Nitroglycerin

 Risk Factor: B*
 Class: CARDIOVASCULAR DRUGS / Vasodilators

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Nitroglycerin (glyceryl trinitrate) is primarily indicated for the treatment or prevention of angina pectoris. Because of the nature of this use, experience in pregnancy is limited. The drug, a rapid-onset, short-acting vasodilator, has been used to control severe hypertension during cesarean section (1,2). Use of nitroglycerin sublingually for angina during pregnancy without fetal harm has also been reported (3). Recent investigations, discussed below, have explored the use of nitroglycerin as both an emergency and routine tocolytic agent.

Reproductive studies in rats and rabbits have been conducted with nitroglycerin (4,5 and 6). No adverse fetal effects or postnatal changes were observed in these experiments.

The Collaborative Perinatal Project recorded seven 1st trimester exposures to nitroglycerin and amyl nitrite plus eight other patients exposed to other vasodilators (7). From this small group of 15 patients, 4 malformed children were produced, a statistically significant incidence (p<0.02). The data did not indicate whether nitroglycerin was taken by any of the mothers of the affected infants. Because of the lack of specific information and the small number of patients, no conclusions as to the relative safety of nitroglycerin in the 1st trimester can be made from this study. Moreover, the authors of this study emphasized that statistical significance could not be used to infer causal relationships and that independent confirmation from other studies was required.

The use of nitroglycerin in pregnancy-induced hypertension has been described (8,9,10 and 11). In three patients, IV infusions of nitroglycerin were effective in rapidly correcting the hemodynamic disturbances of pregnancy-induced hypertension complicated by hydrostatic pulmonary edema, but a rapid improvement in arterial oxygenation did not occur (8). In another study by the same investigators, the effectiveness of IV nitroglycerin to decrease blood pressure in six women with pregnancy-induced hypertension was dependent on the patient's volume status (9). When volume expansion was combined with nitroglycerin therapy, a marked resistance to the hypotensive effect of the drug was observed. In two of the women treated with IV nitroglycerin alone, significant reductions in blood pressure occurred, resulting in fetal heart rate changes that included late decelerations and bradycardia. Recovery occurred after nitroglycerin therapy was terminated and then restarted at a lower dose. In three other fetuses, a loss of beat-to-beat variability (average variability <5 beats/minute) was noted. Therapy was continued and no abnormalities were observed in the umbilical blood gases or Apgar scores.

An abstract published in 1996 described the use of transdermal nitroglycerin patches (releasing 10 mg in 24 hours) in the treatment of gestational hypertension (10). The 24-hour mean systemic and diastolic blood pressures were significantly decreased (5% and 7%, respectively). In a 1995 study, 12 women with severe preeclampsia received an infusion of nitroglycerin starting at 0.25 g/kg/minute with stepwise dosage increases until a diastolic blood pressure of 100 mm Hg was achieved (11). The mean systolic blood pressure decreased from 161 to 138 mm Hg whereas diastolic pressure decreased from a mean of 116 to 103 mm Hg. The umbilical artery pulsatility index changed significantly but not the uterine pulsatility index, implying vasodilation in the umbilical circulation and avoidance of adverse impairment of fetoplacental perfusion (11).

Lowering of maternal blood pressure and a lessening of the hemodynamic responses to endotracheal intubation were beneficial effects obtained from IV nitroglycerin in six women with severe preeclampsia (12). A progressive flattening of fetal heart rate beat-to-beat variability was observed in all six patients. Prevention of an increase in mean arterial pressure of greater than 20% was achieved in only two of the women, and all had nausea, retching, and vomiting that was apparently nondose-related.

Myocardial infarction, secondary to development of a thrombus on an artificial aortic valve, occurred in a 25-year-old woman at 26 weeks' gestation (13). A portion of her initial treatment consisted of both oral and IV nitroglycerin, with the latter being continued for an unspecified interval. Maternal diastolic blood pressure was maintained above 50 mm Hg while on nitroglycerin and, apparently, no fetal distress was observed. A viable 2608-g male infant was eventually delivered at 35 weeks' gestation, but specific details were not provided on his condition.

A 1993 Reference described two women, one with triplets, who suffered myocardial infarctions during pregnancy, at 16 and 28 weeks' gestation, and who were treated with IV nitroglycerin and other agents (14). In addition, mild chest pain occurring during labor was successfully treated with sublingual nitroglycerin in one of the women. Both patients survived and eventually delivered infants apparently unaffected by the treatment. Another report described a woman at 26 weeks' gestation who was treated with IV nitroglycerin and other agents for a myocardial infarction (15). She eventually delivered a healthy female infant by cesarean section at 39 weeks.

