38 Questions
What is the impact of HLA-B*15:02 on patients taking Phenytoin?
Increased risk of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN)
What is the CPIC recommendation for using Phenytoin in patients with HLA-B*15:02?
Avoid use unless benefit outweighs risk
Which of the following drugs is associated with increased risk of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with HLA-B*15:02?
Phenytoin and Carbamazepine
What is the common adverse effect associated with HLA-B*15:02 in patients taking Carbamazepine?
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN)
What is the CPIC recommendation for using Carbamazepine in patients with HLA-B*15:02?
Avoid use unless benefit outweighs risk
What is the significance of HLA-B*15:02 in pharmacogenetics?
Predicts risk of adverse drug reactions
What is the primary function of drug transporters in the body?
To move drugs across biological membranes
What is the consequence of decreased expression of influx transporters?
Drugs may accumulate in the extracellular fluid, leading to toxicity
What is the characteristic of SLC transporters?
They do not require ATP to function
What is the consequence of reduced expression of OATP1B1?
Drugs are prevented from entering hepatocytes, increasing plasma concentrations
What is the primary location of drug transporters in the body?
Liver, kidney, and blood-brain barrier
What percentage of drugs are metabolized by CYP2C9?
15%
What is the effect of genetic factors on drug transporters?
They can impact transporter expression and affect efficacy or toxicity
What is the recommended approach for warfarin dosing?
Genotype-based recommendations
What is the function of efflux transporters?
To move drugs out of cells
What is the characteristic of the 'normal function' phenotype?
Combination of normal function alleles and/or decreased function alleles
How does tramadol interact with CYP2D6?
Tramadol is metabolized by CYP2D6
What is the effect of CYP2C9 on the metabolism of NSAIDs?
CYP2C9 metabolizes NSAIDs to inactive metabolites
What is the recommended approach for dosing in PMs taking celecoxib?
Reduce the dose by 25-50%
What is the effect of CYP2C9 on the metabolism of warfarin?
CYP2C9 metabolizes warfarin to inactive metabolites
What is the recommended approach for dosing in IMs taking meloxicam?
Use an alternative agent
What is the effect of phenytoin on the metabolism of other drugs?
Phenytoin activates the metabolism of other drugs
What is the recommended approach for dosing in RMs taking opioids?
Use an alternative agent
What is the effect of codeine on the metabolism of other drugs?
Codeine inhibits the metabolism of other drugs
What is the effect of inhibiting P-glycoprotein (MDR1) on drug levels?
Increased drug intracellular levels
Which of the following medications is metabolized by MDR1?
Cyclosporine
What is the effect of CYP450 inducers on medication levels?
Decrease medication levels
Which of the following is a CYP450 inducer?
Rifampin
What is the effect of grapefruit juice on CYP450?
Inhibits CYP450
Which of the following is a CYP450 inhibitor?
Cimetidine
What are potential consequences of improper drug metabolism?
Metabolic and respiratory acidosis, hyperkalemia
What is the primary function of Phase I reactions in biotransformation?
Unmasking or inserting a polar group to increase water solubility
Which enzyme is responsible for performing Phase I reactions in the liver?
Cytochrome P450 (CYP450) isoenzyme
What is the purpose of Phase III reactions in biotransformation?
Preparation of a drug for excretion into the bile, urine, or other lumens
What is a significant factor that can affect drug metabolism?
Genetic differences in the activity of CYP450
What can happen when two drugs compete for the same metabolic pathway?
Competitive inhibition of CYP450
What is an example of a direct inhibitor of CYP450?
Amiodarone
What is the result of great genetic variability in the activity of enzymes involved in biotransformation?
Individuals may exhibit significant differences in their ability to metabolize the same drug
Study Notes
Opioids and CYP2C9
- Opioids may have reduced efficacy and increased risk of toxicity with CYP2C9 metabolism.
- Tramadol and codeine have decreased efficacy with CYP2C9 metabolism, with increased risk of toxicity due to increased metabolites.
- Hydrocodone and oxycodone have less affected metabolism, but still require dose adjustments.
NSAIDs and CYP2C9
- NSAIDs, such as celecoxib, flurbiprofen, and ibuprofen, have varying effects on CYP2C9 metabolism.
- Celecoxib has higher concentrations and may require dose adjustments.
- Flurbiprofen and ibuprofen may have increased exposure and require dose adjustments.
Warfarin and CYP2C9
- Warfarin has a dosing algorithm that includes genotype-based recommendations.
- CYP2C9 and VKORC1 genetic polymorphisms can affect warfarin metabolism.
- Narrow therapeutic index (TI) can result in large interpatient variability.
Drug Transporters
- Drug transporters, such as OATP1B1, move drugs across biological membranes.
- Genetic factors can impact transporter expression, affecting efficacy or toxicity.
- OATP1B1 is responsible for moving drugs from blood to hepatocytes, and decreased expression can increase plasma concentrations.
Phenytoin and HLA-B*15:02
- Phenytoin has increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with HLA-B*15:02.
- CPIC recommends avoiding use unless benefit outweighs risk.
Carbamazepine and HLA-B*15:02
- Carbamazepine has increased risk of SJS and TEN with HLA-B*15:02.
- CPIC recommends avoiding use unless benefit outweighs risk.
Phases of Biotransformation
- Phase I reactions: change the drug into a polar metabolite, performed by CYP450 isoenzymes in the liver.
- Phase II reactions: conjugation of the metabolite with compounds to increase water solubility.
- Phase III reactions: further processing of the drug, including preparation for excretion and binding to transport proteins.
Factors Affecting Drug Metabolism
- Genetic differences in CYP450 activity.
- Competitive inhibition of CYP450.
- Direct inhibition of CYP450.
- Induction of CYP450.
- Inhibition of P-glycoprotein.
- Amount of blood flow to the liver.
CYP450 Inducers and Inhibitors
- CYP450 inducers: phenytoin, alcohol, rifampin, carbamazepine, griseofulvin, phenobarbital, smoking, and St. John's Wort.
- CYP450 inhibitors: protease inhibitors, azole antifungals, cimetidine, macrolides, amiodarone, nondihydropyridine calcium channel blockers, and grapefruit juice.
This quiz covers the dosage and agents related to opioids. It includes questions on the percentage of opioid doses and their effects. Test your knowledge of opioid agents and their uses.
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