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Diuretics and heart failure Flashcards

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1
Q

What medical conditions are diuretics useful for?

A
  • Oedema
  • Primary hypertension
  • Chronic heart failure
  • Nephrotic syndrome
  • CKD
  • Other unexpected medical conditions e.g. decompensated liver disease
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2
Q

What are common adverse effects of diuretics?

A
  • 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)
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3
Q

Which diuretics are commonly used?

A
  • Loop diuretics
  • Thiazides
  • Potassium sparing diuretics
  • Aldosterone antagonists
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4
Q

What is the mechanism of action of thiazide/thiazide-like diuretics?

A
  • 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
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5
Q

What are some adverse side effects of thiazide/thiazide-like diuretics?

A
  • Hyperuricaemia
  • Hyperglycaemia
  • Erectile dysfunction
  • Increased LDL
  • Increased triglycerides
  • Hypercalcaemia
  • Hypokalaemia
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6
Q

Why do thiazides cause hyperuricaemia?

A
  • Increase uric acid in blood
  • Competes with uric acid for organic anion transporters to be excreted
  • Leads to gout
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7
Q

Why do thiazides cause hypokalaemia?

A
  • 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
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8
Q

Why do thiazides cause hyperglycaemia?

A
  • Reduces insulin sensitivity in long term
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9
Q

What are the contra-indications of thiazides/thiazide-like diuretics?

A
  • Addison’s disease
  • Hypercalcaemia
  • Hyponatraemia
  • Refractory hypokalaemia
  • Symptomatic gout
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10
Q

What are the DDIs of thiazides/thiazide-like diuretics?

A
  • Alcohol
  • Amlodipine
  • Increased digoxin binding and toxicity
  • B blockers - can cause hyperglycaemia, hyperlipidaemia, gout
  • Steroids - hypokalaemia
  • Lithium toxicity
  • Carbamazepine - hyponatraemia
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11
Q

Give some examples of thiazides/thiazide-like diuretics

A
  • Bendroflumethiazide
  • Indapamide
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12
Q

What is the mechanism of action of loop diuretics?

A
  • Inhibit Na+/K+/2Cl- transporter
  • Reduced Na+/K+/2Cl- reabsorbed
  • H2O follows ions by osmosis so remains in the tubule
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13
Q

Which conditions are loop diuretics used to treat and why?

A
  • 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
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14
Q

What are the adverse side effects of loop diuretics?

A
  • Dehydration
  • Hypotension
  • Hypokalaemia
  • Hyponatraemia
  • Gout
  • Arrhythmia
  • Tinnitus
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15
Q

Why do loop diuretics cause tinnitus?

A
  • Ototoxicity
  • Inner ear contains Na+/K+/2Cl- transporters like in loop of Henle
  • IV furosemide blocks these channels too
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16
Q

Why do loop diuretics cause hypokalaemia?

A
  • 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
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17
Q

What are the contraindications for loop diuretics?

A
  • Hypokalaemia
  • Hyponatraemia
  • Gout
  • Hepatic encephalopathy
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18
Q

What are the DDIs of loop diuretics?

A
  • 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
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19
Q

Give some examples of loop diuretics

A
  • Bumetanide
  • Furosemide
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20
Q

What is the mechanism of action of amiloride?

A
  • 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+
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21
Q

What are the adverse side effects of amiloride?

A
  • Hyperkalaemia
  • Potential arrhythmia
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22
Q

What are the contraindications of amiloride?

A
  • Addison’s disease
  • Anuria
  • Hyperkalaemia
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23
Q

What are the DDIs of amiloride?

A
  • Other K+ sparing drugs
  • ACEi - increased hyperkalaemia and cardiac problems
  • ARBs
24
Q

What is the mechanism of action of spironolactone/eplerenone?

A
  • Mineralocorticoid receptor agonist
  • Increases expression of ENac channels, ROMK, Na+/K+ ATPase in principal cells of collecting duct
25
Q

What are the adverse side effects of spironolactone/eplerenone?

