Diuretics Flashcards
what kind of drugs were developed from sulfanilamides?
thiazides
what are the determinants of diuretics potency?
site of action, ability of downstream tubules to counter effects, ability to reach site of action
site of action for the majority of diuretics? exceptions?
majority act on the luminal (urinary) side; only the carbonic anhydrase and aldosterone inhibiting drugs act intracellularly (CA inhibitors also act luminally)
what are the sites of action for the major diuretics?
in order as one travels toward the urinary system: CA inhibitors (PCT), loop diuretics, Thiazides (DCT), K-sparing diuretics (CD)
name a carbonic anhydrase inhibitor
acetazolamide (Diamox/Diamox Sequel)
what’s are the relevant facts about carbonic anhydrase inhibitors? (acetazolamide)
Location of Action Potency Mechanism of Action Uses Side Effects
intracellular and extracellular location of action
half life is 13 hours (x4) 52 hours effective duration
fairly weak (6% reduction) due to reabsorption of NaCl in loop and distal tubule
mechanism of action: blockage of HCO3 reuptake affects Na/H antiport, prevents reuptake of Na
uses: glaucoma and/or treatment of metabolic alkalosis caused by other treatments
side effects: causes excretion of bicarb, can be beneficial
name some loop diuretics (four names, one brand name)
furosemide (Lasix); bumetanide; torsemide <- sulfonamide derivatives ethacrinic acid (not a sulfonamide derivative)
what are the relevant facts about loop diuretics? (furosemide (Lasix), bumetanide, torsemide)
location potency mechanism of action uses side effects
location of action: Loop of Henle (organic anion transport delivery)
potency: most potent (B>T>F)
mechanism of action: blocks the NKCC2 channel (apical NKCC channel)
uses: diuretic (major edematous states)
side effects: causes excretion of cations (NKCC dependent electronegativity is knocked out, causing positive ions to stay in urine) (hypokalemia, hypomag
depending on speed of delivery can cause blockage of NKCC1 (basolateral NKCC) throughout the body - ear is most susceptible ototoxicity and vestibule toxicity (ethacrynic acid is the worst)
what are the two most common mistakes made with the use of furosemide?
not giving enough dose
not giving the drug often enough (effective duration is only 6 hours - Lasix)
what are the relevant facts about thiazides?
location potency mechanism of action uses side effects
Location of Action: Distal CT (organic anion transport)
Potency: less than loop diuretics (DCT not responsible for much Na reabsorption)
Mechanism of Action: blocks the NaCl cotransporter (limits diluting ability not concentrating ability)
Uses: can be used as a diuretic in patients with hypocalcemia; can be used to attempt to prevent kidney stones (see side effect)
Side Effects: blockage of NaCl for some reason inhibits TRMP6 (a magnesium reuptake channel) which releases TRPV5 (a calcium reuptake channel) from inhibition, resulting in Calcium uptake in the distal tubule; furthermore, the reduction in EABV causes increased Ca reuptake in the proximal tubule; net effect is to greatly increase calcium reuptake in the kidney, preventing deposition and urolithiasis
hypomagnesia is not common but possible
hypercalcemia is possible
hypokalemia and hyponatremia and metabolic alkalosis are more common
what’s the contraindication for most thiazides? what’s the exception?
GFR < 30-40 ml/min; exception is metolazone
name the two types of potassium sparing diuretics; name examples of each
aldosterone inhibiting (mineralocorticoid inhibitors) & ENaC inhibitors
MC inhibitors: spironolactone and epleronone
ENaC inhibitors: amiloride and triamterene
Relevant information for ENaC K sparing diuretics?
Location of Action Potency Mechanism of Action Uses Side Effects Half-life
Location of Action - ENaC transporters on the luminal side of the membrane of the principal cell (organic cation transporters)
Potency - very weak diuretics (1-3%)
Mechanism of Action - directly block a sodium reuptake channel (ENaC)
Uses - diuretics for hypokalemics, secondary diuretic to prevent hypokalemia
Side Effects - Triamterene can cause crystallization in the urine - contraindicated for those with kidney stones
Half-life - 3 hours for triamterene; 6 hours for amiloride
relevant information for MC-inhibiting diruetics?
Location of Action Potency Mechanism of Action Uses Side Effects Contraindications
Location of Action - aldosterone receptors on the basolateral side of the principal cells (organic cation)
Potency - very weak (1-3%)
Mechanism of Action - blocks Na uptake by preventing aldosterone’s action
Uses - spironolactone is used for cirrhotic patients
Side Effects - spironolactone can bind to progesterone and androgen receptors and cause gynecomastia, menstrual irregularities and impotence
epleronone doesn’t have those problems but is pricey and new
Contraindications: all related to potassium balance:
high potassium diet, supplemented potassium, reduced GFR, ACE inhibitors, angiotensin receptor blockers, NSAIDs
