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
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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11
Q
A
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