Pharmacokinetics: Drugs Metabolism

Question 1

What are the sites of drug metabolism?

Answer 1

Liver, kidney, GI tract, lungs, skin.

Question 2

Define metabolism.

Answer 2

The processes by which a drug is chemically altered in a way that facilitates its action or enhances its elimination from the body.

Question 3

What is the main goal of metabolism?

Answer 3

The main goal of metabolism is to chemically alter a drug to produce metabolites that can have therapeutic or toxic effects, or to convert inactive drugs into pharmacologically active compounds.

Question 4

What are the two phases of drug metabolism?

Answer 4

Phase I reactions (oxidation/reduction) and Phase II reactions (conjugation/hydrolysis).

Question 5

What enzymes are involved in Phase I reactions of drug metabolism?

Answer 5

Cytochrome P450 enzymes.

Question 6

What enzymes are involved in Phase II reactions of drug metabolism?

Answer 6

Multiple enzyme types are involved in Phase II reactions

Question 7

What is the superfamily of enzymes that metabolizes more than 75% of drugs used in medicine?

Answer 7

Cytochrome P450 enzymes.

Question 8

What analogy can be used to understand metabolism?

Answer 8

Think of metabolism as essays and markers. The essays are substances that need to be marked, and the markers represent enzymes involved in metabolism.

Question 9

Which organ is considered the biggest pool of markers in the metabolism analogy?

Answer 9

The liver.

Question 10

What is the CP450 system in the metabolism analogy?

Answer 10

It represents the group of all markers involved in metabolism.

Question 11

In the metabolism analogy, what does each marker (enzyme) represent?

Answer 11

each marker represents a specific enzyme, such as CYP2D6.

Question 12

How do different markers (enzymes) in the metabolism analogy function?

Answer 12

Different markers (enzymes) can mark different topics of essays, which means that different isoenzymes metabolize different compounds.

Question 13

What are some factors that can affect metabolism?

Answer 13

Examples include race and ethnicity, functional capacity (age, biological sex, pathologies), environment (stress, temperature, pollution), nutrition, interactions (induction/inhibition), and genetics (pharmacogenetics/pharmacogenomics).

Question 14

How does inhibition affect metabolism in the metabolism analogy?

Answer 14

nhibition refers to having fewer markers available (off sick, small team), leading to slower metabolism.

Question 15

How does induction affect metabolism in the metabolism analogy?

Answer 15

Induction refers to having more markers available (bigger team, volunteers, recruitment), resulting in faster metabolism.

Question 16

What is the effect of enzymatic inhibition on metabolism?

Answer 16

Enzymatic inhibition leads to slower metabolism.

Question 17

What is the effect of enzymatic induction on metabolism?

Answer 17

Enzymatic induction results in faster metabolism.

Question 18

What are the consequences of inhibition or induction on plasma concentration over time?

Answer 18

Inhibition leads to higher plasma concentrations over time, while induction results in lower plasma concentrations over time.

Question 19

What are the potential outcomes of inhibition or induction in terms of drug toxicity?

Answer 19

Inhibition can increase the risk of drug toxicity, while induction may reduce the risk of toxicity.

Question 20

Give an example of a drug that acts as an inhibitor of the CP450 system.

Answer 20

Amiodarone, ciprofloxacin, erythromycin/clarithromycin, metronidazole, and fluconazole are examples of inhibitors of CP450

Question 21

Give an example of a drug that acts as an inducer of the CP450 system.

Answer 21

Carbamazepine, phenytoin, rifampicin, alcohol (chronic use), isoniazid, and grapefruit juice are examples of inducers of CP450.

Question 22

What are some factors that can influence enzymatic induction or inhibition?

Answer 22

Genetic and environmental factors, diet, drugs, medical conditions, and first-pass metabolism can influence enzymatic induction or inhibition.

Question 23

What are some potential outcomes of enzymatic induction or inhibition?

Answer 23

Enzymatic induction or inhibition can affect the therapeutic effect, toxicity, metabolism rate, first-pass metabolism, and bioavailability of a drug.

Question 24

What happens if a drug is a prodrug in the context of enzymatic inhibition or induction?

Answer 24

Enzymatic inhibition or induction can impact the conversion of a prodrug into its active form, affecting its therapeutic effectiveness.

Question 25

What is the process through which a swallowed drug undergoes metabolism?

Answer 25

A swallowed drug passes through the digestive system, enters the hepatic portal system, gets metabolized in the liver, and then reaches the rest of the body.

Question 26

What is “first-pass” metabolism?

Answer 26

First-pass metabolism refers to the initial metabolism of a drug in the liver before it reaches the systemic circulation. This can result in a reduction of the drug’s concentration and effectiveness.

Question 27

How can genetic polymorphisms affect drug metabolism?

Answer 27

Genetic polymorphisms in drug metabolizing enzymes can result in different phenotypes, leading to variations in how individuals handle drugs. This can impact the efficacy and safety of medications.

Question 28

What are the different phenotypes associated with genetic polymorphisms in drug metabolism?

Answer 28

The phenotypes include extensive metabolizers (normal alleles), ultrarapid metabolizers (duplication of normal alleles), intermediate metabolizers (one normal allele and one abnormal allele), and poor metabolizers (two abnormal alleles).

Question 29

What is codeine metabolized into, and what is the significance of this metabolite?

Answer 29

Codeine is metabolized into morphine, which is much stronger and responsible for the pain-relieving effects of codeine.

Question 30

Which enzyme is responsible for the metabolism of codeine into morphine?

Answer 30

The enzyme CYP2D6, which belongs to the CP450 system, is responsible for the conversion of codeine to morphine.

Question 31

What percentage of Caucasians have a non-functional CYP2D6 variant?

Answer 31

Approximately 7% of Caucasians have a non-functional CYP2D6 variant, which affects their ability to metabolize codeine effectively.

Question 32

What are the implications for poor metabolizers of codeine?

Answer 32

Poor metabolizers may experience inadequate pain relief when taking codeine due to their impaired ability to convert it to morphine.

Question 33

What percentage of individuals are classified as CYP2D6 ultrarapid metabolizers, and what risk do they face?

Answer 33

Less than 2% of individuals are classified as CYP2D6 ultrarapid metabolizers. They may be at risk of opioid intoxication when taking codeine due to their faster metabolism of the drug.

Question 34

What updates were made in 2019/20 regarding codeine use?

Answer 34

A CYP2D6 genetic test is recommended for optimizing therapy with codeine, tramadol, and hydrocodone. It is advised to avoid these drugs in ultrarapid or poor metabolizers. Additionally, codeine is contraindicated in children and breastfeeding mothers.