Translocation Of Drug Molecules

Translocation of Drug Molecules

1. Mechanisms of Translocation

• Bulk Flow Transfer
  • Movement of drug molecules along with the flow of blood or lymph.
  • Provides a rapid, long-distance distribution system.
  • All solutes move at the same rate, irrespective of their chemical nature.

• Diffusional Transfer
  • Movement of drug molecules by diffusion, molecule by molecule.
  • Important for short-distance transfer, particularly across cell membranes.

2. Movement Across Cell Membrane Barriers

• Cell membranes separate various aqueous compartments of the body.
• Drugs in these compartments exist in two forms: bound (to proteins) and free (unbound).
• The free form of the drug is able to cross membranes and reach the site of action.
• In fat tissues, drugs exist mainly in the free form.

3. Factors Influencing Movement and Availability of Drugs

• Molecular Size and Shape
  • Smaller and less complex molecules cross membranes more easily.
• Degree of Ionization
  • Non-ionized forms are more lipid-soluble, aiding in membrane permeability.
  • Ionized forms are more water-soluble and have reduced membrane permeability.
• Relative Lipid Solubility of Ionized and Non-ionized Forms
  • Determines how well the drug can cross lipid-rich membranes like the blood-brain barrier.
• Binding to Serum or Tissue Proteins
  • Only the free form of the drug can move across compartments and act pharmacologically.
  • Bound forms act as a reservoir but are pharmacologically inactive.

4. Structure of the Cell Membrane

• Composed of a bilayer of amphipathic lipids:
  • Hydrophilic (water-attracting) heads face outward.
  • Hydrophobic (water-repelling) tails (hydrocarbon chains) face inward, forming a central hydrophobic core.
• This bilayer creates a continuous hydrophobic phase, making it relatively impermeable to highly polar molecules.

Dynamic Nature of the Lipid Bilayer

• Lipid molecules in the bilayer move laterally, contributing to membrane fluidity.
• Cholesterol molecules integrate with phospholipids to:
  • Enhance fluidity, flexibility, and organization of the membrane.
  • Provide high electrical resistance and selective permeability.

5. Role of Membrane Proteins

• Membrane proteins are embedded in the lipid bilayer and serve important functions:
  • Receptors for chemical signals like hormones, neurotransmitters, and drugs.
  • Ion Channels for the selective movement of ions (e.g., Na⁺, K⁺, Ca²⁺, Cl⁻).
  • Transporters for facilitated diffusion or active transport of solutes.
• These proteins play a critical role in transducing electrical or chemical signals across the membrane.
• They also provide selective targets for drug action.