 Prepared by:  Dr Rasol M Hasan

Anti- HYPERTENSIVE Drugs

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Vasodilators Examples: Clonidine Methyldopa Hexamethonium Guanithidine, reserpine, alpha blockers Amyl nitrate Hydralazine (oral) Minoxidil(parenteral) Nesiritide Fenoldopam Na nitroprusside Diazoxide Calicium ch. Blockers ACEI, Angio.recep.blockers ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics CENTRALLY ACTING ALPHA 2 - AGONISTS CLONIDINE,METHYLDOPA decreases the sympathetic response from brainstem to peripheral vessels Stimulate alpha 2 receptors: increase vagus activity, decrease cardiac output and decreases serum epinephrine, norepinephrine & renin release results into reduced peripheral vascular resistance Side effects: - drowsiness, dry mouth and nasal mucosa, dizziness, orthostatic hypotension impotence, sodium and fluid retention. Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers ACE Inhibitors - Angiotensin Antagonists (Angiotensin- Converting Enzyme [ACE] Inhibitors) Action: - Inhibits ACE which in turn inhibits formation of angiotensin II (vasoconstrictor) and blocks the release of aldosterone Side effects: - Constant irritation cough; Nausea; Vomiting; Diarrhea; Fatigue; Hyperkalemia; Tachycardia Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers ACE Inhibitors Indication: - Hypertension (control blood pressure); Prevention of cardiovascular disorders; Preventing kidney damage in people with hypertension or diabetes; Congestive heart failure (CHF); Left ventricular dysfunction Contraindication: - Pregnancy (Lowers placental blood flow); Hypotension Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Vasodilators - Direct Acting Arteriolar Vasodilators eg hydralazine old vasodilator mainly arteriolar dilator Action: - act as blood vessel dilators - relaxes vascular smooth muscles which decrease peripheral vascular resistance and therefore reduces blood pressure Uses of Vasodilators: Systemic and Pulmonary Hypertension Heart Failure Angina Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Vasodilators Side Effects: CNS: Headache; Peripheral neuropathy; Dizziness CVS: Palpitation; Flushing; Reflex tachycardia; Angina; Ischemic arrhythmias GIT: Nausea; Anorexia Skin: Sweating; Lupus erythematosus like syndrome characterized by: Myalgia, Arthralgia, Skin rashes, Fever Renal: Edema hypotension ECG changes Drowsiness Dry mouth Fatigue Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Vasodilators Contraindications: ischemic heart disease Lupus erythematosus acute MI DM tachycardia thyrotoxicosis Precautions: - caution should be used in uncompensated heart disease or peptic ulcer disease Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Vasodilators Pharmacokinetics: - onset, peak, and duration vary widely among products. Most products are metabolized in the liver and excreted in urine Interactions: - varies widely among products Example of PH ARMACOKINETICS OF ` HYDRALAZINE  Oral vasodilator but can be given I/V  Rapidly metabolized by the liver during first pass bioavailability is low averaging 25% variable among individuals.  Well absorbed. Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Ca Channel Blockers 3 CHEMICAL CLASSES: Phenylalkylamines – Verapamil (Calan, Isoptin, Verelan) Benzothiazepines – Diltiazem (C ardizem, Dilacor, Tiazac) Dihydropyridines – Amlodipine (Norvasc), Felodipine (Plendil), Nicardipine (Cardene), Nifedipine (Adalat, Procardia) Mechanism of action: Prevents calcium from entering the excitation-contraction process therefore, prevents muscle contraction and, instead, promotes relaxation of the smooth muscles that surrounds the coronary arteries and causes them to dilate. Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Ca Channel Blockers Indications: Angina Hypertension Supraventricular tachycardia For short-term management of atrial fibrillation and flutter, migraine Headaches. Contraindications: Drug allergy Acute MI Second- or third-degree atrioventricular block Hypotension Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Ca Channel Blockers Adverse Effects: Hypotension Palpitations Tachycardia or bradycardia Nausea Constipation Dyspnea Flushing Peripheral edema Common Drug Interactions Beta-Blockers Digoxin – possible increased digoxin level H2 blockers – elevated levels of Calcium channel blockers Grapefruit can reduce the metabolism of Ca channel blockers Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics 5 groups of drugs: 