Pharmacology Flashcards
bioavailability
AUCx/AUCiv
IV drugs bioavailability=1
volume of distribution
Q (dose)/ Cp (plasma concentration)
constant value for a given drug, depends on which compartments
clearance
CL= UV/Cp
Ke (equilibrium of clearance)
CL/Vd
half life equation
- 7 Vd/ CL or
0. 7/Ke
maintenance dose
MD= (Cp *CL *t)/ F
t= dosing interval
loading dose
LD= (Cp*Vd)/ F
acetazolamide moa
carbonic anhydrase inhibition, blocks generation of H+ in cell which lowers Na reabsorption
acetazolamide toxicity
met acidosis (also blocks bicarb reabsorption)
hypokalemia- high Na and water delivery to distal segments
loop diuretic examples and moa
furosemide. torsemide, bumetanide, etharcrynic acid
inhibit NKCC on loop of henle- reduce Na reabsorption
loop toxicities (4)
hypokalemia- more Na and water delivery, RAAS activation from volume loss (more potent w/ loop)
met alkalosis- aldo promotes H+ secretion along w/ K+
hypocalcemia/hypercalciuria- less Na thru NKCC means less K is secreted thru ROMK, loss of the lumen positivity that normally drives Ca reabsorption paracellularly
-can drive formation of kidney stones, nephrolithiasis
hyperuricemia/gout- compete w/ same proteins for secretion as urea (OAT1, 2, 4, 10)
thiazide examples
HTCZ, chlortalidone, metolazone
thiazide moa
NCC block at the DCT, less potent than loop diuretics
thiazide toxicity (5)
hypokalemia
hypercalcemia- reduciton in intracellular Na causes more activity at basolateral Na/Ca exchanger (moving Ca into interstitium) which stimulates Ca uptake from urine
met alkalosis- RAAS activation, less so than loops
hyperuricemia and gout- competition w/ urate secretion
hyperglycemia/DM- volume reduction causes sympathetic stim, less glucose uptake and a higher serum glucose
-loss of K reduces insulin stimulus, raising glucose
distinguish 2 moas of K sparing drugs
aldo receptor inhibs- sprionolactone and eplerenone
ENaC inhibs- amiloride, tramterene
both cause lack of ENaC fn
K sparing toxicities
met acidosis- inhibition of H secretion (positive lumen w/o Na reabsorption)
- from spironolactone- sex side effects from effects on testosterone (conversion to estradiol, loss of production, displaced from binding, competition at site of action)
- things like gynecomastia, impotence
mannitol moa
IV administration, not reabsorbed or secreted
osmotic force to retain water in urine
mannitol toxicities
hypokalemia and met alkalosis- increasing water content in urine lowers concentration of K and H, creating a gradient for them to be lost in urine
drugs causing T4 RTA (6)
ACEi, ARBs, cyclosporin, tacrolimus
also trimethoprim and NSAIDs (w/ AIN too)
drugs causing AIN (7)
- penicillin
- cephalosporin
- cipro
- vanc
- rifampin
- omeprazole (PPIs)
- lansoprazole
also trimethoprim and NSAIDs
ATN drugs (3)
- aminoglycosides
- ampB
- RC dyes (iohexol)
3 mechanisms for AIN reaction
neoantigen
antigen mimicry
haptenization- drug binds to immunogenic structure, new hapten is also immunogenic
all 3 are recognized by kidney dendritic cells and stimulate inflammation
3 clinical manifestations of AIN beside AKI
rash, fever, eosinophilia
reason for aminoglycoside toxicity
accumulate in renal tubular cells b/c have pKa above 9- positively charged at phys pH and bind to neg lipids in cell membranes
kill cells and result in ATN, can take weeks
gradations of aminoglycoside toxicity
higher affinity for phospholipids= more toxic
worst is neomycin, best is streptomycin
ampB mech for ATN
interacts w/ cholesterol in tubular membranes, makes them more permeable
overall cause of T4 RTA
impaired aldo signaling to kidney- causes hyperkalemia and acidosis
NSAID mech for RTA
block secretion of renin
TMP and CNI mech for RTA
reduce aldo sensitivity- TMP blocks ENac
CNIs reduce amount of aldoR
aldo independent effects of NSAIDs and ACEi on kidney fn
NSAIDs- cause efferent vasoconstriction (block PGs which normally dilate)
ACEi- block angII, dilating efferent (exacerbate loss of GFR w/ renal artery stenosis)
both serve to reduce GFR, urine output
