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LONG ACTING ANGINAL TREATMENT WITH GLYCERYL TRINITRATE Pharmaceutical manipulation teaches an old drug some new tricks Glyceryl trinitrate (nitroglycerin) has been used to treat angina for over l 00 years. With the advent of new dosage forms, more rational treatment and prophylaxis for angina will require a more critical and systematic approach by clinicians. The-accent must be placed on different pharmacokinetic principles, depending on the nature of the disease. If relief of established ischaemia is required then a rapid onset of action is essential, but in the prevention of ischaemia, duration of action and predictability are more important. Careful titration of doses is essential because of the up to 500% variability in dose required to produce a given effect. Sublingual glyceryl trinitrate has a rapid onset of antianginal effect (in l-2 min) which is undetectable after l hour. Acute, brief periods of prophylaxis can thus be given to patients with infrequent but highly predictable angina. Sublingual isosorbide dinitrate has an onset in 3-5 min but, at doses equipotent to glyceryl trinitrate, does not give a longer duration of action. Oral nitrates produce very variable effects because of hepatic clearance, and the high doses required to give a long duration of action (8 hours) may produce severe orthostatic and other adverse reactions. Sustained-release preparations now available may circumvent some of these problems. The problems of variability in absorption and frequent application of cutaneous glyceryl trinitrate ointments have been overcome since the introduction of slow-release cutaneous preparations. Although the onset of action still about 30 min, the absorption is at a constant rate provided over 24 hours. Convincing data on the efficacy and duration of a-ction of these devices are still required and a source of potential concern at the moment is their considerable cost. Another novel dosage form providing gradual and uniform nitrate release is long acting transmucosal glyceryl trinitrate tablets which are applied under the upper lip and adhere to the gingiva. A small mean dose size of 1. 7mg glyceryl trinitrate gives a prolonged effect and studies indicate improved exercise tolerance for 0.5-5 hours. Its combination of rapid onset and predictable effect is unique, and the dosage can be simply regulated by checking whether the tablet has dissolved. It should prove useful both for established angina as well as for acute and continued prophylaxis. Reichek, N. and Sutton, M. St.J.: Annals of Internal Medicine 97: 774 (Nov 1982) 0156-2703/82f1211-0003f0$01.00/0 © ADIS Press INPHARMA 11 Dec 1982 3

LONG ACTING ANGINAL TREATMENT WITH GLYCERYL TRINITRATE

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LONG ACTING ANGINAL TREATMENT WITH GLYCERYL TRINITRATE

Pharmaceutical manipulation teaches an old drug some new tricks Glyceryl trinitrate (nitroglycerin) has been used to treat angina for over l 00 years. With the advent of new dosage forms, more rational treatment and prophylaxis for angina will require a more critical and systematic approach by clinicians. The-accent must be placed on different pharmacokinetic principles, depending on the nature of the disease. If relief of established ischaemia is required then a rapid onset of action is essential, but in the prevention of ischaemia, duration of action and predictability are more important. Careful titration of doses is essential because of the up to 500% variability in dose required to produce a given effect. Sublingual glyceryl trinitrate has a rapid onset of antianginal effect (in l-2 min) which is undetectable after l hour. Acute, brief periods of prophylaxis can thus be given to patients with infrequent but highly predictable angina. Sublingual isosorbide dinitrate has an onset in 3-5 min but, at doses equipotent to glyceryl trinitrate, does not give a longer duration of action. Oral nitrates produce very variable effects because of hepatic clearance, and the high doses required to give a long duration of action (8 hours) may produce severe orthostatic and other adverse reactions. Sustained-release preparations now available may circumvent some of these problems. The problems of variability in absorption and frequent application of cutaneous glyceryl trinitrate ointments have been overcome since the introduction of slow-release cutaneous preparations. Although the onset of action i~ still about 30 min, the absorption is at a constant rate provided over 24 hours. Convincing data on the efficacy and duration of a-ction of these devices are still required and a source of potential concern at the moment is their considerable cost. Another novel dosage form providing gradual and uniform nitrate release is long acting transmucosal glyceryl trinitrate tablets which are applied under the upper lip and adhere to the gingiva. A small mean dose size of 1. 7mg glyceryl trinitrate gives a prolonged effect and studies indicate improved exercise tolerance for 0.5-5 hours. Its combination of rapid onset and predictable effect is unique, and the dosage can be simply regulated by checking whether the tablet has dissolved. It should prove useful both for established angina as well as for acute and continued prophylaxis. Reichek, N. and Sutton, M. St.J.: Annals of Internal Medicine 97: 774 (Nov 1982)

0156-2703/82f1211-0003f0$01.00/0 © ADIS Press INPHARMA 11 Dec 1982 3