PHARMACOLOGY

(B) Alteration of contents of g.i.tract ::

1.Alteration of pH ::

Alteration of pH in the stomach or the intestine by means of interactant is one of the most potent physicochemical change that can occur it may modify drug ionization solubility and stability and thereby markedly affects both the rate and extent of absorption 

Most drugs are weak electrolytes and are most readily absorbed through the lipid containing membranes of the body when they are in the lipid soluble form that is in non-ionized state Therefore lowering of the pH increases the rate of absorption of weakly acidic drugs and vice versa 

        Alkaline antacids in the stomach inhibit absorption of nalidixic acid nitrofurantoin oral anticoagulants phenylbutazone probencid salicylates etc Agents that lower the pH tend to decrease the absorption of basic compounds by making them more highly ionized Thus the basic drugs aminopyrine ephedrine and quinine are not absorbed at the acid pH stomach 

2.Complexation ::

The g.i. absorption of some drugs may be markedly decreased by chelation with aluminium barium calcium and magnesium Thus tetracycline may not be absorbed in the presence of antacids and in presence of dairy products Aluminium decreases tetracycline absorption whereas phosphates glucosamine and other agents may increase absorption Even sodium bichromate decreases tetracycline absorption by 50% even though it contains no chelating metals 

3.Dissolution ::

Disintegration and dissolution rates of some drugs may be considerably inhibited or accelerated by other drugs causing loss of efficacy or increased potency and toxicity For example an enteric coated drug like bisacodyl may be extremely irritating to the stomach if its coating is rapidly removed by simultaneous administration of gastric antacids 

4.Diffusion ::

Dispersion of a drug in the ambient fluids to its sites of g.i. absorption may be inhibited if an interactant drug alters any physical properties such as miscibility and viscosity Thus drugs may be inhibited by adjuants such as gelatin or carboxymethyl cellulose 

5.Osmotic Pressure ::

Increase in osmotic pressure inhibits absorption Magnesium sulfate with its slightly absorbable ions tends to retain water within the tract as well as hasten its passage through the tract and thereby prevent absorption of dissolved medication 

6.Salt formation ::

Iron salts form poorly absorbed insoluble carbonates with antacids and other drugs that contain the carbonate radical This decreases their rate of absorption 

7.Sequestration ::

Absorption of some drugs is prevented when they are sequestered in a lipid substance Absorption of fat soluble Vitamins A D and K is prevented by mineral oil