Individual Differences in Drug Biotransformation

<p>Competition for substrate binding (B)</p> Signup and view all the answers

<p>Step 6 or 7 (A)</p> Signup and view all the answers

<p>Rifampin (C)</p> Signup and view all the answers

<p>Change in the enzyme's affinity for the drug substrate (A)</p> Signup and view all the answers

<p>By impacting the expression level of the enzyme (C)</p> Signup and view all the answers

<p>Severe unconjugated hyperbilirubinemia (D)</p> Signup and view all the answers

<p>UGT1A1*28 (C)</p> Signup and view all the answers

<p>Swedish people (A)</p> Signup and view all the answers

<p>Toxic buildup of isoniazid (A)</p> Signup and view all the answers

<p>Inconsistencies in drug effectiveness and safety (C)</p> Signup and view all the answers

<p>They usually involve the deletion of one member, not the whole family (C)</p> Signup and view all the answers

<p>It influences enzyme structure and drug efficacy (B)</p> Signup and view all the answers

<p>They metabolize drugs too quickly, reducing efficacy. (C)</p> Signup and view all the answers

<p>Newborns (B)</p> Signup and view all the answers

<p>They induce metabolism of contraceptive hormones, possibly leading to unplanned pregnancies. (A)</p> Signup and view all the answers

<p>They can vary the extent of induction based on dose and exposure. (B)</p> Signup and view all the answers

<p>Significant variability due to genetic polymorphisms. (B)</p> Signup and view all the answers

<p>Potential for drug toxicity due to reduced metabolism. (C)</p> Signup and view all the answers

<p>Plant-based foods containing natural product inducers. (D)</p> Signup and view all the answers

<p>CYP3A4 and CYP2D6 (D)</p> Signup and view all the answers

<p>They can affect both enzyme affinity and amount of effective enzyme. (B)</p> Signup and view all the answers

<p>Induction of drug-metabolizing enzymes at negligible levels. (A)</p> Signup and view all the answers

<p>Inhibiting intestinal CYP3A4 (A)</p> Signup and view all the answers

<p>Erythromycin (A)</p> Signup and view all the answers

<p>Step 1 (A)</p> Signup and view all the answers

<p>They occupy the oxygen-binding site (A)</p> Signup and view all the answers

<p>Flavone (C)</p> Signup and view all the answers

<p>Through competitive inhibition (B)</p> Signup and view all the answers

<p>By altering the enzyme protein structure, potentially changing drug affinity. (B)</p> Signup and view all the answers

<p>Increase in the gene's product due to heightened expression. (D)</p> Signup and view all the answers

<p>Crigler-Najjar syndrome leading to severe hyperbilirubinemia. (C)</p> Signup and view all the answers

<p>It influences drug levels and can result in toxicity due to slow acetylation. (C)</p> Signup and view all the answers

<p>Asian and Native Americans (D)</p> Signup and view all the answers

<p>By modifying the enzyme expression levels of drug-metabolizing enzymes. (B)</p> Signup and view all the answers

<p>Change the structure of the enzyme, impacting substrate binding. (A)</p> Signup and view all the answers

<p>Reduced metabolism, potentially leading to drug toxicity. (A)</p> Signup and view all the answers

<p>UGT1A1*28 (D)</p> Signup and view all the answers

<p>They are at risk for toxicity with standard doses of substrates. (D)</p> Signup and view all the answers

<p>Increase in CYP2D6 activity (B)</p> Signup and view all the answers

<p>Charcoal-broiled food (C)</p> Signup and view all the answers

<p>Inhibition of the therapeutic effects of concurrent medications (C)</p> Signup and view all the answers

<p>Ultra-Rapid metabolizers (URM) have a greater risk of drug dependency. (C)</p> Signup and view all the answers

<p>When using herbal supplements alongside prescribed medication (A)</p> Signup and view all the answers

<p>Decreased stability and activity of the enzyme (A)</p> Signup and view all the answers

<p>Malnourished patients exhibit decreased enzyme activity. (B)</p> Signup and view all the answers

<p>It initiates mRNA synthesis for induced enzymes. (A)</p> Signup and view all the answers

Individual differences in how the body processes drugs due to genetic factors.

Single Nucleotide Polymorphism (SNP) in genes affecting the process of breaking down drugs.

A type of SNP in the coding region of a gene that alters the amino acid sequence of a protein, potentially changing enzyme structure/function.

SNP in a gene's promoter region impacting how much of an enzyme is made.

