DRUG INTERACTIONS ( CASE STUDIES RELATED TO ALTERED DRUG ABSORPTION - 3 )

Continuation Of My Previous Blog........

iii) ALTERATION OF GASTRIC MOTILITY/RATE OF GASTRIC EMPTYING :

a) CATHARTICS :

A cathartic, by increasing gastrointestinal motility may increase the rate at which drugs pass through the gastrointestinal tract. This could result in a decreased absorption of the drugs, particularly those that are normally slowly absorbed and require prolonged contact with the absorbing surface or those that are absorbed only at a particular site along the gastrointestinal tract. A similar problem might be noted with enteric-coated and sustained-release formulations.

b) ANTICHOLINERGICS :

Anticholinergics, by decreasing gastrointestinal motility, may also influence drug absorption. The effect is of decreased absorption due to the reduced peristalsis that will retard dissolution. The slowing of gastric emptying will delay absorption from the small intestine. The increased absorption will occur if a drug is retained for a longer period of time in the area from which it is optimally absorbed.

Studies have shown that the anticholinergic PROPANTHELINE can cause an increase in the total amount of riboflavin absorbed, even though absorption is initially delayed. The initial delay in absorption can be due to slower gastric emptying, whereas the overall increase in absorption is due to a longer retention of the drug at intestinal absorption sites because of slower transit of intestinal contents. A similar response pattern has been reported with HYDROCHLOROTHIAZIDE when propantheline was administered concurrently.

c) ACETAMINOPHEN - PROPANTHELINE :

Studies have demonstrated that the rate of acetaminophen absorption depends on the rate of gastric emptying. In one study it was shown that propantheline, by reducing the rate of gastric emptying, caused a significant delay in absorption of acetaminophen even though it does not alter the total amount of the analgesic absorbed.

iv) EFFECT OF SURFACTANTS :

Surfactants can influence the rate and/or the extent of absorption of certain drugs. Surfactants can interact with biological membranes and modify membrane permeability. They also interact with drugs and the dosage form.

a) MINERAL OIL - DIOCTYL SODIUM SULFOSUCCINATE :

Dioctyl sodium sulfosuccinate is used extensively as a faecal softener. This agent should not be given concurrently with mineral oil for prolonged periods since absorption of the latter, which is toxic, might be increased.

v) INHIBITION OF GASTROINTESTINAL ENZYMES :

a) FOLIC ACID - PHENYTOIN :

Folic acid is present in dietary sources in the form of poorly absorbed polyglutamates. To be efficiently absorbed, it must be converted to the readily absorbable monoglutamate form by action of an intestinal conjugase enzyme. Folic acid deficiency anemias are caused in patients receiving phenytoin. The effect is because of the ability of the anticonvulsant to inhibit this enzyme.

b) VITAMINS - ORAL CONTRACEPTIVES :

Use of oral contraceptives may result in deficiency of folic acid, cyanocobalamine, pyridoxine and ascorbic acid. Oral contraceptives may inyterfere with deconjugation of polyglutamate forms of folic acid resulting in folic acid deficiency.

vi) MALABSORPTION STATES :

Certain drugs such as NEOMYCIN, LAXATIVES, COLCHICINE, CHOLESTYRAMINE and AMINOSALICYLIC ACID cause malabsorption problems that result in decreased absorption of vitamins and nutrients from the gastrointestinal tract.

Till now I discussed about the pharmacokinetic drug interactions resulting due to alteration in the rate of absorption. In my upcoming blogs I shall be discussing about the drug interactions that result due to alteration in the rate of distribution..............