1. EXCRETION
Excretion. Elimination of drugs and its metabolites from
body through urinary system is called excretion. Drugs
eliminated from the body either unchanged or converted to
metabolites by excretion. Excretory organs excluding lungs,
eliminate polar compounds more efficiently than substance
with high lipid solubility. Lipid soluble drugs thus are not
readily eliminated until they are metabolized to more polar
compounds.
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3. Functions of the Kidneys
• Excrete metabolic waste products, foreign
chemicals, drugs and hormone metabolites.
• Regulate H2O and electrolyte balances.
• Regulate arterial pressure.
• Regulate acid-base balance.
• Release erythropoietin for erythrocyte
production.
• Produce vitamin D – important in Ca2+
regulation.
• Regulate glucose synthesis.
4. Significance of excretion:
• To regulate external acid base balance
• To excrete carbondioxide
• To balance bicarbonate through secretion
and reabsorption
• To decrease in the half life of the drug ie
decrese drug toxicity.
• To make out unnecessary product from
body
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5. List of Routes of drug elimination:
• Renal elimination:
• Hepatic elimination:
• Fecal elimination:
• Pulmonary elimination:
• Breast Milk:
• Saliva, Sweat and tears:
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6. Hepatic elimination:
• Elimination occurs via biotransformation of
parent drug in the liver to one or more
metabolites or excretion of unchanged
drug.
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7. Fecal elimination:
• Substances excreted in the feces is mainly
unabsorbed. eg, Tetracycline, Erythromycin.
mmr...Secretion is when the substance is
moved from the bloodstream to the kidneys
while reabsorption is when the substance is
moved from the kidneys back into the
bloodstream. Just remember RE-absorption
means it is taken BACK into the bloodstream
because all the material in the kidneys is
taken originally from the blood. 7
8. Pulmonary elimination:
• The pulmonary elimination (in expired air) concerns only a
low number of drugs,
• but for which it can represent the main route of
elimination.
• The concerned drugs are volatile products like some
general anesthetics, halothane for example, from which
60% is eliminated in the expired air.
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9. Breast Milk:
• The excretion of drugs in milk
constitutes only a secondary route of
elimination for the woman, but can
constitute a danger for the neonate.
When it is necessary to prescribe
drugs to the mother, the problem is to
know if it is necessary to stop breast
feeding, either transitorily, or
definitively.
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10. Saliva, Sweat and tears:
• Excretion of drugs into sweat,
saliva and tears is quantitatively
unimportant.
• Sweat can contain traces
of compounds such as iodine,
bromine, ethanol, salicylic acid,
sulphamides and various trace
elements.
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11. Renal elimination
• The kidney which receives with high
pressure approximately 1400 ml/mn of
blood, about a quarter of the cardiac output,
eliminates drugs and various other
compounds from the body. From the
physiological point of view, the nephron,
basic unit of the kidney, acts by three
different mechanisms: glomerular
filtration, tubular secretion and tubular
reabsorption. There are approximately 1
million nephrons per kidney. 11
13. Functions of different parts of nephrone
• Bowman’s capsule: Filtration of low molecular
wt. substances
• Proximal convoluted tubule: active secretion of
weak electrolytes ie acid, reabsorption of water.
• Loope of Henle; re absorption of water.
• Distal tubule : Passive re absorption of lipid
soluble drug and water 13
14. Glomerular’s Filtration:
• only free drug (not plasma protein binding
drug) can pass through the glumerulus as
they have small size. Size appropriate for
the filter pore.
• Glumerular filtration depend on-
• Free drug concentration in plasma
• Molecular weight of drug
• GFR (less in CCF, renal failure and less is
the drug elimination)
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15. Tubular active secretion:
• Tubular active secretion: Drugs that are
actively secreted into proximal convoluted
tubules are as follows- acidic- penicillin,
frusemide, thiazide etc. basic- amiloride,
dopamine, morphine etc.
• Probenecid competes with penicillin for tubular
secretion; so decrease penicillin secretion. This
is important incase of treatment of diseases
where high plasma penicillin concentration is
required for prolonged action.
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16. Tubular reabsorption:
• Tubular reabsorption: Tubular epithelium has the properties of a lipid
membrane. So drugs in glomerular filtrate diffuse back into the blood.
This will depend on pH of urine and chemical nature of drug (acid or
base).
Alkaline urine, acidic drug is more ionized
↓
So lipid insoluble
↓
No reabsorption
So incase of acidic drug poisoning (or overdose) alkalinization of urine is
indicated.eg , aspirin, barbiturates, NaHCO3
So increase pH, Rapid elimination of acidic drug.
Acidification of the urine can be similarly used to accelerate the excretion of
basic drugs, (Amphetamine).
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17. Factors modifying renal excretion:
1. Ionization of drug: Unionized drug-well
reabsorbed from tubules → less excreted ;
ionized drug - poorly reabsorbed → more
excreted.
2. ↑Increased concentration →↑ increased
excretion
3. Ph of drug:
Acidic drug - ↑ Ph more excretion eg. in alkaline
urine, more excretion.
Alkaline drug →↑ ed excretion in acidic urine.
4. Rate of metabolism α excretion. (directly
proportional to excretion) 17
18. • Factors modifying renal excretion
(cont.):
5. Extent of plasma protein binding.
High plasma protein binding → less excretion
Less plasma protein binding → more excretion
6. GFR: more GFR more excretion of drug through the kidney.
7. reabsorption: More re absorption less excretion
8. tubular secretion: More secretion more excretion
9. tubular reabsorption: More reabsorption less excretion
10. Impaired renal function: ↓ re excretion
11. Renal blood flow: increase renal blood flow increase
excretion.
12.PH
of the urine: acidic drug more ionize at basic pH and less
reabsorption and vice versa incase of basic drug. 18
