| Drug | Mechanism of action | Adverse effects |
| Calcium channel blockers -dihydropyridines such as nifedipine, amlodipine, nicardipine, nimodipine, clevidipine | Block L type calcium channels of smooth muscles in blood vessels causing vasodilation | Reflex tachycardia, flushing, headache, edema, hypotension, not preferred in CAD/angina; Clevidipine formulation contains soy and egg so should be avoided in soy or egg allergies |
| Calcium channel blockers -non-dihydropyridines, diltiazem and verapamil | More cardio-specific, block L type calcium channels | Bradycardia, AV block, decreased contractility of the heart, do not combine with beta blockers, less preferred in heart failure |
| Alpha 1 blockers like prazosin, terazosin, doxazosin; Nonselective alpha blockers are phenoxybenzamine and phentolamine | Dilate arteries and veins by blocking alpha receptors on blood vessels | Dizziness, orthostatic hypotension, nasal congestion, headache, reflex tachycardia, fluid retention; Used along with beta blockers preoperatively in pheochromocytoma |
| ACE I or angiotensin inhibiting enzyme inhibitors such as captopril, enalapril, lisinopril, ramipril | Block the enzyme ACE that catalyzes the conversion of angiotensin I to angiotensin II; ACE also breaks down bradykinin, hence ACE I increase bradykinin levels; Dilate arteries and veins, decrease preload and afterload, natriuresis and diuresis, inhibit pathologic cardiac remodelling | Dry cough (from increased bradykinin), hypotension, angioedema (from increased bradykinin), hyperkalemia |
| Angiotensin receptor blockers or ARBs like losartan, valsartan, telmisartan, candesartan, irbesartan | Block angiotensin II receptors on blood vessels and heart, called AT 1; Do not increase bradykinin; (no cough, no angioedema); Dilate arteries and veins, decrease preload and afterload, natriuresis, diuresis, inhibit pathologic cardiac remodelling | Dizziness, hyperkalemia, headache (overall well tolerated drug) |
| Direct acting arterial dilators - hydralazine | Dilates arteries and arterioles, opening of vascular smooth muscle K channels, increase nitric oxide, increased cGMP; Short half-life | Reflex tachycardia, headache, flushing. Lupus-like syndrome; Used in the treatment of hypertensive emergencies, preeclampsia, pulmonary hypertension |
| Nitrates used in HT include nitroprusside and nitroglycerine | Sodium nitroprusside preferentially dilates arteries and arterioles, releases nitric oxide which dilates blood vessels; Nitroglycerine increases nitric oxide formation; Nitric oxide activates smooth muscle guanylyl cyclase to form cGMP which decreases intracellular calcium levels; it also opens K channels causing hyperpolarization | Headache, flushing, postural hypotension, reflex tachycardia, thiocyanate/cyanide toxicity (with nitroprusside); Tolerance to drug may develop;Used in hypertensive emergencies, pheochromocytoma, aortic dissection; Contraindicated with phosphodiesterase inhibitors like sildenafil |
| Ganglion blockers like mecamylamine and trimethaphan; These drugs are rarely used | Non competitive antagonist at nicotinic receptors of autonomic ganglions; Mecamylamine crosses the blood brain barrier while trimethaphan does not | Prolonged neuromuscular block with hypotension, impotence, constipation, urinary retention, dry mouth, stimulates histamine release, cycloplegia; Tremors, choreiform movements, mental status changes with mecamylamine |
| Potassium channel opener like Minoxidil | Open ATP sensitive K channels on vascular smooth muscle causing hyperpolarization and smooth muscle relaxation and vasodilation; Dilate arteries and arterioles | Reflex tachycardia, headache, flushing, edema, fluid retention, hypertrichosis (increases body hair- used to treat balding) |
| Renin inhibitors like aliskiren | Inhibits the renal enzyme renin which catalyzes the conversion of angiotensinogen to angiotensin I; Dilates arteries and veins | Diarrhea, cough, angioedema, hyperkalemia; Contraindicated in pregnancy |
| Diuretics | Thiazides are first line drugs for hypertension; potassium sparing diuretics are used in HT secondary to hyperaldosteronism or in addition to thiazides | |
| Beta blockers like propranolol, atenolol, labetalol etc. | For antihypertensive effect, beta blockers block vascular beta 2 receptors , decrease intracellular cAMP in vascular smooth muscle causing vasodilation; Reduce blood pressure by decreasing cardiac output. Inhibit the release of renin by kidneys | Bradycardia, heart failure, hypotension, AV block, bronchoconstriction; Beta 1 selective blockers do not cause bronchoconstriction in usual doses |
| Centrally acting sympatholytics like clonidine, alpha methyldopa, guanabenz, guanfacine; Methyldopa/aldomet is a prodrug, structurally related to dopamine | Centrally acting alpha 2 agonist that stimulates adrenergic neurons in the rostral ventrolateral medulla and decrease sympathetic outflow to the cardiovascular system | Edema, sedation, dry mouth, depression, bradycardia, orthostatic hypotension, impotence, constipation, gastric upset, rebound hypertension on sudden discontinuation; Methyldopa can cause a Coombs positive hemolytic anemia and lupus-like syndrome. It may be used in pregnancy. |
ACE inhibitors and ARBs are used in diabetes, diabetic nephropathy, chronic renal disorders with proteinuria and left ventricular failure. ARBs are preferred in patients who develop cough due to ACE inhibitor use. Both ACE inhibitors and ARBs are contraindicated in pregnancy and in bilateral renal artery stenosis. In African Americans with HT, a diuretic or calcium channel blocker should be added to ACE I or ARBs to decrease blood pressure.
In patients with cardiovascular risk factors or CAD, beta blockers, ACE inhibitors or ARBs, diuretics and calcium channel blockers are preferred for the treatment of HT.
Treatment of HT urgency and emergency: Patients with HT urgency do not need any specific anti HT therapy, in most cases. Any underlying causes of HT like pain, hyperaldosteronism etc. should be looked for. They should be followed up and treated if blood pressure does not normalize. However, HT emergency is a life threatening condition and should be treated. Blood pressure** **should be lowered by 25% in the first hour and then gradually decreased to 160/100 mmHg within the next 2 to 6 h, and then cautiously to normal over the next 24 to 48 h. However, in aortic dissection, the blood pressure should be decreased within 5-10 minutes to <120 mmHg systolic.
| Condition | Preferred drug |
| Aortic dissection | i.v esmolol, followed by i.v labetalol or nitroglycerine or nitroprusside |
| Pulmonary edema | i.v nitroglycerine, clevidipine or nitroprusside |
| AMI/CAD | i.v esmolol, followed by i.v nitroglycerine if needed; labetalol |
| Renal failure acute | Clevidipine, fenoldopam, nicardipine |
| Eclampsia/ pre eclampsia | Hydralazine, labetalol, nicardipine |
| Cocaine toxicity/pheochromocytoma | Phentolamine, nitroglycerine or nitroprusside; diazepam; Beta blockers should be given only after alpha blockers |
| Intracerebral hemorrhage | Clevidipine, labetalol, nicardipine and urapidil |
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