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Pharmacology 2 > Renin-angiotensin-aldosterone system > Flashcards

Renin-angiotensin-aldosterone system Flashcards

1
Q

Role of Renin-angiotensin-aldosterone system in homeostasis

A
  • The renin-angiotensin-aldosterone system is primarily associated with blood pressure regulation by modulating blood volume, sodium reabsorption, potassium secretion, water reabsorption, and vascular tone.
  • There are three important components to this system: 1) renin, 2) angiotensin, and 3) aldosterone.
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2
Q

Effects of angiotensin II

A

Strong vasoconstrictor = ^ BP
The actions of Ang II are mediated through binding to the Ang-II type 1 receptor (AT1R) which leads to increased blood pressure, fluid retention, and aldosterone secretion. In addition, Ang II is also involved in cell injury, vascular remodelling, and inflammation.

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3
Q

Drugs that work on the Renin-angiotensin-aldosterone system

A

ACE inhibitors (e.g., enalapril),
angiotensin receptor blockers (ARBs, e.g., losartan), and
aldosterone antagonists (e.g., spironolactone)

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4
Q

ACE inhibitor means …

A

Angiotensin converting enzyme inhibitor

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5
Q

MOA
ACE inhibitor

A
  • block angiotensin I conversion to angiotensin II
  • inhibit breakdown of bradykinin (contribute to vasodilation)
  • reduce sodium retention
  • reduced aldosterone (hormone that controls sodium and water retension and therefore controls BP)

ACE inhibitors block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. They reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
## water follows salt … increased salt = increased BP, decreased salt = decreased BP

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6
Q

Indication
ACE inhibitors

A

Hypertension

Chronic heart failure with reduced ejection fraction as part of standard treatment

Diabetic nephropathy

Prevention of progressive renal failure in patients with persistent proteinuria (>1 g daily)

Post MI

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7
Q

Adverse reactions
ACE inhibitors

A
  • hypotension
  • headache
  • dizziness
  • cough (dry / non productive)
  • hyperkalaemia
  • fatigue
  • nausea
  • renal impairment
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8
Q

Practice points
ACE inhibitor

A

*You may feel dizzy when you start taking this medicine. Get up gradually from sitting or lying to minimise this effect; sit or lie down if you become dizzy or light-headed.

Do not take potassium supplements while you are taking this medicine unless your doctor tells you to.*

When starting an ACE inhibitor:
* stop potassium supplements and potassium-sparing diuretics
* in heart failure, consider reducing dose or withholding other diuretics for 24 hours before starting an ACE inhibitor
* review use of NSAIDs (including selective COX‑2 inhibitors)
* start with a low dose
* check renal function and electrolytes before starting an ACE inhibitor and review after 1–2 weeks
* encourage patients to continue ACE inhibitors during the COVID‑19 pandemic as there is no clinical evidence to support stopping treatment

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9
Q

Drug class and indication

Captopril

A

ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
* Post MI in patients with left ventricular dysfunction
* Diabetic nephropathy (type 1 diabetes)

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10
Q

Drug Class and indication

Enalapril

A

ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
* Asymptomatic left ventricular dysfunction

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11
Q

Drug class and indication

Enalapril with hydrochlorothiazide

A

ACE inhibitor + Thiazide diuretic
* Hypertension

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12
Q

Drug class and indication

Fosinopril

A

ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment

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13
Q

Drug class and indication

Fosinopril with hydrochlorothiazide

A

ACE inhibitor + Thiazide diuretic
* Hypertension

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14
Q

Drug class and indication

Lisinopril

A

ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
* Post MI, acute treatment

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15
Q

Drug class and indication

Perindopril

A

ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
* Reduction of risk of MI or cardiac arrest in people with established coronary heart disease without heart failure

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16
Q

Drug class and indication

Perindopril with amlodipine

A

ACE inhibitor + Dihydropyridine Calcium channel blocker
* Hypertension
* Stable coronary heart disease

