Hypertension

HYPERTENSION •

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A sustained diastolic blood pressure of >90 mmHg accompanied by an elevated blood pressure of >140 mmHg resulting from an increased arteriolar resistance and decreased capacitance of the vessels. WHO: BP >160/95 mmHg AHA: BP >140/90 mmHg

CLASSIFICATION OF HYPERTENSION ACCORDING TO ETIOLOGY

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Primary or essential H P N o 90-95% of cases. o Cause: Unknown. o Predisposing factors:  Family history, stressful lifestyle, increased dietary intake of sodium, obesity. Secondary H P N o 5-10% of cases. o Causes:  Renal artery stenosis, Cushing’s syndrome, pheochromocytoma.

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Peripheral vascular o Absence of 1 or more pulses in the extremities except in the dorsalis pedis with or without intermittent claudication o Arterial aneurysms Renal o Serum creatinine >/= 130

MALIGNANT HYPERTENSION

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An accelerated phase of severe HPN with a rapidly progressing damage to end-organs and rising BP which may be signaled by deteriorating renal function, encephalopathy, retinal hemorrhages, angina, stroke, or MI.

MECHANISMS OF CONTROLLING BLOOD PRESSURE • •

Baroreceptor and sympathetic nervous system Renin-angiotensin-aldosterone system

CLASSIFICATION OF BP FOR ADULTS 18 YRS AND OLDER (PHIL. SOCIETY OF HPN) •

Optimal o <120 mmHg / <80 mmHg Recheck in 2 years. • Normal o 120-129 mmHg / 80-84 mmHg Recheck in 2 years. • High normal o 130-139 mmHg / 85-89 mmHg Recheck in 1 year. • Stage 1 (mild) HPN o 140-159 mmHg / 90-99 mmHg Confirm in 2 months. • Stage 2 (moderate) HPN o 160-179 mmHg / 100-109 mmHg Evaluate within a month. • Stage 3 (severe) HPN o 180-209 mmHg / 110-119mmHg Evaluate within a week. • Stage 4 (very severe) HPN o >/=210 mmHg / >/=120 mmHg Evaluate immediately. MANIFESTATIONS OF TARGET-ORGAN DAMAGE •

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Cardiac o Evidence of CAD o Clinical, ECG, radiologic à evidence of LVH or cardiac failure Cerebrovascular o TIA or stroke

TREATMENT STRATEGIES Non-pharmacologic therapy • Low salt diet. • Weight reduction. • Exercise. • Cessation of smoking. • Decreased alcohol consumption. • Psychological methods: Relaxation / meditation. • Dietary decrease in saturated fat. Drug therapy • Stepped Care o Progressive addition of drugs to a regimen, starting with one, usually a

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diuretic, and adding, in a stepwise fashion, a sympatholytic, vasodilator, and sometimes an ACE inhibitor. Monotherapy o Advantageous because of its simplicity, better patient compliance, and relatively low incidence of toxicity.

STEPPED CARE

CATEGORIES OF ANTI-HYPERTENSIVE DRUGS Drugs that alter sodium and water balance à Diuretics. • Loop diuretics • Thiazides • Spironolactone and Triamterene

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- Propranolol - Timolol

VASODILATORS • Direct vasodilators  Diazoxide - Hydralazine  Minoxidil - Nitroprusside  Fenoldopam • Calcium channel blockers  Amlodipine - Nifedipine  Diltiazem - Nimodipine  Felodipine - Nisoldipine  Isradipine - Nitrendipine  Manidipine - Nicardipine  Lacidipine - Verapamil  Lercanidipine - Gallopamil AGENTS THAT BLOCK THE PRODUCTION OR ACTION OF ANGIOTENSIN • ACE inhibitors  Benazepril - Moexipril  Captopril - Quinapril  Enalapril - Perindopril  Fosinopril - Ramipril  Lisinopril - Trandolapril • AT1-receptor blockers  Irbesartan - Losartan  Telmisartan - Valsartan  Candesartan - Eprosartan  Olmesartan DRUGS FOR HYPERTENSIVE EMERGENCIES OR CRISES •

