E2: Diuretics Flashcards
What drug class(s) acts in proximal tubule reabsorption
Carbonic anhydrase inhibitors
what drug class(s) acts in loop of Henle reabsorption
Loop diuretics
what drug class(s) acts in distal tubule reabsorption
Thiazide and related diuretics
what drug class(s) acts in collecting duct reabsorption
Potassium sparing diuretics
Antidiuretic hormone regulation
4 mechanisms of ion absorption in tubule cell
Na+/H+ exchange
Na+/K+/2Cl- co-transport
Na+/Cl- co-transport
Na+ entry through Na+ channels
Compare and contrast the acute and chronic effect of diuretics as antihypertensive therapy
Acutely, diuretics act to
-↓BP by causing diuresis
-↓ plasma vol & SV - ↓ CO & BP
-initial ↓ CO causes a compensatory ↑ in PVR
Over time,
-ECF and plasma vol returns to pretreatment levels and PVR falls below baseline
-↓PVR is responsible for LT hypotensive effects
-thiazides mobilize Na+/water from arteriolar walls to ↓ PVR and ↓BP
Which drug class is a derivative of sulfonamides
True thiazide diuretics (hydrochlorthiazide)
what drug class contains quinazolines or indoline structures
thiazide-like drugs (chlorthalidone, metolazone & indapamide)
Thiazide diuretics MOA, pharm effects (hydrochlorothiazide), indications
- inhibit Na+/Cl- cotransporter at distal tubule to increase excretion of Na+ and Cl- in urine
- ↑Ca2+ reabsorption in proximal tubule by increasing passive reabsorption and in distal tubule by decreasing Na+ which increases Na+/Ca2+ exchange in basolateral membrane
- induce expression of apical Ca2+ channels
↑ NaCl excretion, K+ wasting, ↓ urine Ca2+
HTN, mild HF, nephrolithiasis, nephrogenic diabetes insipidus
Thiazide diuretics uses
- HTN
- Nephrolithiasis (renal calculi, ↓ Ca2+ excretion aka kidney stones)
- nephrogenic diabetes insipidus
Thiazide diuretics ADR
Specific ADR of hydrochlorothiazide
electrolyte imbalances
CNS (dizziness, confusion, irritability)
Hyperuricemia
sexual dysfunction
HYPERURICEMIA, HYPERGLYCEMIA, hypoatremia
thiazide diuretic DI
combo w/other anti-HTN, monitor BP
NSAIDS ↑Na+ retention which antagonizes therapeutic effect of thiazides
Topiramate (↓K,↓Cl)
Digitalis: ↑arrhythmias
Lithium:↓ renal excretion of Li+, toxic
Allopurinol: ↑ allergic response
What patients are loop diuretics preferred over thiazides
CKD when est GFR is <30ml,min.1.73m2 and edema is present
Loop diuretics MOA
Inhibit Na+/K+/2Cl- cotransporter on the apical membrane of cells in the loop of Henle
Result in ↓ reabsorption of Na+ & Cl- –> ↑excretion in urine
↓ the positive transepithelial potential- causes marked ↑ in Ca2+ & Mg2+ secretion –> hypocalcemia & hypomagnesemia
Loop diuretics ADR
Hypotension & volume depletion
Hypokalemia
Alkalosis – due to enhanced H+ secretion
Mg+ wasting
Dose-related ototoxicity – caution w/aminoglycosides
Ethacrynic acid produces GI disturbances
Loop diuretics uses
-Pulmonary & peripheral edema associated w/CHF
-Other edematous conditions: liver cirrhosis and nephrotic syndrome
-Hypercalcemia: enhance Ca2+ excretion
-Hyperkalemia: enhance K+ excretion
-Less useful in treating htn
-Limited efficacy & short t1/2
-Availability more effective & better tolerated antihypertensive agents
Furosemide (Lasix)
Class
MOA
Uses
ADR
-Loop diuretic
-MOA: inhibit reabsorption of Na+ and Cl- by attaching to Cl- binding site of the Na+/K+/2Cl- cotransporters in TAL of Henle
Uses:
-HTN
-HF
-Acites
-Hypercalcemia
-Pulmonary edema
ADR
-Volume depletion
-↓ Na+, ↓Ca2+, ↓K+
-Hyperglycemia
↓-Mg–> ↓Ca2+ & tetany
-Hyperuricemia
-Metabolic alkalosis
Potassium sparing diuretics MOA and MOA of Aldosterone Antagonist
-Block epithelial Na+ channels (ENaC) in the principal cells of DCT & collecting ducts
-Na+ reabsorption is coupled w/K+ secretion – inhibition of Na+ reabsorption —> ↓K+ excretion
-K+ sparing diuretic – poor antihypertensive monotherapy; combination w/thiazides antagonize
-K+ loss –> ↓ risk of ventricular arrythmias
Aldosterone inhibitors ↓biosynthesis of new Na+ channels in principal cells via blockeing aldosterone receptors –> inhibition of Na+ reabsorption
Potassium sparing diuretic drugs and aldosterone antagonist drugs
Amiloride
Amiloride/HCTZ
Triamterene
Triamterene/HCTZ
Spironolactone and eplerenone
Use of potassium-sparing diuretics and use of aldosterone antagonists
adjunct w/thiazides or loop diuretics to prevent hypokalemia
- Adjunct w/thiazides/loop diuretics to
- prevent hypokalemia
- Heart failure
- Ascites in cirrhosis
- Acne & hair loss in women
- Male baldness – topical
- Diagnosis of primary hyperaldosteronism
ADR of potassium sparing diuretics and of aldosterone antagonists
Hyper kalemia: arrhythmias, metabolic acidosis & acute renal failure
Hyperchloremic metabolic acidosis-inhibit H+ secretion in parallel w/K+ secretion
Kidney stones: triamterene- slightly soluble & may precipitate in the urine
Aldosterone inhibitors also have:
Endocrine abnormalities: spironolactone may cause gynecomastia, breast tenderness…
Acetazolamide
Class
Use
MOA
ADR
CI
carbonic anhydrase inhibitors
Use: glaucoma, petit mal seizure (adjuvants), alkalinization of urine, acute mountain sickness
MOA: Reduce HCO3- reabsorption & Na+ uptake in PT
-Inhibit excretion of H+ and coupled Na+ uptake
-Prolonged use –> more alkaline urine & more acidic blood
ADR: monitor electrolyte disturbances, Severe K+ wasting, N, V, sedation, HA, renal calculi, metabolic acidosis
CI: Hepatic cirrhosis
RARELY used today
Mannitol
Class
Use
MOA
ADR
Class: osmotic diuretic
Use: prophylaxis of acute renal failure
MOA: agents are easily filtered, poorly reabsorbed; alter the diffusion of the water relative to Na+ by “binding water”; ↓Net reabsorption of Na+
ADR: headache, nausea
Mannitol and Urea
Class
Use
MOA
ADR
Class: osmotic diuretic
Use: prophylaxis of acute renal failure, reduction of intracranial & intraocular pressure
MOA: agents are easily filtered, poorly reabsorbed; alter the diffusion of the water relative to Na+ by “binding water”; ↓Net reabsorption of Na+
ADR: headache, nausea
