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CPT > Lecture 5 - Diuretics And Heart Failure > Flashcards

Lecture 5 - Diuretics And Heart Failure Flashcards

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1
Q

What are diuretics?

A

Drugs that increase urine output

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2
Q

What does natriuretic mean?

A

Loss of Na+ in urine

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3
Q

What does aquaretic mean?

A

Loss of water without electrolytes

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4
Q

What medical conditions are diuretics used for?

A

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

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5
Q

What are some categories of diuretics?

A

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

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6
Q

What are some common adverse drug effects of diuretics?

A

Hypovolaemia and hypotension

Electrolyte disturbance
Metabolic abnormalities
Anaphylaxis (allergy)

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7
Q

Why can diuretics lead to acute kidney injury?

A

Hypovolaemia and hypotension leads to activation of RAAs

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8
Q

How do Thiazides and thiazide like diuretics act?

A

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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9
Q

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

A

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

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10
Q

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

A

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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11
Q

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

A

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

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12
Q

What are 2 examples of Thiazde and Thiazide like diuretic?

A

Indapamide
Bendroflumethiazide

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13
Q

When are some contraindications to using thiazides?

A

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

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14
Q

What channel do Loop Diuretics block?

A

NKCC channel in the ascending limb of loop of Henle

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15
Q

How do loop diuretics act as a diuretic?

A

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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16
Q

When are loop diuretics given?

A

Acute pulmonary oedema
Fluid overload in heart failure
Nephrotic syndrome

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17
Q

What are the adverse effects of loop diuretics?

A

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

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18
Q

What are some contraindications to loop diuretics?

A

Hypokalaemia
Hyponatraemia
Gout
Hepatic encephalopathy

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19
Q

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

A

Aminoglycosides
Digoxin
Lithium

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20
Q

What is an. Example of an aminoglycosides?

A

Gentamicin

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21
Q

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

A

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

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22
Q

What are some examples of loop diuretics?

A

Furosemide
Bumetanide

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23
Q

How do Potassium sparing drugs work as diuretics?

A

Block ENAC channels in the collecting duct and late DCT

Reduces Na+ reabsorption in DCT
Reduces K+ excretion

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24
Q

What are the adverse drug effects of potasssium sparing diuretics?

A

Hyperkalaemia
Potential Arrythmia

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25
Q

What are the contraindications for potassium sparing diuretics?

A

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

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26
Q

What drugs would you not give potassium sparing diuretics with?

A

Other K+ sparing drugs
ACEi
ARBs

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27
Q

What is an example of a potassium sparing diuretic?

A

Amiloride

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28
Q

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

A

Spironolactone

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29
Q

What is the mechanism of action of Spironolactone?

A

Aldosterone receptor antagonist

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

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30
Q

What are the adverse effects of Spironolactone?

A

Gynaecomastia
Hyperkalaemia
Severe cutaneous adverese reactions (SCARs)

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31
Q

What are contraindications to Spironolactone?

A

Addisons disease
Anuria
Hyperkalaemia

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32
Q

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

A

Alcohol
Amiloride
ACEi
ARBs

33
Q

Where do carbonic anhydrase inhibitors work in the nephron?

A

PCT

34
Q

How do carbonic anhydrase inhibitors work as diuretics?

A

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)

35
Q

Why do carbonic anhydrase inhibitors lead to hypokalaemia?

A

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

36
Q

What is an example of a carbonic anhydrase inhibitor?

A

Acetazolamide

37
Q

What part of the nephron do osmotic agents act in?

A

PCT

38
Q

What is an example of an osmotic diuretic?

A

Mannitol

39
Q

How does mannitol act as an osmotic diuretic?

A

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

40
Q

Why is mannitol often given with increase intracranial pressure?

A

Reduces the production of CSF in brain

41
Q

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

A

Just water is lost so reduced plasma volume

42
Q

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

A

PCT

43
Q

How do SGLT2 inhibitors act as diuretics?

A

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

44
Q

What are some examples of SGLT2 inhibitors?

A

Dapagliflozin
Canagliflozin

End in flozin

45
Q

What does a drug called a aquaretic actually do?

A

ADH antagonists

Tolvaptan
Lithium

46
Q

What is the mechanism of action of Tolvaptan?

A

ADH antagonist

(Its an aquaretic)

47
Q

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

A

Inhibits action of ADH

48
Q

What affect does Alcohol have on urine?

A

Inhibits ADH release causing diuresis

49
Q

How does caffeine cause diuresis?

A

Increased GFR
Decreased tubular Na+ reabsorption

Inhibits vasoconstriction of afferent arterioles in kidneys

50
Q

What is Digoxin?

A

Cardiac glycoside

51
Q

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

A

Make heart contract harder

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

52
Q

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

A

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

53
Q

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

A

Calcium gluconate

54
Q

What is heart failure?

A

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

55
Q

What are the 2 classifications of heart failure?

A

HFrEF
HFpEF

56
Q

What is HFrEF?

A

Heart failure with reduced ejection fraction

57
Q

What is HFpEF?

A

Heart failure with preserved ejection fraction

58
Q

What causes HFrEF?

A

HF with reduced ejection fraction caused by Ischaemic events like MI

59
Q

What causes HFpEF?

A

Structural condition like valves

60
Q

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

A

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

61
Q

What is afterload?

A

The pressure the heart works to pump against

62
Q

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

A

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

63
Q

How does remodelling of the heart affect the heart?

A

Loss of myoctes replaced by fibrosis

Changes chamber size imparing ventricular filling

Impairment of ventricular ejection/empytinggg

64
Q

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

A

A1

65
Q

What does stimulation of B1 receptors do to the heart?

A

inc HR
inc COntractilioty

66
Q

How do you treat chronic heart failure?

A

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

Drugs

67
Q

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

A

Diuretics like furosemide

68
Q

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

A

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

69
Q

What are some adverese effect s of ACE inhibitors?

A

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

70
Q

What is a contraindication for ACE inhibitors?

A

Hereditary Angioedema

71
Q

What drugs should ACEi not be given with?

A

K+ sparing diuretics (Indapamide)
Alcohol

72
Q

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

A

Hypertension adn HF

When person has side effects with ACEi (dry cough)

73
Q

What are some adverese effects of Angiotensin Receptor BLockers?

A

Postural hypotension
Hyperkalaemia
Hypotension

74
Q

What cant be taken with Angiotensin receptor blockers?

A

Alcohol
K+ sparing diuretics (Indapamide and Spironolactone)

75
Q

What cant be taken with Angiotensin receptor blockers?

A

Alcohol
K+ sparing diuretics (Indapamide and Spironolactone)

76
Q

What are some examples of ARBs?

A

Losartan
Candesartan

77
Q

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

A

Sacubitril valsartan
Hydrazine
Digoxin

78
Q

What is Sacubitril valsartan?

A

2 drugs together

Valsartan = ARBs (angiotensin receptor blocker)
Sacubitril = neprilysin inhibitor

79
Q

How does sacubutril work in Heart failure?

A

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

CPT (30 decks)

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