Tricky topic pt 4 Flashcards
if a drug is ionised how can it pass the membrane
via solute carriers (SLC)
types of SLC
Organic cation transporters
Organic anion transporters
–> lots in proximal tubule
bioavailability equation
F= the amount reaching systemic circulation / total drug given IV
volume of distribution
drug dose / [plasma drug]
body compartments
plasma
interstitial
intracellular
excretion via the kidneys
1) glomerular filtration
2) proximal secretion
3) distal tubular reabsorption
codeine converted to
morphine –> stronger agonist
what do phase I enzymes do to drug
oxidation and reduction reactions
what do phase II enzymes do to the druyg
sulphation
N-acetylation
HRH
reduced functional reserve
CYP450 can be
inducted or inhibited
CYP450 induction
increased CYP450 (e.g. high translation rate) means that the drug gets metabolised too quickly (inactive) and decreases plasma conc- doesnt have desired therapeutic effect
example of drug that can cause induction
CBZ- antiepiletic
CYP450 inhibition
not enough CYP450 to metbaolise drug = high plasma conc, increase dtherpaetuic effect
example of CYP450 inhibition
grapefruit
proximal tubule has high expression of
OATs and OCTs
urine pH
6-7.5
muscularis externa in GI - inner
circular
muscularis externa in GI - outer
longitudinal
muscularis externa- stomach
oblique
circular
longitudinal
muscularis externa in bladder
opposite way round
clearance
the vol of plasma cleared of drug/ unit time
ml/m
body clearance =
hepatic clearance and renal clearance
first order drugs
cleared proportional to concentration
- predictable
- enough enzyme to clear
shape of graph for first order drugs
linear
zero order is
non proportional and therefore non predictable (half life)
shape of graph for zero order drugs
non linear
why are zero order drugs non proportional
reliant on functional reserve of enzymes
who should not take zero order drug
those who lack functional reserve
- elderly and young
- HRH
- polypharmacy