In gravid ewes, IV nitroglycerin was effective in counteracting norepinephrine-induced uterine vasoconstriction (16). The antihypertensive effect resulted in a significantly decreased mean aortic pressure but did not significantly change uterine blood flow or uterine vascular conductance. A 1994 abstract reported no adverse effects on fetal cardiorespiratory function in sheep from a 2-hour IV infusion of nitroglycerin at 3 times the minimum effective tocolytic dose (17).

The use of nitroglycerin during cesarean section to allow delivery of babies entrapped by a contracted uterus has been described in two case reports (18,19). In the first case, the head of a baby presenting as a double footling breech was trapped in the hypertonic upper segment (18). Uterine relaxation was achieved with a 1000-g (1-mg) IV bolus of nitroglycerin. The mother's blood pressure fell to 70/30 mm Hg but responded to ephedrine. The Apgar scores of the 3090-g, term infant were 5 and 9 at 1 and 5 minutes, respectively. In the second case, a woman received a 100-g bolus of nitroglycerin to quickly relax a contracted uterus and to allow the successful delivery of her twins (19). Other than a systolic blood pressure decrease (preoperative pressure 120 mm Hg; after nitroglycerin 85 mm Hg) that responded rapidly to ephedrine, no other adverse effects from nitroglycerin were encountered in the mother or her newborns.

Two References have discussed the use of IV nitroglycerin as a short-acting tocolytic agent during intrapartum external cephalic version (20,21) and one involving internal podalic version (22). A woman in premature labor (uterine contractions every 2 minutes with the cervix dilated to 9 cm) at 30 weeks 5 days was given a 50-g IV bolus of nitroglycerin (20). The uterus relaxed palpably within 20 seconds and the fetus was repositioned to allow for vaginal delivery. A decrease in the maternal blood pressure was noted (145/100 to 130/75 mm Hg, then stabilizing at 130/85 mm Hg within 2 minutes), but the heart rate and oxygen saturation remained unchanged. The premature infant was delivered vaginally shortly after rupture of the membranes and start of an oxytocin infusion. A second mother at 39 weeks 4 days of gestation received a 100-g IV bolus dose before external cephalic version (blood pressure decreased from 120/60 to 112/60 mm Hg within 1 minute) and subsequently underwent a vaginal delivery of a healthy infant.

In the second report, a woman delivered one twin vaginally and then received a 50-g IV nitroglycerin bolus to allow external version of the second transverse-lie twin (21). No significant maternal adverse effects (e.g., headache or dizziness) or changes in blood pressure or heart rate were observed. The healthy twin was delivered vaginally 45 minutes after the version.

Internal podalic version and total breech extraction of the second twin was accomplished in a third case with sublingual nitroglycerin by aerosol after the uterus had contracted down upon the operator's forearm (22). Two 400-g boluses were given resulting in uterine relaxation within 30 seconds. No adverse effects on the newborn were observed.

Three cases of total breech extraction, with internal podalic version in two, of the second twin were aided by the use of nitroglycerin spray (0.4 mg) administered sublingually after either contraction of the uterine corpus and lower segment or uterine or cervical contractions with failure of the fetal head to engage (23). Minimal changes were observed in the maternal blood pressures and pulses. All three newborns were doing well.

A 1996 report described nine cases of internal podalic version of a second nonvertex twin with the assistance of an IV bolus of nitroglycerin (1 mg in eight, 1.5 mg in one) (24). One of the women had a panic attack that required general anesthesia for sedation, although the version was successful. In another case, nitroglycerin failed to induce uterine relaxation and an emergency cesarean section was required for fetal distress. Postpartum hemorrhage (2000 ml) occurred in a third woman. A significant fall in maternal blood pressure was observed in all cases, but no adverse effects from the decrease occurred in the mothers or newborns (24).

Transdermal patches of nitroglycerin have been tested as tocolytics in 13 women in preterm labor (2333 weeks' gestation) (25). Most of the women received a single patch that delivered 10 mg of nitroglycerin for 24 hours, but some patients were given a second patch if uterine contractions had not subsided within 1 hour. Patches were changed every 24 hours. The mean prolongation of pregnancy, as of the date of a subsequent report (one woman was still pregnant), was 59 days(26). The babies who had been delivered were all doing well.

