CLASSESNitrites and Nitrates, Plain Show
DESCRIPTIONOrganic nitrate vasodilator; available in many dosage forms. COMMON BRAND NAMESDeponit, GONITRO, Minitran, Nitrek, Nitro Bid, Nitro-Dur, Nitro-Time, Nitrodisc, Nitrolingual, NitroMist, Nitroquick, Nitrostat, Nitrotab, RECTIV, Transdermal-NTG, Tridil HOW SUPPLIEDDeponit/Minitran/Nitrek/Nitrodisc/Nitro-Dur/Nitroglycerin/Transdermal-NTG Percutaneous Film ER: 0.1mg,
0.2mg, 0.3mg, 0.4mg, 0.6mg, 0.8mg, 1h DOSAGE & INDICATIONSFor the treatment of angina pectoris due to coronary artery disease. For acute angina pectoris prophylaxis or the treatment of acute angina pectoris. Sublingual dosage (tablets) Adults 300 to 600 mcg SL 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat dose every 5 minutes as needed. No more than 3 tablets are recommended in a 15-minute period. If chest pain persists after 3 tablets in a 15-minute period, prompt medical attention should be sought.
Sublingual or Translingual dosage (spray) Adults 400 or 800 mcg on or under the tongue 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat 400 mcg every 5 minutes as needed. No more than 1,200 mcg is recommended in a 15-minute period. If chest pain persists after 1,200 mcg in a 15-minute period, prompt medical attention should be
sought. Sublingual dosage (powder) Adults 400 or 800 mcg SL 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat 400 mcg every 5 minutes as needed. No more than 1,200 mcg is recommended in a 15-minute period. If chest pain persists after 1,200 mcg in a 15-minute period, prompt medical attention should be sought. For the treatment of chronic angina pectoris. Oral dosage (extended-release capsules) Adults 2.5 to 6.5 mg PO 3 to 4 times daily, initially. Adjust dose based on symptoms
and adverse effects. Up to 26 mg PO 4 times daily has been used. Topical dosage (2% ointment) Adults 7.5 mg (0.5 inch) topically twice daily every 6 hours, initially. May double dose in persons tolerating but failing to respond. Max: 30 mg/dose. Transdermal dosage (patch) Adults 0.2 to 0.4 mg/hour transdermally for 12 to 14 hours daily with
a 10 to 12 hours daily patch-off period, initially. Adjust dose based on symptoms and adverse effects. Dose range: 0.1 to 0.8 mg/hour. For the treatment of moderate to severe pain associated with chronic anal fissures. Intra-Anal dosage (0.4% rectal ointment) Adults 1.5 mg (1 inch) intra-anally every 12 hours for up to 3 weeks. Guidelines recommend topical calcium channel blockers as
initial treatment due to higher expected healing rates and a lower incidence for headache vs. topical nitrates. Intra-Anal dosage (0.2% rectal ointment)† NOTE: Requires extemporaneous compounding using 2% topical ointment. Adults 1 to 2.4 mg intra-anally every 12 hours for up to 8 weeks. Guidelines recommend topical calcium channel blockers as initial treatment due to higher expected healing rates and a
lower incidence for headache vs. topical nitrates. For controlled hypotension induction during anesthesia; for the treatment of acute congestive heart failure or pulmonary edema, acute angina pectoris or unstable angina, acute myocardial infarction, or acute pulmonary hypertension†; or for treatment of severe hypertension, postoperative hypertension, perioperative hypertension (e.g., during cardiac surgery), or hypertensive emergency. Intravenous dosage Adults 5 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Usual dose range: 5 to 100 mcg/minute. Max: 200 mcg/minute.[50004] [55688] [58787] [61121] Heart failure guidelines suggest nitroglycerin as an
adjuvant to diuretics for relief of dyspnea in patients with acutely decompensated heart failure if symptomatic hypotension is absent.[57101] [62661] Adolescents 5 to 10 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to
5 minutes. Max: 200 mcg/minute. Infants and Children 0.25 to 0.5 mcg/kg/minute continuous IV infusion, initially. Titrate by 1 mcg/kg/minute IV every 15 to 20 minutes to clinical response. Usual dose range: 1 to 5 mcg/kg/minute. Usual Max: 10 mcg/kg/minute; however, rates up to 20 mcg/kg/minute have been used. For use as a uterine relaxant to aid in extraction of a retained placenta†. Intravenous dosage Adult females Limited data indicate that initial doses of 50—100 mcg IV bolus may be effective, with repeat doses of up to a total of 200 mcg IV necessary in some patients; higher initial doses of up to 500 mcg IV have also been used successfully. A dose of 1850 mcg IV (administered as 50 mcg, 100 mcg, 200 mcg, and three 500 mcg IV boluses) was required in one patient for successful placental delivery. To minimize hypotension, all women should
have a rapidly running IV infusion concurrently. Hemodynamic monitoring and immediate access to ephedrine should be considered. Thirty patients with retained placenta (i.e., placenta was retained 30 minutes after infant birth) were administered nitroglycerin 50 mcg IV. All patients received 500 mL IV bolus of a crystalloid solution prior to nitroglycerin administration. If the uterus was sufficiently relaxed 2 minutes after the dose of nitroglycerin, the placenta was delivered; otherwise, 50 mcg
