(ADM) E Flashcards
(30 cards)
define CL
the apparent volume of plasma completely cleared of drug per unit time
2 drugs with the same CL would only have the same half life if…
they have the same Vd
why is CL different in different drugs?
- inefficient extraction through that elimination organ
- additivity of CL, some drugs are cleared in more than 1 organ
what are the normal blood flow values of:
- liver
- kidney
- cardiac output
liver = 1300-1500ml/min
kidney = 1100ml/min
cardiac output = 6000ml/min
what value of Eh is high extraction ratio?
> 0.7
<0.3 is low so hardly eliminated by liver
what is the equation to describe F?
F= Fa . FG . FH
what does it mean that half life is a combined parameter?
influenced by both Vd and CL
why is the liver highly perfused?
high blood flow because has 2 blood supplies; one from hepatic artery and one from portal vein (total approx 1.5L/min)
how can u increase hepatic blood flow?
bed rest, thyrotoxicosis, isoprenaline
how can u decrease hepatic blood flow?
exercise, heart failure, propranolol
give an example of enzyme induction?
rifampicin
smoking and clozapine
give an example of reversible enzyme inhibition and irreversible
reversible: ketokonazole
irreversible: statins and furanocourmarins
what causes liver cirrhosis?
excessive alcohol
hepB and hepC
for a drug to be eliminated into the bile, what are the requirements?
- presence of transporters as takes place by active facilitated transport
- polar molecule
- large molecule (>350MW)
give an example of a drug which is NOT metabolised in liver so excreted unchanged in the kidney?
metformin (by OCT1 transporters)
which also has a very high Fu (none is bound)
what info do you have about the perfusion of the kidney?
highly perfused - gets 20% of cardiac output
what is normal GFR?
120ml/min
if a drug is completely unbound, what route of renal elimination does it go down?
filtration - as this process is only for unbound drugs!
GRF is …
usually constant and relatively indpendant of renal blood flow
how does active tubular SECRETION work?
facilitates excretion by adding drug to tubular fluid and uses transporters so is a saturable process!
what transporters are involved in secretion?
uptake: OAT1 (anionic e.g. penG) and OCT1 (cationic e.g. metformin)
efflux: MRP and MATE
what enzymes are found in proximal tubule of kidney?
metabolic GLUT enzymes
what is the normal urine flow value?
1ml/min
reabsorption is a passive process, what does this mean?
doesn’t need energy to transporters etc
occurs passively for UNBOUND and NONIONISED LIPOPHILIC drugs - so drugs in this form can cross the membrane and be rebabsorbed