Small IV bolus doses of nitroglycerin (60 or 90 g 1 or 2 doses) were used in 24 laboring women for severe fetal distress, related to uterine hyperactivity, that was unresponsive to standard measures (27). Six of the patients developed hypotension with a mean nadir of 93.2 mm Hg (minimum 85 mm Hg) that was reversed with a single dose of ephedrine (4.56 mg). Four newborns had low 1-minute Apgar scores (3, 4, 5, and 6), but all newborns had Apgar scores of 9 or 10 and were vigorous at 5 minutes.

Nitroglycerin has also been used to relax the uterus in postpartum cases with retained placenta (28,29,30 and 31), two of which occurred in patients with an inverted uterus (30,31). The IV bolus dose was 500 g in 15 women (28), 50 g (some patients required two doses) in 23 cases (29,30), and 100 g in 1 woman (31). No significant changes in blood pressure or heart rate were recorded, and no adverse effects, such as headache, palpitations, or prolonged uterine relaxation, were observed.

In summary, the use of nitroglycerin during pregnancy does not seem to present a risk to the fetus. However, the number of women treated during pregnancy is limited, especially during the 1st trimester. With the smaller doses reported, transient decreases in the mother's blood pressure may occur, but these do not appear to be sufficient to jeopardize placental perfusion. Nitroglycerin appears to be a safe, effective, rapid-onset, short-acting tocolytic agent. The use of transdermal nitroglycerin patches may also prove to be effective when longer periods of tocolysis are required. With any route of administration, however, additional studies are required to determine the safest effective dose.

[*Several manufacturers state that animal studies have not been conducted with nitroglycerin and, thus, assign the Risk Factor C. As noted above, however, animal studies have been conducted.]

Breast Feeding Summary

No data are available.

