Pharmacokinetics: Clearance and Bioavailability

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Questions and Answers

What does clearance primarily represent in pharmacokinetics?

The rate at which a compound is eliminated from systemic circulation (correct)

The rate at which a drug is absorbed into the bloodstream

The total volume of blood perfusing an organ

The concentration of a drug in the plasma

Which organs are primarily involved in drug clearance?

Heart and lungs

Liver and kidneys (correct)

Lungs and intestines

Liver and stomach

Which statement regarding bioavailability is accurate?

Bioavailability is the quantity of drug eliminated in urine

Bioavailability measures the percentage of a drug that reaches systemic circulation unchanged (correct)

Bioavailability only considers drugs administered intravenously

Bioavailability is determined solely by hepatic metabolism

What factor does NOT affect the bioavailability of orally administered drugs?

Patient metabolic rate Signup and view all the answers

In first order kinetics, which of these statements is true?

A specific percentage of the drug is metabolized over time Signup and view all the answers

What happens during zero order kinetics with a substance like alcohol?

A constant amount of the drug is metabolized over time, regardless of concentration Signup and view all the answers

Which measurement reflects the extent of drug absorption in pharmacokinetics?

Area under the concentration-time curve (AUC) Signup and view all the answers

Which of the following is NOT a route of drug elimination?

Transdermal absorption Signup and view all the answers

What does the calculation for bioavailability involve when comparing oral and intravenous (IV) routes?

Bioavailability equals the ratio of AUC (oral) to AUC (IV) multiplied by 100% Signup and view all the answers

What is the impact of high fiber foods on drug absorption?

They decrease drug absorption. Signup and view all the answers

How does grapefruit juice affect drug metabolism?

It inhibits the metabolism of certain drugs. Signup and view all the answers

Which of the following is a key focus of pharmacogenetics?

Predicting variability in individual responses to drugs. Signup and view all the answers

What distinguishes pharmacogenetic defects from other inborn errors of metabolism?

Pharmacogenetic defects are silent in the absence of drug challenge. Signup and view all the answers

Which statement correctly describes the genetic subdivisions in pharmacogenetics?

Multigenic variants contribute to complex traits such as height. Signup and view all the answers

What role does heritability play in pharmacogenetics?

They vary significantly based on the effects of different drugs. Signup and view all the answers

What is the primary function of high-calorie food in drug absorption?

It more than doubles the absorption of saquinavir. Signup and view all the answers

Which of the following is NOT a characteristic of genetic polymorphisms?

They always lead to visible symptoms of metabolic changes. Signup and view all the answers

Why can some drug effect variabilities be attributed to genetic factors?

Some genetic variants can modify drug metabolism and effects. Signup and view all the answers

What is a major risk associated with polypharmacy?

Adverse drug reactions Signup and view all the answers

Which enzyme family primarily metabolizes a wide range of drugs including beta-adrenoceptor blockers?

Cytochrome P450 Signup and view all the answers

What condition increases the risk of hemolytic drug reactions due to its effect on red blood cells?

G-6-PD deficiency Signup and view all the answers

What percentage of drug-related fatalities involve alcohol in combination with other drugs?

13% Signup and view all the answers

Which statement is true regarding acetaminophen toxicity?

Alcohol can induce microsomal enzymes that increase toxic metabolites of acetaminophen. Signup and view all the answers

What is the maximum tolerated dose (MTD) aimed to evaluate in drug testing?

The highest dose without unacceptable toxicity Signup and view all the answers

Chronic or heavy alcohol use can alter drug responses primarily through which mechanism?

Enzyme induction Signup and view all the answers

Which factor most significantly distinguishes pharmacokinetic changes from pharmacodynamic changes in drug therapy?

Alterations in drug metabolism Signup and view all the answers

What is the effect of tobacco smoke on drug metabolism?

It accelerates drug metabolism Signup and view all the answers

What can be a consequence of metabolizing certain drugs too rapidly due to environmental exposure?

