Renin-angiotensin-aldosterone system Flashcards
Role of Renin-angiotensin-aldosterone system in homeostasis
- 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.
Effects of angiotensin II
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.
Drugs that work on the Renin-angiotensin-aldosterone system
ACE inhibitors (e.g., enalapril),
angiotensin receptor blockers (ARBs, e.g., losartan), and
aldosterone antagonists (e.g., spironolactone)
ACE inhibitor means …
Angiotensin converting enzyme inhibitor
MOA
ACE inhibitor
- 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
Indication
ACE inhibitors
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
Adverse reactions
ACE inhibitors
- hypotension
- headache
- dizziness
- cough (dry / non productive)
- hyperkalaemia
- fatigue
- nausea
- renal impairment
Practice points
ACE inhibitor
*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
Drug class and indication
Captopril
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)
Drug Class and indication
Enalapril
ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
* Asymptomatic left ventricular dysfunction
Drug class and indication
Enalapril with hydrochlorothiazide
ACE inhibitor + Thiazide diuretic
* Hypertension
Drug class and indication
Fosinopril
ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
Drug class and indication
Fosinopril with hydrochlorothiazide
ACE inhibitor + Thiazide diuretic
* Hypertension
Drug class and indication
Lisinopril
ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
* Post MI, acute treatment
Drug class and indication
Perindopril
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
Drug class and indication
Perindopril with amlodipine
ACE inhibitor + Dihydropyridine Calcium channel blocker
* Hypertension
* Stable coronary heart disease
Drug class and indication
Perindopril with indapamide
ACE inhibitor + Thiazide diuretic
* Hypertension
Drug class and indication
Quinapril
ACE inhibitor
* Hypertension
* Chronic heart failure with reduced ejection fraction as part of standard treatment
Drug class and indication
Quinapril with hydrochlorothiazide
ACE inhibitor + Thiazide diuretic
* hypertension
Drug class and indication
Ramipril
ACE inhibitor
* Hypertension
* Post MI
* Prevention of MI, stroke, cardiovascular death in patients >55 years with: cardio risk factors
Drug class and indication
Ramipril with felodipine
ACE inhibitor + Dihydropyridine calcium channel blocker
* Hypertension
Drug class and indication
Trandolapril
ACE inhibitor
* Hypertension
* Post MI in patients with left ventricular dysfunction
Generic names of ACE inhibitors
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
Drug interactions
ACE inhibitor
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.
