Lecture 5 - Diuretics And Heart Failure Flashcards by Callum Donoher

What are diuretics?

Drugs that increase urine output

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What does natriuretic mean?

Loss of Na+ in urine

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What does aquaretic mean?

Loss of water without electrolytes

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What medical conditions are diuretics used for?

Primary hypertension
Chronic heart failure
Nephrotic syndrome
CKD
Decompensated liver disease (not a lot of albumin made)

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What are some categories of diuretics?

Carbonic anhydrase inhibitors
Osmotic diuretics
SGLT2 inhibitors
Loop diuretics
Thiazides
Potassium sparing diuretics
Aldosterone antagonists
ADH antagonists

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What are some common adverse drug effects of diuretics?

Hypovolaemia and hypotension

Electrolyte disturbance
Metabolic abnormalities
Anaphylaxis (allergy)

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Why can diuretics lead to acute kidney injury?

Hypovolaemia and hypotension leads to activation of RAAs

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How do Thiazides and thiazide like diuretics act?

Inhibit Na+/Cl- Cotransporter in DCT

Means more Na+ and Cl- ini filtrate which helps lose lots of water due to the higher osmotic pressure in the filtrate

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What are some adverse effects of thiazides and thiazide like diuretics?

Hyperuricaemia (uric acid levels inc lead to Gout)
Hyperglycaemia
Erectile dysfunction
Hypercalcaemia
Inc LDL and TG
HYPOKALAEMIA

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How does use of Thiazides and thiazide like diuretics cause hypokalaemia?

Na+/Cl- inhibition
Na+ levels in filtrate higher

More Na+ taken up by ENAC in collecting duct so more K+ leaves via ROMK

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What are some drug-drug interactions that shouldn’t be used at the same time as thiazides and thiazide like diuretics?

Alcohol (diuretic)
Amlodipine (Ca2+ channel blocker)`

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What are 2 examples of Thiazde and Thiazide like diuretic?

Indapamide
Bendroflumethiazide

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When are some contraindications to using thiazides?

Addisons disease (cortisol needed to regulate Na+, without it Na+ low, thiazides can cause hyponatraemia)
Hypercalcaemia
Hyponatraemia
Refractory hypokalaemia
Hyperuricaemia

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What channel do Loop Diuretics block?

NKCC channel in the ascending limb of loop of Henle

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How do loop diuretics act as a diuretic?

Block NKCC channel
Means lots of Na+ K+ and Cl- remain in the filtrate increasing the osmotic pressure

Direct dilation of capacitance veins reducing preload

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When are loop diuretics given?

Acute pulmonary oedema
Fluid overload in heart failure
Nephrotic syndrome

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What are the adverse effects of loop diuretics?

Dehydration
Hypotension
Hypokalaemia
Hyponatraemia
Hypocalcaemia
Hypomagnesemia
Hyperuricemia
Tinnitus (Ototoxicity)
Inc cholesterol and Triglycerides

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What are some contraindications to loop diuretics?

Hypokalaemia
Hyponatraemia
Gout
Hepatic encephalopathy

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What are the drug-drug interactions for loop diuretics that shouldn’t be paired?

Aminoglycosides
Digoxin
Lithium

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What is an. Example of an aminoglycosides?

Gentamicin

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Why can aminoglycosides (gentamicin), digoxin and lithium not be used with loop diuretics?

Aminoglycosides, digoxin and lithium are damaging to the ears (ototoxic) and loop diuretics like furosemide are also ototoxic

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What are some examples of loop diuretics?

Furosemide
Bumetanide

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How do Potassium sparing drugs work as diuretics?

Block ENAC channels in the collecting duct and late DCT

Reduces Na+ reabsorption in DCT
Reduces K+ excretion

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What are the adverse drug effects of potasssium sparing diuretics?

Hyperkalaemia
Potential Arrythmia

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What are the contraindications for potassium sparing diuretics?

Addisons disease (lack of aldosterone also prevents action of ENAC and therefore ROMK, this would worsen it) Anuria Hyperkalaemia

What drugs would you not give potassium sparing diuretics with?

Other K+ sparing drugs ACEi ARBs

What is an example of a potassium sparing diuretic?

Amiloride

What is an example of a drug that acts as a potassium sparing diuretic that’s not amiloride?

Spironolactone

What is the mechanism of action of Spironolactone?

Aldosterone receptor antagonist Aldosterone normally upregulates ENAC to in Na+ reabsorption So if antagonised ENAC expression is reduced so more stays in filtrate

What are the adverse effects of Spironolactone?

Gynaecomastia Hyperkalaemia Severe cutaneous adverese reactions (SCARs)

What are contraindications to Spironolactone?

Addisons disease Anuria Hyperkalaemia

What are some drugs that shouldn’t be paired with Spironolactone?

Alcohol Amiloride ACEi ARBs

Where do carbonic anhydrase inhibitors work in the nephron?

PCT

How do carbonic anhydrase inhibitors work as diuretics?

Inhibit carbonic anhydrase so less Carbonic acid will form in PCT cells Means less protons need moving out of cell so. More Na+ remains in filtrate (Na+/H+ antiporter)

Why do carbonic anhydrase inhibitors lead to hypokalaemia?

Less action of Na+/H+ antiporter in PCT More Na+ in filtrate makes it to collecting DUCT Inc movement across ENAC More Na+ entering cell means inc activity of Na+/K+ ATPase So more action of ROMK leading to more K+ leaking into the filtrate

What is an example of a carbonic anhydrase inhibitor?

