Elimination of the Drug

Drug Elimination

• Drugs must be sufficiently polar to be eliminated from the body.

• Removal of drugs from body occur via number of routes; the most important is elimination through kidney in to urine.

Renal Elimination of Drug

• A drug passes through several process in the kidney before elimination, Glomerular filtration, tubular seceration , and passive tubular reabsorption.

(1) Glomerular filteration :

• Drugs enter the kidney through renal artries, which divide to form a glomerular capillary plexus. Free drug (not bound to albumin) flows through the capillary bed into bowman’s space as a part of glomerular filterate.

> Glomerular filteration rate is normally about 120mL/min. But may decrease sugnificantly in renal disease.

> pH and lipid solubility do not influence the passage of drugs into glomerular filterate.

> Variation in GFR and protein binding to drugs donot affect this process.

> water and polar compounds easily enter in glomerular filterate.

(2) Proximal tubular seceration :

• Drugs that were not transferred into glomerular filterate leave the glomeruli through efferent arterioles, which divide to form capillary plexus sorrounding the nephric lumen into proximal tubule.

> Seceration primarily occur in proximal tubules by two energy requiring active transport system. One for anions and one for cations. Each of these transport system show low specificity and can transport many compounds.

> Premature infants and neonates have an incompeletely developed tubular seceratory mechanism and thus may retain certain drugs in the blood.

(3) Distal Tubulary Reabsorption :

• As a drug mives toward the distal convukated tubules, it’s concentration increases and exceeds that of perivascular space. The drug if uncharged may diffuse out of nephric lumen, back into systemic circulation.

> Generally weak acids can be eliminated by alkalinization of the urine, where as elimination of weak bases may be increased acidification of urine. This process is called ion trapping.

For example : A patient presenting with phenobarbital( weak acid) overdose can be given bicarbonate, which alkalinizes the urine and keeps the drug ionized thereby decreasing its reabsorption.

Excreation by other routes :

• Drugs may be eliminated via the intestines, bile, lungs and breast milk.

> Drugs that are not absorbed after oral administration or drugs that are secerated directly into intestines or into bile are excreated in feces.

• LIVER : It can secerate drug or their metabolites e.g : glucoronides conjugates of opiods into bile that are excreated through feces.

> However some drugs may be reabsorbed into intestine to again enter the circulation, referred as enterohepatic circulation.

• GIT : the drugs which are not well absorbed are excreated through this route. Eg : antihelminthic drugs, Thiocynates & iodides.

• LUNGS : the lungs are primarily involved in the elimination of anesthatic gases. E.g : desflurane.

• BREAST MILK: Elimination of drugs in breast milk may exposed the breast-feeding-infant to medications or metabolities being taken by mother.

• Excreation of most drugs into sweat , saliva, tears, hair and skin occur only to a small extent.

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