of nitroglycerin IV bolus was administered every 2 minutes thereafter as needed, up to a maximum dosage of 200 mcg. Eight patients delivered the placenta after 50 mcg, 10 patients delivered after 100 mcg, 8 patients delivered after 150 mcg, and 4 patients required 200 mcg for delivery. The average duration of the procedure was 5.3 minutes (range 4—8.5 minutes). Systolic and diastolic blood pressure decreases were statistically, but not clinically, significant. No complications were reported; 5
patients reported headaches. In another series of 33 patients, doses of 50—200 mcg IV were required for placenta delivery; all of the placentas were delivered within 4 minutes. Sublingual dosage Adult females Limited data indicate that 1 mg sublingually given sequentially after oxytocin may be effective. Administration of a rapidly running IV infusion may be prudent to minimize decreases in blood pressure. Hemodynamic
monitoring and immediate access to ephedrine should be considered. A randomized, placebo-controlled trial of 24 women who had not delivered the placenta 40 minutes after infant delivery compared the effects of SL nitroglycerin 1 mg to placebo (n = 12 for both groups). Prior to randomization, all women received a total of 15 units of oxytocin (5 units within minutes of delivery of the infant and 10 units 30 minutes later if the placenta had not yet been delivered); controlled cord extraction was
performed 5 minutes after each dose of oxytocin. If these procedures were ineffective, nitroglycerin 1 mg SL or placebo was administered to the patient followed by controlled cord traction 5 minutes later. A rapidly running IV infusion was administered to all women, and all women were monitored for hemodynamic changes. All 12 patients that received nitroglycerin had successful delivery of the placenta within 5 minutes of controlled cord traction compared with only 1 patient in the placebo group
(p < 0.0001). In the women with unsuccessful placental delivery, regional or general anesthesia was required. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly decreased in the group of women receiving nitroglycerin (119 mm Hg vs. 113 mm Hg for SBP, p = 0.003; 76 mm Hg vs. 71 mm Hg for DBP, p = 0.001), although clinically important hypotension was not reported; changes in pulse were not statistically significant. Headache was reported in 4 of the women
that received nitroglycerin and 1 woman that received placebo; all headaches resolved spontaneously within 2 hours of drug administration. For the treatment of extravasation† of vasoactive medications. Topical dosage Adults 1 inch applied topically to the area of extravasation. Topical nitroglycerin has been used in combination with phentolamine for peripheral intravenous access extravasation
of norepinephrine and dopamine. Topical nitroglycerin with or without concomitant terbutaline has also been used after accidental digital epinephrine self-injection with commercially available auto-injectors. †Indicates off-label use MAXIMUM DOSAGEAdults The maximum dosage is dependent on route of administration and indication for therapy. Geriatric The maximum dosage is dependent on route of administration and indication for therapy. Adolescents The maximum dosage is dependent on route of administration and indication for therapy; safety and efficacy of the 0.4% rectal ointment have not been established. Children The usual maximum rate is 5 mcg/kg/min; however, IV rates up to 20 mcg/kg/min have been used. Safety and efficacy of the 0.4% rectal ointment have not been established. Infants Safety and efficacy have not been established. Neonates Safety and efficacy have not been established. DOSING CONSIDERATIONSHepatic Impairment Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Renal Impairment Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Intermittent hemodialysis ADMINISTRATIONNOTE: May need to use nitrate-free interval of 10 to 12 hours/day to avoid development of drug tolerance. When nitrates are to be discontinued following long-term or high-dose administration, avoid abrupt discontinuation to avoid potential for rebound angina. Oral Administration Oral Solid Formulations Extended-release capsules and tablets: Administer with a full glass of water 1 to 2 hours after meals. Nitroglycerin capsules and tablets should be swallowed whole and should not be chewed or crushed. Other Oral Formulations Lingual spray or aerosol Injectable Administration Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Intravenous Administration Significant adsorption (80% of the nitroglycerin in solution) occurs with standard infusion sets made of PVC plastic. Use glass bottles only and special tubing provided by the manufacturer. Continuous
