1: An introduction P450 enzyme metabolism of drugs

Question 1

What role do P450 enzymes play in drug metabolism?

Answer 1

These enzymes break down water insoluble drugs into water soluble metabolites that ar easily absorbed into the bloodstream.

Question 2

Name one specific P450 enzyme commonly involved in drug metabolism.

Answer 2

Cytochrome P450, CYP3A4

Question 3

Define the therapeutic window of a drug.

Answer 3

It is the drug dosage concentration range at which a drug is most efficient with minimal side effects.

Question 4

Why is it important for a drug’s concentration to fall within the therapeutic window for optimal efficacy and safety?

Answer 4

maintaining a drug’s concentration within the therapeutic window is crucial for achieving the desired therapeutic effects while minimizing the risk of adverse events. It requires careful dosing, monitoring, and individualized approaches to drug therapy.

Question 5

With repeated doses, why would
i. The drug reach toxic levels,
ii. The drug concentration drop below an
effective level?

Answer 5

i ) The person who was administrated the drug might be a slow metabolizer, which could lead to the accumulation of the drug and reaching toxic levels.
Drug-to-drug interactions

ii ) Poor absorption
Fast metabolizer
drug to drug interactions
Inducer of the CYP enzymes -Increase CYP synthesis

Question 6

Given your knowledge of CYP metabolism of drugs, what could cause drug
toxicity

Question 7

Given your knowledge of CYP metabolism of drugs, what could cause the drug
failure

Question 8

How can subtherapeutic drug concentrations affect treatment outcomes?

Question 9

What are the potential consequences of having excessive drug concentrations in the body?

Question 10

What does it mean if a drug has a therapeutic index of 2?

Question 11

what is the therapeutic index?

Question 12

If there are substantial changes in hepatic metabolism
of a drug, why is the time frame for toxicity much
shorter and potentially more dangerous?

Question 13

Define drug clearance.

Question 14

How does renal clearance differ from hepatic clearance in the context of drug elimination?

Question 15

How is toxicity generally defined in the context of drug effects?

Question 16

Explain the idea that “harm” from drugs can vary in terms of severity and reversibility.

Question 17

In terms of dosage, how does the potential for harm generally change as drug dosage increases?

Question 18

Define the therapeutic index (TI) and explain its significance in assessing drug safety.

Question 19

How is the therapeutic index calculated, and what does it represent in terms of drug dosage?

Question 20

How can understanding concentration disparities contribute to drug safety and dosing considerations?

Question 21

Discuss the relationship between the effective dose and toxic dose in determining the therapeutic index.

Question 22

How does the therapeutic index help clinicians make decisions about drug dosage and safety?

Question 23

How does renal clearance differ from hepatic clearance in the context of drug elimination?

Question 24

What is meant by the term “first-pass metabolism” in drug administration?

Question 25

How does the first-pass effect influence the bioavailability of orally administered drugs?

Question 26

Identify and explain the barriers to a drug entering the systemic
blood stream.

Question 27

Briefly describe the metabolic processes involved in the first pass of a drug that can
lead to a relatively low concentration of the drug reaching circulation.