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17
Q

Drug class and indication

Perindopril with indapamide

A

ACE inhibitor + Thiazide diuretic
* Hypertension

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18
Q

Drug class and indication

Quinapril

A

ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment

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19
Q

Drug class and indication

Quinapril with hydrochlorothiazide

A

ACE inhibitor + Thiazide diuretic
* hypertension

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20
Q

Drug class and indication

Ramipril

A

ACE inhibitor
* Hypertension
* Post MI
* Prevention of MI, stroke, cardiovascular death in patients >55 years with: cardio risk factors

21
Q

Drug class and indication

Ramipril with felodipine

A

ACE inhibitor + Dihydropyridine calcium channel blocker
* Hypertension

22
Q

Drug class and indication

Trandolapril

A

ACE inhibitor
* Hypertension
* Post MI in patients with left ventricular dysfunction

23
Q

Generic names of ACE inhibitors

A

Captopril
Enalapril
Enalapril with hydrochlorothiazide
Fosinopril
Fosinopril with hydrochlorothiazide
Lisinopril
Perindopril
Perindopril with amlodipine
Perindopril with indapamide
Quinapril
Quinapril with hydrochlorothiazide
Ramipril
Ramipril with felodipine
Trandolapril

24
Q

Drug interactions
ACE inhibitor

A

Triple threat = ACE inhibitor + NSAID + loop or thiazide diuretic
Lithium + ACE inhibitors
Loop diuretics + ACE inhibitors
NSAIDs + ACE inhibitors NSAIDs (including selective COX‑2 inhibitors) may reduce antihypertensive effect of ACE inhibitor and may increase risk of renal impairment and hyperkalaemia (risk is further increased if a thiazide or loop diuretic is also taken). Avoid combination in the elderly or if renal hypoperfusion or impairment exists; monitor BP, weight, serum creatinine and potassium concentration. Use no more than 100–150 mg aspirin daily.
sartans + ACE inhibitors
Sartans given with ACE inhibitors increase the risk of hypotension, hyperkalaemia and renal impairment without additional benefit; avoid combinations (see Treatment with an ACE inhibitor and a sartan).

Members of this class are captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril and trandolapril.

ACE inhibitors can cause potassium retention, which may lead to hyperkalaemia, especially in people with renal impairment or diabetes, or if taken with potassium supplements or with other drugs* that can also cause potassium retention. Avoid combinations if possible or monitor potassium concentration.

Note that aldosterone antagonists are used with ACE inhibitors in patients with heart failure, with routine potassium concentration monitoring.

Monitor potassium concentration if an ACE inhibitor is given with drugs* that can reduce potassium concentration, as hypokalaemia may still occur.

ACE inhibitors also reduce BP; administration with other drugs* that lower BP may result in additional hypotensive effects (which may be intended); avoid combinations or use carefully and monitor BP.

25
Q

SARTANs a.k.a. …

A

angiotensin receptor agonists (ARA)

26
Q

MOA
sartans / ARA

A

Competitively block binding of angiotensin II to type 1 angiotensin (AT1) receptors. They reduce angiotensin II-induced vasoconstriction, sodium reabsorption and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.

27
Q

Indication
sartans / ARAs

A
  • Hypertension
  • Chronic heart failure with reduced ejection fraction as part of standard treatment in patients unable to tolerate ACE inhibitors
28
Q

Adverse effects
sartans

A

dizziness, headache, hyperkalaemia

29
Q

Precautions / contradictions
sartans / ARAs

A

Peripheral vascular disease or atherosclerosis—patients may be more likely to have renal artery stenosis.

Volume or sodium depletion—Monitor combination w/ diuretics (both affect sodium and BP)

Black African or Caribbean descent

Treatment with drugs that can increase potassium concentration,

30
Q

Practice points
sartans / ARAs

A
  • stop K+ and K+ sparing diuretics
  • review use of NSAIDs
  • check renal function
  • used when ACE inhibitors are not tolerated for HTN and chronic heart failure

You may feel dizzy when you start taking this medicine. Get up gradually from sitting or lying to minimise this effect; sit or lie down if you become dizzy or light-headed.