References

1. Snyder SW, Wheeler AS, James FM III. The use of nitroglycerin to control severe hypertension of pregnancy during cesarean section. Anesthesiology 1979;51:5634.
2. Hood DD, Dewan DM, James FM III, Bogard TD, Floyd HM. The use of nitroglycerin in preventing the hypertensive response to tracheal intubation in severe preeclamptics. Anesthesiology 1983;59:A423.
3. Diro M, Beydown SN, Jaramillo B, O'Sullivan MJ, Kieval J. Successful pregnancy in a woman with a left ventricular cardiac aneurysm: a case report. J Reprod Med 1983;28:55963.
4. Oketani Y, Mitsuzono T, Ichikawa K, Itono Y, Gojo T, Gofuku M, Konoha N. Toxicological studies on nitroglycerin (NK-843). 6. Teratological studies in rabbits. Oyo Yakuri 1981;22:63338. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY: Marcel Dekker, 1993:91.
5. Oketani Y, Mitsuzono T, Ichikawa K, Itono Y, Gojo T, Gofuku M, Konoha N. Toxicological studies on nitroglycerin (NK-843). 8. Teratological study in rats. Oyo Yakuri 1981;22:73751. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY: Marcel Dekker, 1993:91.
6. Sato K, Taniguchi H, Ohtsuka T, Himeno Y, Uchiyama K, Koide M, Hoshino K. Reproductive studies of nitroglycerin applied dermally to pregnant rats and rabbits. Clin Report 1984;18:351186. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD: Johns Hopkins University Press, 1992:285.
7. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:3713.
8. Cotton DB, Jones MM, Longmire S, Dorman KF, Tessem J, Joyce TH III. Role of intravenous nitroglycerin in the treatment of severe pregnancy-induced hypertension complicated by pulmonary edema. Am J Obstet Gynecol 1986;154:913.
9. Cotton DB, Longmire S, Jones MM, Dorman KF, Tessem J, Joyce TH III. Cardiovascular alterations in severe pregnancy-induced hypertension: effects of intravenous nitroglycerin coupled with blood volume expansion. Am J Obstet Gynecol 1986;154:10539.
10. Facchinetti F, Neri I, Volpe A. Glyceryl trinitrate lowers blood pressure in patients with gestational hypertension (abstract). Am J Obstet Gynecol 1996;174:455.
11. Grunewald C, Kublickas M, Carlstrom K, Lunell N-O, Nisell H. Effects of nitroglycerin on the uterine and umbilical circulation in severe preeclampsia. Obstet Gynecol 1995;86:6004.
12. Longmire S, Leduc L, Jones MM, Hawkins JL, Joyce TH III, Cotton DB. The hemodynamic effects of intubation during nitroglycerin infusion in severe preeclampsia. Am J Obstet Gynecol 1991;164:5516.
13. Ottman EH, Gall SA. Myocardial infarction in the third trimester of pregnancy secondary to an aortic valve thrombus. Obstet Gynecol 1993;81:8045.
14. Sheikh AU, Harper MA. Myocardial infarction during pregnancy: management and outcome of two pregnancies. Am J Obstet Gynecol 1993;169:27984.
15. Sanchez-Ramos L, Chami YG, Bass TA, DelValle GO, Adair CD. Myocardial infarction during pregnancy: management with transluminal coronary angioplasty and metallic intracoronary stents. Am J Obstet Gynecol 1994;171:13923.
16. Wheeler AS, James FM III, Meis PJ, Rose JC, Fishburne JI, Dewan DM, Urban RB, Greiss FC Jr. Effects of nitroglycerin and nitroprusside on the uterine vasculature of gravid ewes. Anesthesiology 1980;52:3904.
17. Bootstaylor B, Roman C, Heymann MA, Parer JT. Fetal cardiorespiratory effects of nitroglycerin in the near term pregnant sheep (abstract). Am J Obstet Gynecol 1994;170:281.
18. Roblin SH, Hew EM, Bernstein A. Uterine relaxation can be life saving. Can J Anaesth 1991;38:93940.
19. Mayer DC, Weeks SK. Antepartum uterine relaxation with nitroglycerin at Caesarean delivery. Can J Anaesth 1992;39:1669.
20. Belfort MA. Intravenous nitroglycerin as a tocolytic agent for intrapartum external cephalic version. S Afr Med J 1993;83:656.
21. Abouleish AE, Corn SB. Intravenous nitroglycerin for intrapartum external version of the second twin. Anesth Analg 1994;78:8089.
22. Greenspoon JS, Kovacic A. Breech extraction facilitated by glyceryl trinitrate sublingual spray. Lancet 1991;338:1245.
23. Lees C, Campbell S, Jauniaux E, Brown R, Ramsay B, Gibb D, Moncada S, Martin JF. Arrest of preterm labour and prolongation of gestation with glyceryl trinitrate, a nitric oxide donor. Lancet 1994;343:13256.
24. Rosen DJD, Velez J, Greenspoon JS. Total breech extraction of the second twin with uterine relaxation induced by nitroglycerin sublingual spray. Israel J Obstet Gynecol 1994;5:1821.
25. Dufour Ph, Vinatier D, Vanderstichele S, Subtil D, Ducloy JC, Puech F, Codaccionni X, Monnier JC. Intravenous nitroglycerin for intrapartum internal podalic version of the second non-vertex twin. Eur J Obstet Gynecol Reprod Biol 1996;70:2932.
26. Lees C, Campbell S, Martin J, Moncada S, Brown R, Jauniaux E, Ramsay B, Gibb D. Glyceryl trinitrate in management of preterm labour. Authors' reply. Lancet 1994;344:5534.
27. Mercier FJ, Dounas M, Bouaziz H, Lhuissier C, Benhamou D. Intravenous nitroglycerin to relieve intrapartum fetal distress related to uterine hyperactivity: a prospective observational study. Anesth Analg 1997;84:111720.
28. Peng ATC, Gorman RS, Shulman SM, DeMarchis E, Nyunt K, Blancato LS. Intravenous nitroglycerin for uterine relaxation in the postpartum patient with retained placenta. Anesthesiology 1989;71:1723.
29. DeSimone CA, Norris MC, Leighton BL. Intravenous nitroglycerin aids manual extraction of a retained placenta. Anesthesiology 1990;73:787.
30. Altabef KM, Spencer JT, Zinberg S. Intravenous nitroglycerin for uterine relaxation of an inverted uterus. Am J Obstet Gynecol 1992;166:12378.
31. Dayan SS, Schwalbe SS. The use of small-dose intravenous nitroglycerin in a case of uterine inversion. Anesth Anal 1996;82:10913.
    
    

Questions and Answers

Nitroglycerin?, Hey guys, I'm looking for the chemical equation to form nitroglycerin, not the equation for a combustion reaction, also if anyone knows, I need a very simple summary of how nitroglycerin is manufactured.

I'll choose a best asap, thanks!

Please do not attempt to make this oh I found it on the net its not hard to find. Who knows it may not even be real.......