IV Infusion Topical Administration Cream/Ointment/Lotion Formulations Topical (2%) ointment for the treatment of angina Transdermal Patch Formulations Apply nitroglycerin patch to any hairless site. Avoid applying to distal extremities or areas with cuts or calluses. Use firm pressure over patch to ensure contact with skin, especially around edges. If patch becomes loose or falls off, replace with another one. Rectal Administration Rectal (0.4%) ointment for the treatment of pain associated with chronic anal fissures (Rectiv) Extemporaneous Compounding-Rectal Low-strength (0.2%) rectal ointment STORAGEGeneric: CONTRAINDICATIONS / PRECAUTIONSNitrate hypersensitivity Nitroglycerin is contraindicated in patients who have known nitrate hypersensitivity. Head trauma, increased intracranial pressure, intracranial bleeding Nitroglycerin injection, sublingual powder and tablet,
lingual spray, and 0.4% ointment are contraindicated in patients with increased intracranial pressure (e.g., head trauma or intracranial bleeding) because the drug's vasodilatory effect on the meningeal blood vessels could increase cerebrospinal fluid pressure. Anemia Nitroglycerin sublingual powder and tablet, transmucosal spray, and 0.4% ointment are contraindicated in patients with severe anemia because the drug causes oxidation of hemoglobin to
methemoglobin, which could exacerbate anemia. Aortic stenosis, cardiac tamponade, cardiomyopathy, constrictive pericarditis, mitral stenosis, shock Nitroglycerin sublingual powder and lingual spray are contraindicated in patients with acute circulatory failure or shock. Intravenous nitroglycerin is contraindicated in patients with constrictive pericarditis, restrictive cardiomyopathy, or cardiac tamponade because the drug reduces venous return, decreases preload,
and decreases cardiac output, which can be worsened in patients with these conditions. Other nitroglycerin formulations should be administered with caution to patients with these pre-existing cardiovascular conditions. Severe hypotension, particularly with upright posture, may occur even with small doses of nitroglycerin particularly in patients with constrictive pericarditis, aortic stenosis or mitral stenosis, and in patients who may be volume-depleted, or are already hypotensive. Acute myocardial infarction, dehydration, hypotension, hypovolemia, orthostatic hypotension Nitroglycerin should not be given to patients with uncorrected hypovolemia (or dehydration) due to the risk of inducing profound hypotension. Patients with normal or low pulmonary capillary wedge pressures may be unusually sensitive to the hypotensive effects of nitroglycerin. Nitroglycerin should be used with caution in patients with hypotension or orthostatic hypotension because the drug can
worsen hypotension, cause a paradoxical bradycardia, and/or exacerbate angina. Nitrate-induced hypotension has resulted in syncope or fatalities. In a controlled setting, such as during surgery, IV nitroglycerin can be used to produce hypotension. Nitrate therapy can worsen angina due to hypertrophic cardiomyopathy. Sublingual nitroglycerin tablets are contraindicated for use in patients with acute myocardial infarction (MI). Use of any formulation of nitroglycerin during the early days of acute
MI requires particular attention to hemodynamic monitoring and clinical status. Nitroglycerin should be used cautiously in patients who have had a recent MI because drug-induced hypotension and/or tachycardia can worsen ischemia. To minimize the risks of nitrates following acute MI, nitroglycerin should not be administered to patients with systolic blood pressure less than 90 mmHg or a change of 30 mmHg or more below baseline, severe bradycardia (less than 50 beats per minute), tachycardia, or
suspected right ventricular infarction. Geriatric Clinical experience with sublingual nitroglycerin for acute anginal relief has not identified differences in responses between geriatric and younger adults. Chronic oral nitroglycerin or nitroglycerin infusions should be used with caution in geriatric patients, especially those who are volume-depleted, hypotensive, and/or receiving multiple medications. Elderly patients may have reduced baroceptor function and
may be more sensitive to the hypotensive effects of nitrates, which may result in a potential for severe hypotension, even at therapeutic doses. The elderly may be at higher risk for falls due to syncope. Nitrate therapy can also worsen angina due to hypertrophic cardiomyopathy, if present. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function,
