Excretion Of Drugs

Excretion of drugs means the transportation of unaltered or altered form of drug out of the body. 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 (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.
In congestive cardiac failure, the glomerular filtration rate is reduced due to decrease in renal blood flow.
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. Tetracylines which are excreted by biliary tract can be used for treatment of biliary tract infection.
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 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.