Drugs that alter sympathetic nervous system function à Sympatholytic drugs. • Centrally-acting sympatholytics  Clonidine  Guanabenz  Guanfacine  Methyldopa • Peripherally-acting sympatholytics  Guanadrel  Guanethidine  Reserpine • a-blockers  Doxazosin  Prazosin  Terazosin • b-blockers  Acebutolol - Labetalol  Atenolol - Metoprolol  Betaxolol - Nadolol  Bisoprolol - Penbutolol  Carteolol - Pindolol

Carvedilol Esmolol

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Trimethaphan o 1 mg/ml IV infusion; titrate; instantaneous onset Sodium nitroprusside o 5-10 mg/L IV infusion; titrate; instantaneous onset Diazoxide o 300-600 mg Rapid IV push; instantaneous onset Nifedipine o 10-20 mg Sublingual or chewed; onset within 5-30 min. Labetalol o 20-80 mg IV at 10-minute intervals (max.dose: 300mg); immediate onset

MECHANISMS OF DRUG ACTION

DRUG ADVERSE EFFECTS •

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RESERPINE o Interacts with MAO inhibitors. Used with caution in patients with peptic ulcers (inc. GI act.). Sedation, nightmares, severe depression. Nasal stuffiness. GUANADREL o Orthostatic hypotension and syncope. Edema. GI hyperactivity. Interacts with TCAs. ACE Inhibitors: Captopril o Dry cough. Hypotension and syncope. Hyperkalemia. Accumulates in patients with impaired renal function. Renal damage in fetus à CI on the 2nd and 3rd tri of pregnancy. o CAPTOPRIL: Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems

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(teratogenic), Rash, Increased renin, Lower angiotensin II. SODIUM NITROPRUSSIDE o Hypotension, nausea, headache, palpitation (rapid vasodilation). Cyanide toxicity. THIAZIDE DIURETICS o Potassium and magnesium loss. Arrhythmias. Increase in cholesterol concentration. Hyperglycemia. b-BLOCKERS o Precipitates heart failure (abrupt cessation) in patients with left ventricular dysfunction. Use with caution in patients with Bronchial asthma. Decreased HDL. Psoriasis. Abrupt withdrawal à cardiac arrhythmias. VERAPAMIL o Cardiodepression. Hypotension, peripheral edema. Headache, constipation. CLONIDINE o Xerostomia, drowsiness, sedation. Rebound HPN (abrupt cessation). Fluid retention. Sudden withdrawal à dysrhythmias. HYDRALAZINE o Headache, nausea, anorexia, dizziness, and sweating. Worsen Coronary Artery Disease (myocardial stimulation). Reversible lupus-like syndrome esp. in slow acetylators. MINOXIDIL o Pericardial effusion and tamponade in patients with inadequate renal function. Hirsutism. DIAZOXIDE o Severe hypotension. Worsens myocardial ischemia and angina (reflex sympathetic stimulation). Hyperglycemia (inhibits insulin release). Edema (salt and water retention). PRAZOSIN o Sudden syncope, palpitations, fluid retention. Vertigo, weakness, dizziness, drowsiness, headache. METHYLDOPA o Sedation at onset of treatment. Drug fever: Chills and fever with alteration in liver function. Edema (salt and water retention). Rebound HPN (abrupt cessation). Orthostatic hypotension. Hemolytic anemia. NIFEDIPINE o Hypotension, headache. Peripheral edema. DILTIAZEM o Hypotension. Peripheral edema. Cardiodepression.

PRINCIPLES OF DRUG THERAPY •

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Monotherapy is generally reserved for mild to moderate HPN; it has gained popularity because of its simplicity, fewer side effects, and improved patient compliance. More severe HPN may require treatment with several drugs that are selected to minimize adverse effects of combined regimen.

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Treatment is initiated with any of 4 drugs depending on individual patient: Diuretic, bblocker, ACEI, and a Ca-channel blocker; if BP is inadequately controlled, a 2nd-drug is then added. HPN may co-exist with other disease that may be aggravated by some of the anti-HPN agents. Lack of patient compliance is the most common reason for failure of anti-HPN therapy; it is important to enhance compliance by carefully selecting a drug regimen that minimizes adverse effects. Therapy is directed at preventing disease that may occur in the future, rather than in relieving present discomfort of the patient.