Flashcards in Diuretics DSA I Deck (43):
1
topical ophthalmic CAIs
brinzolamide
dorzolamide
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diuretics
increase sodium excretion and amount of urine produced by kidney
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diuretic
increases urine volume
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natriuretic
increased renal sodium excretion
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K in proximal tubule
paracellular pathway
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HCO3 reabsorption in PCT
initiated by action of Na/H exchanger
-luminal membrane of proximal tubule epithelial cell
membrane and cytoplasm carbonic anhydrase catalyze
> H2CO3 to CO2 and H2O at luminal membrane
> and CO2 and H2O H2CO3 in cytoplasm
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straight segment of proximal tubule
acid secretory systems
-organic acids to lumen from blood
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thin descending loop
water reabsorption
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thin ascending loop
water and ion/solute impermeable
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thick ascending limb
Na/K/2Cl cotransporter
NKCC2 or NK2Cl
dilutes luminal fluid
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thick ascending loop potassium?
increased K in cell - back diffusion of K out of cell
-lumen positive charge - drive reabsorption of Mg and Ca
-paracellular pathway
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distal convoluted tubule
Na/Cl cotransporter
calcium channels (regulated by PTH)
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diuretic induced changes in K
occur in collecting tubule
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ENaC
Na channels in collecting tubule
-more Na to CT > more K out of cell > hypokalemia
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aldosterone
increases ENaC and Na/K ATPase
-more Na reabsorption and K secretion
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ADH
aquaporins to apical membrane in collecting tubule
-V2 receotpr
regulated by serum osmolality and volume status
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alcohol
decreased ADH release and increases urine production
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CAI pharmacy
-oral administration
-secreted prox tubule (dosing change renal insufficiency)
-no first pass
-carbonic anhydrase (-) and NHE3 (-)
-45% bicarb reabsorption inhibited > acidosis (30 mins)
-decreased efficiency after multiple days of use
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CAI toxicity
-metabolic acidosis and bicarbonatirua
-renal stones - calcium salts insoluble basic pH
-hypokalemia
-drowsiness and parasthesias
-sulfa allergy
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CAI contraindications
-cirrhosis - decreased urine pH - less ammonia released-
>hyperammonemia and hepatic encephalopathy
-hyperchloremic acidosis or COPD
>worsen metabolic or respiratory acidosis
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CAI clinical use
-rarely as diuretics
-glaucoma - reduces aqueous humor formation
> decreased IOP
>topical formulations
-also used for urinary alkalinization, metabolic alkalosis, acute mountain sickness, epilepsy
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loop diuretic pharmacy
-oral administration
-eliminated by kidney - flitration/secretion
-half life correlates with secretion (act luminal side)
-coadmin with acids - reduced activity (same secretion)
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loop diuretic mechanism
(-) Na/K/2Cl cotransporter
-block Na, K, Cl, Mg, Ca transport
-induce prostaglandin synthesis
-increased K excretion
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loop diuretic toxicity
-overuse - hyponatremia, reduced GFR, circ collapse, thrombohemolysis, hepatic encephalopathy
-hypokalemic metabolic alkalosis (K and H loss)
-precipitate gout attacks (hyperuricemia)
-hearing loss (ototoxicity)
-sulfa allery (furosemide, bumetanide, torsemide)
-hypomagnesemia
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sulfa loop diuretics
furosemide, bumetanide, torsemide
-cause sulfa allergies
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contraindications for loop diuretics
-sulfa allergy
-hepatic cirrhosis, renal failure, heart failure
-postmenopause osteopenia - hypocalcemia
-aminoglycoside interaction
-lithium interaction
-digoxin interaction
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loop diuretic drug interactions
aminoglycoside - ototoxicity
lithium
digoxin
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loop diuretics clinical use
-edematous states
-HTN and heart failure
-mild hyperkalemia
-ARF
-anion overdose - bromide fluoride, iodide
-hypercalcemic states
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thiazide diuretics pharmacy
-oral admin
-secreted in PCT (competes uric acid)
-enhanced Ca reabsorpion (PCT volume contraction/DCT enhanced Na/Ca basolateral exchange)
-weak CAI
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chlorothiazide
not lipid soluble - given IV
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chlorthalidone
long acting thiazide diuretic
-T1/2 - 47 hours
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thiazide diuretic toxicity
hypokalemic metabolic acidosis and hyperuricemia
-decrease glucose tolerance - hyperglycemia (impaired insulin release from pancreas)
-hyperlipidemia
-hyponatremia
-weak, fatigable, paresthesia, impotence
-sulfa allergy
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contraindiciations for thiazide diuretics
-diabetics
-efficacy reduced when NSAIDs and COX-2 inhibitors co-administered
-hepatic cirrhosis, renal failure, heart failure
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thiazide diuretic clinical use
-HTN and heart failure
-nephrolithiasis (due to hypercalciuria)
-diabetes insipidus
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HCTZ in diabetes insipidus
nephrogenic
-inhibits Na/Cl tranport in DCT
> increased diuresis and reduce ECF volume
> decreased GFR
> tubuloglomerular feedback
> less sodium and water to collecting duct (decrease urine output)
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K-sparing - MR antagonists pharmacy
spironolactone and eplerenone
-oral admin
-first pass effect
-eplerenone - greater affinity for MR
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K-sparing - Na channel inhibitor pharmacy
amiloride and triamterene
-oral admin
-triamterene - first pass (give more than amiloride)
-amiloride - no first pass
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K-sparing MR antagonist mechanism
competitive (-) of aldosterone binding to MR
-decreased ENaC and Na/K ATPase activity
-reduced Na reabsorption in collecting tubule
-reduced K secretion****
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only diuretics not requiring access to lumen
MR antagonists - K sparing
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K-sparing ENaC (-)
block ENaC in collecting tubule
-reduced K secretion****
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K-sparing toxicity
hyperkalemia - increased w/ renal disease, RAAS (-), or when combined with other K-sparing diuretics
-metabolic acidosis
-gynecomastia, impotence, BPH (bc MR antagonists are steroids)
-triamterene > kidney stones with indomethacin
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K-sparing contraindications
chronic renal insufficiency
-use with NSAIDs, beta-blockers, ACE (-), ARB
-liver disease
-strong (-) of CYP3A4 - increased levels of eplerenone
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