wort, Rifampicin, carbamazepine, phenytoin
Enzyme inducers
CBZ, phenytoin, phenobarbitones, alcohol, sulfonamides, rifampicin
CYP metabolising warfarin?
CYP2C9. Metabolism inhibited by omeprazole, amiodarone, metronidazole, cimetidine.
What CYP is substrate for clopidogrel metabolism?
CYP2C19 - inhibited by PPIs
Also acts as an inhibitor of CYP2C19
What classes of antibiotics dependen on time above MIC?
Lincosamides, beta lactam
Which class of antibiotics depends on Cmax?
Aminoglycosides
Which class of antibiotics depend on total exposure above MIC?
Vancomycin
Mechanism of action of indapamide?
Thiazide like diuretic, inhibits Na-Cl in DCT and also inhibits response to pressor stimuli
Mechanism of action of amiloride?
Inhibits ENaC in late DCT, potassium sparing
Which factors DO affect the bioavailability of an orally administered drug?
1st pass metabolism, rate of GI transit; presence of other drugs in GIT; lipid solubility of drug
What factor DOES NOT affect bioavailability of an orally administered drug?
dose
acidic drugs like phenytoin bind primarily to which plasma protein?
albumin
how is lithium cleared?
100% renally
which PD factor is most important in determining the efficacy of beta lactams and lincosamides?
time the concentration is above the MIC (should be at least 40-50% of the dosing interval)
The proportion of drug reabsorbed in the renal tubule depends on the
urine pH
MOA of Ivabradine for stable angina
slows heart rate
During a constant rate of IV infusion of Taz, which factor determines the steady state drug concentration?
dose rate
PD factor important in determining efficacy of aminoglycosides and quinolones
ratio of the max concentration over the MIC (maximum plasma drug concentration at the binding site)
Diuretic that inhibits renal K secretion at the distal nephron by mineralocorticoid-independent mechanism
Amiloride
Diuretic that inhibits the apical DCT epithelium Na-Cl co-transporter and decreaeses PVR
Indapamide
Drugs that are important for albumin binding
Warfarin, Digoxin, NSAID, benzodiazepines, phenytoin
What drug is dependent on the total exposure of the body to the antibiotic to MIC?
Vancomyin (as indicated by the ratio of the Area under the concentration-time curve during a 24hour period AUC0-24)
CYP 2C9 inhibitors
Omeprazole, Metronidazole, Cimetidine, Amiodarone
Tacrolimus MOA
engages FKBP12 -> forms complex that inhibits calcineurin phosphatase and T cell activation
Ciclosporin MOA
engages cyclophilin -> forms complex that engages calcineurin which normally dephosphorylates NFATc -> moves to nucleus of T cell and increases genes for IL2 and related cytokines
