(ADM) E Flashcards
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
in what kind of drugs is equilibrium via reabsorption hardly ever achieved?
in polar strong acid and basic drugs
what is normal urine pH?
4.5-7.5
give an example of an drug affected by urine pH?
amphetamine (people take Na bicarb with it to allow for more reabsorption)
when is renal CL dependent on urine flow?
when reabsorption tends to equilibrium (so not in strong acidic or basic polar drugs)
when is dose adjustment needed in renal disease?
- if elimination for that drug is mainly via the kidney
- if drug has narrow TW
- if drug forms active metabolites
- if they have impaired metabolism (as 2 probs now)
which one mechanism of renal excretion is active rather than the other 2 which are passive?
secretion - uses transporters
