Exam 5 Flashcards
Number 1 on website for Pharmacogenomics
CPIC
Pathogens can exist as
Bacteria
Viruses
Fungi
Parasites
When discussing the patient and antimicrobial agent, what else must be taken into consideration?
Pathogen
Goals of Pharmacogenomics in ID
Ensure optimal dosing to achieve desired drug concentrations at the site of infection
Avoid drug toxicity due to supratherapeutic dosing
HLA-B is responsible for
Presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens
A variant allele, HLA-B*57:01 is associated with
Increased risk of hypersensitivity reaction to the anti-HIV drug ABACAVIR
*Abacavir is NOT recommended
Guideline for Efavirenz is based on what P450 CYP?
CYP2B6
Efavirenz - 2B6 -> 8-hydroxyefavirenz (inactive) -2B6-> 8,14 dihydroxyefavirenz (inactive)
Efavirenz -2B6-> 7-hydroxyefavirenz (inactive)
WITHOUT CYP2B6 or with CYP2B6 variant allele, Efavirenz will stay active
- With Variant CYP2B6 516 G>T
- Leads to increased EFV concentrations and CNS toxicity
- EFV dose reductions may benefit patients with 516 G>T
Normal Efavirenz symptoms
CNS Toxicity which leads to
Poor Quality of Life
Decreased Adherence
Treatment Discontinuation
Symptoms begins within 1 to 2 days after initiation and may resolve within 2 to 4 weeks of continued therapy.
Atazanavir INHIBITS
UGT1A1
UGT1A1 28/28 is a significant risk factor for
Severe Hyperbilirubinemia among patients taking atazanavir
Voriconazole is metabolized by
CYP2C19
*17 in CYP2C19 represents poor metabolizer or ultrarapid?
Ultrarapid
In Adults take Voriconazole and is a CYP2C19 ultrarapid, rapid, or poor metabolizer, should you consider an alternative agent?
Yes
In Pediatrics taking Voriconazole and is a CYP2C19 Ultrarapid or poor metabolizer, should an alternative agent be considered?
Yes
PPIs are METABOLIZED BY
CYP2C19
Omeprazole/Esomeprazole is 90% CYP2C19 to
Inactive 5-hydroxy-omeprazole
The mitochondrion contains its own circular dsDNA. mtDNA is solely present in ova, resulting in strict maternal inheritance. mtDNA contains 37 genes
- 13 protein-encoding genes involved in oxidative phosphorylation
- 24 genes involved in protein translation
- 22 tRNA
- 2 rRNA genes
- MT-RNR for 12S rRNA*
MT-RNR1 1555A>G producees a mitochondrial 12s rRNA that is structurally similar to bacterial rRNA
MT-RNR1 1555A>G variant + Aminoglycoside Exposure
Irreversible Ototoxicity
= Decrease mitochondrial protein synthesis, ATP production in the cochlea, and apoptosis
With warfarin
Balance risk of thrombosis vs bleeding
S-Warfarin inhibits
VKORC1 and uses CYP2C9 to inactivate metabolites
CYP2C9 affects PK or PD
PK, metabolism of S-warfarin
VKORC1 affects PK or PD
PD, warfarin target
VKORC1 -1693G>A polymorphism
GA = reduced warfarin dose
AA greatly reduced warfarin dose (more sensitive)
85-90% of Clopidogrel is converted to inactive acid metabolite. What P450 Cytochrome is used to convert clopidogrel to an active form?
CYP2C19
If Clopidogrel Biotransformation and Platelet Inhibition Decreases and the patient has Loss of Function of Alleles
Risk of CV Events Increase
Although a study proved that ticagrelor/prasugrel is noninferior to Clopidogrel in terms of thrombotic events, the two medication does
Lower bleeding risk
If a patient is genotyped as an Intermediate Metabolizer or Poor Metabolizer (has any variant gene), they should be treated how?
Prasugrel 10 mg QD or Ticagrelor 90 mg BID
Adverse of Effects of Statins
Myalgia
Myopathy
Rhabomyolysis
Simvistatin relies on ________ for uptake of activated simvastatin
SLCO1B1
If there is an variant on SLCO1B1
the adverse effects are at an increase
For a poor metabolizerof SLCO1B1
Consider an alternative agent (pravastatin, rosuvastatin, fluvastatin)
A 62 year old female has STEMI treated with PCI and DES. Her CYP2C19 genotype is ordered and returns as 1/2. Which therapy is best?
A. Prasugrel 5 mg daily
B. Clopidogrel 75 mg daily
C. Ticagrelor 90 mg BID
D. Clopidogrel 150 mg daily
C
A 62 year old female has STEMI treated with PCI and DES. Her CYP2C19 genotype is ordered and returns as 1/1. Which therapy is best?
A. Clopidogrel 75 mg daily
B. Prasugrel 5 mg daily
C. Clopidogrel 150 mg daily
D. Ticagrelor 90 mg BID
A
