Pharmacology Chapter on Drug Distribution

Drug Distribution

• Drug distribution is the movement of a drug from the bloodstream into the interstitial fluid and/or tissues.
• Factors influencing drug distribution include blood flow, capillary permeability, protein binding, and tissue binding.

Blood Flow

• Blood flow varies between tissues, impacting drug distribution.
• Organs like the brain, liver, and kidney receive more blood flow than skeletal muscles.
• Adipose tissue has lower blood flow.
• High blood flow and lipid solubility allow drugs like thiopental to rapidly reach the central nervous system (CNS) for anesthesia.

Capillary Permeability

• Capillary structure varies depending on the junctions between endothelial cells.
• The blood-brain barrier (BBB) is formed by tight junctions between endothelial cells and surrounding glial cells.
• Only lipid-soluble, unionized drugs can cross the BBB.
• The placental barrier allows lipid-soluble, unionized drugs to pass through, potentially affecting the fetus.

Drug Binding

Plasma Protein Binding

• Most drugs in the bloodstream bind to plasma proteins, primarily albumin for acidic drugs and alpha-acid glycoprotein for basic drugs.
• Only the unbound fraction of a drug is pharmacologically active, while the bound fraction acts as a reservoir.
• Protein binding varies for each drug, influencing its duration of action.
• Hypoalbuminemia can alter the level of free drug.

Tissue Binding

• Drugs can accumulate in tissues, leading to higher concentrations compared to plasma.
• Tissue binding can prolong drug action or cause local toxicity.
• Examples include the accumulation of acrolein, a cyclophosphamide metabolite, in the kidney leading to renal toxicity.

Volume of Distribution (Vd)

• Vd is a hypothetical volume representing the distribution of a drug throughout body compartments.
• Vd is calculated by dividing the amount of drug in the body by the plasma concentration.
• Vd is influenced by drug properties and body composition.
• A large Vd implies that the drug is widely distributed in the body, potentially leading to a longer half-life.

Body Water Compartments

• Drugs distribute into different body water compartments based on their properties.
• Plasma compartment: Drugs with large molecular weight or high plasma protein binding remain confined to the plasma.
• Extracellular fluid: Hydrophilic drugs with low molecular weight distribute into the plasma and interstitial fluid.
• Total body water: Hydrophobic drugs with low molecular weight can distribute into plasma, interstitial fluid, and intracellular fluid.

Drug Displacement

• Drugs with high affinity for albumin can compete for binding sites.
• Displacement interactions can occur when two drugs compete for the same binding site, potentially altering the free drug concentration and therapeutic effects.
• For example, sulfonamide antibiotics can displace warfarin from albumin, increasing the free warfarin concentration and the risk of bleeding.

Clinical Significance of Vd

• Vd is important for calculating drug dosage and understanding drug elimination.
• Drugs with large Vd are harder to remove by hemodialysis due to their extensive distribution.

This quiz covers essential concepts of drug distribution, including factors such as blood flow, capillary permeability, and tissue binding. It explores how these elements impact the movement of drugs throughout the body and their accessibility to various organs. Mastering these concepts is crucial for understanding drug action and efficacy.