Diuretics Flashcards
Kidney Functions
Water/electrolyte balance
BP regulation
Excretion
Endocrine functions (renin, 1-alpha-hydroxylase [Vit-D], erythropoietin [RBC productiobn])
Three main functions of nephron
Filtration
Reabsorption
Secretion
Strength of diuretics
Loop<Thiazide<Vasopressin
Natriuretic
Increase renal sodium excretion
Aquaretic
Increase solute-free water excretion
Osmotic diuretics, ex: Mannitol
Filtered in the kidneys but not reabsorbed
Occurs in the proximal tubule, descending limb of loop
Increase water excretion and small Na+ excretion
I: acute renal failure, enhance urinary excretion following overdose, reduce acute intraocular/intracranial pressure
SE: hyponatremia (causes headache, nausea, vomiting), expansion of fluid volume, acute kidney injury
C: anuria, dehydration, heart failure due to transient expansion of extracellular fluid volume, renal impairment
Carbonic Anhydrase (CA) Inhibitors ex: Acetazolamide
Inhibits CA, more NaHCO3 kept in urine and not reabsorbed
Leads to alkaline urine, acidic body, metabolic acidosis
Occurs at proximal convoluted tubule
Diuretic effect only occurs for a few days as NaCl reabsorption increases as bicarb is depleted
I: metabolic alkalosis, glaucoma (reduce forming aqueous humor), infantile epilepsy, acclimation to high altitutde (to decrease CSF formation and lower pH of CSF and brain), urinary alkalization to solubilize acidic drugs
SE: renal stones (due to Ca less soluble in alkaline pH), rashes, interstitial nephritis, hypokalemia and hypophosphatemia
Causes tubular reabsorption of weak basic drugs (like apmhetamines)
C: patients with hepatic cirrhosis (decreases excretion of ammonium leading to hyperammonemia and hepatic encephalopathy)
Dapagliflozin
Farxiga
Empagliflozin
Jardiance
Canagliflozin
Invokana
SGLT2 Inhibitor
Inhibition of sodium glucose contransporter 2 (SGLT2)
I: DM (increases glucose excretion), heart failure (BP lowering due to slight diuretic effect)
SE: Increase of genital fungal infection and UTI, low incidence of hypoglycemia, ketoacidosis, Invokana has increased risk of lower extremity amputation
Loop diuretics
Furosemide, bumetanide, torsemide, ethacrynic acid
Inhibits Na/K/2Cl carrier by combining with Cl- binding site, prevent reabsorption of electrolytes
Occurs at ascending limb of loop of Henle
MOST POWERFUL DIURETIC
Increases renal blood flow
I: edema, hypertension if GFR < 30mL/min, hyperkalemia/hypercalcemia, acute renal failure (blood flow increased), anion overdose
SE: hypovolemia/hypotension, low electrolytes, metabolic alkalosis (excretion of H+), hyperuricemia (problem for gout patients), slight hyperglycemia, ototoxicity, allergic reactions since these are sulfonamides (except ethacrynic acid)
Protein-bound
Secreted by organic acid transport mechanism
Lasix has t1/2 of 90 min and duration of 2-3 hours (best to take in the morning so as not to interfere with sleep)
C: Sulfonamide allergies, excessive use can cause hepatic cirrhosis, renal failure, heart failure, caution with gout
Thiazide diuretics
HCTZ, chlorothiazide, chlorthalidone, metolazone, indapamide
Inhibits Na/Cl contransporter by binding to Cl- site
Distal convoluted tubule
Increased excretion of Na and Cl, mild to moderate diuretic response, mild vasodilation effector
Low-ceiling of effect, most receive 12.5-25 mg, high concn don’t have much effect, but do increase side effects
I: HTN, mild heart failure, severe resistant edema (synergizes with loop diuretic), nephrolithiasis
SE: hyponatremia/kalemia/magnesemia, HYPERcalcemia, HYPERuricemia, HYPERglycemia, HYPERlipidemia, erectile dysfuntion, allergic rxn and photosensitivity to sulfonamide moiety
Chlorothiazide is the only thiazide available as IV
Chlorthalidone has much longer t1/2 (47 hours)
C: excessive use, caution with gout, considered ineffective when creatinine clearance < 30 mL/min
Potassium-Sparing diuretics
Aldosterone works on an intracellular receptor with ATP to pump Na+ out and K+ in the cell, K+ then can enter urine
Aldosterone antagonists (spironolactone, eplerenone, finerenone) compete with aldosterone to inhibit K+ secretion into cell
ENaC inhibitors (amiloride, triameterene) inhibit Na+ reabsorption (causes reduced K+ excretion)
I: prevent hypokalemia when combined with loop diuretics or thiazides
Resistant hypertension
Aldosterone antagonists in heart failure
Spironolactone has anti-androgenic effects (acne, hirsutism, premenstrual syndrome polycystic ovary)
Finerenone is a selective non-steroidal mineralocorticoid receptor antagonist, used for CKD associated with DM2
SE: hyperkalemia (bad for heart), metabolic acidosis, spironolactone can cause gynecomastia, menstrual disorders, testicular atrophy
DI: Strong CYP3A4 inhibitors can increase levels of eplerenone and finerenone but not spirolactone
C: renal insufficiency can cause fatal hyperkalemia
Vasopressin (ADH) Antagnoists
Conivaptan (IV) and Tolvaptan (Oral-more selective for V2 in kidney)
V1a, V1b, (Oboth in vasculature and CNS) and V2 (kidney) are vasopressin receptors
Causes an aquaretic effect (increase secretion of water but not electrolytes), results in increase of serum sodium concn.
I: hypervolemia, euvolemic hyponatremia, Syndrome of Inappropriate secretion of Antidiuretic Hormone (SIADH), hypothyroidism, adrenal insufficiency, live cirrhosis, nephrotic syndrome
SE: Polyuria, thirst, hypernatremia
CI: hypovolemia, anuria
