Pharmacology

Question 1

bioavailability

Answer 1

AUCx/AUCiv

IV drugs bioavailability=1

Question 2

volume of distribution

Answer 2

Q (dose)/ Cp (plasma concentration)

constant value for a given drug, depends on which compartments

Question 3

clearance

Answer 3

CL= UV/Cp

Question 4

Ke (equilibrium of clearance)

Answer 4

CL/Vd

Question 5

half life equation

Answer 5

0. 7 Vd/ CL or

0. 7/Ke

Question 6

maintenance dose

Answer 6

MD= (Cp *CL *t)/ F

t= dosing interval

Question 7

loading dose

Answer 7

LD= (Cp*Vd)/ F

Question 8

acetazolamide moa

Answer 8

carbonic anhydrase inhibition, blocks generation of H+ in cell which lowers Na reabsorption

Question 9

acetazolamide toxicity

Answer 9

met acidosis (also blocks bicarb reabsorption)

hypokalemia- high Na and water delivery to distal segments

Question 10

loop diuretic examples and moa

Answer 10

furosemide. torsemide, bumetanide, etharcrynic acid

inhibit NKCC on loop of henle- reduce Na reabsorption

Question 11

loop toxicities (4)

Answer 11

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)

Question 12

thiazide examples

Answer 12

HTCZ, chlortalidone, metolazone

Question 13

thiazide moa

Answer 13

NCC block at the DCT, less potent than loop diuretics

Question 14

thiazide toxicity (5)

Answer 14

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

Question 15

distinguish 2 moas of K sparing drugs

Answer 15

aldo receptor inhibs- sprionolactone and eplerenone

ENaC inhibs- amiloride, tramterene

both cause lack of ENaC fn

Question 16

K sparing toxicities

Answer 16

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

Question 17

mannitol moa

Answer 17

IV administration, not reabsorbed or secreted

osmotic force to retain water in urine

Question 18

mannitol toxicities

Answer 18

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

Question 19

drugs causing T4 RTA (6)

Answer 19

ACEi, ARBs, cyclosporin, tacrolimus

also trimethoprim and NSAIDs (w/ AIN too)

Question 20

drugs causing AIN (7)

Answer 20

• penicillin
• cephalosporin
• cipro
• vanc
• rifampin
• omeprazole (PPIs)
• lansoprazole

also trimethoprim and NSAIDs

Question 21

ATN drugs (3)

Answer 21

• aminoglycosides
• ampB
• RC dyes (iohexol)

Question 22

3 mechanisms for AIN reaction

Answer 22

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

Question 23

3 clinical manifestations of AIN beside AKI

Answer 23

rash, fever, eosinophilia

Question 24

reason for aminoglycoside toxicity

Answer 24

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

Question 25

gradations of aminoglycoside toxicity

Answer 25

higher affinity for phospholipids= more toxic worst is neomycin, best is streptomycin

Question 26

ampB mech for ATN

Answer 26

interacts w/ cholesterol in tubular membranes, makes them more permeable

Question 27

overall cause of T4 RTA

Answer 27

impaired aldo signaling to kidney- causes hyperkalemia and acidosis

Question 28

NSAID mech for RTA

Answer 28

block secretion of renin

Question 29

TMP and CNI mech for RTA

Answer 29

reduce aldo sensitivity- TMP blocks ENac CNIs reduce amount of aldoR

Question 30

aldo independent effects of NSAIDs and ACEi on kidney fn

Answer 30

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