Drugs affecting the renin-angiotensin system Flashcards
ACE inhibitors inhibit the conversion of (?) to (?)
Angiotensin I to angiotensin II
Why should potassium supplements and potassium-sparing diuretics be discontinued before introducing an ACE inhibitor?
Risk of hyperkalaemia
EXCEPT a low dose of spironolactone may be beneficial in severe heart failure
In severe heart failure what is the only potassium-sparing diuretic that you can used with an ACE inhibitor?
Low dose spironolactone
- Initially 25 mg once daily, then adjusted according to response to 50 mg once daily.
When you introduce an ACE inhibitor to patients with heart failure who are already taking a high dose of a loop diuretics (e.g. furosemide 80 mg daily or more), which side effect are you concerned about?
Profound first-dose hypotension
Temporary withdrawal of the loop diuretic reduces the risk, but may cause severe rebound pulmonary oedema.
Therefore, for patients on high doses of loop diuretics, the ACE inhibitor may need to be initiated under specialist supervision.
In which context does a patient with heart failure may need to be under specialist supervision you an ACE inhibitor is initiated?
Patients taking a high-dose of loop diuretics (e.g. furosemide 80 mg daily or more)
An ACE inhibitor can be initiated in the community in patients who are receiving a low dose of a diuretic or who are not otherwise at risk of serious hypotension; nevertheless, care is required and a very low dose of the ACE inhibitor is given initially.
What is the most appropriate initial drug for hypertension in Caucasian patients under the age of 55?
ACE inhibitor
What is the most appropriate drug for the treatment of hypertension in patients with diabetes?
ACE inhibitor
Which patients with hypertension DO NOT respond less well to an ACE inhibitor? (3)
- Black African or African-Caribbean origin
- Aged > 55 years
- Primary aldosteronism
Do ACE inhibitors have a role in the management of diabetic nephropathy?
YES
What are the 4 main indications for the use of ACE inhibitors?
- Heart failure
- Hypertension
- Diabetic nephropathy
- Prophylaxis of cardiovascular events
In which contexts should an ACE inhibitor be initiated under specialist supervision? (9)
- Severe heart failure
- Multiple or high-dose diuretic therapy
- Concomitant angiotensin II receptor antagonist or aliskiren
- Hypovolaemia
- Hyponatraemia (plasma sodium concentration below 130 mmol/L)
- Hypotension (systolic BP < 90)
- Unstable heart failure
- High-dose vasodilator therapy
- Known renovascular disease
Which drug increases the risk of renal damage when combined with an ACE inhibitor?
NSAIDs
What may happen if you prescribe an ACE inhibitor in patients with severe bilateral renal artery stenosis (or severe stenosis of the artery supplying a single functioning kidney)?
Reduction of glomerular filtration causing severe and progressive renal failure
ACE inhibitor treatment is unlikely to have an adverse effect on overall renal function in patients with severe unilateral renal artery stenosis and a normal contralateral kidney, but glomerular filtration is likely to be reduced (or even abolished) in the affected kidney and the long-term consequences are unknown.
ACE inhibitors can cause a very rapid fall in BP in (?)-depleted patients
volume
Patients taking high-dose diuretics need close observation after administration of the first dose of ACE inhibitor, for at least 2 hours or until the blood pressure has stabilised
Describe the close observation required of a patient who is taking a high-dose diuretic during their first-dose of an ACE inhibitor?
Close observation after the administration of the first dose of ACE inhibitor, for at least 2 hours or until the BP has stabilised
Why would you switch a patient from an ACE inhibitor to an ARB?
Persistent cough
Why would a patient develop a persistent cough when taking an ACE inhibitor?
Due to increased levels of bradykinin
ACE inhibitor inhibit the breakdown of bradykinin
Which angiotensin-II receptor antagonists (ARBs) are licensed as adjuncts to ACE inhibitors under specialist supervision, in the management of heart failure when other treatments are unsuitable? (2)
Candesartan cilexetil
Valsartan
Angiotensin-II receptor antagonists (ARBs) should be used with caution in…
renal artery stenosis
(?) is a renin inhibitor that is licensed for the treatment of hypertension
Aliskiren
- Oral: 150 mg once daily, increased if necessary to 300 mg once daily.
