Special Considerations Flashcards
Pharmacogenetics Test for Ethanol
No FDA approved test yet
Pharmacogenetics Test for Phenytoin
No FDA approved test yet.
In theory:
Inactive CYP2D6 and CYP2C19
alleles – ↓ phenytoin dose
Hyperactive MDR1 promoter allele – ↑ dose
Low affinity VGSC allele – switch to different anti-seizure medication w/ diff MOA such as topirimate
Pharmacogenetics Test for 5-fluorouracil (5FU)
Yes, FDA recommended for inactive A allele.
↓ 5FU dose for inactive ‘A’ allele
No FDA approved test yet for 2R/2G,2R/2Cor3R/3C allele of TS gene
Choose different cytotoxic drug for 3R/3G allele
Pharmacogenetics Test for Codeine
Yes, FDA recommended test for CYP2D6 allele
For poor metabolizers replace codeine with opioid analgesic not dependent on CYP2D6 conversion to active metabolite (e.g. hydrocodone)
For ultra-metabolizers: ↓ dose of codeine
Pharmacogenetics Test for Warfarin
Yes, FDA has approved the Nanosphere test for warfarin ADR
This tests looks at CYP2C9 and VKORC1 alleles
Nanosphere does not test for bleeding susceptibility alleles that are common in the African American population
Benzimidazole resistance
Switch β-tubulin isotype 1
(sensitive) to isotype 2 (resistant)
Point mutation in β-tubulin isotype 1 that changes phenylalanine (wild-type) to tyrosine (mutation) at position 200
Ivermectin resistance
P-glycoprotein ↑ regulation
Mutation in glutamate- gated Cl- channel
Pyrantel Pamoate resistance
Typically not a problem
Diethylcarbamazine resistance
Typically not a problem
Praziquantal resistance
Typically not a problem
May have mutation in VGCC
mech of resistance for Artemisinins
Counterfeit drug threat to resistance
mech of resistance for Chloroquine Phosphate
Pfcrt (efflux pump) mutations → gene amplification → pumps drug out
mech of resistance for Quinne Sulfate
Pfmdr1 (efflux pump)gene amplification → pumps drug out
mech of resistance for Atovaquone
Cyt b mutations → inhibit drug binding
ACT with Lumefantrine special considerations
Take with high fat meal to ↑ absorption
Substantial drug‐drug interactions w/ ARV/protease inhibitors (may need to ↑ ACT dose)
Can only get from the CDC by request
Chloroquine Phosphate special considerations
Loading dose requires
Must monitor doses due to potentially lethal plasma concentrations
Quinne Sulfate special considerations
Combination/adjunctive therapy to ↓ duration/toxicity → doxycycline, clindamycin and tetracyclines (inhibit protein translation)
Atovaquone special considerations
Resistance to monotherapy
Combo w/ proguanil
Proguanil special considerations
Enhances atovaquone effect
Isoniazid (INH) special considerations
Fast acetylaters of INH → don’t have enough drug won’t be effective
Slow acetylaters of INH → too much drug will become toxic
Depletes pyridoxine → give pyridoxine vitamin
Mech of resistance of Isoniazid (INH)
KatG deletion/mutation → if its compromised it won’t activate the drug and won’t work
InhA overexpression→ plenty of the protein that the drug isn’t binding to
Mech of resistance of Pyrazinamide
pcnA mutations bc if not converted it won’t work
Mech of resistance of Ethambutol
embB mutations → inhibits binding of drug
Mech of resistance of Rifampin
rpoB mutations → mutates binding site and durg can’t bind