and of concomitant disease or other drug therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that nitrates may cause headaches, dizziness, lightheadedness, faintness, or symptomatic orthostatic hypotension, particularly when initially started or when taken with antihypertensives. Hepatic disease Nitroglycerin should be used cautiously in patients with hepatic disease because metabolism of the drug can be impaired, resulting in an increased risk of methemoglobinemia. Abrupt discontinuation When nitroglycerin is to be discontinued following long-term or high-dose administration, avoid abrupt discontinuation to avoid potential for rebound angina. Defibrillation (cardioversion), magnetic resonance imaging (MRI) Remove nitroglycerin transdermal systems prior to defibrillation (cardioversion). Some nitroglycerin patches contain aluminum, which may result in damage to the paddles or burns to the patient. Additionally, skin burns have been reported at the patch site in several patients wearing an aluminized transdermal system during a magnetic resonance imaging (MRI) scan. It is recommended to remove the patch before undergoing an MRI. Pregnancy There are insufficient data regarding the use of nitroglycerin during pregnancy to determine a
drug-associated risk of major birth defects or miscarriage. No adverse developmental effects were observed during animal reproduction studies when nitroglycerin was administered intravenously to rabbits or intraperitoneally to rats during organogenesis at doses greater than 64 times the human dose. Nitroglycerin should be given to a pregnant woman only if clearly needed. Breast-feeding It is not known if nitroglycerin is present in human breast milk or if
nitroglycerin has effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for nitroglycerin and any potential adverse effects on the breastfed child from nitroglycerin or from the underlying maternal condition. GI disease Extended-release nitroglycerin products should be avoided in patients with GI disease such as hypermotility or malabsorption syndromes. This dosage form may not dissolve and may be excreted intact in these conditions. Diabetes mellitus Monitor serum glucose in patients with sub-clinical or overt diabetes mellitus when administering intravenous nitroglycerin solutions containing dextrose. ADVERSE REACTIONSSevere bradycardia / Rapid / Incidence not known Moderate hypotension / Rapid / 4.0-4.0 Mild headache / Early /
50.0-64.0 DRUG INTERACTIONSAcetaminophen; Aspirin, ASA; Caffeine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively.
Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised. PREGNANCY AND LACTATIONPregnancy There are insufficient data regarding the use of nitroglycerin during pregnancy to determine a
drug-associated risk of major birth defects or miscarriage. No adverse developmental effects were observed during animal reproduction studies when nitroglycerin was administered intravenously to rabbits or intraperitoneally to rats during organogenesis at doses greater than 64 times the human dose. Nitroglycerin should be given to a pregnant woman only if clearly needed. It is not known if nitroglycerin is present in human breast milk or if nitroglycerin has effects on milk production.
Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for nitroglycerin and any potential adverse effects on the breastfed child from nitroglycerin or from the underlying maternal condition. MECHANISM OF ACTIONSimilar to other nitrites and organic nitrates, nitroglycerin is converted to nitric oxide (NO), a reactive free radical. Nitric oxide, the active intermediate compound common to all agents of this class, activates the enzyme guanylate cyclase, thereby stimulating the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP). This second messenger then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber and the subsequent release, or extrusion, of calcium ions. The contractile state of smooth muscle is normally maintained by a phosphorylated myosin light chain (stimulated by an increase in calcium ions). Thus, the nitrite- or nitrate-induced dephosphorylation of the myosin light chain signals the cell to release calcium, thereby relaxing the smooth muscle cells and producing vasodilation. It is believed that nitrates correct myocardial oxygen imbalances by reducing systemic and pulmonary arterial pressure (afterload) and decreasing cardiac output secondary to peripheral dilation rather than coronary artery dilation. Nitrates therefore relax peripheral venous vessels, causing a pooling of venous blood and decreased venous return to the heart, which decreases preload. Nitrates reduce both arterial impedance and venous filling pressures, resulting in a reduction of the left ventricular systolic wall tension, which decreases afterload. Thus, nitrate-induced vasodilation increases venous capacitance and decreases arteriole resistance, thereby reducing both the preload and afterload, and lowering the cardiac oxygen demand. Total coronary blood flow can be increased by nitrites and nitrates in patients with normal hearts, but in patients with ischemia, nitroglycerin does not increase total coronary blood flow but simply redistributes blood to ischemic areas. This effect is believed to be due to the drug's preferential dilation of the larger conductive vessels of the coronary circulation, which, in the presence of coronary atherosclerosis, redirects the distribution