Flashcards in 3 Medical Mathematics: Excretion of Drugs Deck (26):
What is Excretion of Drugs?
It is the removal or clearance of the drug out of the body
List the Routes of excretion
What is included in Renal excretion?
Active tubular secretion
What Factors affect glomerular filtration?
Glomerular filtration rate
Plasma protein binding
What is Glomerular filtration rate?
Arterial blood pressure forces the blood through the glomerular capillaries into the Bowman’s capsule to form the ultrafiltrate
How does molecular size affect glomerular filtration?
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.
How does molecular charge affect glomerular filtration?
Larger negatively charged drug molecules are inhibited by negatively charged
proteins in the capillary wall (basement membrane and podocytes)
How does plasma protein binding affect glomerular filtration?
Only unbound drugs can be filtered and are eliminated at a rate equal to their creatinine clearance rate
Describe Active tubular secretion
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.
Describe Active tubular secretion (continued)
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).
Describe Tubular reabsorption
Passive tubular reabsorption occurs in the proximal and distal convoluted tubules for nonionized forms of weak acids and weak bases
What factors affect tubular reabsorption?
Physicochemical properties of the drugs
Degree of ionization
Rate of glomerular filtration
Active tubular reabsorption
What drugs are secreted in urine? (Physicochemical properties of the drugs)
Water soluble, ionized, and polar drugs are excreted in urine
Describe Degree of ionization
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.
Describe Rate of glomerular filtration
Fluid therapy and diuretics also enhance renal excretion of drugs by reducing the time needed for tubular reabsorption
Active tubular reabsorption occurs where?
Occurs mainly in the distal tubules for some drugs through membrane transporters from the lumen back into the blood
What factors affect renal excretion?
Urine pH modifiers
Plasma protein binding
The dose and rate of absorption
Describe Hepatic excretion
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.
Describe Hepatic excretion (continued)
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.
Describe Feces as a route of excretion
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.
Describe Milk as a route of excretion
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.
What is the Significance of excretion of drugs in milk?
Treatment of mastitis systemically
Possible adverse effect on the newborn
Describe Semen as a route of excretion
Generally, similar to excretion in milk
Treatment of prostatitis and male genital tract infections
Describe saliva as a route of excretion
Inhibition of intestinal flora in herbivores by antibiotics
Describe eggs as a route of excretion
Drug-residues in laying birds