Diuretics and heart failure Flashcards
What medical conditions are diuretics useful for?
- Oedema
- Primary hypertension
- Chronic heart failure
- Nephrotic syndrome
- CKD
- Other unexpected medical conditions e.g. decompensated liver disease
What are common adverse effects of diuretics?
- Hypovolaemia and hypotension: activates RAAS and can lead to kidney injury
- Electrolyte disturbance (Na+, K+, Mg2+, Ca2+)
- Metabolic abnormalities (depends on individual drug)
- Anaphylaxis/photosensitivity rash (rare)
Which diuretics are commonly used?
- Loop diuretics
- Thiazides
- Potassium sparing diuretics
- Aldosterone antagonists
What is the mechanism of action of thiazide/thiazide-like diuretics?
- Inhibits Na+/Cl-co-transporter in DCT
- Reduces how much Na+ and Cl- are reabsorbed into the blood
- So reduces how much water leaves tubule and moves into blood
What are some adverse side effects of thiazide/thiazide-like diuretics?
- Hyperuricaemia
- Hyperglycaemia
- Erectile dysfunction
- Increased LDL
- Increased triglycerides
- Hypercalcaemia
- Hypokalaemia
Why do thiazides cause hyperuricaemia?
- Increase uric acid in blood
- Competes with uric acid for organic anion transporters to be excreted
- Leads to gout
Why do thiazides cause hypokalaemia?
- Work in DCT
- Cause increased Na+ in DCT
- This leads to increased Na+ in collecting duct too
- So more Na+ is absorbed via ENac channels
- And therefore more K+ is secreted via ROMK channels
Why do thiazides cause hyperglycaemia?
- Reduces insulin sensitivity in long term
What are the contra-indications of thiazides/thiazide-like diuretics?
- Addison’s disease
- Hypercalcaemia
- Hyponatraemia
- Refractory hypokalaemia
- Symptomatic gout
What are the DDIs of thiazides/thiazide-like diuretics?
- Alcohol
- Amlodipine
- Increased digoxin binding and toxicity
- B blockers - can cause hyperglycaemia, hyperlipidaemia, gout
- Steroids - hypokalaemia
- Lithium toxicity
- Carbamazepine - hyponatraemia
Give some examples of thiazides/thiazide-like diuretics
- Bendroflumethiazide
- Indapamide
What is the mechanism of action of loop diuretics?
- Inhibit Na+/K+/2Cl- transporter
- Reduced Na+/K+/2Cl- reabsorbed
- H2O follows ions by osmosis so remains in the tubule
Which conditions are loop diuretics used to treat and why?
- Direct dilation of capacitance veins - reduces preload
- Likely primary benefit in heart failure
- Acute pulmonary oedema
- Fluid overload in heart failure
- Adjunct in nephrotic syndrome
What are the adverse side effects of loop diuretics?
- Dehydration
- Hypotension
- Hypokalaemia
- Hyponatraemia
- Gout
- Arrhythmia
- Tinnitus
Why do loop diuretics cause tinnitus?
- Ototoxicity
- Inner ear contains Na+/K+/2Cl- transporters like in loop of Henle
- IV furosemide blocks these channels too
Why do loop diuretics cause hypokalaemia?
- Less absorption of Na+ at loop of Henle means that concentration of Na+ in collecting duct is much higher
- ENac channels of collecting duct work harder to remove Na+ downstream
- ROMK channels therefore secrete more K+ to balance charges within cells
What are the contraindications for loop diuretics?
- Hypokalaemia
- Hyponatraemia
- Gout
- Hepatic encephalopathy
What are the DDIs of loop diuretics?
- Aminoglycosides (can cause ototoxicity)
- Digoxin
- Lithium
- Excreted renally - loop diuretics compete with these drugs to be excreted
- Leads to increased digoxin binding and toxicity
- Steroids - hypokalaemia
Give some examples of loop diuretics
- Bumetanide
- Furosemide
What is the mechanism of action of amiloride?
- Block ENac channels
- Reduces Na+ absorption in DCT
- Reduces K+ excretion - K+ sparing
- Often used as adjunct to loop or thiazide diuretics in heart failure to limit loss of K+
What are the adverse side effects of amiloride?
- Hyperkalaemia
- Potential arrhythmia
What are the contraindications of amiloride?
- Addison’s disease
- Anuria
- Hyperkalaemia
What are the DDIs of amiloride?
- Other K+ sparing drugs
- ACEi - increased hyperkalaemia and cardiac problems
- ARBs
What is the mechanism of action of spironolactone/eplerenone?