A
  • Gynaecomastia (enlargement of breast tissue)
  • Hyperkalaemia
  • Severe cutaneous adverse reactions
26
Q

What are the contraindications of spironolactone/eplerenone?

A
  • Addison’s disease
  • Anuria
  • Hyperkalaemia
27
Q

What is the mechanism of action of carbonic anhydrase inhibitors?

A
  • Inhibit carbonic anhydrase in PCT
  • Leads to increased Na+ delivery at collecting duct
  • Increased secretion of K+ via ROMK
28
Q

Give an example of an osmotic agent

A
  • Mannitol
29
Q

What is the mechanism of action of osmotic agents?

A
  • Act on PCT and descending limb of loop of Henle
  • Oppose action of ADH
  • Prevent normal absorption of water
  • Reduced intracellular volume
  • Hypernatraemia risk
30
Q

What is the mechanism of action of SGLT2 inhibitors?

A
  • 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
31
Q

Give some examples of ADH agonists?

A
  • Tolvaptan
  • Lithium
32
Q

What is the mechanism of action of tolvaptan?

A
  • ADH antagonist
  • Diuretic but not natriuretic
  • Used to treat hyponatraemia
33
Q

What is the mechanism of action of lithium?

A
  • Also inhibits action of ADH
  • Unwanted side effect
  • Diuretic but not natriuretic
34
Q

Which drinks cause diuresis?

A
  • Alcohol (inhibits ADH release)
  • Caffeine (increases GFR and decreases tubular Na+ reabsorption)
35
Q

What challenges can prevent diuretic delivery to the renal tubules?

A
  • 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
36
Q

What is more effective than giving patients diuretics?

A
  • Ensure they are consuming the correct amount of salt in their diet
37
Q

Define heart failure

A
  • Clinical syndrome of reduced cardiac output, tissue hypoperfusion, increased pulmonary pressures and tissue congestion
38
Q

What are the symptoms of heart failure?

A
  • Exercise intolerance
  • Dyspnoea
  • Fatigue
  • Oedema
39
Q

What are the causes of heart failure?

A
  • Ischaemic heart disease
  • Hypertension
  • Valvular disease e.g. aortic stenosis
  • Cardiomyopathies
  • Arrhythmias
40
Q

How do we classify heart failure?

A
  • Heart failure with reduced ejection fraction
  • Heart failure with preserved ejection fraction
41
Q

Outline the pathophysiology of heart failure

A
  • 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
42
Q

What happens to the heart as failure progresses?

A
  • 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
43
Q

How is chronic heart failure treated?

A
  • Correct underlying cause
  • Non-pharmacological treatment: reduce salt and liquid intake and avoid salt substitutes
  • Pharmacological treatment
44
Q

What are the aims of heart failure treatment?

A
  • Reduction in symptoms
  • Managed increase in exercise tolerance
  • Address arrhythmias, hyperlipidaemia, diabetes
  • Increase quality of life and slow morbidity
45
Q

How is HFPEF treated?

A
  • Offer diuretics for congestive symptoms and fluid retention
  • Manage co-morbidities
  • Offer personalised exercise-based cardiac rehabilitation programme unless condition is unstable
46
Q

How is HFREF treated?

A
  • 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
47
Q

What are ACEi used to treat?

A
  • Hypertension and heart failure
48
Q

What are the adverse side effects of ACEi?

A
  • Dry cough
  • Angioedema
  • Hypotension
  • Renal impairment
  • Tinnitus
  • Vertigo
49
Q

What are the contraindications of ACEi?

A
  • Hereditary angioedema
50
Q

What are the DDIs of ACEi?

A
  • K+ sparing diuretics
  • Alcohol
51
Q

What are some examples of ACEi?

A
  • Ramipril
  • Lisinopril
52
Q

What are ARBs used to treat?

A
  • Hypertension and heart failure
53
Q

What are the adverse side effects of ARBs?

A
  • Postural hypotension
  • Hyperkalaemia
  • Hypotension
54
Q

What are the DDIs of ARBs?

A
  • Alcohol
  • K+ sparing diuretic
55
Q

What are some examples of ARBs?

A
  • Losartan
  • Candesartan

CPT (22 decks)

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