Acetazolamide

What part of the nephron do osmotic agents act in?

PCT

What is an example of an osmotic diuretic?

Mannitol

How does mannitol act as an osmotic diuretic?

Stays in filtrate increasing the osmolarity in the PCT drawing water with it

Why is mannitol often given with increase intracranial pressure?

Reduces the production of CSF in brain

Why is there a risk of hypernatraemia with the use of osmotic diuretics like mannitol?

Just water is lost so reduced plasma volume

Where do SGLT2 inhibitors affect in the nephron to act as diuretics?

PCT

How do SGLT2 inhibitors act as diuretics?

Inhibit SGLT2 channels Means more Na+ and Glucose remains in filtrate increasing the osmolarity in the filtrate

What are some examples of SGLT2 inhibitors?

Dapagliflozin Canagliflozin End in flozin

What does a drug called a aquaretic actually do?

ADH antagonists Tolvaptan Lithium

What is the mechanism of action of Tolvaptan?

ADH antagonist (Its an aquaretic)

What is the mechanism of action of lithium as an aquaretic?

Inhibits action of ADH

What affect does Alcohol have on urine?

Inhibits ADH release causing diuresis

How does caffeine cause diuresis?

Increased GFR Decreased tubular Na+ reabsorption Inhibits vasoconstriction of afferent arterioles in kidneys

What is Digoxin?

Cardiac glycoside

What is the mechanism of action of digoxin/cardiac glycosides?

Make heart contract harder Stops Na+/K+ATPase Na+ builds up in cell Na+/Ca2+ flips Ca2+ pumped into cell leading to stronger contractions

Why are higher doses of furosemide needed as a diuretic in a patient with nephrotic syndrome of liver cirrhosis or failure?

Furosemide binds to albumin as a transport protien and patients in this. Case would have low serum albumin levels

What drug is given to patients with Hyperkalaemia to help protect the heart?

Calcium gluconate

What is heart failure?

Clinical syndrome of reduced CO, tissue hypoperfusion, increased pulmonary pressures and tissue congestion

What are the 2 classifications of heart failure?

HFrEF HFpEF

What is HFrEF?

Heart failure with reduced ejection fraction

What is HFpEF?

Heart failure with preserved ejection fraction

What causes HFrEF?

HF with reduced ejection fraction caused by Ischaemic events like MI

What causes HFpEF?

Structural condition like valves

What is the neuro hormonal response involving baroreceptors that worsens heart failure?

Reduced CO causes Reduced BP Detect b baroreceptors Increases sympathetic drive increasing HR and TPR This increases AFTERLOAD INCREASING CARDIAC WORK = BAD

What is afterload?

The pressure the heart works to pump against

What is the neuro hormonal response involving the RAAS that worsens heart failure?

Dec cardiac output = dec BP Reduced Renal perfusion leads to activation of RAAS AGII leads to inc ADH and inc Na+ and water retention due to inc aldosterone leading to INC PRELOAD AGII also enehances sympathetic activity leading to vasoconstriction leading to INC AFTERLOAD INC PRELOAD + INC AFTERLOAD. = INC CARDIAC WORKK

How does remodelling of the heart affect the heart?

Loss of myoctes replaced by fibrosis Changes chamber size imparing ventricular filling Impairment of ventricular ejection/empytinggg

What receptor is found in vascular smooth muscle leading to vasoconstriction?

What does stimulation of B1 receptors do to the heart?

inc HR inc COntractilioty

How do you treat chronic heart failure?

Correct underlying cause (repair valve) Reduce salt and liquid intake Drugs

What drugs are given immediately for any type of chronic heart failure?

Diuretics like furosemide

What drugs do you give a patient that has Heart Failure with reduced ejection fraction after having given a loop diuretic?

ACEi and Beta blocker (ramipril and bisoprolol) If still symptoms give Mineralocorticoid receptor antagonist like Spironolactone

What are some adverese effect s of ACE inhibitors?

Drug cough (high bradykinin) Angioedema Hypotension Renal impairment Tinnitus Vertigo

What is a contraindication for ACE inhibitors?

Hereditary Angioedema

What drugs should ACEi not be given with?

K+ sparing diuretics (Indapamide) Alcohol

What are Angiotensin receptor blockers used to treat and when are they used?

Hypertension adn HF When person has side effects with ACEi (dry cough)

What are some adverese effects of Angiotensin Receptor BLockers?

Postural hypotension Hyperkalaemia Hypotension

What cant be taken with Angiotensin receptor blockers?

Alcohol K+ sparing diuretics (Indapamide and Spironolactone)

What cant be taken with Angiotensin receptor blockers?

Alcohol K+ sparing diuretics (Indapamide and Spironolactone)

What are some examples of ARBs?

Losartan Candesartan

What are some drugs that are given for heart failure if the first line treatment doesn’t work?

Sacubitril valsartan Hydrazine Digoxin

What is Sacubitril valsartan?

2 drugs together Valsartan = ARBs (angiotensin receptor blocker) Sacubitril = neprilysin inhibitor

How does sacubutril work in Heart failure?

Neprilysin inhibitor Inhibits natriuretic inactivating enzyme meaning inc effect of ANP so lots of Na+ lost in urine Also stops breakdown of bradykinin leading to vasodilation