3 Medical Mathematics: Excretion of Drugs

Question 0

List the Routes of excretion

Answer 0

Renal
Hepatic
Feces
Milk
Semen
Saliva
Eggs
Hair
Feathers
Sweat glands
Expired air

Question 1

What is Excretion of Drugs?

Answer 1

It is the removal or clearance of the drug out of the body

Question 2

What is included in Renal excretion?

Answer 2

Glomerular filtration
Active tubular secretion
Tubular reabsorption

Question 3

What Factors affect glomerular filtration?

Answer 3

Glomerular filtration rate
Molecular size
Molecular charge
Plasma protein binding

Question 4

What is Glomerular filtration rate?

Answer 4

Arterial blood pressure forces the blood through the glomerular capillaries into the Bowman’s capsule to form the ultrafiltrate

Question 5

How does molecular size affect glomerular filtration?

Answer 5

Molecules of MW less than 7000 Da charged or uncharged are freely filtered
through the gomerular membrane achieving equal concentration in the ultrafiltrate to that in plasma.
Molecules MW 7000-70,000 Da are filtered at a rate which is proportional to their molecular mass.

Question 6

How does molecular charge affect glomerular filtration?

Answer 6

Larger negatively charged drug molecules are inhibited by negatively charged
proteins in the capillary wall (basement membrane and podocytes)

Question 7

How does plasma protein binding affect glomerular filtration?

Answer 7

Only unbound drugs can be filtered and are eliminated at a rate equal to their creatinine clearance rate

Question 8

Describe Active tubular secretion

Answer 8

The proximal convoluted tubule has an organic anion system for secretion of organic acids and another organic cation system for secretion of organic bases.
Both systems require energy which is provided by the sodium pump in the basolateral membrane.
They also involve secondary and tertiary active transport and use a facilitated diffusion step.
Transporter or carrier-mediated transport is characterized by saturability and inhibition.
In active transport, drugs move against their electrochemical gradient.

Question 9

Describe Active tubular secretion (continued)

Answer 9

Organic cation transporters (OCTs) transport endogenous organic bases such as choline or
dopamine, and organic basic drugs such as cimetidine, procainamide, or nicotine.
These organic bases may be lipophilic or hydrophilic.
Organic anion transporters (OATs) transport endogenous organic acids such as uric acid
and organic acidic drugs such as penicillins, thiazide diuretics, or loop diuretics.
Hydrophilic organic acids are transported across the basolateral membrane against an
electrochemical gradient in exchange with intracellular -ketoglutarate (-KG-2).

Question 10

Describe Tubular reabsorption

Answer 10

Passive tubular reabsorption occurs in the proximal and distal convoluted tubules for nonionized forms of weak acids and weak bases

Question 11

What factors affect tubular reabsorption?

Answer 11

Physicochemical properties of the drugs
Degree of ionization
Rate of glomerular filtration
Active tubular reabsorption

Question 12

What drugs are secreted in urine? (Physicochemical properties of the drugs)

Answer 12

Water soluble, ionized, and polar drugs are excreted in urine

Question 13

Describe Degree of ionization

Answer 13

Acidification of the urine pH by ammonium chloride or methionine enhances renal excretion of weak basic drugs such as amphetamine.
Alkalinization of the urine pH by sodium bicarbonate enhances renal excretion of weak acidic drugs such as aspirin or phenobarbital.

Question 14

Describe Rate of glomerular filtration

Answer 14

Fluid therapy and diuretics also enhance renal excretion of drugs by reducing the time needed for tubular reabsorption

Question 15

Active tubular reabsorption occurs where?

Answer 15

Occurs mainly in the distal tubules for some drugs through membrane transporters from the lumen back into the blood

Question 16

What factors affect renal excretion?

Answer 16

Liver disease
Kidney disease
Age
Urine pH modifiers
Fluid therapy
Diuretics
Plasma protein binding
The dose and rate of absorption

Question 17

Describe Hepatic excretion

Answer 17

The liver is the second important organ for excretion of drugs.
Drugs may be transported from the hepatic cells to bile or blood by passive diffusion or active transport.
High lipid soluble drugs are usually metabolized first.
Molecular weight greater than 300 and the presence of a polar group in a compound facilitates its biliary excretion.
Drugs are excreted in bile either unchanged or as glucuronides.
Acidic, basic and neutral drugs can be excreted in bile by active transport.

Question 18

Describe Hepatic excretion (continued)

Answer 18

Steroid hormones, erythromycin, nafcillin, digitoxin and glucuronides of chloramphenicol and morphine are examples of compounds significantly excreted in bile.
Conjugates of lipophilic compounds excreted in bile can be hydrolyzed in the intestine (by
bacterial -glucuronidases) to lipid soluble free drugs that can be reabsorbed (enterohepatic circulation).
Significant enterohepatic circulation prolongs the half-life of the drug.

Question 19

Describe Feces as a route of excretion

Answer 19

Orally administered non absorbed drugs.
Drugs excreted in bile and are not reabsorbed.
Drugs that move from the plasma to the GI tract by passive diffusion.

Question 20

Describe Milk as a route of excretion

Answer 20

Is not a significant route of drug excretion.
Drugs are excreted in milk by simple diffusion.
Basic drugs are excreted in milk in large amounts because of ion trapping.

Question 21

What is the Significance of excretion of drugs in milk?

Answer 21

Drug residues
Treatment of mastitis systemically
Possible adverse effect on the newborn

Question 22

Describe Semen as a route of excretion

Answer 22

Generally, similar to excretion in milk

Treatment of prostatitis and male genital tract infections

Question 23

Describe saliva as a route of excretion

Answer 23

Inhibition of intestinal flora in herbivores by antibiotics

Question 24

Describe eggs as a route of excretion

Answer 24

Drug-residues in laying birds

Question 25

Describe expired air as a route of excretion

Answer 25

Volatile compounds such as inhalation anesthetics