Many drugs for hypertension can increase blood pressure or interfere with other drugs used to treat hypertension. Oral contraceptives, for example, cause a small increase in systolic and diastolic blood pressure. Hypertension is two to three times more common in patients who use oral contraceptives for more than 5 years than in patients who haven’t used them at all. A patient who uses oral contraceptives has an increased risk of developing hypertension, with increasing age, duration of use, and body weight.

Estrogen, when used as a postmenopausal replacement therapy, increases blood pressure in some women. All women receiving hormone replacement therapy should have their blood pressure routinely monitored.

Cyclosporine, which is used as an immunosuppressant to prevent organ rejection in transplant recipients, causes vasoconstriction and reduces renal blood flow. Cyclosporine also increases the reabsorption of sodium, water, and urea and has a direct toxic effect on the nephrons. Vasoconstriction and sodium retention lead to hypertension in 50% to 70% of organ transplant recipients taking cyclosporine and in about 20% of nontransplant patients taking the drug for other reasons. Similarly, corticosteroids used to produce immunosuppression in organ transplant recipients can cause hypertension.

Monoamine oxidase (MAO) inhibitors, which are used for treating depression, can cause a severe hypertensive crisis. This condition results from an interaction of the MAO inhibitors with foods such as cheese, bananas, beer, wine, yeast, yogurt, and meat extracts containing tyramine, dopa, or serotonin. Patients who use MAO inhibitors should have their blood pressure monitored regularly.

Erythropoietin-a hormone that acts on bone marrow cells to stimulate red blood cell (RBC) production-causes increased blood pressure in one-third of patients with end-stage renal disease. Although the exact mechanism of action is unknown, erythropoietin may increase systemic vascular resistance by increasing blood viscosity and reversing hypoxic vasodilation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can increase blood pressure by blocking the production of prostaglandins in the kidneys, which leads to sodium and water retention. These drugs also antagonize the effects of some antihypertensive drugs, such as diuretics, by blocking sodium excretion. And NSAIDs cause vasoconstriction by affecting the renin-angiotensin-aldosterone system. African-Americans, diabetic patients, and the elderly are most vulnerable to the effects of NSAIDs. Keep in mind that the elderly commonly use NSAIDs for arthritis.

Cold remedies, nasal decongestants, and appetite suppressants also can cause hypertension. Generally, cold remedies and nasal decongestants are powerful vasoconstrictors that increase systolic and diastolic blood pressures. Appetite suppressants such as amphetamines, however, increase blood pressure by stimulating the CNS. Other types of appetite suppressants, such as dexfenfluramine, can cause primary pulmonary hypertension without affecting systemic blood pressure. Patients with advanced atherosclerosis, cardiovascular disease, or moderate to severe hypertension shouldn’t take appetite suppressants.

By interfering with calcium ion influx across the cell membrane, calcium channel blockers inhibit calcium-dependent contraction of vascular smooth muscle. This decreases total peripheral vascular resistance and after load, which reduces blood pressure.Calcium channel blockers include diltiazem hydrochloride, felodipine, nicardipine, nifedipine, and verapamil.

Indications and Contraindications

Physicians commonly prescribe these drugs to treat patients with angina pectoris. However, several oral forms are used to treat vasospasm and mild to moderate hypertension. Parenteral forms are used to treat hypertension, atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. But sustained-release nifedipine is only used to treat hypertension.

Use calcium channel blockers cautiously in patients with heart failure, hypotension, hepatic injury, and renal disease. Do not administer a calcium channel blocker to patients with sick sinus syndrome, second-degree or third-degree heart block, hypotension, acute MI, or pulmonary congestion. Do not administer verapamil to patients with cardiogenic shock or severe heart failure, and administer it cautiously to patients taking beta-blockers.

Adverse Effects and Interactions

The most serious adverse effects of calcium channel blockers include cardiovascular changes such as hypotension, arrhythmias, and worsened eart failure. Other common effects include headache, dizziness, flushing, weakness, and persistent peripheral edema. Your patient may also experience nausea, vomiting, diarrhoea, muscle fatigue, cramps, worsened angina, skin eruptions, photosensitivity, pruritus, nasal congestion, and mood changes.

