Diuretics Flashcards
Acetazolamide (Diamox) Type& indication
Used as a backup diuretic (weak); Glaucoma (reduction of aqueous humor), urinary alkalinization (to treat overdose or some kidney stones), high-altitude sickness.
Acetazolamide (Diamox) site of action
PCT, use organic acid transporter to get into lumen, modifies SALT excretion.
Acetazolamide (Diamox) MOA
Carbonic anhydrase inhibitor.
Acetazolamide (Diamox) Effects
body bicarb is excreted (metabolic acidosis) along with Na. Na/K pump in Collecting Tubule gets extra sodium load and wastes K.
Acetazolamide (Diamox) Route of Admin
oral
Acetazolamide (Diamox) Contraindication
Cirrhosis–increased urine pH (excretion of bicarb, base) causes less NH3 binding and increases serum NH3
Acetazolamide (Diamox) Adverse Effects
metabolic acidosis, hypokalemia, CaP stones (alkalynization of urine), drowsiness, paresthesias and hypersensitivity rxns (allergy and then can’t use similar drugs).
Acetazolamide (Diamox) Notes/Reminder
Others we have to know: Dichlorphenamide (30x more potent than aceta); Methazolamide (5x more potent); Dorzolamide (topical for ocular, not systemic absorb)
Acetazolamide (Diamox) Urinary Electrolyte Pattern
+NaCl, +++NaHCO3, +K. Alkaline Urine. Alkaline urine can lead cause ppt of Calcium salts and formation of renal stones, also less excretion of ammonia!
Acetazolamide (Diamox) Serum Electrolyte Pattern
Acidosis in blood. Hypokalemia. Possible hyperammonemia if pre-existing hepatic issues.
Mannitol Type& indication
Osmotic diuretic. Used to maintain or increase urine volume (flush kidney of contrast dye or myoglobinemia, also ACUTE renal failure), reduce ICP (neuro), IOP (glaucoma)
Mannitol site of action
filtered at glomerulus, affects salt and water excretion mainly at PCT
Mannitol MOA
Osmotic diuretic.
Mannitol Effects
volume of urine is increased, will help maintain high urine flow (good if renal blood flow is reduced or overload from hemolysis or rhabdomyolysis). Reduce ICP and IOP.
Mannitol Route of Admin
IV
Mannitol PK
IV administration causes expansion of IV volume. Powerful diuretic effect in kidney. Is NOT orally absorbed–MUST give IV! Short t1/2!
Mannitol Adverse Effects
major toxicity due to increased plasma osmolality. With reduced GFR (CHF or renal failure), mannitol can be retained in ECF where it will draw H2O out of cells–see hyponatremia and pulmonary edema.
Mannitol More notes
other drugs classified with Mannitol but rarely used are: Glycerin, Isosorbide and Urea.
Furosemide (Lasix) Type& indication
Treatment of severe edematous states like CHF, Ascites, Acute Pulmonary Edema, Severe Hypercalcemia (like in malignancy). Also good for Hypercalcemia.
Furosemide (Lasix) site of action
TAL, use organic acid transporter to get into lumen, modifies SALT excretion.
Furosemide (Lasix) MOA
inhibits Na/K/Cl- transporter in loop of henle. K+ wasting, Ca wasting, hypokalemia
Furosemide (Lasix) Effects
huge diuresis, need to give pt. K+ as well.
Dehydration Hyponatremia
Hypokalemia
Hyperuricemia
Impaired diabetes control
Increased LDL/HDL
Hypomagnesemia Hypocalcemia
Ototoxicity
Furosemide (Lasix) PK
Very short 1/2 life–duration of action generally about 4h
Furosemide (Lasix) Contraindication
hypocalcemia (will worsen), diabetics (if on sulfonylureas will get hyperglycemic), watch heart patients (interaction w/B-Block, Digoxin and Quinidine), no renal insufficiency (will potentiate hyperkalemia), hyperuricemia (can lead to GOUT)
Furosemide (Lasix) Adverse Effects
OTOTOXICITY. Hypokalemic metabolic alkalosis (due to efflux of H+. ) *See note about uric acid handling with thiazides. *note that K-wasters can precipitate hypokalemia which is associated with arrythmias (ectopic pacemakers) and increased AP length can presuppose to EADs. This can mess up digitalis.
