Diuretics DSA I Flashcards
topical ophthalmic CAIs
brinzolamide
dorzolamide
diuretics
increase sodium excretion and amount of urine produced by kidney
diuretic
increases urine volume
natriuretic
increased renal sodium excretion
K in proximal tubule
paracellular pathway
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
straight segment of proximal tubule
acid secretory systems
-organic acids to lumen from blood
thin descending loop
water reabsorption
thin ascending loop
water and ion/solute impermeable
thick ascending limb
Na/K/2Cl cotransporter
NKCC2 or NK2Cl
dilutes luminal fluid
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
distal convoluted tubule
Na/Cl cotransporter calcium channels (regulated by PTH)
diuretic induced changes in K
occur in collecting tubule
ENaC
Na channels in collecting tubule
-more Na to CT > more K out of cell > hypokalemia
aldosterone
increases ENaC and Na/K ATPase
-more Na reabsorption and K secretion
ADH
aquaporins to apical membrane in collecting tubule
-V2 receotpr
regulated by serum osmolality and volume status
alcohol
decreased ADH release and increases urine production
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
CAI toxicity
- metabolic acidosis and bicarbonatirua
- renal stones - calcium salts insoluble basic pH
- hypokalemia
- drowsiness and parasthesias
- sulfa allergy
CAI contraindications
-cirrhosis - decreased urine pH - less ammonia released-
>hyperammonemia and hepatic encephalopathy
-hyperchloremic acidosis or COPD
>worsen metabolic or respiratory acidosis
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
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)
loop diuretic mechanism
(-) Na/K/2Cl cotransporter
- block Na, K, Cl, Mg, Ca transport
- induce prostaglandin synthesis
- increased K excretion
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
sulfa loop diuretics
furosemide, bumetanide, torsemide
-cause sulfa allergies
contraindications for loop diuretics
- sulfa allergy
- hepatic cirrhosis, renal failure, heart failure
- postmenopause osteopenia - hypocalcemia
- aminoglycoside interaction
- lithium interaction
- digoxin interaction
loop diuretic drug interactions
aminoglycoside - ototoxicity
lithium
digoxin
loop diuretics clinical use
- edematous states
- HTN and heart failure
- mild hyperkalemia
- ARF
- anion overdose - bromide fluoride, iodide
- hypercalcemic states
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
chlorothiazide
not lipid soluble - given IV
chlorthalidone
long acting thiazide diuretic
-T1/2 - 47 hours
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
contraindiciations for thiazide diuretics
- diabetics
- efficacy reduced when NSAIDs and COX-2 inhibitors co-administered
- hepatic cirrhosis, renal failure, heart failure
thiazide diuretic clinical use
- HTN and heart failure
- nephrolithiasis (due to hypercalciuria)
- diabetes insipidus
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)
K-sparing - MR antagonists pharmacy
spironolactone and eplerenone
- oral admin
- first pass effect
- eplerenone - greater affinity for MR
K-sparing - Na channel inhibitor pharmacy
amiloride and triamterene
- oral admin
- triamterene - first pass (give more than amiloride)
- amiloride - no first pass
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**
only diuretics not requiring access to lumen
MR antagonists - K sparing
K-sparing ENaC (-)
block ENaC in collecting tubule
-reduced K secretion**
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
K-sparing contraindications
chronic renal insufficiency
- use with NSAIDs, beta-blockers, ACE (-), ARB
- liver disease
- strong (-) of CYP3A4 - increased levels of eplerenone
K-sparing clinical use
hyperaldosteronism
-Conn’s syndrome, heart failure, hepatic cirrhosis, nephritic
-thiazides and loop diuretics can cause secondary hyperaldosteronism (use K-sparing to stop this)
MR antagonists - heart failure
