Pharmacology Drug Distribution

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Questions and Answers

What characterizes a drug with a single compartment distribution?

It passes freely across cell membranes.

It has low molecular weight.

It is primarily water soluble.

It is confined to the plasma. (correct)

Which of the following drugs is likely to have a two-compartment distribution?

Barbiturates

Insulin (correct)

Heparin

Thiopentone

What type of distribution pattern allows drugs to pass through cell membranes?

Single compartment

Two compartments

Multi-compartment (correct)

Tissue reservoirs

Which factor can increase the apparent volume of distribution (Vd) of a drug?

Renal failure Signup and view all the answers

What is the correct formula to calculate the amount of drug in the body (M)?

M = Vd x C Signup and view all the answers

Which of the following statements about tissue reservoirs is true?

Arsenic is stored in hair. Signup and view all the answers

Which characteristic is associated with drugs that have small volumes of distribution (Vd)?

They are highly bound to plasma proteins. Signup and view all the answers

Which among the following substances is known to be a tissue reservoir for calcium?

Bone Signup and view all the answers

Which of the following statements about drug binding to plasma proteins is true?

The protein bound fraction acts as a depot form. Signup and view all the answers

What effect do aspirin and phenytoin have on drug interactions related to plasma protein binding?

They displace drugs from their protein binding sites. Signup and view all the answers

Which type of drugs can easily cross the Blood Brain Barrier (BBB)?

Lipid soluble, non-ionized drugs. Signup and view all the answers

Which statement regarding the effects of meningitis on the BBB is correct?

Meningitis increases the permeability of the BBB. Signup and view all the answers

Which substances can cross the Blood Brain Barrier by active transport?

Glucose, vitamins, and amino acids. Signup and view all the answers

Which of the following is a characteristic of the endothelial cells in brain capillaries?

They contain more mitochondria than other endothelial cells. Signup and view all the answers

What type of drugs are least likely to pass through the placental barrier?

Water soluble drugs. Signup and view all the answers

What is a consequence of drugs that extensively bind to plasma proteins?

Decreased pharmacological activity. Signup and view all the answers

Study Notes

Drug distribution

After uptake, drugs are distributed to different tissues and body fluids: Plasma, interstitial fluid, intracellular fluid.
Four patterns of drug distribution:
- Single compartment (intravascular):
  - Drug stays in the blood compartment.
  - Examples: Heparin, dextran.
  - These drugs bind to plasma protein.
- Two compartments (intravascular + interstitial):
  - Drugs cross capillary walls but not cell membranes.
  - Localized in extracellular fluid.
  - Examples: Insulin, quaternary ammonium compounds, electrolytes.
- Multi-compartment (extracellular + intracellular):
  - Drugs can pass through cell membranes, are lipid-soluble, and have low molecular weight.
  - Examples: Barbiturates, tertiary amines.
- Tissue reservoirs:
  - Some drugs accumulate in specific tissues.
  - Examples:
    - Hair: Arsenic
    - Thyroid: Iodine
    - Bone: Calcium
    - Fat: Thiopental
    - Liver: Chloroquine

Apparent Volume of Distribution (Vd)

Vd is a term used to quantify how a drug distributes between plasma and the rest of the body.
It represents a hypothetical volume where the drug is distributed to reach the estimated concentration.
Vd can be calculated: Vd = Total amount of drug in the body / Plasma concentration of the drug.
The amount of drug in the body can be estimated: M = Vd x C
Factors affecting Vd:
- Increased Vd: Renal failure (fluid retention), liver failure (increased body fluid, decreased plasma protein binding).
- Decreased Vd: Dehydration.
Relationship between Vd and drug binding:
- High plasma protein binding: Small Vd.
- High tissue protein binding: High Vd.
- Digoxin has a slow clearance and does not require dialysis due to its low Vd.

Drug Binding to Plasma Proteins

Most drugs bind to plasma proteins reversibly.
Albumin is the major binding protein.
Bound fraction:
- Pharmacologically inactive.
- Not active.
- Not filtered.
- Not metabolized.
- Not excreted.
- Serves as a drug depot.
Free fraction:
- Active.
- Filtered.
- Metabolized.
- Excreted.
Examples of drugs extensively bound to plasma proteins:
- Phenylbutazone.
- Dicoumarol.
- Tolbutamide.
- Long-acting sulfonamides.
- Thiopental.
- Diazoxide.

Aspirin, phenytoin, sulfonamides can displace drugs from their protein binding sites, leading to:
- Increased free drug concentration.
- Increased risk of adverse effects.
- Examples:
  - Oral anticoagulants (e.g., Warfarin): Hemorrhage.
  - Oral hypoglycemic agents (e.g., Tolbutamide): Hypoglycemia.
  - Bilirubin in newborns: Jaundice and kernicterus.

Passage of Drugs to the Central Nervous System (CNS)

Blood-brain barrier (BBB) limits drug entry to the CNS.
BBB is a lipid barrier composed of:
- Brain capillary endothelium: Lacks water channels.
- Adjacent glial tissue.
Only lipid-soluble (non-ionized) drugs can pass the BBB along their concentration gradient.
Inflammation (meningitis, encephalitis) increases BBB permeability, allowing agents like penicillin to enter the CNS.
BBB characteristics:
- Tight junctions: High electrical resistance, preventing ion passage.
- No fenestrae (pores).
- Minimal pinocytosis.
- Only water, small lipophilic molecules, and actively transported substances can cross.
- Brain capillary endothelial cells have 2-4 times more mitochondria than other endothelial cells to maintain electrochemical gradients and tight junctions.

Passage of Drugs to the Fetus

Lipid-soluble (non-ionized) drugs can cross the placental barrier.
Drugs that pass the placenta poorly:
- Water-soluble drugs.
- Drugs with high molecular weight.
- Drugs actively transported out of the fetus.

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Description

This quiz covers the various patterns of drug distribution in the body, including single, two, and multi-compartment systems as well as tissue reservoirs. Understand how drugs are distributed to plasma, interstitial fluids, and intracellular fluids with the help of specific examples. Test your knowledge on pharmacokinetics and the behavior of drugs within different compartments.