SM44_DrugElimination

Question 1

What has a longer half-life in plasma (ie. what is not as readily excreted) = water-soluble, polar drugs or lipid soluble drugs

Answer 1

lipid soluble drugs

Question 2

Why is albumin not filtered through glomerular filtration

Answer 2

Larged, negatively charged plasma proteins are not filtered because of a three-layer membrane that is rich in negatively charged glycoproteins

Question 3

layers of the glomerular filtration barrier

Answer 3

1. glomerular capillary endothelium (fenestrated)
2. Porous glomerular basement membrane
3. Podocytes with interdigitating foot processes

Question 4

Transporters involved in tubular secretion

Answer 4

Basolateral side (facing capillaries): SLC22 perform major uptake of ionized drugs from plasma

Apical side (lumen facing): SLC family and ABC transporters

OCTs responsible for weak bases

OATs transport weak acids

p-glycoprotein mediates secretion of amphipathic anions

MRP2 mediates secretion of conjugated metabolites

Question 5

Factors affecting passive tubular reabsorption

Answer 5

same as the usual requirements for passive diffusion: lipid solubility, pKa of a drug, pH of tubular fluid

Question 6

Hepatic Clearance Calculation

Answer 6

Product of hepatic blood flow (Qh) and drug extraction ratio (E). E is the proportional difference between drug concentration in blood in the portal vein (entering liver) and hepatic veins (leaving liver)

Question 7

For _____ _____ drugs, the metabolic capacity of the liver is in excess. These drugs have high E values

Answer 7

high extraction

Question 8

For low extract drugs, hepatic clearance is dictated by ___

Answer 8

intrinsic hepatic metabolic capacity, fraction of free drug (not protein bound) in blood

Question 9

Excretion in the bile is especially important for what kind of drugs?

Answer 9

drugs of high molecular weight (>300)

Question 10

Genetic defect in ABCG5/8

Answer 10

causes sitosterolemia – elevated plasma levels of cholesterol and phytosterol. Clinical manifestation of xanthomas, joint pain, premature atherosclerosis

Question 11

Genetic defect in OAT protein SLCO1B1

Answer 11

associated with myotoxicity risk

Question 12

Drugs secreted in bile leave the body through the ____

Answer 12

gut –> feces

Question 13

______ _______ is an intestinal bacteria responsible for cleavage of _______ from drug conjugates

Answer 13

beta-glucuronidase, glucuronide

Question 14

If treated with a broad spectrum _________, enterohepatic recirculation of a drug may be disrupted

Answer 14

Antibiotic