Biotrans/PD/CT

Question 1

What types of xenobiotics can be excreted via the kidneys?

Answer 1

polar or with small molecular volumes

Question 2

What is the first pass effect?

Answer 2

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

Question 3

Examples of phase I reactions

Answer 3

reduction, oxidation, hydrolysis

*less commonly, hydroxylation, epoxidation, dealkylation, deamination, desulfuration, dechlorination

Question 4

Examples of phase II reactions

Answer 4

a reaction that adds on an endogenous group such as glucuronic acid, sulfuric acid, acetic acid, or an amino acid

Question 5

Individuals with what enzymatic defect have difficulty metabolizing succinylcholine

Answer 5

pseudocholinesterase

Question 6

What does it mean to be a slow acetylator?

Answer 6

• 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

Question 7

What are common enzyme inducers?

Answer 7

• 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

Question 8

What does grapefruit juice do?

Answer 8

• it irreversibly inhibits CYP3A4
• The inhibition alters the oral bioavailability of many classes of drugs, including antihypertensives, immunosuppressant, antidepressants, antihistamines, and statins.

Question 9

What is the most important factor in regards to decreased drug metabolism with age?

Answer 9

liver and kidney disease

Question 10

Explain why acetaminophen is toxic at high levels

Answer 10

• hepatic GSH is depleted faster than it is regenerated

- Toxic metabolites accumulate resulting in hepatotoxicity

Question 11

What is cytochrome P450 2D6 used for?

Answer 11

• β blockers, antidepressants, antipsychotics, and opioid analgesics
• variations lead to different results: codeine being metabolized to too much or too little morphine

Question 12

What is CYP2C19 used for?

Answer 12

• proton-pump inhibitors
• antidepressants
• antiepileptics
• antiplatelet drugs

Question 13

Uridine 5′-Diphosphoglucuronosyl Transferase 1 (UGT1A1)

Answer 13

• 28 allele variation gives you Gilbert’s syndrome

- increased unconjugated bilirubin

Question 14

ThiopurineS-Methyltransferase (TPMT)

Answer 14

• 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

Question 15

G6PD

Answer 15

• exclusive source of NADPH in RBCs

- deficiency leads to early destruction of RBCs

Question 16

Patient presents with hemolytic anemia post anti malarial drugs. You susceptible?

Answer 16

• G6DP deficiency
• fava beans, anti=malarial drugs, aspirin, nitrofurantoin, NSAIDS, quinidine, quinine, sulfa drugs are hard for people with Gilbert syndrome

Question 17

ORGANIC ANION TRANSPORTER (OATP1B1)

Answer 17

• responsible for the hepatic uptake of mainly weakly acidic drugs and endogenous compounds (statins,methotrexate, and bilirubin)

Question 18

What does rs4149056 mean? how should you alter care?

Answer 18

• 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

Question 19

What does rs2231142 mean? how should you alter care?

Answer 19

• 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

Question 20

CYP2C9 & VKORC1

Answer 20

• 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

Question 21

What is -1639G>A?

Answer 21

individuals with decreased VKORC1 expression, eg, carriers of the -1639G>A polymorphism, are at increased risk for excessive anticoagulation following standardwarfarindosages