Furosemide (Lasix) Drug interactions
Aminoglycosides (potentiate oto and nephrotoxicity), Anticoagulants (increased activity, prone to bleeds), B-Blockers (hyperglycemia /lipidemia /uricemia as well as increased levels of propranolol, Digoxin (risk of hypokalemia and increased action), NSAIDS (reduced effect, increased risk of salicylate toxicity), Quinidine (increased risk of torsades de pointes), Steroids (increased risk of hypokalemia)
Furosemide (Lasix) Notes/Reminder
Bumetanide (40X more potent, shorter t 1/2), Torsemide (Longer 1/2 life, longer duration, oral absorb), Ethacrynic Acid (last resort, no CA inhibition, can be nephro/oto toxic)
Furosemide (Lasix) More notes
Thick ascending limb is impermeable to H20! Note that loop diuretics increase blood sugar if pts on sulfonylureas (problem for diabetics, insulin resistance).
Furosemide (Lasix) Urinary Electrolyte Pattern
++++NaCl, ++K, +H Acidotic urine. Increased Ca in urine which can lead to CaP kidney stones.
Furosemide (Lasix) Serum Electrolyte Pattern
Alkalosis in blood. Hypokalemia. Decreased Ca/Mg. (Ca is coupled to K+ reabsorption in Loop of Henle).
Hydrochlorothiazide Type& indication
Used for HTN, CHF, reduce Ca excretion to prevent kidney stones. Also: Nephrogenic Diabetes Inspidus.
Hydrochlorothiazide site of action
DCT, use organic acid transporter to get into lumen, modifies SALT excretion.
Hydrochlorothiazide MOA
inhibits Na/Cl cotransporter in distal tubule. Not as strong because most Na has already been pumped. Protective against kidney stones.
Hydrochlorothiazide Effects
Thiazide, K+ wasting, Ca2+ saver. increase volume of urine moderately. K+ wasting due to increased Na presented to collecting duct. hyperglycemia, increased LDL/HDL, hyponatremia, hypokalemia, hypercalcemia
Hydrochlorothiazide Route of Admin
oral
Hydrochlorothiazide PK
good oral absorption and LONG half life, duration of action is 6-12 hours which is much longer than loop diuretics.
Hydrochlorothiazide Contraindication
hypercalcemia (will worsen), watch heart patients (interaction w/B-Block, Digoxin and Quinidine), no renal insufficiency (will potentiate hyperkalemia), hyperuricemia (can lead to GOUT),
Hydrochlorothiazide Adverse Effects
Metabolic alkalosis due to efflux of H+. Uric acid handling is mainly in proximal tubule but Thiazide (DCT) and Loop Diuretics (LOH) increase net reabsorption or reduce secretion leading to hyperuricemia in some cases.
Hydrochlorothiazide Drug interactions
Anticoagulants (decreased activity, prone to clots), B-Blockers (hyper glycemia/lipidemia/uricemia as well as increased levels of propranolol), Carbamazapine/Chlorpropamide (hyponatremia), Digoxin (risk of hypokalemia and increased action), NSAIDS (reduced effect, increased risk of salicylate toxicity), Quinidine (increased risk of torsades de pointes), Steroids (increased risk of hypokalemia)
Hydrochlorothiazide Notes/Reminder
Cholorothiazide (1/10 the potency), Cholorthalidone (same potent, 1/2 life 44 h) Metolozone (10x more potent), Indapamide (20x more potent),
Hydrochlorothiazide More notes
Metolozone & Indapamide are the only ones that can be used if GFR is low. Remember Ca mech going on at DCT.
Hydrochlorothiazide Urinary Electrolyte Pattern
++NaCl, +H+, +K Acidotic Urine. Decreased Ca in urine which is protective against kidney stones.
Hydrochlorothiazide Serum Electrolyte Pattern
Alkalosis in blood. Hypokalemia. Increased Ca (Na affect on Calcium transporters in DCT)
Spironolactone Type& indication
Used for primary (Conn’s Syndrome)/secondary hyperaldosteronism, drug of choice for edema assoc w/liver cirrhosis, As a combination therapy for HTN.
