what is furosemide?
loop diuretic
what are the indications for furosemide?
- salt/water overload associated with oedema
- acute pulmonary oedema
- CHF (common indication)
- renal failure
- liver cirrhosis
mechanism of action of loop diuretics (eg. furosemide)
act at thick ascending limb of Loop of Henle to block Na+/K+/2Cl- co-transporter
- decrease Na+, Mg2+ and Ca2+ reabsorption
what are the adverse effects of loop diuretics?
- hypokalaemia
- hyperuricaemia
- hypovolaemia (dizziness, weakness, nausea, cramps, hypotension)
- hearing loss
- cardiac arrhythmias
what is the mechanism of action of thiazides?
act at distal tubule to inhibit Na+/Cl- co-transporter
- enhance reabsorption of Ca2+ via Ca2+ channels (luminal membrane)
how do thiazides lead to hypokalaemia?
increased Ca2+ into tubular epithelial cell → more Na+ pumped into cell via Ca2+/Na+ antiporter (basolateral) → upregulate Na+/K+ ATPase pump → more K+ excreted
what is the drug to avoid with thiazides?
digoxin
due to digoxin toxicity
- nausea, vomiting, visual disturbances
what is spironolactone?
aldosterone antagonist (K+ sparing diuretic)
what are the indications for thiazides?
- mild to moderate hypertension
- oedema due to mild to moderate CHF (combine with loop diuretics)
what are the indications for aldosterone antagonist (spironolactone)?
- hyperaldosteronism
- CHF
- resistant hypertension
what is the mechanism of action of aldosterone antagonist?
act at late distal tubule/collecting duct
- competes with aldosterone for mineralocorticoid receptor → inhibits Na+/K+ ATPase pump → decrease K+ excretion → hyperkalaemia
- block new Na+ channels from forming
what drug should be avoided with aldosterone antagonist (K+ sparing diuretic)?
RASi → similar effects to K+ sparing diuretics → increase hyperkalaemia
what is amiloride?
sodium channel blocker (K+ sparing diuretic)
what is the mechanism of action of sodium channel blocker (K+ sparing diuretic)?
block Na+ channels → less Na+ reabsorbed → less K+ secreted into lumen
what is mannitol?
osmotic diuretic
what are Dapagliflozin and Empagliflozin?
SGLT2 inhibitors
indications for SGLT2 inhibitors
- hypertension
- diabetes
- CVD (decreased mortality)
what is tolvaptan?
V2 receptor antagonist
vasopressin acts on V2 receptor → anti-diuretic effects
tolvaptan inhibits v2 receptor → promote diuresis
