Nitrates (Nitroglycerine)

-are endothelium-independent vasodilators that both increase myocardial blood flow by coronary
vasodilation and
reduce myocardial oxygen demand
-The latter effect results from arteriolar and venous dilation leading to reduced myocardial afterload,
preload, and ventricular wall stress.
-If the patient is experiencing ischemic pain, nitrates should initially be given sublingually o
r by
buccal spray (0.3 to 0.6 mg).
-If pain persists after three sublingual tablets (or buccal sprays) administered at 5-minute intervals,
intravenous
nitroglycerin by use of nonabsorbing tubing (5 to 10 g/min) is recommended.
-The rate of the nitroglycerin infusion may be increased by 10 g/min every 3 to 5 minutes until relief of
symptoms occurs or
systolic blood pressure falls to below 100 mm Hg.2 Although there is no absolute maximum dose, a dose of
200 g/min is generally used as
a ceiling.
-Contraindications to the use of nitrates are hypotension and the use of sildenafil or related
phosphodiesterase type 5 inhibitors within the
previous 24 to 48 hours.
-Topical or long-acting oral nitrates can be used if the patient has been pain free for 12 to 24 hours.
-produce vasodilation by nitric oxidedependent elevation of cyclic GMP in vascular smooth muscle.
-onset of action is 1-2 minutes, often relieves pain within 3 minutes.
-Patients should be instructed to seek medical attention immediately if three tablets taken over a 15- minute
period do not relieve a sustained attack because this situation may be indicative of myocardial infarction or
another cause of the pain.

Sublingual administration:
-Venous drainage from the mouth is to the superior vena cava, which protects the drug from rapid hepatic first-pass
metabolism.
-For example, nitroglycerin is effective when retained sublingually because it is nonionic and has very high lipid
solubility. Thus, the drug is absorbed very rapidly
-If a tablet of nitroglycerin were swallowed, the accompanying hepatic metabolism would be sufficient to prevent the
appearance of any active nitroglycerin in the systemic circulation.
Cutaneous/topical administration:
-Absorption of those that do is dependent on the surface area over which they are applied and their lipid solubility
because the epidermis behaves as a lipid barrier.
-The dermis, however, is freely permeable to many solutes; consequently, systemic absorption of drugs occurs much
more readily through abraded, burned, or denuded skin.
-Absorption through the skin can be enhanced by suspending the drug in an oily vehicle and rubbing the resulting
preparation into the skin. Because hydrated skin is more permeable than dry skin, the dosage form

may be modified or an occlusive dressing may be used to facilitate absorption.

-Effects are apparent within 30 to 60 minutes (although absorption is variable) and last for 4 to 6 hours.
Mechanism of action:
-lead to the formation of the reactive free radical NO.
-NO can activate guanylyl cyclase, increase the cellular level of cyclic GMP, activate PKG (the cyclic GMP
dependent protein kinase), and modulate the activities of cyclic nucleotide phosphodiesterases (PDEs 2, 3,
and 5) in a variety of cell types.
-In smooth muscle, the net result is reduced phosphorylation of myosin light chain, reduced Ca2+
concentration in the cytosol, and relaxation.
-One important consequence of the NO-mediated increase in intracellular cyclic GMP is the activation of
PKG, which catalyzes the phosphorylation of various proteins in smooth muscle.

Lingual dosage: 0.4mg per spray as needed

as needed
Ointment: 2.5-5cm, topically to skin every 4-8 hours
10ug/min to a max of 400ug/min
Tablet/capsule: 2.5-9mg, 2-4 times daily
EFFECTS
Cardiovascular:

Tablet for sublingual use: 0.3-0.6mg

IV: 10-20ug; increments of

Adverse effects

CNS: Headache, apprehension, restlessness, weakness, vertigo, dizziness, faintness

CV: Tachycardia, retrosternal discomfort, palpitations, hypotension, syncope, collapse,

orthostatic hypotension, angina

Dermatologic: Rash, exfoliative dermatitis, cutaneous vasodilation with flushing, pallor,

perspiration, cold sweat, contact dermatitistransdermal preparations, topical allergic
reactionstopical nitroglycerin ointment

GI: Nausea, vomiting, incontinence of urine and feces, abdominal pain

Local: Local burning sensation at the point of dissolution (sublingual)

Other: Ethanol intoxication with high-dose IV use (alcohol in diluent)