Other antihypertensive agents: choose the class that fits the patient
Blood pressure is determined mainly by cardiac output × systemic vascular resistance. Antihypertensive medicines lower blood pressure by reducing salt and water, relaxing arterioles, suppressing the renin–angiotensin system, reducing sympathetic tone, or combining these effects.
This lesson complements the separate ACE inhibitor and beta-blocker lessons. The practical priorities are correct indication, contraindication screening, safe combination therapy, laboratory monitoring and recognition of hypertensive emergency.
1. First-line treatment framework
For adults who need drug treatment, WHO recommends a medicine from one of three major classes: thiazide/thiazide-like diuretics, ACE inhibitor/ARB, or long-acting dihydropyridine calcium-channel blocker. The best first choice depends on age, pregnancy potential, kidney function, albuminuria, heart failure, ischaemic disease, diabetes, pulse, electrolytes, availability and cost.
| Class | Primary action | Common examples | High-yield caution |
|---|---|---|---|
| Thiazide / thiazide-like diuretic | Promotes sodium excretion; later reduces vascular resistance | Hydrochlorothiazide, chlorthalidone, indapamide | Hypokalaemia, hyponatraemia, gout, glucose rise |
| Dihydropyridine CCB | Arteriolar calcium-channel blockade and vasodilation | Amlodipine, nifedipine LA, felodipine | Peripheral oedema, flushing, headache |
| ARB | Blocks AT1 receptor | Losartan, valsartan, telmisartan, candesartan | Pregnancy, hyperkalaemia, renal monitoring |
| Mineralocorticoid antagonist | Blocks aldosterone receptor | Spironolactone, eplerenone | Hyperkalaemia; spironolactone gynaecomastia |
| Central sympatholytic | Reduces sympathetic outflow | Methyldopa, clonidine | Rebound hypertension with abrupt clonidine withdrawal |
2. Diuretics
Thiazide and thiazide-like diuretics
These block sodium–chloride reabsorption in the early distal convoluted tubule. Early BP lowering comes from reduced extracellular volume and cardiac output; with continued use, peripheral vascular resistance falls. Chlorthalidone and indapamide are longer acting; local formularies determine preferred choice.
- Uses: uncomplicated hypertension; combination treatment; selected older patients and salt-sensitive hypertension.
- Adverse effects: hypokalaemia, hyponatraemia, hypomagnesaemia, dehydration, hyperuricaemia/gout, hyperglycaemia, photosensitivity and erectile dysfunction.
- Monitoring: BP, sodium, potassium, creatinine/eGFR, uric acid where relevant, glucose in at-risk patients and symptoms of dehydration.
- Interactions: NSAIDs reduce effect and increase renal risk; digoxin toxicity risk increases with hypokalaemia; lithium levels may rise.
Loop diuretics
Furosemide and torsemide act in the thick ascending limb of the loop of Henle. They are powerful diuretics but are not routine first-line treatment for uncomplicated hypertension. Use mainly for oedema, heart failure, advanced CKD with fluid overload, or when thiazides are ineffective at low eGFR. They can cause marked volume depletion, hypokalaemia, hypomagnesaemia and ototoxicity at high IV doses.
Potassium-sparing diuretics and aldosterone antagonists
Spironolactone and eplerenone antagonise the mineralocorticoid receptor; amiloride blocks epithelial sodium channels. Spironolactone is a key add-on for resistant hypertension and has major benefit in HFrEF, but check potassium and renal function. Spironolactone may cause gynaecomastia, menstrual disturbance and sexual adverse effects; eplerenone is more selective but often more costly.
3. Calcium-channel blockers (CCBs)
CCBs block L-type calcium channels. Their clinical effect depends on whether they act mainly on vascular smooth muscle or also on cardiac tissue.
Act mainly on arterioles, causing vasodilation and lowering BP. Amlodipine is long acting and commonly once daily. Typical effects are dose-related ankle oedema, flushing, headache, dizziness, palpitations and gingival hyperplasia. The ankle oedema is due to precapillary dilation—not necessarily fluid overload—so adding a loop diuretic may not solve it.
Also depress sinus rate, AV conduction and contractility. Useful for selected rate-control and angina patients but not routine first-line BP medicines. Avoid or use extreme caution with beta blockers because the combination can cause severe bradycardia, AV block and heart failure worsening.
Immediate-release nifedipine is not used to rapidly “crash” BP
Rapid, uncontrolled BP reduction can cause cerebral, myocardial or renal hypoperfusion. Hypertensive emergencies require monitored IV therapy and management of the underlying target-organ injury; asymptomatic severe BP elevation is reduced gradually with oral treatment and close follow-up.
4. Angiotensin-receptor blockers (ARBs) and aliskiren
ARBs block the angiotensin-II AT1 receptor. They provide RAAS blockade without substantially increasing bradykinin, so cough is less common than with ACE inhibitors. They are used for hypertension, albuminuric CKD, HFrEF when appropriate, and ACE-inhibitor intolerance.
- Examples: losartan, candesartan, valsartan, telmisartan, irbesartan, olmesartan.
- Adverse effects: hypotension, hyperkalaemia and creatinine rise. Angioedema is less frequent but still possible.
- Contraindications: pregnancy and major RAAS-related safety concerns similar to ACE inhibitors.
- Never routinely combine: ACE inhibitor + ARB, or ARB + aliskiren, because of hypotension, hyperkalaemia and kidney injury.
