Biotrans/PD/CT Flashcards
What types of xenobiotics can be excreted via the kidneys?
polar or with small molecular volumes
What is the first pass effect?
The process by which oral drugs are absorbed in the small intestine and transported to the liver via the hepatic portal system, where they undergo extensive metabolism
Examples of phase I reactions
reduction, oxidation, hydrolysis
*less commonly, hydroxylation, epoxidation, dealkylation, deamination, desulfuration, dechlorination
Examples of phase II reactions
a reaction that adds on an endogenous group such as glucuronic acid, sulfuric acid, acetic acid, or an amino acid
Individuals with what enzymatic defect have difficulty metabolizing succinylcholine
pseudocholinesterase
What does it mean to be a slow acetylator?
- autosomal recessive trait with a decrease in N-acetyltransferase levels in the liver
- isoniazid (used to treat tuberculosis), hydralazine (used to treat hypertension), caffeine, and other similar amines are metabolized at slower rates, which can lead to hepatotoxicity
What are common enzyme inducers?
- phenytoin (anticonvulsant)
- chronic ethanol (CYP2E1)
- aromatic hydrocarbons such as benzo[a]pyrene (tobacco smoke)
- rifampin (anti-tuberculosis)
- phenobarbital and other barbiturates
*can be bad to speed tings up because if the phase I produces a toxic product it may accumulate
What does grapefruit juice do?
- it irreversibly inhibits CYP3A4
- The inhibition alters the oral bioavailability of many classes of drugs, including antihypertensives, immunosuppressant, antidepressants, antihistamines, and statins.
What is the most important factor in regards to decreased drug metabolism with age?
liver and kidney disease
Explain why acetaminophen is toxic at high levels
- hepatic GSH is depleted faster than it is regenerated
- Toxic metabolites accumulate resulting in hepatotoxicity
What is cytochrome P450 2D6 used for?
- β blockers, antidepressants, antipsychotics, and opioid analgesics
- variations lead to different results: codeine being metabolized to too much or too little morphine
What is CYP2C19 used for?
- proton-pump inhibitors
- antidepressants
- antiepileptics
- antiplatelet drugs
Uridine 5′-Diphosphoglucuronosyl Transferase 1 (UGT1A1)
- 28 allele variation gives you Gilbert’s syndrome
- increased unconjugated bilirubin
ThiopurineS-Methyltransferase (TPMT)
- Three thiopurine drugs are used clinically:
1. azathioprine
2. 6-mercaptopurine (6-MP)
3. 6-thioguanine (6-TG). - variation in activity (high, intermediate, low) can lead to toxicity
G6PD
- exclusive source of NADPH in RBCs
- deficiency leads to early destruction of RBCs
Patient presents with hemolytic anemia post anti malarial drugs. You susceptible?
- G6DP deficiency
- fava beans, anti=malarial drugs, aspirin, nitrofurantoin, NSAIDS, quinidine, quinine, sulfa drugs are hard for people with Gilbert syndrome
ORGANIC ANION TRANSPORTER (OATP1B1)
- responsible for the hepatic uptake of mainly weakly acidic drugs and endogenous compounds (statins,methotrexate, and bilirubin)
What does rs4149056 mean? how should you alter care?
- the common variant, inSLCO1B1 that increases systemic exposure ofsimvastatin
- this variant reduces transport of OATP1B1 substrates in vitro
- identified to have the single strongest association with simvastatin-induced myopathy
- reduce dose or give alternative statin
What does rs2231142 mean? how should you alter care?
- variant of BCRP, ABCG2
- associated with changes in response to the xanthine oxidase inhibitor,allopurinol, the statin rosuvastatin, and toxicity to various anticancer drugs
- popular variant in Asian populations
CYP2C9 & VKORC1
- pharmacologic action ofwarfarinis mediated through inactivation of VKORC1
- warfarinis administered as a racemic mixture ofR- andS-warfarin, and patients with reduced-function CYP2C9 genotypes are at increased risk for bleeding due to decreased metabolic clearance of the more potentS-warfarin enantiomer
What is -1639G>A?
individuals with decreased VKORC1 expression, eg, carriers of the -1639G>A polymorphism, are at increased risk for excessive anticoagulation following standardwarfarindosages