Spironolactone site of action
Aldo-R inhibitor, Collecting Tubule. Gets into cell via basolateral (blood) side-no transporter needed.
Spironolactone MOA
competitive inhibitor of aldosterone receptor (intra-cytoplasmic R) Anti-androgenic effects as well. (DHT R)
Spironolactone Effects
K+ sparing diuretic, mild diuresis, interferes directly with action of aldosterone
Spironolactone Route of Admin
oral
Spironolactone PK
very SLOW onset (for non-emergent cases), very SLOW offset (24-48h). metabolized in the liver
Spironolactone Contraindication
hyperkalemia or in patients that can have a state causing hyperkalemia (diabetes, myeloma, renal dx, renal insuff). Or with ACEI’s or ARBS (hyperk risk!)
Spironolactone Adverse Effects
Hyperkalemic metabolic acidosis (due to sparing of H+.) Gynecomastia, antiandrogenic effects (not w/newer eplerenone)
Spironolactone Drug interactions
ACE inhibitors/ATII inhibitors (block production of K-waster aldosterone–potentiate hyperkalemia situation), K+ supplements (due to risk of hyperkalemia), NSAIDS (can exacerbate hyperkalemia)
Spironolactone Notes/Reminder
Eplerenone, a newer one–does not have some of the side effects of Spironolactone.
Spironolactone Urinary Electrolyte Pattern
+NaCl, -K. Alkalotic urine. Decreased K in urine (interference w/natural site of K wasting, the CCT)
Spironolactone Serum Electrolyte Pattern
Acidosis in blood. May cause hyperkalemia. Most helpful in combo with a K waster like thiazide.
Amiloride Type& indication
K+ sparing diuretic, mild diuresis. Used for edema, hypertension. Mainly used in combo with K-wasting diuretics to spare K to treat HTN.
Amiloride site of action
CCT, use organic base transporter, modifies SALT excretion.
Amiloride MOA
blocks Na+ channels in the principle cells of collecting duct
Amiloride Effects
works on the channels that aldosterone promotes in CCT (does not interfere with aldosterone directly though)
Amiloride Contraindication
hyperkalemia, no ACEI’s or ARBS either.
Amiloride Adverse Effects
Hyperkalemic metabolic acidosis (due to sparing of H+.)
Amiloride Notes/Reminder
Also Triamterene which has a shorter 1/2 life than Amiloride.
Demeclocycline Type& indication
SIADH patients. Has been replaced in use with Tolvaptan.
Demeclocycline site of action
Collecting Duct: ADH-R, modify water excretion
Demeclocycline MOA
ADH antagonist.
Demeclocycline Adverse Effects
see Tolvaptan, selective ADH receptor antagonist.
Demeclocycline Drug interactions
- do not confuse these with ADH agonist desmopressin
Demeclocycline Notes/Reminder
replaced by Tolvaptan group (selective)
Lithium Type& indication
Main use is in Psych. Can be nephrotoxic, so is not used really to treat SIADH.
Lithium site of action
Collecting Duct: ADH-R, modify water excretion
Lithium MOA
ADH antagonist,
Lithium Effects
can cause nephrogenic diabetes insipidus
Lithium Notes/Reminder
replaced by Tolvaptan group (selective)
Tolvaptan Type& indication
Use for patient w/Hyponatremia (dilutional) either Eu or Hypervolumia, where saline will worsen patient. SIADH, hypothyroidism, adrenal insufficiency, congestive HF, cirrhosis, nephrotic syndrome, small cell carcinoma (secretes ADH like substance) are examples.
Tolvaptan site of action
Collecting Duct: ADH-R, modify water excretion
Tolvaptan MOA
selective antagonist of Vassopressin (ADH) V2 receptor
Tolvaptan Effects
increase serum Na (keep Na) but increase H2O output (get rid of excess water)
Tolvaptan Contraindication
does not alter normal serum electrolyte balance!
Tolvaptan Notes/Reminder
replaces Demeclocycline/Li, other drugs like it are Lixivaptan and OPC-31260
Tolvaptan Urinary Electrolyte Pattern
very dilute urine
Tolvaptan Serum Electrolyte Pattern
increases serum Na
