Renal-Diuretics

Question 1

Thiazides

Answer 1

• Thiazides
  
  • Prototype: Hydrochlorothiazide (HCTZ)
  • Site of action: Ascending loop of Henle and distal convoluted tubule
  • Action: Impairs Na+ and Cl- cotransporter, therefore impairs reabsorption Na+
    
    • Results in urinary excretion of Na+, Cl-, and K+
  • Precautions: K+ depleting

Question 2

HCTZ

Answer 2

• Thiazide diuretic; Enhance Na+ and H2O excretion
• Antihypertensive – peripheral vasodilation (requires weeks to develop)
• Anesthesia Concerns:
  
  • Hypokalemia, Hypochloremia, Hypomagnesemia
  • Muscle weakness; Potentiates muscle relaxants
  • Nephropathy
  • ↑ r/f Dig toxicity
  • Fluid volume status

Question 3

Furosemide

Answer 3

• Loop Diuretic
• Impairs Na+-K+-2Cl- transport protein in thick ascending loop of Henle
• Diuresis begins 2-10 min following IV injection, most potent diuretic w/ dose-dependent response
• Dose 0.1 – 1.0 mg/kg (titrate)
• Rapid onset (5-10 min)
• DOA 2-6 hrs
• Extensive protein binding
• Excreted by Glomerular filtration and renal tubular secretion

Question 4

Furosemide

Uses

Answer 4

• Mobilization of edema fluid (good for CHF)
  
  • Peripheral vasodilation precedes onset of diuresis
• Reduction of ICP: ↓venous return, ↓ CSF production
• Differential diagnosis of oliguria (0.1 mg/kg)

Question 5

Loops: Effects/Side Effects

Answer 5

• HypoK, hypoCl
• Presynaptic effect potentiates NDMRs
  
  • Interferes w/ Ach mobilization via cAMP inhibition
• ^^r/f nephrotoxicity when given w/ aminoglycosides & cephalosporins!
• Ototoxicity, transient or permanent; esp. w/ aminoglycosides (rare)
• Possible cross reactivity if sulfonamide allergy
• Decreases renal clearance of lithium
• Avoid in acute renal insufficiency
• Volume status!

Question 6

Mannitol

MOA/Pk

Answer 6

• Osmotic diuretic
• 6 carbon sugar-Hexose, cleared from plasma by glomerular filtration, renal tubular fluid osmolarity ↑ → H₂O, Na⁺, Cl^-, HCO₃^- excreted
• ALSO ↑ PLASMA OSMOLARITY!!-draws fluid from IC to EC space → ↑intravascular volume (problematic w/ poor LV function- pulm edema)
• Does not enter cells– must give IV
• Clearance- 100% by glomerular filtration- none reabsorbed

Question 7

Mannitol

Uses

Answer 7

• Differential diagnosis of oliguria
• Prophylaxis- Acute Renal Failure
• ↓ ICP, ↓ IOP
• Scavenger of oxygen-free radicals→ prevents cellular injury

Question 8

Mannitol

Dose/Pk

Answer 8

• Mannitol 0.25 – 1.00 g/kg IV
• Onset: 10-15 min
• DOA: 2 hrs

Question 9

Mannitol

Anesthesia Concerns

Answer 9

• Pulmonary edema
• Hypovolemia
• Electrolyte changes
  
  • Hypokalemic, Hypochloremic alkalosis

Question 10

Potassium Sparing Diuretics

Answer 10

• Epithelial Na⁺ Channel Blockers
  
  • Triamterene
• Aldosterone Antagonists
  
  • Spironolactone

Question 11

Triamterene

Answer 11

• K-sparing diuretic
• Site of action: Collecting duct
• MOA: Na+ channel blockade (luminal membrane; independent of aldosterone)
• Precautions: Can cause hyperkalemia
• Comments: combo + HCTZ

Question 12

Spironolactone

Answer 12

• K+-sparing diuretic
• Aldosterone- hormone that increases reabsorption of Na+ and H₂O & secretion of K⁺→ ↑ volume & BP
• Spironolactone- synthetic 17-lactone drug -competitive aldosterone antagonist
  
  • Primarily to treat heart failure, ascites, HTN, hypoK, and Conn’s syndrome (hyperaldosteronism)
  • Spironolactone is weak diuretic and usually combined w/ other diuretics (HCTZ)

Question 13

Carbonic Anhydrase Inhibitor

Answer 13

• Acetazolamide (Diamox)- Used to Rx Glaucoma, altitude sickness, ICP
• Carbonic Anhydrase catalyzes H⁺ and HCO₃^- released from CO₂ and H₂O. H⁺ is then excreted in exchange for Na⁺ on the renal luminal membrane & HCO₃^- is reabsorbed w/ Na⁺
• Acetazolamide blocks action of CA therefore increasing amounts of Na+ and H₂O in urine (and decreasing HCO₃^- reabsorption).

Question 14

Dopaminergic Agents

Answer 14

• Low dose Dopamine
• Fenoldopam

Question 15

Dopaminergic Agents

Low dose Dopamine

Answer 15

• 1-3 mcg/kg/min
• Renal vasodilation
• Inhibition Na-K-ATPase pump/decreases renal O2 consumption
• Effect diminished after 48 hrs-down-regulation of dopaminergic receptors/contraction intravascular volume
• No evidence dopamine has a renal protective effect despite ↑ UOP

Question 16

Dopaminergic Agents

Fenoldopam

Answer 16

• Selective for D1 receptor w/ moderate action at alpha 2
  
  • Arterial/arteriolar dilation leading to ↓ in BP via activation of peripheral D1 receptors
  • Increases renal perfusion and UOP
• Rapid onset, short half-life (10 min)
• Short term rx of severe HTN