| Drug | Mechanism of action | Adverse effects |
| Calcium channel blockers - dihydropyridines such as nifedipine, amlodipine, nicardipine, nimodipine, clevidipine | Block L-type calcium channels in vascular smooth muscle, causing vasodilation | Reflex tachycardia, flushing, headache, edema, hypotension; not preferred in CAD/angina; clevidipine formulation contains soy and egg, so it 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 cardiac contractility; 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 ACE, which converts angiotensin I to angiotensin II; ACE also breaks down bradykinin, so ACE I increase bradykinin levels; dilate arteries and veins, decrease preload and afterload, promote natriuresis and diuresis, and 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 (AT 1) receptors on blood vessels and the heart; do not increase bradykinin (no cough, no angioedema); dilate arteries and veins, decrease preload and afterload, promote natriuresis and diuresis, and inhibit pathologic cardiac remodelling | Dizziness, hyperkalemia, headache (overall well tolerated drug) |
| Direct acting arterial dilators - hydralazine | Dilates arteries and arterioles; opens vascular smooth muscle K channels; increases nitric oxide and cGMP; short half-life | Reflex tachycardia, headache, flushing; lupus-like syndrome; used in hypertensive emergencies, preeclampsia, and pulmonary hypertension |
| Nitrates used in HT include nitroprusside and nitroglycerine | Sodium nitroprusside preferentially dilates arteries and arterioles and releases nitric oxide; 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 may develop; used in hypertensive emergencies, pheochromocytoma, and aortic dissection; contraindicated with phosphodiesterase inhibitors like sildenafil |
| Ganglion blockers like mecamylamine and trimethaphan; these drugs are rarely used | Noncompetitive antagonists at nicotinic receptors in autonomic ganglia; mecamylamine crosses the blood brain barrier, while trimethaphan does not | Prolonged neuromuscular block with hypotension, impotence, constipation, urinary retention, dry mouth, histamine release, cycloplegia; tremors, choreiform movements, and mental status changes with mecamylamine |
| Potassium channel opener like Minoxidil | Opens ATP-sensitive K channels in vascular smooth muscle, causing hyperpolarization, smooth muscle relaxation, and vasodilation; dilates arteries and arterioles | Reflex tachycardia, headache, flushing, edema, fluid retention, hypertrichosis (increases body hair - used to treat balding) |
| Renin inhibitors like aliskiren | Inhibits renal 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, decreasing intracellular cAMP in vascular smooth muscle and causing vasodilation; reduce blood pressure by decreasing cardiac output; inhibit renin release by the kidneys | Bradycardia, heart failure, hypotension, AV block, bronchoconstriction; beta 1 selective blockers do not cause bronchoconstriction at usual doses |
| Centrally acting sympatholytics like clonidine, alpha methyldopa, guanabenz, guanfacine; methyldopa/aldomet is a prodrug, structurally related to dopamine | Centrally acting alpha 2 agonists that stimulate 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 with sudden discontinuation; methyldopa can cause a Coombs positive hemolytic anemia and a 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 specific anti-HT therapy in most cases. Look for underlying causes of HT (for example, pain, hyperaldosteronism, etc.). Follow up and treat if blood pressure does not normalize. HT emergency is life threatening 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, 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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