pharmocokinetics Flashcards
Q: Why is pharmacokinetics important for drug safety?
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.
Q: What is the therapeutic window in pharmacokinetics?
A:
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.
Q: What is clearance (Cl) in pharmacokinetics?
:
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.
Q: What is the volume of distribution (Vd)?
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.
Q: How does the volume of distribution (Vd) relate to drug lipophilicity?
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
Q: What is half-life (t1/2) in pharmacokinetics?
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.
Q: What are Cmax and Tmax in pharmacokinetics?
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.
Q: How is clearance (Cl) determined?
A:
Measurement: Determined from the area under the plasma concentration-time curve (AUC) following intravenous administration.
Formula: Cl = Dose / AUC.
Q: What is the significance of bioavailability (F)?
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).
Q: What happens to the concentration of a drug in the body during absorption and elimination?
A:
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.
Q: What is the elimination constant (kel)?
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.
Q: What is the one-compartment model in pharmacokinetics?
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.
Q: What is the two-compartment model in pharmacokinetics?
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.
Q: What is the three-compartment model in pharmacokinetics?
A:
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.
Q: What is population pharmacokinetics?
A:
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.
Q: What is signal transduction in the context of kinase inhibitors?
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.
Q: What are kinase pathways and their significance in cancer?
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.
Q: What is imatinib and its therapeutic use?
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.
Q: What is BCR/Abl and why is it an ideal therapeutic target in CML?
A:
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.
Q: What is hepatocellular carcinoma and its major risk factors?
A:
Definition: Primary liver cancer.
Risk Factors: Major risk factors include infections with Hepatitis B and C viruses.
Q: What is tumor angiogenesis?
A:
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.
Q: What is sorafenib and its therapeutic use?
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.
Q: What are the adverse effects of imatinib and sorafenib?
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.
Q: How do kinase inhibitors like imatinib and sorafenib work?
A:
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.
Q: What is the significance of phosphorylation in signal transduction?
A:
Function: Phosphorylation by protein kinases activates or deactivates proteins, regulating various cellular processes.
Termination: Phosphatases dephosphorylate these proteins, terminating the signal.