- Mineralocorticoid receptor agonist
- Increases expression of ENac channels, ROMK, Na+/K+ ATPase in principal cells of collecting duct
What are the adverse side effects of spironolactone/eplerenone?
- Gynaecomastia (enlargement of breast tissue)
- Hyperkalaemia
- Severe cutaneous adverse reactions
What are the contraindications of spironolactone/eplerenone?
- Addison’s disease
- Anuria
- Hyperkalaemia
What is the mechanism of action of carbonic anhydrase inhibitors?
- Inhibit carbonic anhydrase in PCT
- Leads to increased Na+ delivery at collecting duct
- Increased secretion of K+ via ROMK
Give an example of an osmotic agent
- Mannitol
What is the mechanism of action of osmotic agents?
- Act on PCT and descending limb of loop of Henle
- Oppose action of ADH
- Prevent normal absorption of water
- Reduced intracellular volume
- Hypernatraemia risk
What is the mechanism of action of SGLT2 inhibitors?
- Prevents absorption of glucose
- If glucose isn’t absorbed at PCT, Na+ can’t be absorbed either
- Given to diabetic patients to remove glucose from blood
- Can lead to hyponatraemia
Give some examples of ADH agonists?
- Tolvaptan
- Lithium
What is the mechanism of action of tolvaptan?
- ADH antagonist
- Diuretic but not natriuretic
- Used to treat hyponatraemia
What is the mechanism of action of lithium?
- Also inhibits action of ADH
- Unwanted side effect
- Diuretic but not natriuretic
Which drinks cause diuresis?
- Alcohol (inhibits ADH release)
- Caffeine (increases GFR and decreases tubular Na+ reabsorption)
What challenges can prevent diuretic delivery to the renal tubules?
- Gut oedema can affect absorption
- Low blood albumin - drug can’t travel to target
- OATs not working properly - drug can’ be secreted into tubular lumen
What is more effective than giving patients diuretics?
- Ensure they are consuming the correct amount of salt in their diet
Define heart failure
- Clinical syndrome of reduced cardiac output, tissue hypoperfusion, increased pulmonary pressures and tissue congestion
What are the symptoms of heart failure?
- Exercise intolerance
- Dyspnoea
- Fatigue
- Oedema
What are the causes of heart failure?
- Ischaemic heart disease
- Hypertension
- Valvular disease e.g. aortic stenosis
- Cardiomyopathies
- Arrhythmias
How do we classify heart failure?
- Heart failure with reduced ejection fraction
- Heart failure with preserved ejection fraction
Outline the pathophysiology of heart failure
- Compromised cardiac function
- Decreased arterial BP
- Baroreceptor reflex
- Increased sympathetic outflow
- Increased RAAS and vasoconstriction
- Increased preload and afterload
- Increased myocardial O2 demand
- HF worsens
What happens to the heart as failure progresses?
- Remodelling
- Leads to decreased cardiac output
- RAAS and sympathetics activated
- Increased vasoconstriction, blood volume and Na+
- Increased preload and afterload
- Increased cardiac workload
- Vicious cycle
How is chronic heart failure treated?
- Correct underlying cause
- Non-pharmacological treatment: reduce salt and liquid intake and avoid salt substitutes
- Pharmacological treatment
What are the aims of heart failure treatment?
- Reduction in symptoms
- Managed increase in exercise tolerance
- Address arrhythmias, hyperlipidaemia, diabetes
- Increase quality of life and slow morbidity
How is HFPEF treated?
- Offer diuretics for congestive symptoms and fluid retention
- Manage co-morbidities
- Offer personalised exercise-based cardiac rehabilitation programme unless condition is unstable
How is HFREF treated?
- Offer diuretics for congestive symptoms and fluid retention
- Offer ACEi and beta blockers
- Consider ARB if intolerant to ACEi
- Give spironolactone if symptoms continue
- If symptoms persist despite first-line treatment, seek specialist advice
What are ACEi used to treat?
- Hypertension and heart failure
What are the adverse side effects of ACEi?
- Dry cough
- Angioedema
- Hypotension
- Renal impairment
- Tinnitus
- Vertigo
What are the contraindications of ACEi?
- Hereditary angioedema
What are the DDIs of ACEi?
- K+ sparing diuretics
- Alcohol
What are some examples of ACEi?
- Ramipril
- Lisinopril
What are ARBs used to treat?
- Hypertension and heart failure
What are the adverse side effects of ARBs?
- Postural hypotension
- Hyperkalaemia
- Hypotension
What are the DDIs of ARBs?
- Alcohol
- K+ sparing diuretic
What are some examples of ARBs?
- Losartan
- Candesartan