Greater risk of toxicity Signup and view all the answers

Study Notes

Clearance (CL)

Clearance is a critical ADME parameter reflecting the rate at which compounds are removed from systemic circulation.
Primary organs involved are the liver (metabolism and biliary excretion) and kidneys (urinary excretion).
Drug clearance does not change and is a quantitative measure of drug elimination.
Routes of drug elimination include hepatic biotransformation, kidney and bile excretion, exhalation, and fecal excretion.
Clearance is expressed in terms of volume of body fluid cleared of a drug per unit time.

Bioavailability

Bioavailability measures the percentage of unchanged drug entering the systemic circulation post-administration.
AUC (area under the curve) reflects drug absorption and is calculated as:
- Bioavailability = [AUC (oral) / AUC (IV)] x 100%
Factors affecting bioavailability include:
- Drug formulation affecting dissolution time.
- Drug interactions in the GI tract, such as complex formation.
- Biotransformation before entering systemic circulation.

Kinetics of Drug Metabolism

First Order Kinetics:
- Drug metabolism is concentration-dependent with a constant percentage metabolized and constant half-life.
Zero Order Kinetics:
- Metabolism is independent of concentration with a constant amount metabolized; half-life varies, leading to overdose risks with large initial doses (e.g., alcohol).

Polypharmacy

Defined as concurrent use of multiple medications (over five), which can raise the risk of adverse drug reactions.
Important to balance between needed therapies and avoiding unnecessary medications.

Cytochrome P450 (CYP)

A superfamily of membrane-bound hemoprotein isozymes crucial for xenobiotic (e.g., drug) metabolism.
Predominantly functions in the liver, intestines, and kidneys with highest levels in the liver.
Defective metabolism may affect drug dosing significantly (e.g., debrisoquine affected by CYP2D6).

Genetic Factors in Drug Responses

Genetic variations can impact drug metabolism leading to adverse reactions (e.g., G-6-PD deficiency).
Over 400 million people carry G-6-PD deficiency, increasing hemolytic reactions to certain drugs.
Pharmacogenetics helps predict individual drug responses based on genetic makeup.

Therapeutic Misadventures

Alcohol interactions with other medications can lead to toxicity even at so-called "safe" doses.
13% of drug-related fatalities involve alcohol and other drugs.
Anxiolytics are frequently implicated in fatal interactions, particularly regarding respiratory and cardiac functions.

Toxic Interactions

Toxic interactions with substances like alcohol can occur via:
- Physicochemical: Prior to administration.
- Pharmacokinetic: Altered absorption or elimination (e.g., gastric pH, plasma binding).
- Pharmacodynamic: Changes in drug effects on the body (e.g., acetaminophen toxicity leads to acute liver failure).

Dose Determination

Dose impacts whether a substance is beneficial or toxic:
- Example beneficial doses: Aspirin (300-1000 mg), Vitamin A (300-1000 mg), Oxygen (20% air).
- Toxic doses significantly exceed beneficial ones.

Maximum Tolerated Dose (MTD)

MTD refers to the highest dose that produces the desired effect without unacceptable toxicity.
Helps in assessing long-term health effects of chemical exposure without leading to premature mortality.

Environmental Factors in Drug Therapy

Microsomal enzyme inducers (e.g., tobacco smoke) lead to increased drug metabolism rates.
Pollution can also induce P450 enzymes influencing drug efficacy and safety.

Food-Drug Interactions

Certain foods can affect drug absorption:
- Calcium foods inhibit tetracycline absorption.
- High-calorie meals can enhance drug absorption (e.g., saquinavir).
- Grapefruit juice can significantly increase blood levels of drugs like felodipine by inhibiting CYP3A.

Importance of Pharmacogenetics

Aids in identifying individuals' variability in drug responses and optimizing dosage.
Genetic polymorphisms relate to ADME processes - affecting pharmacokinetics and dynamics.
Differences can stem from monogenic (single gene) or multigenic (multiple gene) variations.

Genetic Variants

Monogenic variants often lead to significant drug metabolism issues due to enzyme absence.
Multigenic traits impact complex phenotypes influenced by both genetics and environment.

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Description

This quiz covers essential concepts in pharmacokinetics, focusing on clearance and bioavailability. It examines how drugs are eliminated from the body, the significance of various organs, and the factors influencing bioavailability. Test your understanding of these critical pharmacological parameters.