Pharmacokinetics II Drug Elimination & Multiple Dosing Flashcards

Question

Explain and define zero-order kinetics.

Answer 1

Drugs that are eliminated primarily by metabolism may display zero-order kinetics of elimination. A fixed amount of drug is metabolized per unit time (zero-order kinetics).

Answer 2

(zero order) When metabolic pathways are saturated, metabolism occurs at a fixed rate, i.e. it does not change in proportion to drug concentration. A fixed amount of drug is metabolized per unit time (zero-order kinetics).

Answer 3

By looking at t(1/2) which is NOT constant in zero order

Answer 4

first order has log scale y axis zero order has linear y axis scale (and thus half life is not constant)

Answer 5

dC/dt=-k PHENYTOIN, ETHANOL

Answer 6

``` Aspirin Ethanol Heparin Phenylbutazone Phenytoin Salicylates Theophylline Tolbutamide Warfarin ```

Answer 7

When a drug’s elimination is mediated predominantly by metabolism, its elimination will tend to follow first-order kinetics when concentrations are well below the KM of the metabolic enzymes but will follow zero-order kinetics at doses that greatly exceed the KM of the metabolic enzymes.

Answer 8

Volume of plasma cleared of drug per unit time. Units are ml/min or L/hr (flow)

Answer 9

kidneys, the liver, the lung, and other organs. liver and kidney are primary Total Clearance is equal to the sum of all these individual and simultaneously occurring organ clearances: CLtotal = CLrenal + CLhepatic + CLother

Answer 10

time to eliminate 50% of the body content of the drug t(1/2)= 0.69Vd/CL

Answer 11

Elimination clearance and volume of distribution

Answer 12

Impaired renal function often results in reduced clearance of drugs that are eliminated primarily by the kidneys. Daily drug dose must be reduced by the ratio of measured clearance in renal failure (CLRF) over expected normal, average clearance (CLN).

Answer 13

reducing the dose, increasing the dosing interval, or both.

Answer 14

Creatinine clearance rate (CrCL) is the volume of blood plasma that is cleared of creatinine per unit time and is the most commonly used measure for approximating the glomerular filtration rate (GFR). CrCL is not the same as clearance of a drug—it only provides a relative measure of how well the kidney is functioning. It can be used to adjust drug dosing in a patient with renal failure. ``` The ratio of CrCL in renal failure to CrCL in a patient with normal renal function can also be used to adjust the dosing rate. ```

Answer 15

1. Hepatic Blood Flow (Rate of drug delivery to the eliminating organ) 2. Plasma Protein Binding (Fraction of drug available for clearance, drugs that are protein bound cannot distribute to the liver) 3. Intrinsic Clearance (Hepatocellular metabolism and/or biliary excretion) -ability of liver's metabolic enzymes to clear the drug or excrete it in bile

Answer 16

Drugs with low hepatic extraction (Q is much greater than F x CLint) CLh= f x CLint Little "first pass metabolism" when given orally. A change in binding or drug metabolism/excretion activity will have a greater effect on hepatic clearance than changes in liver blood flow. Capacity-limited clearance. Examples: warfarin, phenytoin

Answer 17

Drugs with high hepatic extraction (Q is much smaller than f x CLint) Examples: lidocaine, propranolol CLh=Q Hepatic clearance is sensitive to changes in liver blood flow and less sensitive to alterations in binding or intrinsic clearance. Flow-dependent clearance: conditions that reduce hepatic blood flow (CHF, hypotension) will reduce hepatic clearance.

Answer 18

reduce hepatic blood flow and therefore can decrease lidocaine clearance

Answer 19

``` Individual variability Patient compliance Disease states Pharmacogenetics Age and gender Medication interactions ```