Pharmacokinetics: L11

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Questions and Answers

What determines the Volume of Distribution (Vd) of a drug?

Total concentration in tissues and plasma binding (correct)

Rate of drug metabolism by the liver

Affinity for receptor sites in the bloodstream

Size of the drug molecule

Which protein is primarily responsible for binding acidic drugs such as warfarin?

Fibrinogen

Alpha-1 acid glycoprotein

Albumin (correct)

Lipoprotein

What is a characteristic of the blood-brain barrier?

It contains tight junctions between endothelial cells (correct)

It allows all drug types to easily pass into the brain

It consists of large pores that facilitate drug diffusion

It is permeable to polar components in the plasma

Which of the following statements about drug entry into the brain is true?

Very lipid-soluble drugs can penetrate the blood-brain barrier Signup and view all the answers

What role do active transporters play in the blood-brain barrier?

Transport essential nutrients into the CNS and waste products out Signup and view all the answers

Which tissue has the highest perfusion rate?

Lungs Signup and view all the answers

What is a key characteristic of well-perfused tissues in drug distribution?

Reach equilibrium more rapidly than poorly perfused tissues Signup and view all the answers

Which of the following factors can affect the extent of drug distribution?

Plasma protein binding Signup and view all the answers

In the case of thiopentone, what primarily causes the cessation of its anesthetic action?

Redistribution into muscle Signup and view all the answers

After thiopentone administration, which phase indicates a rapid effect but a short duration of action?

Redistribution phase Signup and view all the answers

Which of the following poorly perfused tissues has the lowest perfusion rate?

Bone Signup and view all the answers

What effect does liver disease have on drug distribution?

Decreases albumin synthesis Signup and view all the answers

How is the rate of drug partitioning into tissues affected?

By organ blood flow and cardiac output Signup and view all the answers

Which of the following tissues is considered poorly perfused?

Fat Signup and view all the answers

What is the primary reason for differences in drug concentration across various tissues over time?

Perfusion rate variations Signup and view all the answers

What is the primary purpose of metabolism in drug elimination?

To transform lipid-soluble drugs into water-soluble molecules Signup and view all the answers

Which statement accurately describes the relationship between drug metabolism and its metabolites?

The drug is considered eliminated once transformed into its metabolite. Signup and view all the answers

Which of the following factors is least likely to affect drug metabolism?

The time of day the drug is administered Signup and view all the answers

What characterizes Phase 1 drug metabolism?

It introduces functional side groups to drugs. Signup and view all the answers

How does drug metabolism generally impact the therapeutic effect of a drug?

It is independent of the dose administered. Signup and view all the answers

What is the role of oxidation in Phase 1 drug metabolism?

To introduce functional groups into the drug molecule Signup and view all the answers

Which type of molecules requires metabolism for elimination due to their lipid solubility?

Lipid-soluble drugs Signup and view all the answers

What might excessive saturation of drug metabolism enzymes lead to?

Variable responses to drug therapy Signup and view all the answers

Which route is NOT typically associated with the excretion of drug metabolites?

Sweat Signup and view all the answers

In drug elimination, what does the term 'excretion' most accurately refer to?

The physical removal of drugs and metabolites from the body Signup and view all the answers

What does the slope of the distribution phase indicate about drug distribution?

It reflects the rate of drug distribution. Signup and view all the answers

On a logarithmic scale, what can be inferred from the two phases observed in the plasma concentration vs. time graph?

There are distinct phases of distribution. Signup and view all the answers

Which factor is NOT mentioned as influencing the rate of drug distribution?

Body temperature variations. Signup and view all the answers

In the context of drug distribution, what does the phase labeled 'Phase 1' likely represent?

Rapid increase in plasma concentration. Signup and view all the answers

Which term best describes the condition when the amount of drug in the blood and tissues is constant over time?

Equilibrium phase. Signup and view all the answers

What is the significance of the 'elimination slope' in drug plasma concentration graphs?

It shows how quickly the drug is removed from circulation. Signup and view all the answers

In the two-component model of drug distribution, what aspect does the first component primarily relate to?

Initial distribution of the drug. Signup and view all the answers

Which option best describes the overall trend noted in the plasma concentration when comparing linear and logarithmic scales?

Only logarithmic scale effectively demonstrates distribution phases. Signup and view all the answers

What is the role of levodopa in the treatment of Parkinson's disease?

It serves as a precursor to dopamine. Signup and view all the answers

Why is levodopa administered instead of dopamine in treating Parkinson’s disease?

Dopamine cannot cross the blood-brain barrier. Signup and view all the answers

What is the primary function of carbidopa in the treatment regimen including levodopa?

To inhibit dopa-decarboxylase and reduce peripheral conversion. Signup and view all the answers

How do lipid-soluble drugs differ from water-soluble drugs in terms of plasma binding?

Lipid-soluble drugs have a higher affinity for protein binding. Signup and view all the answers

What is meant by the 'distribution rate' of a drug?

