EXCRETIONExcretion. 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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The Kidney

Pelvis

Ureter Medulla organised in pyramids

Cortex

Outer membrane

Renal Vein

Renal artery

Urine

Nephrons(2 million)

© 2008 Paul Billiet ODWS

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.

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

body4

List of Routes of drug elimination:• Renal elimination:

• Hepatic elimination:

• Fecal elimination:

• Pulmonary elimination:

• Breast Milk:

• Saliva, Sweat and tears:

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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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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

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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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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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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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.

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The nephronBowman’s capsule

Glomerulus

Proximal convoluted tubule

Capillary

Loop of Henlé

Collecting duct

Distil convoluted tubule

Branch of renal vein

Branch of renal artery

© 2008 Paul Billiet ODWS

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 water13

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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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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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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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

• Factors modifying renal excretion (cont.):

5. Extent of plasma protein binding.High plasma protein binding → less excretionLess plasma protein binding → more excretion6. GFR: more GFR more excretion of drug through the kidney.7. reabsorption: More re absorption less excretion8. tubular secretion: More secretion more excretion9. tubular reabsorption: More reabsorption less excretion10. 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