Term
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Definition
| Rate of elimination/ C NB that for most drugs is constant - this is cause the drugs we use are at lower conc (i.e lower then Km on the CL curve and secondly cause CYP450 has a huge reserve). NB that this is first order elimination, which also means that it has a exponential decay |
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Term
| What is another formula for CL? |
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Definition
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Term
| What is an Extraction Ratio (NB that >0.7 is high and <0.3 is low)? |
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Definition
| CL-liver/ Q (blood flow to liver) NB that CL-liver is the intrinsic clearance based on the liver enzymes |
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Term
| High or low ER tell us if the CL is? |
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Definition
| Blood flow-dependent for high ER or Capacity Limited for low ER |
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Term
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Definition
| Morphine, Lidocaine, Verapamil, Propranolol & Nitroglycerin |
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Term
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Definition
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Term
| Drugs with intermediate ER are? |
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Definition
| Aspirin, Quinidine, Codeine & Nortriptyline |
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Term
| Bioavailability of a drug (F) is? |
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Definition
| f (degree of absorption) X (1 - ER) |
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Term
| Volume of Distribution (Vd) is (NB that this value is only apparent)? |
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Definition
Dose/ C (plasma drug conc)
NB that Vd is the vol. that would be required to contain all of the drug in the body at the same conc as in blood. For e.g Quinacrine has a very high Vd as most of the drug is bound to peripheral tissues |
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Term
| Vd is is determined via injecting a poor sucker and measuring his plasma conc on a time interval, what does the curve show? |
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Definition
| 2 Phases the first illustrating distributional (alpha) sharp drop and the second shows a elimination (Beta) phase. NB that each phase has its own unique T1/2 |
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Term
| What does extrapolating of the elimination curve give u? |
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Definition
| C-0 that is the plasma conc if the dose had instantly distributed |
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Term
| Kinetics of drug elimination (K-e) us given by? |
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Definition
| K-e = CL/ V-d => CL = K-e X V-d (NB that K-e = 0.693/ T 1/2) |
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Term
| Half-life in kinetics of drug elimination is (50% for T1/2 1, 75% for T1/2 2, 90% for T1/2 3.3)? |
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Definition
| The time required to change the amount of drug in the body by 50% during constant fusion or elimination and NB that it usually takes 4 half lives to attain steady state and also to be eliminated. Note that dose or rate of infusion does not affect the T 1/2 and thus the time to reach Css (steady-state conc) |
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Term
| When drug conc exceeds Km then nonlinear kinetics is observed, which equation explains this relationship? |
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Definition
Michaelis-Menten
Rate of elimination = (Vmax X C)/ (Km + C)
NB that in the nonlinear region, the increment in elimination rate becomes less as drug conc increases |
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Term
| When the drug conc is significantly higher then Km, the new equation is? |
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Definition
| Rate of elimination = (Vmax X C)/ C => Vmax (NB that this means that the rate of elimination is independent of drug conc and is said to have a zero-order i.e a constant amount vs a constant fraction as seen in 1st-order) |
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Term
| Which drugs (only a few) show zero-order elimination? |
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Definition
| Aspirin at high doses, Ethanol, Phenytoin (Antiepileptic) |
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Term
| Recall that for 1st-order kinetics the rate of elimination was exponential but what is it for zero-order? |
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Definition
| Linear (However NB that CL is not constant as it is in 1st-order, in this case it varies with conc of drug: CL = Vmax/ (Km + C), thus as C increases the CL decreases) |
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Term
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Definition
Dosing rate X dosing interval
(Dosing rate-ss = rate of elimination-ss = (CL X TC)/ F) |
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Term
| What are the two reasons to use a loading dose? |
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Definition
| If the therapeutic conc needs to be achieved rapidly and the Vd is large. Loading dose = (Vd X TC)/ F |
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Term
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Definition
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Term
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Definition
| Infusion rate/ CL (NB that if infusion rate is doubled, steady-state plasma conc is doubled) |
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Term
| Half-life doesnt depend on the dose but depends on? |
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Definition
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Term
| Unlike IV administration the fixed doses show? |
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Definition
| fluctuations thus no Scc. NB that upon giving multiple IV injections with intervals under 4 T1/2, the drug accumulates until the rate of loss equals the rate of administration |
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Term
| Any drug not given by continous IV has to? |
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Definition
| Oscillate about a mean but it can still reach a Scc |
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Term
| Accumulation factor (AF) is? |
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Definition
1/ Fraction lost in one dosing interval => 1/ (1 - Fraction remaining)
NB that the AF predicts the ratio of the peak Css to peak conc after first dose --> thus PC-ss = PC1 X AF |
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Term
| What is the maintenance dose calculation? |
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Definition
| Dose = (dosing rate/ F) X dosing interval |
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