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Fenoldopam mesylate - Corlopam ®

Fenoldopam is a rapid-acting vasodilator. It is an agonist for D1-like dopamine receptors and binds with moderate affinity to α2-adrenoceptors. Fenoldopam: effective as nitroprusside, however, it has the advantages of increasing renal blood flow (6 times as potent as dopamine in producing renal vasodilitation) and sodium excretion, of not being associated with the accumulation of toxic metabolites, and not requiring shielding from light. Fenoldopam can be safely used in all hypertensive emergencies, and may be particularly beneficial in patients with renal insufficiency.

Dosing (Adults):  After a starting dose of 0.1 to 0.3 mcg/kg/minute, the dose is titrated at 15 minute intervals, depending on the BP response. May be increased in increments of 0.05 to 0.1 mcg/kg/minute every 15 minutes until target blood pressure is reached. Maximal infusion rate reported in clinical studies: 1.6 mcg/kg/minute. Onset/duration: 5-10 minutes/~ 1 hour.

Supplied: Injection (soln): 10 mg/mLl(1 ml, 2 ml)

Hydralazine - APRESOLINE ®

Direct arteriolar vasodilator with little or no effect on the venous circulation. Precautions are needed in patients with underlying coronary disease or an aortic dissection. Beta-blocker should be given concurrently to minimize reflex sympathetic stimulation. The hypotensive response to hydralazine is less predictable than that seen with other parenteral agents.

Dosing (Adults):  Initial (Acute hypertension): 10 mg slow IV bolus (maximum dose being 20 mg) every 4 to 6 hours as needed. May increase to 40 mg/dose (generally speaking - do not exceed 20mg/dose). Change to oral therapy as soon as possible. The fall in blood pressure begins within 10 to 30 minutes and lasts 2 to 4 hours. May also be given IM.

Supplied: Injection (soln): 20 mg/ml (1 ml vial). Tablet: 10 mg, 25 mg, 50 mg, 100 mg.

Nesiritide (Natrecor ®)

Human B-type atriuretic peptide (hBNP). Indicated for the IV treatment of patients with acutely decompensated CHF who have dyspnea at rest or with minimal activity. There is limited experience with administering Natrecor for longer than 48 hours. Blood pressure should be monitored closely during Natrecor administration. Produces venous and arterial vasodilation, plus mild diuretic effect. Patients experiencing hypotension during the infusion: Hold infusion. May attempt to restart at a lower dose (reduce initial infusion dose by 30% and omit bolus).

Dosing (Adults):  IV bolus of 2 mcg/kg (over 1 minute) followed by a continuous infusion of 0.01 mcg/kg/min. Withdraw bolus dose from the infusion bag. Higher initial dosages are not recommended. At intervals of 3 hours, the dosage may be increased by 0.005 mcg/kg/minute (preceded by a bolus of 1 mcg/kg), up to a maximum of 0.03 mcg/kg/minute.
Supplied: Injection (pwd for reconstitution): 1.5 mg vial.

Nicardipine - Cardene ®

Dihydropyridine calcium channel blocker. Advantages: Does not depress LV function; does not adversely increase ICP (acceptable choice in stroke patients). Major limitation: longer half-life, which precludes rapid titration. Contraindicated in heart block, recent AMI, and renal failure.
Dosing (Adults):
(Acute hypertension) - The initial dose is 5 mg/hour and can be increased to a maximum of 15 mg/hour. Effects seen within 15 minutes. Initial dose of 5 mg/hr can be increased by 2.5 mg/hour every 15 minutes to the previously listed maximum of 15 mg/hour. Consider reduction to 3 mg/hour after response is achieved. Monitor and titrate to lowest dose necessary to maintain stable blood pressure. Preparation: Dilute to 0.1 mg/ml (25 mg in D5W 250 ml).

Substitution IV to oral therapy (approximate):
0.5 mg/hr IV = ~ 20mg po q8h.
1.2 mg/hr IV = ~ 30mg po q8h.
2.2 mg/hr IV = ~ 40mg po q8h.

(Other indications):
Angina: Immediate release capsule: 20 mg orally 3 times daily. Usual range: 60-120 mg/day. Increase dose at 3 day intervals.

Hypertension: Immediate release capsule: Initial: 20 mg orally 3 times daily. Usual: 20-40 mg 3 times daily (allow 3 days between dose increases). Sustained release capsule: Initial: 30 mg orally twice daily - titrate up to 60 mg twice daily.
Note: The total daily dose of immediate-release product may not automatically be equivalent to the daily sustained-release dose - use caution in converting.

