Metabolism L.7 Flashcards
1
Q
drugs recently shown to have increased bioavailability when taken with grapefruit juice
A
- Triazolam
- Midazolam
- Cyclosporine
- Coumarin
- Nisoldipine
- Felodipine
2
Q
factors that affect the hepatic clearance of a drug include
A
- (1) blood flow to the liver,
- (2) intrinsic clearance, and
- (3) the fraction of drug bound to protein.
3
Q
High-Extraction Ratio Drugs
A
- >0.7
- the drug is removed by the liver almost as rapidly as the organ is perfused by blood in which the drug is contained.
- an increase in blood flow to the liver will increase the rate of drug removal by the organ.
- Propranolol, a b-adrenergic blocking agent, decreases hepatic blood flow by decreasing cardiac output. In such a case, the drug decreases its own clearance through the liver when given orally.
4
Q
Intrinsic clearance (Clint)
A
- used to describe the total ability of the liver to metabolize a drug in the absence of flow limitations, reflecting the inherent activities of the mixed-function oxidases and all other enzymes.
- a distinct characteristic of a particular drug, reflects the inherent ability of the liver to metabolize the drug.
5
Q
Low-Extraction Ratio Drugs
A
- For drugs with low extraction ratios (eg, theophylline, phenylbutazone, and procainamide), the hepatic clearance is less affected by hepatic blood flow.
- more affected by the intrinsic activity of the mixed-function oxidases.
- Smoking, for example, can increase the intrinsic clearance for the metabolism of many drugs.
6
Q
restrictive clearance
A
- protein-bound drugs are not easily metabolized
- clearance of these drugs is proportional to the fraction of unbound drug
- change in binding generally alters drug clearance
7
Q
NONRESTRICTIVE CLEARANCE
A
- extracted by the liver regardless of drug bound to protein or free
- its hepatic extraction ratio (ER) > fraction of free drug (fu)
- rate of drug clearance is unchanged when the drug is displaced from binding
- elimination half-life of a nonrestrictively cleared drug is not significantly affected by a change in the degree of protein binding.
8
Q
BILIARY EXCRETION OF DRUGS
A
- molecular weights in excess of 500
- a strongly polar group bile are metabolites, very often glucuronide conjugates
- glycosides, bile salts, cholesterol, steroids, and indomethacin
- drugs given orally may be extracted by the liver into the bile to a greater extent than the same drugs given intravenously.
9
Q
Enterohepatic Circulation
A
- in which the drug is absorbed, excreted into the bile, and reabsorbed
- Drugs that undergo enterohepatic circulation sometimes show a small secondary peak in the plasma drug–concentration curve.
10
Q
Patient variability and changes in intrinsic clearance may be due to
A
- (1) patient factors such as age and genetic polymorphism,
- (2) enzymatic induction or inhibition due to coadministered drugs, and
- (3) modification of influx and efflux transporters in the liver and the bile canaliculi.
11
Q
A