you've been eliminated

unlike reality shows, you can't vote a drug off your system if you want to eliminate it.

a drug gets eliminated by either ZERO ELIMINATION CONSTANT or FIRST ORDER ELIMINATION.

a zero order elimination is when the plasma concentration of a drug decreases linearly with time:


a drug with first order elimination has a rate of elimination proportional to the drug concentration:



from the graph you can see, the more drug in the system (the higher the plasma conc.), the faster the drug is eliminated.

drugs are also metabolized in the system propr to elimination. there are 2 phases of this metabolism.

phase I includes reduction, oxidation and hydrolysis. it yields water soluble metabolites. sometimes a drug is activated after phase I metabolism. the cytochrome p450 system is connected to phase I. old patients lose phase I first!

phase II @ conjugation includes acetylation, glucuronidation, sulfation and yields inactive metabolites that are renally excreted.

pharma calculations recall

let's go over the 4 most basic pharma equations:

1. Vd (volume of distribution) = concentration of drug given (IV) / concentration of drug in plasma
   
   you have to take bioavailability (how much of the drug is subjected to first pass metabolism) into account if drug is not given IV.
   
2. clearance = (0.7 x Vd)/ t1/2
                            
                               or    K x Vd  (where K = elimination constant = 0.7 / t1/2 )
3. loading dose = concentration of steady state x Vd
   *conc of steady state = desired conc
   
4. maintenance dose = (concentration of steady state x clearance) / bioavailability                    

so for maintenance doses, you can see from the equation that it is determined by clearance. why do you need to know this? clearance rates are affected in patients with renal/ hepatic disease. in a patient with renal disease, maintenance dose is DECREASED (coz clearance is decreased), but Vd remains the same (does not depend on kidney function), therefore loading dose remains the same.

t1/2 is the amount of time it takes for a drug to reach 1/2 it's plasma concentration.

if you infuse a drug, it takes 4t1/2s to achieve a steady state of 94%. likewise, it take 4t/12s for 94% of said drug to be eliminated.

(remember that 1t1/2 = 50% of conc, 2t1/2s = 75% [50% + 25%], 3t1/2s = 87.5% and 4 t1/2s = 94%)

on my next post, we'll touch elimination constants and drug metabolism.