Aliskiren is a (?) inhibitor that is licensed for the treatment of hypertension
renin
- Oral: 150 mg once daily, increased if necessary to 300 mg once daily.
Aliskiren is a renin inhibitor that is licensed for the treatment of (?)
Hypertension
- Oral: 150 mg once daily, increased if necessary to 300 mg once daily.
Why should you give combination therapy with two drugs that affect the renin-angiotensin system? (3)
Increased risk of:
- hyperkalaemia
- hypotension
- renal impairment
Exception: selected patient with heart failure whom other treatments are unsuitable, only under specialist supervision with close monitoring of BP, renal function and electrolytes (potassium)
Renin converts (?) to (?)
angiotensinogen to angiotensin I
What is the only indication for the use of aliskiren?
Essential hypertension
- Oral: 150 mg once daily, increased if necessary to 300 mg once daily.
What are the contraindications for the use of the renin inhibitor, aliskiren?
- Concomitant treatment with an ACE inhibitor or ARB in patients with eGFR < 60 mL/minute/1.73 m^2
- Concomitant treatment with an ACE inhibitor or an ARB in patients with diabetes mellitus
- Hereditary angioedema
- Idiopathic angioedema
Which two drinks can greatly decrease aliskiren concentrations and plasma renin activity?
Apple juice
Orange juice
What are the common side effects of the renin inhibitor aliskiren? (4)
Arthralgia
Diarrhoea
Dizziness
Electrolyte imbalance
Patients with a history of (?) need to be closely monitored during treatment with aliskiren
angioedema
What are the indications for the use of the ARB, azilsartan medoxomil? (2)
Hypertension
- Oral: Initially 40 mg once daily, increased if necessary to 80 mg once daily.
Hypertension with intravascular volume depletion
- Oral: Initially 20–40 mg daily, increased if necessary to 80 mg daily.
What are the contraindications for all angiotensin-II receptor antagonists (ARBs)? (2)
- The combination of an ARB with aliskiren in patients with an eGFR < 60 mL/minute/1.73 m^2
- The combination of an ARB with aliskiren in patients with diabetes mellitus
In which contexts should you consider stopping an angiotensin-II receptor antagonist (ARB) in an elderly patient because the prescription is potentially inappropriate (STOPP criteria)?
- Hyperkalaemia
2. Persistent postural hypotension i.e. recurrent drop in systolic BP >/= 20 mmHg (risk of syncope and falls)
What are the common side effects of angiotensin-II receptor antagonists?
- Abdominal pain
- Asthenia (weakness)
- Back pain
- Cough
- Diarrhoea
- Dizziness
- Headache
- Hyperkalaemia
- Hypotension
- Nausea
- Postural hypotension
- Renal impairment
- Vertigo
- Vomiting
Should angiotensin-II receptor antagonists be used during pregnancy?
NO (unless essential)
- they may adversely effect fetal and neonatal BP control and renal function
- neonatal skull defects and oligohydramnios have been reported
Which electrolyte needs to be monitored in all patients taking an angiotensin-II receptor antagonist (ARB)?
Potassium
Especially in the elderly and in patients with renal impairment
What are the indications for the use of the ARB, candesartan cilexetil? (5)
- Hypertension
- Hypertension with intravascular volume depletion (initial starting dose is half of just hypertension - 4 mg once daily instead of 8 mg)
- Heart failure with impaired left ventricular systolic function when ACE inhibitors are not tolerated
- Heart failure with impaired left ventricular systolic function in conjunction with ACE inhibitor (under expert supervision)
- Migraine prophylaxis (unlicensed)
In addition to the contraindications for all ARBs, what is an additional contraindication specifically for candesartan cilexetil?
