Pharmacokinetics 2: Drug Metabolism and Elimination

Flashcards covering key concepts in pharmacokinetics, focusing on drug metabolism, volume of distribution, elimination, and pharmacokinetic parameters.

What is volume of distribution (Vd)?

The volume into which the drug appears to be uniformly distributed at the concentration measured in the plasma.

How is volume of distribution (Vd) determined?

By measuring plasma concentration immediately after administering a known dose.

What does a large volume of distribution indicate?

The drug has left the plasma and is likely found in body fat or highly bound to tissues.

What is the volume of distribution (Vd) of digoxin?

640 L.

What does a small volume of distribution indicate?

The drug is confined to plasma, often due to high plasma protein binding.

What is the volume of distribution (Vd) of warfarin?

10 L.

What is steady-state plasma concentration (Css)?

When the rate of drug going into the body equals the rate going out.

What is a loading dose?

A high single dose used to rapidly establish a desired plasma concentration (Cp).

How is a loading dose calculated?

Loading Dose = Target Css x Vd.

Why is drug metabolism necessary?

It transforms lipophilic substances into more water-soluble metabolites for excretion.

What are the two phases of drug metabolism?

Phase I reactions (small modifications) and Phase II reactions (conjugation reactions).

What is primarily responsible for Phase I metabolism?

The cytochrome P450 (CYP450) superfamily.

Where are CYP450 enzymes primarily located?

In the liver, with minor contributions from the kidney, lung, and skin.

What does 'constitutive' mean in enzyme terminology?

Synthesis of enzyme at a constant rate.

What does 'inducible' mean in enzyme terminology?

Enzyme number and activity increases following exposure to a drug.

What is 'competitive inhibition'?

When another compound blocks the enzyme's active site, inhibiting substrate metabolism.

Give an example of a drug that is a substrate of CYP3A4.

Cyclosporin.

What is the result of taking St John’s Wort with cyclosporin?

It can lead to acute tissue rejection due to increased metabolism of cyclosporin.

What happened to the cancer patient treated with fentanyl and verapamil?

The patient experienced respiratory depression due to increased fentanyl metabolism.

What is the concept of drug elimination?

The removal of drugs from the body, often described in terms of renal clearance.

What is the majority route of drug excretion?

Renal excretion.

What influences the elimination rate of a drug?

It is proportional to the concentration of the drug.

What are first-order kinetics in drug elimination?

The rate of elimination is proportional to the drug concentration.

What does half-life refer to in pharmacokinetics?

The time taken for the plasma concentration of a drug to fall by half.

How is renal clearance (Clren) calculated?

Clren = Cu x Vu / Cp, where Cu is concentration in urine, Vu is rate of urine production, and Cp is plasma concentration.

What is zero-order kinetics?

When some drugs are metabolized at a constant rate, regardless of concentration.

What example is given for zero-order kinetics?

Ethanol, which is metabolized at a constant rate of approximately 10 g/hr.

What is the average elimination rate of ethanol?

Produces a linear elimination rate.

What happens when drug elimination follows zero-order kinetics?

The elimination rate remains constant, not proportional to the concentration.

What can cause a decrease in renal clearance?

A low glomerular filtration rate (GFR) due to kidney disease.

What does a high volume distribution (Vd) suggest about a drug's characteristics?

It suggests the drug has a tendency to distribute widely in body tissues.

What factors can influence the pharmacokinetics of a drug in the body?

Drug interactions, metabolic pathways, and individual patient characteristics.

Why is understanding pharmacokinetics important in medicine?

It helps optimize drug therapy and minimize adverse drug reactions.

What happens to phase I metabolites during phase II reactions?

They undergo conjugation reactions, usually resulting in larger, more water-soluble compounds.