1.Beta-adrenergic blockers 2.Centrally acting alpha2-agonists 3.Alpha-adrenergic blockers 4.Adrenergic neuron blockers (Peripherally acting sympatholytics) 5.Alpha1 and Beta1 adrenergic blockers Sympatholytics:[anti-adrenergic] - reduces the physiological effects caused by stimulation of the sympathetic nervous system Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics BETA-ADRENERGIC BLOCKERS (Beta-blockers) Step 1- antihypertensive drugs Step 2 - in combination with diuretics - also used as antianginals and antidysrhythmics - reduces cardiac output by blocking the SympathNS response thus decreasing basal sympathetic tone - continued use: reduces vascular resistance and lowers BP - reduces HR, contractility and renin release - can cross the placental barrier and enter breast milk Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics BETA-ADRENERGIC BLOCKERS (Beta-blockers) Types: 1.Nonselective inhibits beta 1 (heart) and beta 2 (bronchial) receptors decrease BP secondary to decrease and bronchoconstriction occurs 2.Cardioselective act mainly on beta 1 ; bronchoconstriction less likely to occur Oral Beta-blockers Onset of action: 30 mins. or less Duration: 6 to 12 hours Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics BETA-ADRENERGIC BLOCKERS (Beta-blockers) IV Beta-blockers Onset of action: immediate Peak: 20 mins. Duration: 4 to 10 hours Side Effects: - dizziness, weakness, wheezes, shortness of breath, Adverse Reactions: - Bradycardia, bronchospasms, markedly decrease BP Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics BETA-ADRENERGIC BLOCKERS (Beta-blockers) Precaution: Should not be used by clients with 2 nd - or 3 rd - degree AV block or sinus bradycardia. Noncardioselective beta-blocker should not be given in patients with COPD Inform patients that herbs can interfere with beta-blockers Example of drugs: Propanolol Metoprolol Acebutolol Atenolol Bisoprolol Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics CENTRALLY ACTING ALPHA 2 - AGONISTS Adverse reactions: - Peripheral edema Example of drugs: Clonidine Methyldopa Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics ALPHA-ADRENERGIC BLOCKERS blocks alpha-adrenergic receptors which results in vasodilation and decrease BP maintains renal blood flow rate useful in clients with lipid abnormalities safe for diabetic patients because it does not affect glucose metabolism Side effects: - dizziness, headache, vomiting, nausea, drowsiness, and nasal congestion, dry mouth Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics ALPHA-ADRENERGIC BLOCKERS Adverse reactions: - orthostatic hypotension Example of drugs: Prazosin Terazosin Doxazosin Phentolamine Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics ADRENERGIC NEURON BLOCKERS blocks norepinephrine release, thus lowers BP decreases cardiac output and peripheral vascular resistance Side effects: - dizziness, weakness, nausea, drowsiness Adverse reactions: - Orthostatic hypotension, peripheral edema Example of drugs: Reserpine Guanethidine Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Sympatholytics ALPHA 1 AND BETA 1 ADRENERGIC BLOCKERS blocking alpha 1 receptor results in dilation of the arterioles and veins. decreases BP and moderately decreased PR Side effects: - dizziness, weakness, nausea and vomiting, nervousness, dry mouth and fatigue Adverse reactions: - Orthostatic hypotension Example of drugs: Labetalol Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Indications: Hypertension, alone or when in combination with other anti-hypertensive drugs. Nephropathy in type II DM Heart failure in those intolerant to ACE inhibitors Reduce risk of stroke Contraindications and Special Considerations Drug Allergy Pregnancy and lactation Elderly patients Patients with renal dysfunction Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Examples: Losartan (Cozaar) Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapo) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Sympatholytics

ACE Inhibitors Vasodilators Diuretics Ca Channel Blockers Angiotensin Receptor Blockers Serious Side Effects: Altered Liver Function Kidney Impairment Hyperkalemia Orthostatic hypotension Toxicity and Management Overdose may manifest: Hypotension Tachycardia, bradycardia occurs less often treatment is symptomatic and supportive. It includes the administration of IVFs to expand the blood volume Drug to Drug Interaction - can interact with cimetidine, Phenobarbital, and rifampin. Sympatholytics