Excretion of Drug
Excretion is the passage out of systemically absorbed drug. Excretion of drug decreases its duration of action. This in turn decreases the toxicity. Drugs may be excreted in an active or inactive form. The various routes through which drugs can be eliminated are –
The kidney is responsible for excreting all water soluble substances. The amount of drugs or its metabolites ultimately present in urine is the sum total of glomerular filtration, tubular re-absorption and tubular secretion.
- Glomerular filtration: Most of the drugs are eliminated by this mechanism. Glomerular filtration of a drug depends on its plasma protein binding and renal blood flow. Glomerular filtration rate declines progressively after the age of 50 and is low in renal failure.
- Tubular re-absorption: This depends on lipid solubility and ionization of the drug at the existing urinary ph. Lipid soluble drugs filtered at the glomerulus back diffuse in the tubules because of 99% of glomerular filtrate is re-absorbed, but non-lipid soluble and highly ionized drugs are unable to do so. Changes in urinary ph affect tubular re-absorption of drugs that are partially ionized weak bases ionize more and are less re-absorbed in alkaline urine.
- Tubular secretion: This is the active transfer of organic acids and bases. Active transfer of drug across tubules reduces concentration of its free from in the tubular vessels and promotes dissociation of protein bound drug, which again is secreted. E.g.penicillin, probenacid, uric acid, salicylates, quinine,cimetidine and thiazides.
Most of the drugs present in feces are derived from bile. Liver actively transports into bile organic acids, organic bases and steroids by separate non-specific active transport mechanism. E.g.ampicillin, erythromycin,rifampicin and tetracyclines.
Gases and volatile liquids are eliminated by lungs. Lungs also serve to trap and extrude any particulate matter injected i.v.
Saliva and Sweat:
These are of minor importance for drug excretion. E.g. lithium, potassium iodide, rifampicin and heavy metals.
The excretion of drug in milk is not important for the mother but the suckling infant receives the drug. Most drugs enter breast milk by passive diffusion. As such more lipid soluble and less protein drugs cross better. It is advisable to administer any drug to a lactating women only when essential.E.g. acetazolamide, gentamicin, mebendazole,lignocaine ,pethidine,chloramphenicol, aspirin,clonidine, amantadine etc.
Arsenic and heavy metals like mercury are excreated in small quantities through the skin. Arsenic gets incorporated in the hair follicles on prolonged administration.
The plasma half-life of a drug is the time taken for its plasma concentration to be reduced to half of its original value. The plot has two slopes. Initial rapidly declining(α)phase –due to distribution. Later less declined(β)phase- due to elimination.
At least two half-lives (distribution t1/2 and elimination t1/2) can be calculated from the two slopes. The elimination half-life derived from the β slope is simply called the half-life of the drug.
Where ln 2 is the natural logarithm of 2(or 0.693) and k is the elimination rate constant of the drug.
Where, CL= clearance and V= volume of distribution.
Half live of some drugs are as follows—
Aspirin ———- 4 hr digoxin —————— 40 hr
Penicillin G ——— 30 min digitoxin —————— 7 days
Prolongation of drug action
Prolonging the action of drug is helpful for patient by following ways-
- Frequency of administration is reduced.
- Improved patient compliance.
- Large fluctuation in plasma concentration is avoided.
- Side effect will be minimized.
- Drug effect could be maintained overnight without disturbing sleep.
Methods utilized for prolonging drugs action are as follows
By prolonging absorption from site of administration
- Sustained release tablets, capsules etc.; drug particles are coated with resins, plastic materials which slowly release the active materials in the g.i.t. such preparations prolong the action by 4-6 hours. The s.c and i.m injection of drug in insoluble form (procaine penicillin, lente insulin) prolong the action. Inclusion of vasoconstrictor with the drug will also delay absorption (adrenaline with local anaesthetic).
- By increasing plasma protein binding – To prepare highly plasma protein bound form so, prolonged the action of drug. E.g. sulfamethoxypyridazine.
- By retarding rate of metabolism – Addition of ethinyl group to estradiol makes it longer acting and suitable for use as oral contraceptive. Inhibition of specific enzyme by one drug can prolong the action of another drug. E.g. physostigmine prolong the action of acetylcholine.
- By retarding renal excretion — Probenacid prolongs duration of action of penicillin and ampicilli.