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Renin Angiotensin Mechanism.

Introduction to Pharmacology-3 (Distribution)


What is Distribution of drugs?

  • After absorption drugs get distributed to various body tissues and fluids through the blood, the phenomenon is called as "Drug Distribution".
  • The rate of phenomenon depends on,
  1. Regional blood flows to the organ.
  2. Cardiac output,
  3. Physical properties of the drug. 

    Factors affecting drug distribution:

    1. Plasma Protein Binding.
    2. Physical Properties of the drug.
    3. The presence of special barriers.
    4. The presence of active transport mechanism.
    5. Diseased Conditions.
    6. Route of drug administration.

    1) Plasma Protein Binding:

    • Plasma contains various proteins viz. albumin, lipoprotein, globulin etc. which offers binding sites for drugs which have an affinity towards them.
    • The drugs in blood exist in two forms, one is bound to plasma proteins and other is unbound.
    • The portion of drug bound to plasma proteins is pharmacologically inactive i.e. it can not be metabolized as well as it does not show any effect.
    • Only unbound portion of drug present is available for metabolism, excretion, and action.
    • The unbound and bound form are in a state of chemical equilibrium when part of unbound drug gets excreted the bound form releases an equal amount of drug in the blood.
    • Thus "drug-plasma protein complex" serves as a depot and influence the biological half-life of the drug.
    • Greater the plasma protein binding greater will be half life of the drug and vice a versa.

    2) Physical Properties of the drug:

    • All biological membranes are lipoidal in nature and hence the drugs with greater lipid solubility shows greater distribution than those with good water solubility.

    3) The presence of special barriers:

    • Vital organs like brain are provided with special barriers like Blood Brain Barrier (BBB), while a fetus is protected by "placenta barrier".
    • BBB is very specific and allows entry of certain drugs and substances, while placental barrier restricts entry of many drugs.
    • Drugs with higher lipid solubility easily pass these barriers.
    • e.g. alcohol, L-DOPA etc.

    4) The presence of active transport mechanism:

    • Active transport mechanism involves a carrier molecule.
    • Saturation or deficiency of these carriers results in poor distribution.

    5) Route of drug administration:

    • In intravenous route of administration as drugs are directly introduced into the systemic circulation, the drugs administered by this route shows good and wide distribution as compared to the drugs administered by oral route.




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