H3i / 18A16: Compare and contrast the pharmacology of frusemide and acetazolamide

18A16: Exam Report

Compare and contrast the pharmacology of furosemide (frusemide) and acetazolamide.

30% of candidates passed this question.

The use of a table assisted with both clarity and the ability to compare the two drugs. Writing separate essays about each makes it difficult to score well. It was expected that candidates would follow a standard pharmacology format and discuss pharmaceutics, pharmacokinetics, pharmacodynamics and adverse drug reactions. Both of these drugs are ‘Level A’ in the
syllabus and a suitable level of detail was expected.

It was expected candidates would discuss in detail the mechanism of action, electrolyte and acid-base effects. Pharmacokinetic values were poorly answered. Qualitative terms such as ‘moderate, good and some’ are vague and should be avoided. Only correct numerical values (or ranges) attracted full marks.

H3i / 18A16: Compare and contrast the pharmacology of frusemide and acetazolamide

Chemical

Frusemide

LOOP diuretic

Acetazolamide

A CARBONIC ANHYDRASE inhibitor

Use

Frusemide

  1. Oedema
  2. Renal impairment
  3. HTN
  4. ↑ICP

Acetazolamide

  1. Metabolic alkalosis
  2. Glaucoma
  3. Altitude sickness

Presentatation

Frusemide

Photosensitive solution (brown ampoules) 10mg/mL

20/40/500mg tabs

Acetazolamide

PO 250mg tablets

Dose

Frusemide

Threshold Dose

Ceiling dose

Varies depending on clinical situation

Acetazolamide

250 – 1000mg Q4h

MoA

Frusemide

  • Inhibits Na/K/2Cl transporter on Thick Asc. LoH
  • Most potent diuretic
  • 25% filtered Na+ not reabsorbed, thus increased presentation of solute to distal tubule
  • Potent diuresis
  • Late in tubule ∴ minimal compensation
  • Loss of counter-current multiplier of medulla nephrons
  • Loss of K+ recycling generating +ve luminal voltage
  • ∴loss of Mg2+ & Ca2+

Acetazolamide

  • Non-competitive inhibition of CA
  • CA present in PCT (heaps), Thick Asc. LoH
  • Intercalated cells of Collecting Duct
    • ↓H+ supply in cell of tubule
    • H/Na antiporter can’t work
    • Na not reabsorbed
    • Na+, HCO3–, H2O lost in urine

PD

Frusemide

Renal

  • Diuresis
  • ↑RBF
  • ↓O2 consumption of LoH

CVS

  • Pulm & systemic VD = symptomatic relief of breathlessness prior to diuresis

Metabolic

  • ↓K, ↓Mg2+, ↓Ca2+
  • Metabolic alkalosis

Acetazolamide

Renal: excretion of alkaline urine, modest diuresis

Metabolic: hyperchloraemic metabolic acidosis

Resp: ↑MV due to metabolic acidosis

CNS: ↓CSF & intraocular P by ↓rate of CSF & aqueous humour formation

PK

Frusemide

A

60 – 70%

D

96% PPB

VD 0.1L/kg

M

Renal to glucuronide

E

80% in urine unchanged

Glucuronated frusemide

Faecal

t ½ 45 – 90mins

Acetazolamide

A

OBA 100%

D

90% PPB, high lipid solubility, crosses BBB

E

Not metabolised

K

Unchanged in urine t ½ 7hrs

A/E

Frusemide

  • Electrolyte imbalances
  • ↓insulin sensitivity = hyperglycaemia

Toxicity

  • Auditory n. damage
  • Pancreatitis
  • Interstitial nephritis (high doses)
  • BM depression

Acetazolamide

  • ↓Na+, ↓K+
  • Paraesthesia
  • Fatigue
  • Drowsiness
  • Depression