Diuretics Flashcards
Three basic renal fxns
filtration, reabsorption, secretion
-reabsorb substances that body needs, maintain acid-base balance, excrete waste and foreign products
NaCl movement will result in
water movement- osmotic equilibrium
-increasing or decreasing Na+ reabsorption the kidney increases or decreases body fluid volume
Diuretic drugs act by
blocking sodium and chloride reabsorption to inc osmotic pressure in tubules, which prevent osmotic reabsorption of water and increases urine volume
Drugs acting early (loop diuretics) will produce
greatest diuresis
Drugs acting late (potassium sparing diuretics) result in
weaker diuresis
Clinical apps for diuretics
heart failure (loop diuretics), htn (thiazide diuretics), acute/chronic renal failure, nephrotic syndrome, cirrhosis
Acetazolamide
- BlocksNaHCO3 reabsorption, and blocks Na reabsorption
- Effectiveness diminishes over several days because bicarbonate depletion enhances NaCl reabsorption
- Mainly used to treat glaucoma because ciliary body secretes bicarbonate to increase intraocular pressure– acetazolamide will decrease pressure
Carbonic Anhydrase inhibitors
Act on proximal convuluted tubule
-Oral and opthalmic preparations available
Toxicities: hyperchloremic metabolic acidosis, alkalinizing urine can cause calcium phosphate salts. can cause renal potassium wasting because more Na reaches collecting duct, more K is secreted
Sodium Glucose Cotransporter 2 (SGLT2) inhibitors
Not diuretics!
- 3rd line tx for type 2 DM
- Dapagliflozin, canagliflozin, empagliflozin
- Inhibits Na, Glucose reabsorption to reduce hbA1c
- Leads to weight loss
Loop diuretics
Furosemide, butanemide, torsemide, ethacyrnic acid (not sulfonamide derivative)
- Inhibits Na/K/2Cl cotransporter- decreased NaCl reabsorption
- work on ascending limb of henle’s loop
- Also, additional Mg, Ca excretion because lower K potential difference cannot drive Mg and Ca to be reabsorbed paracellularly (Ca will be reabsorbed in distal tubule, but Mg will be excreted leading to hypomagnesemia)
- Most effective diuretics available
- Eliminated by tubular secretion and filtration
Hypokalemia caused by loop diuretics
Inc delivery of Na to distal convoluted tubule–> enhances K and H secretion
Loop diuretics and renin release
Reduced NaCl reabsorption– more Na in tubular fluid–> reduced NaCl influx into macula densa –> inc secretion of prostaglandins–> increased renin secretion (from juxtaglomerular cell)
Clinical use of loop diuretics
- relief pulmonary edema
- Hypercalcemia
- htn (only if thiazides do not work)
- severe hyperkalemia (enhance K secretion)
- acute renal failure
Loop diuretics AE
- ototoxicity (reversible) because Na/K/2Cl transporter in ear for transport for endolymph production in cochlea
- hyperuricemia and gout attacks- hypovolemia associated inc uric acid reabsorption in proximal tubule
- allergic reactions (more common with sulfonamides)
- hypokalemia (can lead to arrythmias)
- dehydration and hyponatremia
Thiazide and Thiazide like diuretics
- names end in thiazide
- All are sulfonamides
- Inhibit Na/Cl- cotransport
- Enhanced Ca2+ reabsorption bc of inc Na gradient across basolateral membrane in distal convoluted tubule
- more effective antihtn in AA and elderly
- can lead to hyperuricemia because secreted by same system as uric acid
- inc K+ secretion in collecting duct- hypokalemia
- reduce Ca2+ excretion by enhancing reabsorption (decreased Na+ in)
Thiazide like drugs
-Chlorthalidone, indapamide, metolazone, guinethazone
Clinical uses for thiazides
- htn at low dose
- chf at higher dose second to loop diuretics
- nephrolithiasis for hypercalciuria
- nephrogenic diabetes insipidus to reduce polyuria and polydipsia (not known how it works bc pts already lose a lot of water)
AE for thiazides
hyperuricemia, hypokalemic metabolic alkalosis, hyperglycemia, hyperlipidemia, hyponatremia
- allergic rxns- photosensitivity
- hemolytic anemia, thrombocytopenia, acute necrotizing pancreatitis
- weakness, fatigability, ED in elderly men
Potassium sparing diuretics
- Act on collecting tubule
- Act on transport mechanisms that reabsorb Na (Na channel)- which is regulated by aldosterone
- high aldosterone, more Na reabsorbed, which causes K to be secreted
- both classes of drugs cause reduced K secretion
- weak diuretics, used in combination with loop or thiazide to reduce hypokalemia
K sparing diuretics clinical uses
-used for chf, primary mineralocorticoid hypersecretion (ACTH), secondary aldosteronism
aldosterone antagonists
- potassium sparing
- eplerenone, spironolactone
- aldosterone binds to receptors and increases Na+ reabsorption and K, H secretion– this mechanism will be blocked
Na channel blockers
- potassium sparing
- Amiloride, triamterene
- block apical Na+ channels to cause loss of potential (decreases driving force for K secretion) and reduce K and H secretion
Potassium sparing duretics toxicity
-hyperkalemia, hyperchloremic metabolic acidosis (H secretion reduced), gynecomastia (spironolactone), kidney stones with triamterene
Vaptans: ADH antagonists
- conivaptam, tolvaptan
- ADH regulates number of aquaporins in luminal mmebrane of collecting tubule
- Dilutes urine
- vasopressin receptor antagonists
- inhibit effects of ADH
- Used to manage inappropriate ADH secretion, and added to drug regimen of CHF when ADH elevated
- Na needs to be monitored closely
Osmotic diuretics
- Mannitol
- Filtered by glomerulus but not reabsorbed–> inc osmolarity of ultrafiltrate and prevents water reabsorption–> promotes water diuresis
- used for emergency situations- reduce intracranial pressure
- IV
- severe dehydration, hypernatremia, headache, nausea, vomiting
In HF, diuretics will
reduce ECF volume–> reduce preload–> reduce cardiac work
-first choice- furosemide (ethacrynic acid if allergic to sulfonamides)
-
Htn, diuretic use
Thiazides
- chlorathalidone (longer 1/2 life) at low dose for htn (high dose for diuresis)
- monotherapy for mild to moderate htn
Which diuretic for GFR >30 ml/min
thiazide diuretics
Which diuretic for GFR <30 ml/min
loop diuretics
