Pharmacokinetics 2

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Questions and Answers

What is a potential outcome of genetic polymorphisms in drug-metabolizing enzymes?

Decreased risk of drug-drug interactions

Increased systemic clearance of drugs

Uniform therapeutic effects across the population

Altered metabolite profiles leading to toxicity (correct)

Which of the following best describes pharmacogenomics?

The study of drug formulations and their chemical properties

The study of genetic variations influencing drug responses (correct)

The investigation of nutrient interactions with drugs

The analysis of drug metabolism through enzyme inhibition

How does a genetic factor like being an ultrarapid metabolizer affect drug therapy?

Lower risk of adverse drug reactions

Increased drug toxicity due to excessive drug accumulation

Higher likelihood of therapeutic failure due to rapid clearance (correct)

Uniform drug response in all individuals

Which enzyme's genetic variations are notably involved in warfarin metabolism?

CYP2C9 Signup and view all the answers

What impact does enzyme inhibition have on co-administered drugs?

It increases the risk of adverse reactions Signup and view all the answers

What is a notable characteristic of poor metabolizers in drug therapy?

They are at higher risk for drug accumulation and toxicity. Signup and view all the answers

Which factor does NOT typically affect age-related drug metabolism?

Increased muscle mass Signup and view all the answers

Which of the following drugs is a known competitive inhibitor affecting microsomal enzyme activity?

Ketoconazole Signup and view all the answers

Which factor is least likely to affect the biotransformation of drugs in patients with advanced age?

Genetic predisposition Signup and view all the answers

What is the primary consequence of enzyme induction on drug metabolism?

Accelerated metabolism of both the inducing drug and others Signup and view all the answers

Which of the following statements best describes the impact of CYP2D6 enzyme variations?

They can lead to variable drug responses among individuals. Signup and view all the answers

How does genetic polymorphism affect drug metabolism?

It can cause different individuals to metabolize drugs at differing rates. Signup and view all the answers

Which disease condition is most likely to decrease the metabolism of drugs by affecting hepatic blood flow?

Cirrhosis Signup and view all the answers

What is one potential outcome of drug-drug interactions caused by enzyme induction?

Therapeutic failure due to reduced drug action duration Signup and view all the answers

Which factor does NOT typically enhance drug biotransformation?

Higher plasma protein binding capacity Signup and view all the answers

What role do hepatic transporters play in drug metabolism?

They determine the rate at which drugs enter hepatocytes for metabolism. Signup and view all the answers

What is the primary role of the CYP2D6 enzyme in relation to codeine?

It converts codeine into morphine. Signup and view all the answers

What is a significant risk associated with ultrarapid CYP2D6 metabolizers when using codeine?

Higher-than expected levels of morphine in breast milk. Signup and view all the answers

Why is pharmacogenomics important for personalized medicine?

It allows for customized drug therapy to improve outcomes. Signup and view all the answers

What factor contributes to the slower reactions of drug metabolism in young children and the elderly?

Underdeveloped organ systems. Signup and view all the answers

What condition is caused by a deficiency in the bilirubin-conjugating enzyme UGT in neonates?

Hyperbilirubinemia. Signup and view all the answers

What percentage of Caucasians are estimated to be poor CYP2D6 metabolizers?

5-10% Signup and view all the answers

What does the term 'personalized medicine' refer to in the context of pharmacogenomics?

Using genetic information to tailor drug therapy for individual needs. Signup and view all the answers

How does the blood-brain barrier (BBB) affect neonates in relation to drug metabolism?

An immature BBB increases susceptibility to drug toxicity. Signup and view all the answers

Study Notes

Enzyme Induction

Drug toxicity can increase due to enzyme induction; for instance, rifampicin can heighten hepatotoxicity risk when combined with paracetamol by increasing toxic intermediate metabolites.
Tolerance development is seen with certain drugs like carbamazepine, which induces its own metabolism, necessitating dosage adjustments over time.

Enzyme Inhibition

Some drugs can inhibit microsomal enzyme activity, resulting in significant drug-drug interactions; ketoconazole is an example that competitively inhibits the metabolism of co-administered drugs.
Grapefruit juice can also act as an enzyme inhibitor, impacting drug metabolism.
Omeprazole is a potent inhibitor of CYP isozymes, affecting warfarin metabolism and increasing plasma warfarin concentrations, leading to increased bleeding risks.

Genetic Factors

Genetic polymorphisms such as SNPs and gene deletions can alter drug metabolism efficacy or cause adverse drug reactions, classifying individuals as "ultrarapid" or "poor" metabolizers.
Genetic variations in drug-metabolizing enzymes can result in decreased systemic clearance, altered metabolite profiles, increased drug-drug interactions, and modifications in therapeutic effects.

Pharmacogenomics

Pharmacogenomics studies genetic variations affecting individual drug responses, aiming for personalized medicine by tailoring drug therapy to individual genetic profiles.
Codeine requires conversion to morphine by CYP2D6 for analgesic effects—poor metabolizers may experience inadequate pain relief, while ultrarapid metabolizers face higher risks of opioid toxicity.

Factors Affecting Drug Biotransformation

Drug entry into the liver is influenced by plasma protein binding, hepatic transporters, and conditions that reduce blood flow.
Plasma protein binding can significantly affect drug metabolism—conditions like uremia and inflammation may alter binding capacities of proteins such as albumin and α1-acid glycoprotein.
Hepatic transporters, such as OATP1B1, are crucial for effective drug uptake; for example, pravastatin metabolism relies on this transporter.

Age

Biotransformation reactions are generally slower in young children and the elderly. Neonates can perform certain oxidative reactions at birth, but their enzyme systems mature gradually.
Neonatal jaundice occurs due to UGT enzyme deficiency, leading to hyperbilirubinemia, particularly in premature infants. This condition is complicated by their underdeveloped enzyme activity and immature blood-brain barrier.

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