DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Nitrolingual (Nitroglycerin) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

Animal carcinogenesis studies with sublingual nitroglycerin have not been performed. Rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes. At high dose, the incidences of hepatocellular carcinomas in both sexes were 52% vs. 0% in controls, and incidences of testicular tumors were 52% vs. 8% in controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice. Nitroglycerin was weakly mutagenic in Ames tests performed in two different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, p.o., or in in vitro cytogenic tests in rat and dog tissues.

In a three-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for six months prior to mating of the F0 generation with treatment continuing through successive F1 and F2 generations. The high dose was associated with decreased feed intake and body weight gain in both sexes at all matings. No specific effect on the fertility of the F0 generation was seen. Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high-dose males. In this three-generation study there was no clear evidence of teratogenicity.

PREGNANCY

Pregnancy Category C

Animal teratology studies have not been conducted with nitroglycerin-pumpspray. Teratology studies in rats and rabbits, however, were conducted with topically applied nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day, respectively. No toxic effects on dams or fetuses were seen at any dose tested. There are no adequate and well-controlled studies in pregnant women. Nitroglycerin should be given to pregnant women only if clearly needed.

OVERDOSAGE

Signs and Symptoms

Nitrate overdosage may result in: severe hypotension, persistent throbbing headache, vertigo, palpitation, visual disturbance, flushing and perspiring skin (later becoming cold and cyanotic), nausea and vomiting (possibly with colic and even bloody diarrhea), syncope (especially in the upright posture), methemoglobinemia with cyanosis and anorexia, initial hyperpnea, dyspnea and slow breathing, slow pulse (dicrotic and intermittent), heart block, increased intracranial pressure with cerebral symptoms of confusion and moderate fever, paralysis and coma followed by clonic convulsions, and possibly death due to circulatory collapse.

Methemoglobinemia

Case reports of clinically significant methemoglobinemia are rare at conventional doses of organic nitrates. The formation of methemoglobin is dose-related and in the case of genetic abnormalities of hemoglobin that favor methemoglobin formation, even conventional doses of organic nitrates could produce harmful concentrations of methemoglobin.

Treatment of Overdosage

Keep the patient recumbent in a shock position and comfortably warm. Passive movement of the extremities may aid venous return. Administer oxygen and artificial ventilation, if necessary. If methemoglobinemia is present, administration of methylene blue (1% solution), 1-2 mg per kilogram of body weight intravenously, may be required. If an excessive quantity of Nitrolingual® Pumpspray has been recently swallowed gastric lavage may be of use.

WARNING

Epinephrine is ineffective in reversing the severe hypotensive events associated with overdosage. It and related compounds are contraindicated in this situation.

CONTRAINDICATIONS

Allergic reactions to organic nitrates are rare. Nitroglycerin is contraindicated in patients who are allergic to it. Nitrolingual® Pumpspray is contraindicated in patients taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), as their concomitant use can cause severe hypotension. The time course and dose-dependency of this interaction are not known.

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017