Aliskiren directly inhibits renin. It is not commonly first choice; avoid inappropriate dual RAAS blockade, particularly in diabetes or renal impairment.
5. Sympatholytics and alpha blockers
Central agents
- Methyldopa: converted centrally to an alpha2 agonist, reducing sympathetic outflow. It has a long history in pregnancy hypertension. Adverse effects include sedation, dry mouth, depression, hepatitis, positive Coombs test and rarely haemolytic anaemia; monitor according to protocol.
- Clonidine: central alpha2 agonist that lowers sympathetic tone. It can cause dry mouth, sedation, constipation and bradycardia. Never stop abruptly: rebound sympathetic activity may cause severe hypertension, tachycardia and headache.
Alpha1 blockers
Prazosin, doxazosin and terazosin relax arterioles and veins. They can improve lower-urinary-tract symptoms from benign prostatic enlargement but are usually not first-line antihypertensives. The important adverse effect is first-dose postural syncope; start low, often at bedtime, and counsel patients to rise slowly.
Alpha + beta blockers
Labetalol and carvedilol produce both alpha1 vasodilation and beta blockade. Labetalol is important in selected acute and pregnancy-related hypertension protocols. Carvedilol is particularly valuable in stable HFrEF.
6. Direct vasodilators
| Medicine | Role | Important adverse effects / precautions |
|---|---|---|
| Hydralazine | Direct arteriolar dilator; selected resistant hypertension, pregnancy protocols, and with nitrates in some HFrEF patients | Reflex tachycardia, fluid retention, headache, lupus-like syndrome, peripheral neuropathy |
| Minoxidil | Potent arteriolar K+-channel opener for severe resistant hypertension | Fluid retention and tachycardia—usually needs loop diuretic + beta blocker; hypertrichosis; rare pericardial effusion |
| Sodium nitroprusside | Rapid IV arterial and venous dilator in selected ICU hypertensive emergencies | Requires invasive/continuous monitoring; cyanide/thiocyanate toxicity risk with prolonged/high-dose use or renal/hepatic dysfunction |
| IV nitroglycerin | Mainly venodilator; useful when emergency hypertension accompanies acute pulmonary oedema or myocardial ischaemia | Headache, hypotension, tolerance; avoid with PDE-5 inhibitors |
7. Resistant hypertension and combination therapy
Resistant hypertension means BP remains above target despite adherence to an appropriate three-drug regimen at tolerated doses, commonly including a RAAS blocker, long-acting dihydropyridine CCB and diuretic—or BP is controlled only with four or more medicines. Before labelling it resistant, confirm correct BP measurement, adherence, adequate doses, interfering medicines (especially NSAIDs), excess alcohol/salt, and secondary causes such as CKD, primary aldosteronism, obstructive sleep apnoea or renal-artery disease.
- Optimise the foundational regimen and use a thiazide-like diuretic where suitable.
- Consider spironolactone as a common fourth-line option if potassium/eGFR allow.
- Monitor potassium, renal function, pulse, postural BP and adverse effects after each change.
8. Hypertensive urgency versus emergency
Assess symptoms, repeat correctly measured BP, restart/intensify oral therapy, address adherence and arrange close follow-up. The BP number alone does not define emergency.
Features may include encephalopathy, stroke, acute pulmonary oedema, acute coronary syndrome, aortic dissection, acute kidney injury, eclampsia or retinal injury. Admit, monitor closely and use diagnosis-specific IV therapy. BP goals and speed of reduction depend on the condition.
9. Nursing assessment and education
- Measure BP correctly; assess postural symptoms and target-organ symptoms—chest pain, neurological deficit, dyspnoea, confusion, reduced urine output or visual disturbance.
- Review all medicines including OTC NSAIDs, herbal products, decongestants, oral contraceptives and adherence barriers.
- For diuretics: monitor weight, fluid balance, sodium, potassium, magnesium, creatinine and gout symptoms.
- For RAAS blockers/spironolactone: monitor potassium and renal function; avoid potassium salt substitutes unless prescribed.
- For CCBs: assess ankle oedema, flushing, constipation with verapamil and pulse/ECG effects with non-dihydropyridines.
- Teach patients not to stop clonidine or beta blockers suddenly, to rise slowly with alpha blockers, and to seek urgent care for symptoms of hypertensive emergency.
- Pregnancy requires a distinct protocol: ACE inhibitors, ARBs and aliskiren are avoided; do not improvise treatment outside obstetric guidance.
10. High-yield knowledge check
- WHO first-line antihypertensive classes: thiazide/thiazide-like diuretic, ACE inhibitor/ARB, long-acting dihydropyridine CCB.
- Amlodipine commonly causes dose-related ankle oedema.
- Verapamil/diltiazem + beta blocker can cause dangerous AV block and bradycardia.
- Thiazides: hypokalaemia, hyponatraemia, hyperuricaemia and hyperglycaemia.
- Spironolactone: hyperkalaemia and gynaecomastia; key add-on in resistant hypertension.
- Clonidine must be tapered to prevent rebound hypertension.
- In phaeochromocytoma, alpha blockade precedes beta blockade.
- Hypertensive emergency is severe BP with acute target-organ injury.
Further study and reference sources
- Antihypertensive drugs reference slide deck (SlideShare)
- WHO guideline for pharmacological treatment of hypertension in adults
- DailyMed: amlodipine prescribing information
Educational resource. Prescribing and emergency management must follow current local protocol, formulary, patient assessment and supervision requirements.
