Drug Metabolism and Conjugation

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Questions and Answers

What is the primary reason for drug metabolism?

To decrease the absorption of the drug

To increase the activity of the drug

To convert the drug to a more polar metabolite for easy excretion (correct)

To increase the distribution of the drug

What type of reaction is responsible for the conversion of enalapril to enalaprilat?

Phase I reaction (correct)

Phase II reaction

Non-synthetic reaction

Synthetic reaction

Which of the following is an example of a drug that is converted to a toxic metabolite?

Paracetamol (correct)

Prednisone

Diazepam

Enalapril

What is the effect of renal disease on pharmacokinetics?

It affects the pharmacokinetics of the drug Signup and view all the answers

What is the role of genetic variability in drug metabolism?

It affects the metabolism of the drug Signup and view all the answers

What is the primary difference between Phase I and Phase II reactions?

Phase I is non-synthetic, while Phase II is synthetic Signup and view all the answers

What is the effect of an enzyme inducer on pharmacokinetics?

It increases the metabolism of the drug Signup and view all the answers

What is the primary location of drug metabolism?

Liver Signup and view all the answers

What is the primary function of the glucuronyl transferase enzyme system?

To convert non-polar drugs to polar metabolites Signup and view all the answers

What is the result of enzyme induction on the metabolism of a drug?

Increased tolerance to the drug Signup and view all the answers

Which of the following is a characteristic of microsomal enzymes?

Liable for induction and inhibition Signup and view all the answers

What is the effect of liver cell failure on biotransformation?

Decreased metabolism of drugs Signup and view all the answers

What is the primary function of cytochrome P450 enzymes?

To catalyze Phase I reactions Signup and view all the answers

Which of the following is an example of a Phase II reaction?

Conjugation of a drug with glucuronic acid Signup and view all the answers

What is the effect of pharmacogenetic variations on biotransformation?

Variable metabolism of drugs Signup and view all the answers

What is the result of enzyme inhibition on the metabolism of a drug?

Decreased metabolism of the drug Signup and view all the answers

What is the consequence of enzyme induction on the metabolism of other drugs?

Increased metabolism of other drugs, leading to failure of therapeutic effect Signup and view all the answers

What is the effect of phenobarbitone on the elimination of bilirubin in neonatal jaundice?

Enhanced elimination of bilirubin Signup and view all the answers

What is the clinical value of enzyme inhibition?

Decreased metabolism of drugs, leading to increased level and risk of toxicity Signup and view all the answers

What is the consequence of rifampicin on the metabolism of oral contraceptives?

Increased metabolism of oral contraceptives, leading to pregnancy Signup and view all the answers

What is the effect of erythromycin on the metabolism of theophylline?

Inhibition of theophylline metabolism Signup and view all the answers

What is the primary route of excretion for most drugs?

Kidney Signup and view all the answers

What is the consequence of enzyme inhibition on the metabolism of warfarin?

Decreased metabolism of warfarin, leading to bleeding Signup and view all the answers

What is the mechanism of overcoming the effects of enzyme induction?

Increase the dose of other drugs Signup and view all the answers

Study Notes

Drug Metabolism (Biotransformation)

Occurs mainly in the liver and also in other organs, such as the intestinal lumen or wall, lung, plasma, skin, and kidney
The main aim is to convert the drug to a more polar (ionized) metabolite, which is easily excreted

Phase I Reactions

Include oxidation, reduction, and hydrolysis
Result in an inactive polar metabolite
Examples: glucuronic acid, glycine, glutathione, and sulfate conjugation

Phase II Reactions

Include glucuronyl transferase and sulfate conjugation
Result in an inactive polar conjugate
Examples: glucuronyl transferase and sulfate conjugation

Enzyme Induction

Certain drugs stimulate the activity and amount of microsomal enzyme systems responsible for metabolism
Reversible, occurs over a few days, and passes off over 2-3 weeks after withdrawal of the inducer
Examples of enzyme inducers: phenobarbitone, phenytoin, carbamazepine, rifampicin, and nicotine
Clinical value:
Increase its own metabolism (→ tolerance)
Increase the metabolism of other drugs metabolized by these enzymes
Increase metabolism of endogenous substrates

Enzyme Inhibition

Certain drugs inhibit the microsomal enzyme systems, leading to a decrease in their activity
Reversible, occurs over a few days, and passes off over 2-3 weeks after withdrawal of the inhibitor
Examples of enzyme inhibitors: chloramphenicol, erythromycin, ciprofloxacin, and valproate
Clinical value: ↓ metabolism of drugs given simultaneously → ↑ level → risk of toxicity

Drug Excretion

The kidney is the most important route of excretion
Other sites for drug excretion:
Lungs (e.g., volatile anesthetics)
Saliva (e.g., iodides)
Bile (e.g., rifampicin)

Factors Affecting Biotransformation

Physiological changes in metabolizing activity due to age and sex
Pathological factors affecting hepatic activity (e.g., liver cell failure)
Pharmacogenetic variations in metabolizing enzymes
Enzyme induction and enzyme inhibition

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Description

This quiz covers the process of drug metabolism, including the conversion of non-polar metabolites to polar conjugates, making them more soluble and easier to eliminate. It also covers the enzymes involved in this process, such as cytochrome P450 and glucuronyl transferase.