Antihypertensives Flashcards
ACE Inhibitors: Common drug names (5):
Captopril
Enalapril
Perindopril
Ramipril
Lisinopril
Fosinopril
ACE Inhibitors: Mode of action (3)?
- Block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin.
- Reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release.
- Reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
ACE-Inhibitors: Indications for prescription
- Hypertension
- Chronic heart failure with reduced EF (part of standard treatment)
- Diabetic nephropathy
- Post MI (commonly due to LV dysfunction)
ACE Inhibitors: Precautions (4):
- Volume or sodium depletion:
(Reduce/remove diuretic before treatment/monitor closely) - Primary hyperaldosteronism:
(ACE inhibitors ineffective) - Black African/Caribbean descent:
(Effect of ACE-i reduced -> CCB preferred) - Drugs that increase K+ concentration (ciclosporin, trimethoprim)
(Increases risk of hyperkalaemia w/ ACE-i in combination)
Can ACE-inhibitors be safely used in pregnancy?
No, Avoid use
Use in 2nd & 3rd trimester may cause fetal renal dysfunction, oligohydramnios, fetal death
ACE-Inhibitors: Common adverse effects:
- Hypotension
- Headache
- Cough (persistent, non-productive cough, not dose dependent)
- Hyperkalaemia
- Renal impairment
Explain the MOA of ACE Cough
The possible mediators that play a role in the development of cough are bradykinin and substance P, which are destroyed by ACE.
Bradykinin and substance P accumulate in the upper and lower respiratory tracts by inhibition of this enzyme by ACE-I.
The cough may be mild and tolerable, however, some patients need to stop treatment (usually improves within 1–4 weeks of stopping).
ACE Inhibitors: Practice Points
- Most ACE-i (except captopril) maintain an antihypertensive effect for up to 24 hours and can be given once daily
- Check renal function and electrolytes before starting an ACE inhibitor and review after 1-2 weeks of use
- Stop potassium supplements and potassium-sparing diuretics
ARBs: Drug names (6):
Candesartan
Irbesartan
Valsartan
Telmisartan
Losartan
Eprosartan
ARBs: Mode of action (3)?
- Competitively block binding of angiotensin II to type 1 angiotensin (AT1) receptors.
- Reduce angiotensin II-induced vasoconstriction, sodium reabsorption and aldosterone release.
- Reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
ARBs: Indications:
Hypertension
ARBs Precautions (4):
- Volume or sodium depletion:
(Reduce/remove diuretic before tx/ monitor closely) - Primary hyperaldosteronism:
(ACE inhibitor ineffective) - Black African/Caribbean descent:
(Effect of ACE-i reduced –> CCB blocker preferred) - Drugs that increase K+ concentration (ciclosporin, trimethoprim)
(Increases risk of hyperkalaemia - avoid ACE-i in combination)
ARBs Common Adverse Effects (3):
Dizziness
Headache
Hyperkalaemia
ARBs Practice points (4):
- Patients may feel dizzy when starting this medication, most common side effect
- When commencing an ARB
- Stop potassium supplements and potassium-sparing diuretics
- Check renal function and electrolytes before starting 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
- Maximum antihypertensive effect occurs about 4–6 weeks after starting treatment
CCBs: Drug subclasses:
Dihydropyridines
Non-dihydropyridines
CCBs: Dihydropyridine drug names (6):
- Amlodipine (PO)
- Felodipine (PO controlled release)
- Nifedipine (PO controlled release)
- Lercanidipine (PO)
- Clevidipine (injection)
- Nimodipine (injection)
CCBs Mode of action:
- Block inward current of Ca++ into cells via L-type calcium channels in:
○ Vascular smooth muscle
○ Myocardium
○ Cardiac conducting system - Act on coronary arteriolar smooth muscle to reduce vascular resistance and myocardial oxygen requirements, relieving angina symptoms.
How do the subclasses of CCB change in their MOA?
Dihydropyridines: - Act mainly on arteriolar smooth muscle to reduce peripheral vascular resistance and BP.
- They have minimal effect on myocardial cells.
Non-dihydropyridines:
Diltiazem and verapamil act on cardiac and arteriolar smooth muscle. They reduce cardiac contractility, heart rate and conduction, with verapamil having the greater effect. Diltiazem has a greater effect on arteriolar smooth muscle than verapamil.
Define: Chronotropic
The ability to influence heart rate.
- Positively chronotropic drugs (e.g., adrenaline) Increase HR
- Negatively chronotropic drugs (e.g., beta blockers) Decrease HR
Define: Inotropic
The ability to influence the force of cardiac muscle contraction.
Positively inotropic drugs (e.g., catecholamines) increase the force of contraction
Negatively inotropic drugs (e.g., beta blockers) decrease the force of contraction
CCBs Indications:
- Hypertension
- Angina
- Preterm labour (nifedipine only)
- Subarachnoid haemorrhage (nimodipine)
- Raynaud’s phenomenon (nifedipine, felodipine)
CCBs Precautions (4):
- Myasthenia-like neuromuscular disease: (Calcium channel blockers may increase risk of muscle weakness and respiratory depression (esp. verapamil))
- Contraindicated in cardiogenic shock
- In aortic stenosis, dihydropyridines may cause coronary hypoperfusion and systemic hypotension
- CCBs may further depress myocardial function in patients with heart failure with reduced ejection fraction; diltiazem and verapamil are contraindicated
CCB Adverse Effects:
- Nausea
- Vasodilatory effects (headache, flushing, dizziness, hypotension)
- Peripheral oedema
CCB: MOA of Peripheral oedema?
Dihydropyridines commonly cause peripheral oedema due to redistribution of extracellular fluid (rather than fluid retention); this does not respond to treatment with diuretics, which may put patient at risk of volume depletion.
