Diuretics Flashcards
What occurs during Edematous State?
• NaCl reabsorption which allows for water retention & an increase of blood volume
Examples:
• Heart failure • Hepatic ascites • Nephrotic syndrome • Premenstrual edema
What is a diuretic?
• Inhibitors of renal ion transporters that decrease the reabsorption of Na+ at different sites in the nephron (natriuretics)
What are the Loop Diuretic and what is their function?
Furosemide
- aka ‘High-Ceiling’ diuretics
- Highest efficacy in removing Na+ & Cl- from body
- Act on ascending limb of Loop of Henle
Clinical applications:
• Diuretics of choice for managing edema associated with heart failure, hepatic or renal disease
• Hypertension (moderate-severe)
What is the Loop Diuretic Mechanism of Action
- Act in the ascending limb of the loop of Henle
- Block NKCC2 Na+/Cl-/K+ cotransporter
- increase [Na+] & [Cl-] & [K+] in tubular fluid which leads to H20 excretion
Passive Increased Ca2+ excretion and Mg2+ excretion due to charge potential difference of the ROMK channel not working creating a negative potential in the lumen
• Decreased renal vascular resistance
• Increased renal blood flow
• Increased prostaglandin synthesis
What are the Loop Diuretics adverse effects?
- Ototoxicity( messed up charge movement)
- Hyperuricemia( build up of uric acid in the blood because it uses the organic acid and base secreting system which is messed up)
- Acute hypovolemia
- K+ depletion
- Hypomagnesemia
- Allergic reactions
Loop Diuretic Summary?
Increased Urinary Excretion: Na+ K+ Mg2+ Ca2+ Urine volume
Decreased Urinary Excretion: nothing
What are the Thiazides and what is their clinical applications?
Hydrochlorothiazide / Chlorthalidone / Metolazone
• Act on distal tubule – all have equal maximum effects
Clinical applications:
• Hypertension (either alone or in combination with other antihypertensives)
- Heart failure (mild-moderate)
- Hypercalciuria (inhibit Ca2+ excretion, particularly useful for kidney stones)
- Diabetes insipidus (produce hyperosmolar urine)
- Premenstrual edema
What are the thiazides mechanism of action?
Act predominantly in distal convoluted tubule
- Block NCCT Na+/Cl- cotransporter
- increase [Na+] & [Cl-] in tubular fluid which leads to H20 excretion
- Increased Na+ & Cl- excretion
- Increased K+ excretion and Increased Mg2+ excretion
- Decreased urinary Ca2+ excretion
- Decreased peripheral vascular resistance
What are the adverse effects of Thiazides?
- Hypokalemia
- Hyponatremia
- Hyperuricemia
- Hyperglycemia
- Hyperlipidemia
- Hypersensitivity
- Sexual dysfunction
Thiazide Summary?
Decreased Urinary Excretion: Ca2+
Increased Urinary Excretion: Na+ K+ Mg2+ Urine volume
What are the K+ sparing drugs?
Aldosterone antagonists:
Aldosterone antagonists: Spironolactone / Eplerenone
• Used alone when there is excess aldosterone
- Potassium levels must be closely monitored
- Act mainly in collecting tubule
Clinical applications:
• Heart failure: used as an adjunct to prevent cardiac remodeling
- Hypertension (adjunct to standard therapy)
- Primary hyperaldosteronism (diagnosis & treatment)
- Edema (associated with excessive aldosterone excretion)
What is the mechaism of action of K+ sparing drugs Aldosterone antagonists:?
- Act in collecting duct
- Antagonize aldosterone at intracellular cytoplasmic receptor sites (prevents translocation of receptor complex to the nucleus)
- Decreased Na+ reabsorption & decreased K+ excretion
What is the K+ sparing Aldosterone antagonists adverse effects?
Aldosterone antagonists: Spironolactone, Eplerenone
• Gastric upset & peptic ulcers
• Endocrine effects (antiandrogen)
• Hyperkalemia
• Nausea, lethargy, mental confusion (rare)
What are the K+ sparing Na+ Channel Inhibitors?
Na+ Channel Inhibitors: Amiloride / Triamterene
• Block Na+ transport channels ( decrease Na+/K+ exchange)
- Do not rely on presence of aldosterone
- Usually used in combination (not very efficacious)
- Can prevent K+ loss associated with thiazides & furosemide
What is the K+ sparing Na+ Channel Inhibitors mechanism of action?
• Act in collecting duct
• Directly block epithelial sodium channel (ENaC) which
decreasing Na+/K+ exchange
•decreased Na+ reabsorption & decreased K+ excretion
What are the K+ sparing Na+ Channel Inhibitors adverse effects?
- Hyperkalemia
- Hyponatremia
- Leg cramps
- GI upset
- Dizziness, pruritus, headache & minor visual changes
What is the K+ sparing summary?
Aldosterone antagonists: Spironolactone / Eplerenone Na+ Channel Inhibitors: Amiloride / Triamterene
Decreased Urinary Excretion: K+
Increased Urinary Excretion: Na+ Urine volume
What is the Carbonic Anhydrase inhibitor and its clinical applications?
Acetazolamide
• Act mainly in proximal tubular epithelial cells
- Less efficacious than other diuretics
- Often used for other pharmacological properties
Clinical applications:
• Glaucoma • Epilepsy (used alone or with other antiepileptics) • Mountain sickness prophylaxis • Metabolic alkalosis
What is the Carbonic Anhydrase inhibitor mechanism of action?
- Inhibits intracellular carbonic anhydrase
- Decreases ability to exchange Na+ for H+
- Decreases activity of Na+/K+ ATPase (diuresis)
- HCO3- is retained in lumen (increasing urinary pH)
What is the Carbonic Anhydrase inhibitor adverse effect?
- Metabolic acidosis
- Hyponatremia
- Hypokalemia
- Crystalluria
- Malaise, fatigue, depression, headache, GI upset, drowsiness, paresthesia
What is the Carbonic Anhydrase inhibitor summary?
Decreased Urinary Excretion: nothing
Increased Urinary Excretion Na+ K+ HCO3- Urine volume
What are the osmotic diuretics and their clinical applications?
Mannitol
• Raises osmotic pressure of the plasma thus draws
H20 out of body tissues & produces osmotic diuresis
- Does not effect Na+ excretion directly
- Only drug that truly increases urine volume
Clinical applications :
• Increase urine flow in patients with acute renal
failure • Reduce increased intracranial pressure &
treatment of cerebral edema • Promote excretion of toxic substances
What are the adverse effects of osmotic diuretics?
- Extracellular water expansion (can lead to hyponatremia)
- Tissue dehydration
Contraindications: • Congestive Heart Failure • Pulmonary edema
What are the ADH Anatgonist and their clinical applications/
- ADH controls permeability of collecting tubule to H20
- In the absence of ADH, tubule is H20 impermeable which leads to dilute urine
Conivaptan is an antagonist at V1 and V2 receptors
C linical applications :
• Euvolemic and hypervolemic hyponatremia • SIADH (syndrome of inappropriate ADH secretion) • Heart failure (only when benefits outweigh risks – safety not established)
What are the adverse effects of ADH antagonists?
- Infusion site reactions
- Thirst
- Atrial fibrillation
- GI & electrolyte disturbances
- Nephrogenic diabetes insipidus
Contraindications: • Hypovolemic hyponatremia • Renal failure