Supplied: Injection (soln): 2.5 mg/ml (10 ml). Capsule (IR): 20 mg, 30 mg. Capsule (SR): 30 mg, 45 mg, 60 mg

Ranolazine - RANEXA®

CLINICAL PHARMACOLOGY - Mechanism of Action------------------------
The mechanism of action of ranolazine's antianginal effects has not been determined. Ranolazine has anti-ischemic and antianginal effects that do not depend upon reductions in heart rate or blood pressure. It does not affect the rate-pressure product, a measure of myocardial work, at maximal exercise. Ranolazine at therapeutic levels can inhibit the cardiac late sodium current (INa). However, the relationship of this inhibition to angina symptoms is uncertain.

INDICATIONS AND USAGE----------------
Ranexa is indicated for the treatment of chronic angina.

DOSAGE AND ADMINISTRATION-------------------
500 mg twice daily and increase to 1000 mg twice daily, based on clinical symptoms.

DOSAGE FORMS AND STRENGTHS------------------
Extended-release tablets: 500 mg, 1000

Nitroglycerin

Primarily a venous dilator (lesser degree - arteriolar dilator). It may be most useful in patients with symptomatic coronary disease and in those with hypertension following coronary bypass. Drug of choice for hypertensive emergencies with coronary ischemia. It should not be used with hypertensive encephalopathy because it increases ICP. Tolerance may occur within 24-48 hours. Nitrate-free interval (10-12 hours/day) is recommended to avoid tolerance development.

Dosing (Adults):
(IV): Initial dose: 5 mcg/min IV infusion. Increase by 5 mcg/minute every 3-5 minutes to 20 mcg/minute. If no response at 20 mcg/minute increase by 10 mcg/minute every 3-5 minutes, up to a maximum of 200 mcg/minute. Onset: 2 to 5 minutes. Duration: 5 to 10 minutes.
Initial increments of 5 micrograms/minute can be made every 3 to 5 minutes. If no response is seen at 20 micrograms/minute, larger increments of 10 to 20 micrograms/minute can be considered. As partial response is achieved, dosing increments should become more cautious.

Angina/coronary artery disease:
Oral: 2.5mg to 9 mg bid - qid (up to 26 mg qid). Topical ointment: Apply 0.5" to 2" every 6 hours with a nitrate free interval (10-12hrs). Patch (transdermal): 0.2-0.4 mg/hour initially and titrate to doses of 0.4-0.8 mg/hour. Remove patch to provide nitrate free interval (10-12hrs). Sublingual: 0.2-0.6 mg every 5 minutes for maximum of 3 doses in 15 minutes.
Esophageal spastic disorders (unlabeled use): 0.3-0.4 mg 5 minutes before meals. Translingual: 1-2 sprays into mouth under tongue every 3-5 minutes for maximum of 3 doses in 15 minutes, may also be used 5-10 minutes prior to activities which may provoke an attack prophylactically.

Supplied: Capsule (ER): 2.5 mg, 6.5 mg, 9 mg. Injection (Soln): 5 mg/ml (5 ml, 10 ml). Ointment: 2% (1 g, 30 g, 60 g). Sublingual tablet: 0.3 mg, 0.4 mg, 0.6 mg. Patch (Transdermal ): 0.1 mg/hour; 0.2 mg/hour; 0.4 mg/hour; 0.6 mg/hour.

Sodium Nitroprusside - Nipride ®

Arteriolar and venous dilator. Considered to be the most effective parenteral drug for most hypertensive emergencies (except myocardial ischemia or renal impairment). It dilates both arteries and veins, and it reduces afterload and preload. Onset: within seconds. Duration: 2-3 minutes. Constant monitoring of the blood pressure is required.
Alternatives to nitroprusside include intravenous labetalol, nicardipine, and fenoldopam. Hypotension is uncommon with these drugs and cyanide toxicity is not an issue.

Dosing (Adults)Initial: 0.3-0.5 mcg/kg/minute. Increase in increments of 0.5 mcg/kg/minute -- titrating to the desired hemodynamic effect or the appearance of headache or nausea. Usual dose: 3 mcg/kg/minute (rarely need >4 mcg/kg/minute). Maximum: 10 mcg/kg/minute.

When treatment is prolonged (>24 to 48 hours) or when renal insufficiency is present, the risk of cyanide and thiocyanate toxicity is increased. Doses > 2 mcg/kg/min exceed the capacity of the body to detoxify cyanide. Maximum doses of 10 mcg/kg/min should never be given for more than 10 minutes. An infusion of sodium thiosulfate can be used in affected patients to provide a sulfur donor to detoxify cyanide into thiocyanate.

Supplied: Injection (Soln): 25 mg/ml - 2 ml (vial).

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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Vasodilators