Diuretics

Question 1

Thiazide diuretics? Site of action? action? precaution?

Anesthesia considerations?

Answer 1

• Prototype: Hydrochlorothiazied
• Site of action: ascending loop of henle and distal convoluted tubule
  
  • enhance Na and H2O ecretion
• action: impairs Na and Cl cotransporter and therefore impairs the reabsorption Na
  
  • results in urinary excretion Na, Cl, and K
  • antihypertensize- peripheral vasodilation (requires weeks to develoo)
• Precaution: K depleting
• Anesthesia conerns:
  
  • ​hypokalemia, hypochloremia, hypomagnesemia
  • muscle weakness
  • potentiates muscle relaxants
  • nephropathy
  • increased risk dig toxicity
  • fluid volume status

Question 2

Loop diuretics? MOA? Pharmacokinetic/dynamics

Answer 2

MOA:

• Impairs Na-K-2Cl transport protein in the thick ascending loop of henle
• diuresis begins 2-10 min following IV injection, most potent diuretic with dose-dependent resposne

Pharmacokinetic/dynamic

• Dose 0.1-1 mg/kg (titrate)
• extensive protein binding
• excreted by GF and renal tubular secretion
• rapid onset (5-10 min)
• DOA 2-6 hours

Question 3

Loop diuretic uses?

Answer 3

• Mobilization of edema fluid (good for CHF)
  
  • peripheral vasodilation precedes onset of duiresis
• Reduction of ICP- decrease venous return, decreases CSF production (typically give mannitol)
• LOOp diuretics are used to treat hypercalcemia as they inhibit absorption
• differential diagnosis of oliguria (0.1 mg/kg)

Question 4

Loop diuretic S/E?

Answer 4

• Hypokalmeia, hypochloremia
• presynpatic effect potentiates NDMR
• Enhances possiblity of nephrotoxicity when adminsitered with aminoglycosides and cephalosporins
• decreases renal clearance of lithium
• possible cross reactivity with sulfa allergy
• volume status!
• avoid in acute renal insufficiency
• ototoxicity, transient or permanent especially in use with aminoglycosides (although rare)

Question 5

What is mannitol?

Answer 5

• 6 carbon sugar- hexose, cleared form plasma by glomerular filtration, renal tubular fluid oxmolarity increases–> water, Na, Cl, HCO3 excreted
• also increases plasma osmolarity- draws fluid form IC to EC space–> increase in intravascular volume (problematic with poor LV function- can cause pulmonary edema)
• does not enter cells- must give IV
• Clearnace- 100% by glomerular filtration- none reabsorbed

Question 6

Uses of mannitol?

Answer 6

• Differential diagnosis of oliguria
• prophylaxis- acute renal failure
• reduction of ICP
• reduciton of IOP- can be use din eye sx when eye is too tight
• scavenger of oxygen free radicals- prevent cellular injury

Question 7

Dose mannitol?

Answer 7

• 0.25-1 gram/kg IV
• Exerts effects in 10-15 min and lasts 2 hours

Question 8

Anesthesia concerns with mannitoil?

Answer 8

• Pulmonary edema
• hypovolemia
• electrolyte changes
• hypokalemic hypochloremic alkalosis

Question 9

What are some potassium sparing duiretics?

Answer 9

• Epitheleal sodium channel blockers
  
  • triamterene
• Aldosteron antagonist
  
  • spironolactone

Question 10

What is triamterene?

Answer 10

• Site of action: collecting duct
• action: (ENaC)Na channel blockade (luminal membrane; indpeendent of aldosteron)
• precautions: can cause hyperkalemia
• comments: combo with HCTZ because it’s not too effective of a diuretic by itself

Question 11

What is spironalactone?

Answer 11

• • Spironalactone- synthetic 17-lactone drug
    
    • competitive aldosterone antagonist
      
      • works in collecting duct to antagonize aldosterone
        
        • Aldosteron- hormone that increases reabsorption of sodium and water and secreiton of potassium–> increases the volume and BP
      • Na-K ATPase in collecting duct
    • primarily to treat HF, ascites, low-renin HTN, hypokalemia and Conn’s syndrome
    • weak diuretic and usually combined with other diuretics (HCTZ)

Question 12

What is diamox?

Answer 12

carbonic anhydrase inhibitor

• Acetazolamide (diamox) used to rx glaucoma, altitude sickness, ICP
• normal- Carbonic anhydrase- catalyzes H and HCO3 rleased form CO2 and H2O. H is then excreted in exchange for Na on the renal luminal membrane and HCO3 is reabosrbed with Na
• Acetazolamide blocks the action of carbonic anhydrase, therefore increasing amounts of HCO3, Na and H2o in the urine

Question 13

What are some dopaminergic agents?

Answer 13

• Low dose dopamine 1-3 mcg/kg/min
• Renal protection
  
  • vasodilation
  • inhibition Na-K-ATPase pump/decreases renal O2 consumption
  • effect diminished after 48 hours- down regulation of dopaminergic receptors, contraction intravascular volume
• Fenoldapam
  
  • ​selective for D1 receptor with moderate action at alpha 2
  • rapid onset, short half-life (10 mintes)
  • short term treatment of pt with severe HTN