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Excretion of drugs ( Elimination ) Excretion of drugs means the transportation of unaltered or altered form of drug out of the body – terminating its activity. The major processes of excretion include renal excretion, hepatobiliary excretion and pulmonary excretion. The minor rout...

Excretion of drugs ( Elimination ) Excretion of drugs means the transportation of unaltered or altered form of drug out of the body – terminating its activity. The major processes of excretion include renal excretion, hepatobiliary excretion and pulmonary excretion. The minor routes of excretion are saliva, sweat, tears, breast milk, vaginal fluid, nails and hair. The rate of excretion influences the duration of action of drug. The drug that is excreted slowly, the concentration of drug in the body is maintained and the effects of the drug will continue for longer period. Different routes of drug excretion: a) Renal excretion: A major part of excretion of chemicals is metabolically unchanged or changed. The excretion of drug by the kidney involves. i) Glomerular filtration ii) Active tubular secretion iii) Passive tubular reabsorption. The function of glomerular filtration and active tubular secretion is to remove drug out of the body, while tubular reabsorption tends to retain the drug. i) Glomerular filtration: It is a process, which depends on: (1) the concentration of drug in the plasma. (2) molecular size, shape and charge of drug. 1 (3) glomerular filtration rate. Only the drug which is not bound with the plasma proteins can pass through glomerulus. All the drugs which have low molecular weight can pass through glomerulus e.g. digoxin, ethambutol, etc. ii) Active tubular secretion: The cells of the proximal convoluted tubule actively transport drugs from the plasma into the lumen of the tubule e.g. acetazolamide, benzyl penicillin, dopamine, pethidine, thiazides, histamine. iii) Tubular reabsorption: The reabsorption of drug from the lumen of the distal convoluted tubules into plasma occurs either by simple diffusion or by active transport. When the urine is acidic, the degree of ionization of basic drug increase and their reabsorption decreases. Conversely, when the urine is more alkaline, the degree of ionization of acidic drug increases and the reabsorption decreases. b) Hepatobiliary excretion: the conjugated drugs are excreted by hepatocytes in the bile. Molecular weight more than 300 daltons and polar drugs are excreted in the bile. Excretion of drugs through bile provides a back up pathway when renal function is impaired. After excretion of drug through bile into intestine, certain amount of drug is reabsorbed into portal vein leading to an enterohepatic cycling which can prolong the action of drug e.g. chloramphenicol, oral estrogen are secreted into bile and largely reabsorbed and have long duration of action. 2 Tetracylines which are excreted by biliary tract can be used for treatment of biliary tract infection. Enterohepatic recirculation: some drugs, or their metabolites, which are concentrated in the bile then excreted into the intestines, can be reabsorbed into the bloodstream from the lower GI tract c) Gastrointestinal excretion: When a drug is administered orally, a part of the drug is not absorbed and excreted in the faeces. The drugs which do not undergo enterohepatic cycle after excretion into the bile are subsequently passed with stool 3 e.g. aluminium hydroxide changes the stool into white colour, ferrous sulfate changes the stool into black and rifampicin into orange red. d) Pulmonary excretion: Drugs that are readily vaporized, such as many inhalation anaesthetics and alcohols are excreted through lungs. The rate of drug excretion through lung depends on the volume of air exchange, depth of respiration, rate of pulmonary blood flow and the drug concentration gradient. e) Sweat: A number of drugs are excreted into the sweat either by simple diffusion or active secretion e.g. rifampicin, metalloids like arsenic and other heavy metals. f) Mammary excretion: Many drugs mostly weak basic drugs are accumulated into the milk. Therefore lactating mothers should be cautious about the intake of these drugs because they may enter into baby through breast milk and produce harmful effects in the baby e.g. ampicillin, aspirin, chlordiazepoxide, coffee, diazepam, furosemide, morphine, streptomycin etc. Clearance of a drug: It is the volume of plasma cleared of the drug by metabolism (hepatic) and excretion (renal) and other organs. Total clearance will be calculated by Ct = Ch + Cr + C others Ct = total clearance Ch = hepatic clearance 4 Cr = Renal clearance Half life: Half life (t1/2) of a drug is the time taken for the concentration of drug in the blood or plasma to decline to half of original value or the time taken for half amount of the drug to be eliminated. It has two phases i.e half-life of distribution and half-life of elimination. A half-life value can be readily determined for most drugs by administering a dose of the drug to a subject, taking blood samples at various time intervals and then assaying the samples., For example if a blood level of drug A is 8.6 mg/ml at 10 minutes and 4.3 mg/ml at 60 minutes, so the half – life of that drug is 50 minutes. 5