Nitrates transdermal

Each of the transdermal nitroglycerin systems is effective in treating angina pectoris when worn for 12—16 h followed by an off period. The FDA recommends the period without dmg (8—12 h) to mitigate the possibiUty of the patient acquiring a tolerance to the antianginal effects of nitrate therapy. Thus, a noncontinuous dosing schedule of nitrates is recommended even with the transdermal deflvery system (81). 

The nitrates are available in various forms (eg, sublingual, transmucosal, translingual spray, and inhalation). Some adverse reactions are a result of the metiiod of administration. For example, sublingual nitroglycerin may cause a local burning or tingling in the oral cavity. However, die patient must be aware that an absence of this effect does not indicate a decrease in the drug s potency. Contact dermatitis may occur from use of die transdermal delivery system. 

Promoting an Optimal Response to Therapy N URATES The nitrates may be administered by die sublingual (under die tongue), buccal (between the cheek and gum), oral, IV, or transdermal route Nitroglycerin may be administered by die sublingual, buccal, to peal, transdermal, oral, or IV route If die buccal form of nitroglycerin has been prescribed, die nurse instructs die patient to place die buccal tablet between die cheek and gum or between die upper lip and gum above die incisors and allow it to dissolve The nurse shows the patient how and where to place die tablet in die mouth. Absorption of sublingual and buccal forms is dependent on salivary secretion. Dry mouth decreases absorption. 

Nitrate products are available in both oral and transdermal formulations for chronic use. Commonly used products are listed in Table 4-8. All nitrate products are equally effective at preventing the recurrence of angina when used appropriately. 

For sustained daytime angina prophylaxis, nitrates are of limited value because "nitrate pauses of about 12 h are appropriate if nitrate tolerance is to be avoided. If attacks occur during the day, ISDN, or its metabolite isosorbide mononitrate, may be given in the morning and at noon (e.g ISDN 40 mg in extended-release capsules). Because of hepatic presystemic elimination, NTG is not suitable for oral administratioa Continuous delivery via a transdermal patch would also not seem advisable because of the potential development of tolerance. With molsidomine, there is less risk of a nitrate tolerance however, due to its potential carcinogenicity, its clinical use is restricted. 

Patients who are using certain drugs for erectile dysfunction (eg, sildenafil citrate), because these drugs have been shown to potentiate the hypotensive effects of organic nitrates (sublingual tablets, lingual spray, transdermal). 

Nitrates are required for symptomatic relief of chest pain they are not proven to improve hard outcomes such as MI or death. Nitrates should be given initially sublingually or by spray, followed by oral or transdermal routes if pain is relieved. Lack of pain relief mandates i.v. administration. Beta-blockers such as metoprolol are used and may reduce the risk of subsequent MI. Calcium channel blockers such as dilfiazem, verapamil, or long-acting di-hydropyridines can be added for symptom control if nitrates and beta-blockers do not suffice they do not improve outcomes. In fact, they may worsen outcomes in the presence of left ventricular dysfunction or CHF in acute coronary syndrome. 

Nitroglycerin, the prototype of the nitrates is characterized by a rapid onset and short duration of action. It is usually administered sublingually (via the oro-mucosal route), which allows a rapid and efficient absorption and avoids the strong first pass effect after oral administration. Nitroglycerin is available as tablets, capsules (for sublingual administration) but also as transdermal preparations, sprays, and ointments. 

To help avoid nitrate tolerance, clinicians should employ the smallest effective dose and administer the compound infrequently. A daily nitrate-free period is also recommended, particularly with use of the transdermal patches or ointment. A better understanding of the pharmacokinetic profile achieved with these sustained-release formulations should result in more effective dosing regimens. 

Contraindications Allergy to adhesives (transdermal), closed-angle glaucoma, constrictive pericarditis (IV), early MI (sublingual), GI hypermotility or malabsorption (extended-release), head trauma, hypotension (IV), inadequate cerebral circulation (IV), increased intracranial pressure (ICP), nitrates, orthostatic hypotension, pericardial tamponade (IV), severe anemia, uncorrected hypovolemia (IV)... 

With continuous exposure to nitrates, isolated smooth muscle may develop complete tolerance (tachyphylaxis), and the intact human becomes progressively more tolerant when long-acting preparations (oral, transdermal) or continuous intravenous infusions are used for more than a few hours without interruption. 

S. Savonitto, M. Motolese, and E. Agabiti-Rosei. Antianginal effect of transdermal nitroglycerin and oral nitrates given for 24 hours a day in 2456 patients with stable angina pectoris. Int. J. Clin. Pharmacol. Ther. 33 194—203, 1995. 

Nitrate therapy may be used to terminate an acute anginal attack, to prevent effort- or stress-induced attacks, or for long-term prophylaxis, usually in combination with j3-blockers or calcium channel antagonists. Suhhngual, huccal, or spray nitroglycerin products are preferred for alleviation of anginal attacks because of rapid absorption (Table 11-1). Symptoms may be prevented by prophylactic oral or transdermal products (usually in combination with j3-blockers or calcirun channel antagonists), but development of tolerance may be problematic. 

---