Do not take potassium supplements while you are taking this medicine unless your doctor tells you to.

when starting a sartan:
stop potassium supplements and potassium-sparing diuretics
in heart failure, consider reducing dose or withholding other diuretics for 24 hours before starting a sartan
review use of NSAIDs (including selective COX‑2 inhibitors)
start with a low dose
check renal function and electrolytes before starting a sartan and review after 1–2 weeks
unlike ACE inhibitors, sartans do not inhibit the breakdown of bradykinin and may be useful if an ACE inhibitor is not tolerated because they:
cause less cough than ACE inhibitors
may be used if there is a history of angioedema caused by an ACE inhibitor (with close monitoring as there is a small risk of recurrence)
maximum antihypertensive effect occurs about 4–6 weeks after starting treatment
encourage patients to continue sartans during the COVID‑19 pandemic as there is no clinical evidence to support stopping treatment

31
Q

Drug class and indication

Candesartan

A

sartan / ARA
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment in patients unable to tolerate ACE inhibitors

32
Q

Drug class and indication

Candesartan with hydrochlorothiazide

A

sartan / ARA + thiazide diuretic
Hypertension

33
Q

Drug class and indication

Eprosartan

A

sartan / ARA
Hypertension

34
Q

Drug class and indication

Eprosartan with hydrochlorothiazide

A

sartan / ARA + thiazide diuretic
Hypertension

35
Q

Drug class and indication

Irbesartan

A

sartan / ARA
* Hypertension
* Reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 hours) or proteinuria (>900 mg/24 hours)

36
Q

Drug class and indication

Irbesartan with hydrochlorothiazide

A

sartan /ARA + thiazide diuretic
Hypertension

37
Q

Drug class and indication

Losartan

A

sartan / ARA
* Hypertension
* Reduction of renal disease progression in patients with type 2 diabetes, hypertension and proteinuria (urinary albumin to creatinine ratio greater than or equal to 300 mg/g or proteinuria >500 mg per 24 hours)

38
Q

Drug class and indication

Olmesartan

A

sartan / ARA
Hypertension

39
Q

Drug class and indication

Olmesartan with amlodipine

A

sartan / ARA + Dihydropyridine calcium channel blocker
Hypertension

40
Q

Drug class and interaction

Olmesartan with amlodipine and hydrochlorothiazide

A

sartan / ARA + Dihydropyridine calcium channel blocker + thiazide diuretic
Hypertension

41
Q

Drug class and interaction

Olmesartan with hydrochlorothiazide

A

sartan / ARA + thiazide diuretic
Hypertension

42
Q

Drug class and indication

Telmisartan

A

sartan / ARA
* Hypertension
* Prevention of cardiovascular morbidity and mortality in patients with coronary artery disease, peripheral artery disease, high-risk diabetes, previous stroke or TIA

43
Q

Drug class and indication

Telmisartan with amlodipine

A

sartan / ARA + Dihydropyridine calcium channel blocker
Hypertension

44
Q

Drug class and indication

Telmisartan with hydrochlorothiazide

A

sartan / ARA + thiazide diuretic
Hypertension

45
Q

Drug class and indication

Valsartan

A

Sartan / ARA
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment in patients unable to tolerate ACE inhibitors
* Left ventricular failure/dysfunction after MI, when clinically stable

46
Q

Drug class and indication

Valsartan with hydrochlorothiazide

A

Sartan / ARA + Thiazide diuretic
Hypertension

47
Q

Generic names of Sartans / ARA

A

Candesartan
Candesartan with hydrochlorothiazide
Eprosartan
Eprosartan with hydrochlorothiazide
Irbesartan
Irbesartan with hydrochlorothiazide
Losartan
Olmesartan
Olmesartan with amlodipine
Olmesartan with amlodipine and hydrochlorothiazide
Olmesartan with hydrochlorothiazide
Telmisartan
Telmisartan with amlodipine
Telmisartan with hydrochlorothiazide
Valsartan
Valsartan with hydrochlorothiazide

48
Q

Tripple Whammy

A

NSAID + [Sartan(ARB) OR ACE] + diuretic

Sounds like satan ate enough said

Pharmacology 2 (41 decks)

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