Diuretics

Question 1

hydrochlorothiazide: class, use

Answer 1

• class
  
  • Thiazide Diuretic (prototype)
• use
  
  • maintenance and tx of essential HTN
  • Mobilization of edema from renal/hepatic failure
  • Treatment of edema r/t CHF
  • Less powerful and better tolerated than loop diuretic

Question 2

hydrchlorothiazide: MOA

Answer 2

• site of action: acscending loop of henle and distal convulted tube
• action: Impairs Na+ and Cl- co transporter, impairing the reabsorption of Na+
  
  • results in the urinary excretion of Na+, Cl-, K+
• poorly understood vasodilatory effect

Question 3

hydrochlorothiazide: PK

Answer 3

• onset: 2 hrs
• peak: 4 - 6 hrs
• DOA: 6 -24 hrs
• E1/2life: 6 - 15 hrs
• Pb:68%
• Vd: 3.5 - 8 L/kg
• Not metabolized
• Excreted unchanged in the urine

Question 4

hydrochlorothiazide: SE

Answer 4

• metabolic alkalosis
• hypokalemia, hypochloremia, hypomagnesemia
  
  • increased risk of arrhythmias and muscle weakness with decreased K
• orthostatic hypotension
• nephropathy

Question 5

hydrchlorothiazide: cautions/drug interactions

Answer 5

• CAUTIONS
  
  • fluid volume status
  • electrolyte balance
• DRUG INTERACTIONS
  
  • potentiaties muscle relaxants
  • increased risk of dig toxicity

Question 6

hydrochlorothiazide: dose

Answer 6

• 25 -100 mg/day PO
• max daily dose 200mg

Question 7

furosemide (lasix): class, use

Answer 7

• class
  
  • loop diuretic
• use
  
  • Mobilization of edema fluid (good for CHF)
  • peripheral vasodilation precedes onset of diuresis
  • Reduction of ICP- ↓venous return, decreases CSF production
  • Differential diagnosis of oliguria (0.1 mg/kg)

Question 8

furosemide (lasix): MOA

Answer 8

• Impairs the Na+-K+-2Cl- transport protein in the thick ascending loop of Henle
• blocks reabsorption of Cl, Na and H20, excretion of Na, Cl, H2O, K, Ca, Mg

Question 9

furosemide (lasix): PK

Answer 9

• Onset: IV, 5 min - 10 min; oral, 30-60 mins
• DOA: IV, 2-6 hours; oral, 6-8 hours
• E1/2t: < 1 hour
• PB: 90%
• Metabolism: hepatic
• Eliminiation:
  
  • 50% excreted by glomerular filtration and renal tubular secretion
  • 1/3 dose metabolized or excted unchanged by the bile

Question 10

furosemide (lasix): SE

Answer 10

• Neuro:
  
  • dizziness, HA, blurred vision, ototoxicity
• CV:
  
  • hypotension, volume depletion
• GI:
  
  • N/V, diarrhea
  • electrolyte imbalances (↓ K, Cl, Mg, Ca; ↑ Na)
  • metabolic alkalosis
• Renal:
  
  • nephrotoxicity
  • urinary frequency

Question 11

furosemide (lasix): cautions/contraindications/drug interactions

Answer 11

• CAUTIONS/CONTRAINDICATIONS
  
  • Volume status!
  • Avoid in acute renal insufficiency - could cause a pre renal injury
• DRUG INTERACTIONS
  
  • Presynaptic effect potentiates NDMRs
    
    • Interferes with acetylcholine mobilization via cAMP inhibition
  • ENHANCES POSSIBILITY OF NEPHROTOXICITY WHEN ADMINISTERED WITH AMINOGLYCOSIDES AND CEPHALOSPORINS
  • Ototoxicity, transient or permanent- especially in use with aminoglycosides (although rare)
  • Decreases renal clearance of lithium
  • Possible cross reactivity if sulfonamide allergy

Question 12

furosemide (lasix): dose

Answer 12

• 0.1 – 1.0 mg/kg IV (titrate)
• most potent diuretic with dose-dependent response

Question 13

mannitol: class, structure, use

Answer 13

• class
  
  • Osmotic Diuretic
  • O2 free radical scavenger
• stucture
  
  • 6-carbon sugar
• use
  
  • Differential diagnosis of Oliguria
  • Prophylaxis- Acute Renal Failure
  • Reduction of ICP, IOP
  • Scavenger of oxygen-free radicals → prevents cellular injury

Question 14

mannitol: MOA

Answer 14

• increases plama osmolarity by drawing fluid from IC to EC space → ↑intravascular volume
• followed by diuresis, drug filtered but NOT reabsorbed
• during filtration mannitol pulls fluid and electrolytes (Na, Cl, HC03) into the urine; increasing urine output

Question 15

mannitol: PK

Answer 15

• onset- 15 min
• DOA- 3-6 hrs
• E1/2- 1.5 hr
• No metabolism
• Clearance: 100% unchanged by glomerular filtration, none is reabsorbed
• does not cross BBB

Question 16

mannitol: SE

Answer 16

• headache
• blurry vision - ↓ ICP & IOP
• seizure
• N/V
• dramatic increase in intravascular volume
• pulmonary edema in pt with poor myocardial function
• hypovolemia/ electrolyte imbalance in prolonged use
  
  • hypokalemic, hypochloremic alkalosis

Question 17

mannitol: cautions/contraindications/drug interactions

Answer 17

• CAUTIONS/CONTRAINDICATIONS
  
  • current hypovolemia/electrolyte imbalances
  • LV dysfunction (unable to handle rapid expansion of intravascular volume
  • pulmonary edema
  • severe kidney disease
  • active intracranial bleeding
• DRUG INTERACTIONS
  
  • lithium toxicity (with diuretic induced hyponatremia)

Question 18

mannitol: dose

Answer 18

• 0.25 – 1.00 g/kg/ IV over 30 - 60 min
• concentrations > 20% should be administered with in line 5 micron filter set