Lecture 5 - Diuretics And Heart Failure Flashcards
What are diuretics?
Drugs that increase urine output
What does natriuretic mean?
Loss of Na+ in urine
What does aquaretic mean?
Loss of water without electrolytes
What medical conditions are diuretics used for?
Primary hypertension
Chronic heart failure
Nephrotic syndrome
CKD
Decompensated liver disease (not a lot of albumin made)
What are some categories of diuretics?
Carbonic anhydrase inhibitors
Osmotic diuretics
SGLT2 inhibitors
Loop diuretics
Thiazides
Potassium sparing diuretics
Aldosterone antagonists
ADH antagonists
What are some common adverse drug effects of diuretics?
Hypovolaemia and hypotension
Electrolyte disturbance
Metabolic abnormalities
Anaphylaxis (allergy)
Why can diuretics lead to acute kidney injury?
Hypovolaemia and hypotension leads to activation of RAAs
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
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
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
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)`
What are 2 examples of Thiazde and Thiazide like diuretic?
Indapamide
Bendroflumethiazide
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
What channel do Loop Diuretics block?
NKCC channel in the ascending limb of loop of Henle
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
When are loop diuretics given?
Acute pulmonary oedema
Fluid overload in heart failure
Nephrotic syndrome
What are the adverse effects of loop diuretics?
Dehydration
Hypotension
Hypokalaemia
Hyponatraemia
Hypocalcaemia
Hypomagnesemia
Hyperuricemia
Tinnitus (Ototoxicity)
Inc cholesterol and Triglycerides
What are some contraindications to loop diuretics?
Hypokalaemia
Hyponatraemia
Gout
Hepatic encephalopathy
What are the drug-drug interactions for loop diuretics that shouldn’t be paired?
Aminoglycosides
Digoxin
Lithium
What is an. Example of an aminoglycosides?
Gentamicin
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
What are some examples of loop diuretics?
Furosemide
Bumetanide
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
What are the adverse drug effects of potasssium sparing diuretics?
Hyperkalaemia
Potential Arrythmia
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?
A1
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