Calcium channel blockers can interact with beta-blockers, causing heart block and heart failure. When diltiazem is taken with cimetidine, its effect increases. And when it’s administered with cimetidine or ranitidine, felodipine levels increase. Nicardipine increases the effects of digitalis glycosides, neuromuscular blockers, and theophylline. And when nifedipine is administered in combination with theophylline, beta­blockers, other antihypertensives, or digitalis glycosides, it increases their effects.

Quinidine decreases the effects of nifedipine. The hypotensive effects of verapamil increase when the drug is given with prazosin and quinidine. Verapamil also decreases the effects of lithium and increases the blood levels of digoxin, theophylline, cyclosporine, and carbamazepine. Verapamil is incompatible with albumin, amphotericin B, ampicillin, dobutamine, hydralazine, mezlocillin, nafcillin, oxacillin, and sodium bicarbonate.

Direct vasodilators act on arteries and veins. They dilate arteriolar smooth muscle by direct relaxation, reducing systolic and diastolic blood pressure while increasing heart rate and CO.Direct vasodilators include diazoxide, hydralazine hydrochloride, minoxidil, and nitroprusside.

Indications and Contraindications

A physician prescribes diazoxide and nitroprusside to treat patients in hypertensive crisis when an urgent decrease in diastolic blood pressure is needed. Oral hydralazine is used to treat patients with primary hypertension; parenteral hydralazine is used in patients with severe primary hypertension and heart failure. Minoxidil is prescribed when severe hypertension is unresponsive to other therapy.

Don’t administer hydralazine to patients with CAD or rheumatic heart disease. Do not use minoxidil in patients with acute MI, dissecting aortic aneurysm, or pheochromocytoma. And do not administer nitroprusside to patients with compensatory hypertension.

Don’t use diazoxide in patients with hypersensitivity to thiazides or sulfonamide or in patients whose hypertension is caused by coarctation of the aorta, dissecting aortic aneurysm, atrioventricular shunt, or pheochromocytoma. And use it cautiously in patients with tachycardia, fluid and electrolyte imbalances, or impaired cerebral or cardiac circulation.

Adverse Effects and Interactions

Direct vasodilators commonly produce adverse effects related to reflex activation of the sympathetic nervous system, such as palpitations, angina, tachycardia, ECG changes, edema, rash, breast tenderness, fatigue, and headache. Severe pericardial effusions can develop. And alkaline phosphatase, BUN, and creatinine levels may increase.

Diazoxide commonly causes headache, anorexia, nausea, and diaphoresis. It can also cause excessive hypotension, and in diabetic patients, it may cause hyperglycemia. If more serious effects occur, such as rash, urticaria, polyneuritis, GI hemorrhage, anemia, and pancytopenia, diazoxide should be discontinued.

Hydralazine commonly causes headache, diarrhea, constipation, dizziness, orthostatic hypotension, facial flushing, shortness of breath, nasal congestion, urinary hesitancy, edema, tremors, and muscle cramps. It may also cause impotence.

Minoxidil commonly produces hair growth on the face, arms, and back. It also causes reflex tachycardia and fluid retention. When minoxidil is taken with guanethidine, orthostatic hypotension can occur.

Nitroprusside causes headache, dizziness, nausea, vomiting, abdominal pain, and thiocyanate or cyanide toxicity . Severe hypotension occurs when nitroprusside is administered with ganglionic blockers, volatile liquid anesthetics, halothane, enflurane, and circulatory depressants. Nitroprusside is incompatible with any drug in syringe or solution.

When diazoxide is administered with a thiazide diuretic, another antihypertensive drug, warfarin, guanethidine, or a sympathomimetic, its effects increase. It’s incompatible with other drugs in a syringe or solution. Hyperglycemia and hyperuricemia can result when diazoxide is combined with thiazides and other diuretics. The effects of both diazoxide and sulfonylureas decrease when the drugs are given together.

When hydralazine is used with epinephrine or norepinephrine, tachycardia and angina increase. Hydralazine increases the effects of beta-blockers. And it is incompatible with aminophylline, ampicillin, edetate calcium disodium, chlorothiazide, ethacrynic acid, hydrocortisone, mephentermine, methohexital sodium, nitroglycerin, phenobarbital, verapamil, fructose 10%, dextrose 10%, and lactated Ringer’s solution.