The time taken between dosing and equilibrium of plasma and tissues. Signup and view all the answers

Which characteristic of levodopa enhances its ability to cross the blood-brain barrier?

It is less polar than dopamine. Signup and view all the answers

In the context of drug distribution, what does 'extent' refer to?

The ratio of drug concentration in tissues compared to plasma. Signup and view all the answers

What is a consequence of giving high doses of levodopa in treatment?

Increased risk of side effects. Signup and view all the answers

Study Notes

Pharmacology Lecture 3: Pharmacokinetics

Distribution Continued: The rate and extent of a drug moving from blood to tissues, and back to blood during elimination, are crucial aspects of pharmacokinetics.

Interactions Affecting Drug Distribution

Plasma and Tissue Binding: Acidic drugs bind to albumin (e.g., warfarin), while basic drugs bind to alpha-1-acid glycoprotein (e.g., propranolol). Free drug (unbound) is the active form. The volume of distribution (V_d) depends on total in tissues or tissue binding compared to total in plasma or plasma binding.

Blood-Brain Barrier (BBB)

Physiological Basis: The BBB is a homeostatic mechanism maintaining a constant central nervous system (CNS) environment. It prevents polar plasma components from entering the brain. Small membrane pores, tight junctions, and active transporters play critical roles. Essential nutrients and P-glycoprotein are part of this system.
Area Postrema: This region lacks a BBB and directly responds to circulating chemicals, initiating emesis (vomiting).
Drug Entry into Brain: Lipid-soluble drugs enter the brain more rapidly (e.g., thiopentone) than water-soluble drugs (e.g., salicylate).

Parkinson's Disease

Dopamine Pathway: Dopamine in the substantia nigra is essential for dopaminergic activity in the nigrostriatal pathway. However, dopamine itself does not cross the BBB, leading to the lack of therapeutic effect.
Levodopa: Levodopa is a precursor to dopamine, enabling it to cross the BBB for therapeutic use. The amino acid structure allows it entry.
Carbidopa: Carbidopa is used with levodopa to prevent premature conversion into dopamine in the periphery.

Parkinson's Disease cont.

Mechanism of action: Levodopa- Carbidopa combinations allow Dopa Decarboxylase to function effectively in the brain to increase Dopamine.

Drug Distribution

Rate and Extent: RATE describes the time taken for plasma and tissue equilibrium, while EXTENT compares drug concentration in tissues to plasma at equilibrium.
Distribution Profiles: Well-perfused tissues equilibrate rapidly with blood. Conversely, poorly perfused tissues show a slower equilibration rate. This accounts for differences in drug distribution in different parts of the body.

Elimination

Definition: Elimination removes drugs from the body through metabolism or excretion into various body fluids (liquid, solid or gaseous waste).

Metabolism

Process: Lipid-soluble drugs must be metabolised for easier elimination, otherwise they cannot be easily eliminated and remain active in the body.
Requirement: Metabolism transforms lipid-soluble drugs into water-soluble metabolites, for easier elimination (e.g., through the urine)

Drug Routes of Excretion:

Various ways in which drugs are excreted include exhalation, urine, bile etc.

Drug Metabolism

Removal and Effect: The conversion of the drug into an inactive metabolite is recognized as removal from the body. The rate of metabolism dictates the duration of a drug's therapeutic effect, as metabolites are inactive.

Factors Affecting Drug Metabolism

Variations Impact: Drug metabolism can be affected by age, sex, ethnic origins, and disease state. Enzyme saturation and other pharmacokinetic processes are usually not affected at therapeutic doses.

Phases of Drug Metabolism

Phase 1: Oxidation, reduction, or hydrolysis reactions introduce functional groups to the drug molecule for better metabolism.
Phase 2: Conjugation reactions create covalent bonds between Phase 1 metabolites and endogenous substrates (e.g., glucuronic acid). This process transforms the drug into a water-soluble metabolite for easier excretion.

Phase 1 Reactions

List of Oxidative reactions: Detailed descriptions and reactions for oxidation reactions during the initial stage of drug metabolism, emphasizing the importance of these processes.

Radioactivity and Tissue Distribution

Areas of Radioactivity: The light areas on imaging represent high drug concentrations. This example shows the distribution of a drug throughout the body.

Drug Distribution Graph:

Interpretation and Two Phases: The IV bolus graph on a linear scale shows two phases. A logarithmic plot demonstrates clear differences in rate between tissues, influenced by their relative blood perfusion.

Thiopentone

Distribution Profile: Thiopentone, a short-acting anesthetic, quickly reaches peak effect after intravenous administration. It rapidly distributes from the blood, but the duration of its effect is quite short due to rapid metabolic degradation and redistribution to other tissues.

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Description

Test your knowledge on the principles of pharmacokinetics, focusing on the Volume of Distribution (Vd) and the various factors that influence drug distribution in the body. Explore topics including protein binding, the blood-brain barrier, and the effects of perfusion rates on drug action.