of the coronary blood supply to ischemic areas. Nitrates cause a transient compensatory increase in heart rate and myocardial contractility that normally would increase myocardial oxygen consumption, yet the nitrate-induced decrease in ventricular wall tension results in a net decrease in myocardial oxygen demand and amelioration of the pain of angina pectoris. In addition, nitroglycerin relaxes all other types of smooth muscle including bronchial, biliary, GI, ureteral, and uterine. Following intra-anal administration of the 0.4% rectal ointment, nitroglycerin reduces anal sphincter tone resulting in decreased resting intra-anal pressure. Nitrites and nitrates are functional antagonists of acetylcholine, norepinephrine, and histamine. In individuals who have minimal reflex tachycardia, syncope can result from the decrease in blood pressure that occurs following higher doses of nitrates and nitrites. Although this is not likely to occur with doses of nitrates that do not cause blood pressure reduction, patients should be sitting or lying down during and immediately after administration of several dosage forms of nitroglycerin. The antihypertensive actions of nitroglycerin are secondary to pharmacologic properties that make it an effective antianginal agent but are primarily a result of its peripheral vasodilatory effects. With the exception of greater vascular (venous) specificity and the greater variety of pharmaceutical preparations available, nitroglycerin (NTG) is similar to nitroprusside in many respects. Both agents are capable of producing venous (more so with NTG) and arterial dilation, with beneficial effects on redistribution of myocardial blood flow. PHARMACOKINETICSNitroglycerin can be administered by the oral, lingual (spray), sublingual, intrabuccal, topical (transdermal), rectal, or intravenous routes. Irrespective of the route of administration, organic nitrates are virtually completely metabolized by the enzyme glutathione-organic nitrate reductase, so the systemic or presystemic hepatic biotransformation is the key determinant of the bioavailability and duration of action of the various preparations. Nitroglycerin distributes widely throughout the body tissues and is approximately 60% plasma protein-bound. The metabolites of nitroglycerin, 1,3- and 1,2-glyceryl dinitrate, are much less potent than the parent compound and have a half-life of approximately 40 minutes, compared to a parent half-life of 1 to 3 minutes. The metabolites are excreted by the kidneys. Oral Route Nitroglycerin is well absorbed across the oral mucosa and following systemic oral administration. The sublingual absorption of nitroglycerin is higher following the administration of sublingual powder compared to sublingual spray. The onset of action for each nitroglycerin preparation is as follows: translingual, 2 to 4 minutes; extended-release capsules and tablets, 20 to 45 minutes; sublingual, 1 to 3 minutes; transmucosal (buccal) extended-release tablets, 2 to 3 minutes. Duration of action is as follows: translingual, 30 to 60 minutes; extended-release capsules and tablets, 8 to 12 hours; sublingual, 30 minutes; transmucosal (buccal) extended-release, 5 hours. Intravenous Route The onset of action for nitroglycerin is immediate after IV administration. Duration of action is several minutes (dose-dependent) after IV administration. Topical Route Nitroglycerin is well absorbed transdermally. The onset of action for each nitroglycerin preparation is as follows: ointment, 20 to 60 minutes; and transdermal, 40 to 60 minutes. Duration of action is as follows: ointment, 4 to 8 hours; and transdermal, 18 to 24 hours. Other Route(s) Rectal Route What special considerations must be made for IV nitroglycerin?Dizziness, lightheadedness, or faintness may occur, especially when you get up quickly from a lying or sitting position. Getting up slowly may help. This medicine may cause headaches. These headaches are a sign that the medicine is working.
What is the most common adverse effect of nitroglycerin for which the patient is monitored?Some patients can be more sensitive to the hypotension caused by nitrates, potentially resulting in nausea, vomiting, diaphoresis, pallor, and collapse even at therapeutic doses. There have also been reports of flushing, exfoliative dermatitis, and drug rash in some patients taking nitroglycerin.
How is nitroglycerin usually self administered by a patient in an emergency situation?Adults—1 or 2 sprays on or under the tongue at the first sign of an chest pain. Sprays may be repeated every 5 minutes as needed.
When administering GTN what precautions and guidelines should the nurse follow?Patient should be sitting or lying prior to administration of GTN. Constant supervision and regular monitoring of vital signs (including respiratory rate, Heart rate, Blood pressure and oxygen saturations for all clients with chest pain is essential.
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