Variations in the UGT1A1 gene affecting bilirubin breakdown, potentially causing conditions like Gilbert's or Crigler-Najjar syndrome.

Severe condition due to UGT1A1 gene deletion, leading to dangerously high bilirubin levels.

A less severe condition from a reduced UGT1A1 gene, where the body still clears bilirubin but less efficiently.

A variation in NAT2 gene affecting how quickly the body processes certain drugs, like isoniazid.

Individuals who process certain drugs, like Isoniazid, at a slower rate, leading to potential toxicity.

Individuals who metabolize certain drugs quickly.

Drug-metabolizing enzymes are low, especially UGT. Use caution with drugs cleared by glucuronidation.

Drug-metabolizing ability slightly declines with age.

Some drugs increase the activity of other drug-metabolizing enzymes.

Rifampin increases CYP3A4 activity, which can affect how other drugs are metabolized.

Genetic variations in CYP2D6 affect its activity, leading to different responses to drugs.

Individuals with reduced CYP2D6 activity may require lower drug doses to avoid toxicity.

Drugs can sometimes block the action of other drugs by competing for the same metabolic pathway.

Certain illnesses can decrease the activity of drug-metabolizing enzymes.

The amount and/or activity of drug metabolizing enzymes may be different between individuals.

A drug that is metabolized by the CYP3A4 enzyme.

Ritonavir inhibits CYP3A4, preventing the metabolism of indinavir or saquinavir, increasing their blood levels.

Some drugs bind tightly to CYP3A4, preventing it from metabolizing other drugs. This is a longer-lasting binding interaction, compared to reversible binding.

Grapefruit juice inhibits intestinal CYP3A4, reducing drug metabolism, leading to increased drug absorption.

Bioflavonoids, like flavone and naringenin, can inhibit CYP3A4 and/or P-gp transporters by competing for binding sites.

CYP450 can be blocked at various steps; step 1 involves competition, step 3 affects oxygen binding, and steps 6 or 7 involve binding of inhibitory metabolites.

Our genes influence how our body breaks down drugs. Variations in these genes can lead to faster or slower drug processing, affecting drug effectiveness and potential side effects.

Single Nucleotide Polymorphisms (SNPs) are small changes in DNA letters that can affect how drug-metabolizing enzymes work.

A non-synonymous SNP changes an enzyme's amino acid sequence, potentially altering its shape and ability to interact with drugs.

A SNP in the promoter region of a gene can influence how much of a specific drug-metabolizing enzyme is produced.

Variations in the UGT1A1 gene affect bilirubin breakdown. Severe deletions can cause Crigler-Najjar syndrome with dangerous bilirubin build-up, while reduced expression leads to Gilbert's syndrome, often asymptomatic.

Variations in the NAT2 gene influence how quickly the body breaks down drugs like isoniazid used for tuberculosis treatment. Slow acetylators have increased risk of toxicity.

Individuals with slower drug processing due to NAT2 polymorphism may build up a drug in their body, potentially leading to toxicity.

The frequency of slow acetylators varies by population group, with Asians and Native Americans having lower rates compared to Swedish people.

Drug-metabolizing enzymes are less active in newborns and the elderly. This means they may need lower doses or special considerations during drug treatment.

Some drugs or substances (like rifampin) can increase the activity of other drug-metabolizing enzymes (like CYP450).

Tailoring drug therapy to individual patients based on their unique genetic and environmental factors, including their drug biotransformation profile.

Ritonavir is intentionally co-administered with indinavir or saquinavir in AIDS patients to inhibit the metabolism of these drugs by CYP3A4, leading to higher blood levels and improved treatment efficacy.

Some drugs can bind very tightly to CYP3A4, preventing the metabolism of other drugs for a much longer duration, almost as if the binding is 'irreversible.'

Drugs containing an imidazole ring, like ketoconazole, can block CYP3A4 by occupying the oxygen-binding site, preventing the enzyme from functioning properly.

Grapefruit juice inhibits intestinal CYP3A4 and P-gp (P-glycoprotein), reducing drug metabolism and increasing drug absorption, leading to higher drug levels in the body.

Bioflavonoids, like flavone and naringenin, can inhibit CYP3A4 and P-gp by competing for binding sites, leading to decreased drug metabolism and increased drug absorption.

CYP450 can be inhibited at different steps of the metabolic process: Step 1 involves competition, Step 3 involves preventing oxygen binding, and Steps 6 or 7 involve tight binding of inhibitory metabolites.