pharmocokinetics

Question 1

Q: Why is pharmacokinetics important for drug safety?

Answer 1

A:

Pharmacokinetics is crucial for therapeutic drug monitoring, especially for drugs with a low therapeutic index (TI).
It ensures that plasma concentrations remain above the minimum effective level but below the toxic level, optimizing drug efficacy and minimizing adverse effects.

Question 2

Q: What is the therapeutic window in pharmacokinetics?

Answer 2

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The therapeutic window is the range of drug concentrations in the blood that provides efficacy without causing toxicity.
It lies between the minimum effective concentration and the minimum toxic concentration.

Question 3

Q: What is clearance (Cl) in pharmacokinetics?

Answer 3

:

Definition: Clearance is the volume of plasma from which a drug is completely removed per unit time.
Types: Includes hepatic clearance (liver) and renal clearance (kidneys).
Importance: Indicates how efficiently a drug is eliminated from the body.

Question 4

Q: What is the volume of distribution (Vd)?

Answer 4

A:

Definition: a measure, a Theoretical volume used to describe the extent to which a drug spreads throughout the body. How much space the drug would occupy if it were all present in the same concentration as in the blood plasma
Implications: A larger Vd indicates more extensive distribution into body tissues, while a smaller Vd indicates the drug remains largely in the bloodstream.

Question 5

Q: How does the volume of distribution (Vd) relate to drug lipophilicity?

Answer 5

A:

High Lipophilicity: Drugs with high lipophilicity can easily cross cell membranes, resulting in a higher Vd.
Hydrophilicity: Hydrophilic drugs tend to remain in the plasma, resulting in a lower Vd

Question 6

Q: What is half-life (t1/2) in pharmacokinetics?

Answer 6

A:

Definition: The time required for the concentration of the drug in the plasma to reduce by half.
Significance: Determines the duration of action of a drug and influences dosing intervals.

Question 7

Q: What are Cmax and Tmax in pharmacokinetics?

Answer 7

A:

Cmax: The maximum concentration of a drug in the plasma.
Tmax: The time taken to reach Cmax after drug administration.
Significance: Cmax and Tmax help determine the onset, intensity, and duration of a drug’s effect.

Question 8

Q: How is clearance (Cl) determined?

Answer 8

A:

Measurement: Determined from the area under the plasma concentration-time curve (AUC) following intravenous administration.
Formula: Cl = Dose / AUC.

Question 9

Q: What is the significance of bioavailability (F)?

Answer 9

A:

Definition: The fraction of an administered dose of a drug that reaches the systemic circulation in an active form.
Comparison: Oral bioavailability is compared to the bioavailability of the same dose administered intravenously (F = AUC_oral / AUC_IV).

Question 10

Q: What happens to the concentration of a drug in the body during absorption and elimination?

Answer 10

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Absorption Phase: Drug concentration rises as absorption exceeds elimination.
Peak: Drug concentration peaks when absorption and elimination rates are equal.
Elimination Phase: Drug concentration falls as elimination exceeds absorption.

Question 11

Q: What is the elimination constant (kel)?

Answer 11

A:

Definition: The rate at which a drug is removed from the body.
Determination: Obtained from the slope of the elimination phase on a concentration-time graph.

Question 12

Q: What is the one-compartment model in pharmacokinetics?

Answer 12

A:

Concept: Assumes the body is a single, uniform compartment where the drug distributes instantaneously.
Application: Useful for drugs that distribute rapidly and evenly throughout the body.

Question 13

Q: What is the two-compartment model in pharmacokinetics?

Answer 13

A:

Concept: The body is divided into a central compartment (blood and well-perfused tissues) and a peripheral compartment (less perfused tissues).
Dynamics: Drug distributes between compartments, typically following first-order kinetics.

Question 14

Q: What is the three-compartment model in pharmacokinetics?

Answer 14

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Concept: Adds a third compartment to account for slower distribution phases, such as those involving bone or fat.
Use: For drugs that distribute into deep tissue compartments at different rates.

Question 15

Q: What is population pharmacokinetics?

Answer 15

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Definition: The study of variability in drug concentrations within a patient population receiving clinically relevant doses of a drug.
Goal: To understand how different factors (e.g., age, weight, genetics) affect drug kinetics and to optimize dosing regimens.

Question 16

Q: What is signal transduction in the context of kinase inhibitors?

Answer 16

A:

Definition: Signal transduction is a mechanism within cells by which a signal received at the plasma membrane is transduced to switch on gene transcription in the nucleus.
Process: It involves a ligand (e.g., growth factor or hormone) binding to a membrane receptor with kinase activity, initiating a cascade of intracellular events.
Key Components: Protein kinases mediate phosphorylation, and the actions are terminated by phosphatases.

Question 17

Q: What are kinase pathways and their significance in cancer?

Answer 17

A:

Function: Kinase pathways control the growth and survival of cancer cells and facilitate processes like angiogenesis (formation of new blood vessels).
Target: Inhibiting these pathways can help control the spread and growth of cancer cells.

Question 18

Q: What is imatinib and its therapeutic use?

Answer 18

A:

Type: Tyrosine kinase inhibitor.
Use: Treatment of chronic myelogenous leukemia (CML), characterized by the over-production of granulocytes.
Mechanism: Inhibits the BCR/Abl fusion gene, which drives abnormal kinase activity and tumor growth.

Question 19

Q: What is BCR/Abl and why is it an ideal therapeutic target in CML?

Answer 19

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Definition: BCR/Abl is a fusion gene formed by the translocation of chromosomes 9 and 22.
Function: Drives abnormal kinase activity that stimulates tumor growth.
Significance: Targeting BCR/Abl with kinase inhibitors like imatinib is effective in treating CML.

Question 20

Q: What is hepatocellular carcinoma and its major risk factors?

Answer 20

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Definition: Primary liver cancer.
Risk Factors: Major risk factors include infections with Hepatitis B and C viruses.

Question 21

Q: What is tumor angiogenesis?

Answer 21

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Definition: The process by which tumors send signals to endothelial cells to generate new blood vessels.
Mechanism: Tumors switch on angiogenesis by releasing growth factors that activate receptors on endothelial cells.

Question 22

Q: What is sorafenib and its therapeutic use?

Answer 22

A:

Type: Orally active kinase inhibitor.
Use: Treatment of hepatocellular carcinoma.
Mechanism: Inhibits multiple kinases involved in tumor cell proliferation and angiogenesis.
Metabolism: Primarily metabolized by CYP3A4.

Question 23

Q: What are the adverse effects of imatinib and sorafenib?

Answer 23

A:

Common Adverse Effects: Include hand-foot syndrome (cracked skin, difficulty using hands and feet), other dermal toxicities, and gastrointestinal toxicities.
Specifics: Adverse effects are generally rare but more common with sorafenib. Sorafenib is also the only drug used to treat liver cancer.

Question 24

Q: How do kinase inhibitors like imatinib and sorafenib work?

Answer 24

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Mechanism: They inhibit kinase activity by blocking the ATP-binding site, preventing phosphorylation and downstream signaling.
Result: This inhibition leads to reduced tumor growth and angiogenesis.

Question 25

Q: What is the significance of phosphorylation in signal transduction?

Answer 25

A:

Function: Phosphorylation by protein kinases activates or deactivates proteins, regulating various cellular processes.
Termination: Phosphatases dephosphorylate these proteins, terminating the signal.