Cholestasis
In addition to the side effects for all ARBs, what is an additional common side effect specifically for candesartan cilexetil?
Increased risk of infection
What is the only indication for use of the ARB eprosartan?
Hypertension
In addition to the side effects for all ARBs, what are 2 additional common side effect specifically for eprosartan?
Gastrointestinal disorder
Rhinitis
What are the indications for the use of the ARB, irbesartan? (4)
- Hypertension
- Hypertension in patient receiving haemodialysis
- Renal disease in hypertensive type 2 diabetes mellitus
- Renal disease in hypertensive type 2 diabetes in patients receiving haemodialysis
In addition to the side effects for all ARBs, what is an additional common side effect specifically for irbesartan?
Musculoskeletal pain
What are the indications for use of the ARB losartan potassium?
- Diabetic nephropathy in type 2 diabetes mellitus
- Chronic heart failure when ACE inhibitors are unsuitable or contra-indicated
- Hypertension (including reduction of stroke risk in hypertension with left ventricular hypertrophy)
- Hypertension with intravascular volume depletion
In addition to the side effects for all ARBs, what are 3 additional common side effects specifically for losartan potassium?
Anaemia
Hypoglycaemia
Postural disorders
What is the only indication for the ARB, olmesartan medoxomil?
Hypertension
In addition to the contraindications for all ARBs, what is an additional contraindication specifically for olmesartan medoxomil?
Biliary obstruction
In addition to the side effects for all ARBs, what are 10 additional common side effect specifically for irbesartan?
- Arthritis
- Bone pain
- Chest pain
- Dyspepsia
- Haematuria
- Hypertriglyceridaemia
- Hyperuricaemia
- Increased risk of infection
- Influenza like illness
- Oedema
What are the indications for use of spironolactone? (8)
- Oedema
- Ascites in cirrhosis of the liver
- Malignant ascites
- Nephrotic syndrome
- Oedema in congestive heart failure
- Moderate to severe heart failure (adjunct)
- Resistant hypertension (adjunct)
- Primary hyperaldosteronism in patients awaiting surgery
What are the contraindications for use of spironolactone? (3)
Addison’s disease
Anuria
Hyperkalaemia
What is the mode of action of spironolactone?
Aldosterone antagonist
Competitively binding to the aldosterone receptor which increases sodium and water excretion and potassium retention
In which contexts should you consider stopping an aldosterone antagonist (e.g. spironolactone) in an elderly patient because the prescription is potentially inappropriate (STOPP criteria)?
When taking concurrent potassium-conserving drugs without monitoring serum potassium
Risk of dangerous hyperkalaemia
What should you monitor in patients taking spironolactone?
Electrolytes
In severe heart failure monitor potassium and creatinine 1 week after initiation and after any dose increase, monthly for first 3 months, then every 3 months for 1 year, and then every 6 months
What are the two indications for use of the ARB telmisartan?
- Hypertension
- Prevention of cardiovascular events in patients with established atherosclerotic cardiovascular disease, or type 2 diabetes mellitus with target organ damage
In addition to the contraindications for all ARBs, what are 2 additional contraindication specifically for telmisartan?
Biliary obstructive disorders
Cholestasis
What are the indications for the use of the ARB, valsartan?
- Hypertension
- Hypertension with intravascular volume depletion (initially half the dose than if they were not volume depleted - 40 mg instead of 80 mg)
- Heart failure when ACE inhibitors cannot be used, or in conjunction with an ACE inhibitor when a bet-blocker cannot be used
- Myocardial infarction with left ventricular failure or left ventricular systolic dysfunction
In addition to the contraindications for all ARBs, what are 2 additional contraindication specifically for valsartan?
Biliary cirrhosis
Cholestasis
When prescribing an ARB for hypertension by the patient has intravascular volume depletion, what should the initial dose be?
Half of the dose that you would give if they were not volume depleted
ARBs that you can give:
- valsartan
- losartan potassium
- candesartan cilexetil
- alisartan medoxomil