Nitroglycerin Recipe by the Jolly Roger

Like all chemists I must advise you all to take the greatest care
and caution when you are doing this. Even if you have made this stuff
before.
This first article will give you information on making
nitroglyerin, the basic ingredient in a lot of explosives such as
straight dynamites, and geletin dynamites.
Making nitroglycerin
1. Fill a 75-milliliter beaker to the 13 ml. Level with fuming
red nitric acid, of 98% pure concentration.
2. Place the beaker in an ice bath and allow to cool below room
temp.
3. After it has cooled, add to it three times the amount of
fuming sulferic acid (99% h2so4). In other words, add to the
now-cool fuming nitric acid 39 ml. Of fuming sulferic acid.
When mixing any acids, always do it slowly and carefully to
avoid splattering.
4. When the two are mixed, lower thier temp. By adding more ice
to the bath, about 10-15 degrees centigrade. (Use a
mercury-operated thermometer)
5. When the acid solution has cooled to the desired temperature,
it is ready for the glycerin. The glycerin must be added in
small amounts using a medicine dropper. (Read this step about
10 times!) Glycerin is added slowly and carefully (i mean
careful!) Until the entire surface of the acid it covered with
it.
6. This is a dangerous point since the nitration will take place
as soon as the glycerin is added. The nitration will produce
heat, so the solution must be kept below 30 degrees
centigrade! If the solution should go above 30 degrees,
immediately dump the solution into the ice bath! This will
insure that it does not go off in your face!
7. For the first ten minutes of nitration, the mixture should be
gently stirred. In a normal reaction the nitroglycerin will
form as a layer on top of the acid solution, while the sulferic
acid will absorb the excess water.
8. After the nitration has taken place, and the nitroglycerin has
formed on the top of the solution, the entire beaker should be
transferred slowly and carefully to another beaker of water.
When this is done the nitroglycerin will settle at the bottem
so the other acids can be drained away.
9. After removing as much acid as posible without disturbing the
nitroglycerin, remove the nitroglycerin with an eyedropper and
place it in a bicarbonate of soda (sodium bicarbonate in case
you didn't know) solution. The sodium is an alkalai and will
nuetralize much of the acid remaining. This process should be
repeated as much as necesarry using blue litmus paper to check
for the presence of acid. The remaining acid only makes the
nitroglycerin more unstable than it already is.
10. Finally! The final step is to remove the nitroglycerin from
the bicarbonate. His is done with and eye- dropper, slowly
and carefully. The usual test to see if nitration has been
successful is to place one drop of the nitroglycerin on metal
and ignite it. If it is true nitroglycerin it will burn with
a clear blue flame.
** Caution **
Nitro is very sensative to decomposition, heating dropping, or
jarring, and may explode if left undisturbed and cool.
-------------Jolly Roger

What happens if nitroglycerin is in you body?, what happens if you smoke a cigarette covered with nitroglycerin?
would you explode, or your lungs, or nothing, or would you just cough?

nitroglycerin acts as a vasodilator in your body. In other words it causes your blood vessels to become a larger diameter. This is why people with heart problems are given nitroglycerin, to open up the vessels and let the blood flow easier.

It also has a nasty side affect of giving you a nasty migraine headache.

as far as putting it on a cig, well yes it would explode and probably take your head with it.

What effects can Nitroglycerin have on children?, My girlfriends Daughter just got into her nitroglycerin tablets and ate some...we dont know how many yet. She is taking her to the hospital right now and I am just sitting here worried to death about the girl. She is currently in another state 1000 miles away visiting family or i would be there with her. So my question is what kind of ill effects could happen to a 2 year old that ingested nitroglycerin tablets?

Nitroglycerin dialates the blood vessels, most especially in the arteries. This would result in a large drop in blood pressure, which can be dangerous. Usually, they take supportive measures, which could include gastric lavage (washing out the stomach), and intravenous fluids to maintain the blood pressure. Fatal overdoses are rare. It would depend on how old the child was, and how many tablets she took. There are also medications which would not necessarily counteract the nitro, but would keep the blood pressure up, like neosynephrine by constricting the blood vessels. I hope your g.f realizes that she needs to child-proof all medications and chemicals, including household cleaners. THe good news it that it is a short-acting medication. Tonight will be hairy, but I hope the girl will be okay.

How fast does nitroglycerin act when used to treat a myocardial infarction, i.e. when given in tablet form?, I have been trying to find information online about the speed and efficacy of nitroglycerin in tablet form when used to treat a myocardial infarction. It's for a short story I am writing, and I can't finish until I find this information. I don't want to just make something up.

Nitroglycerin doens't actually do anything to treat a myocardial infarction. It is best for angina- the squeezing pain people get in their chest when the blood vessels around their heart are constricted but not completely closed. For angina, it works in seconds to relieve the pain and relax those blood vessels so the heart gets more blood.
During a heart attack, the coronary vessels close completely, and blood flow to part of the heart is cut off. A person who takes nitroglycerin for angina should worry that they are having a heart attack if they take nitroglycerine and the pain does not go away. They should take an aspirin immediately and go to the ER to be given other meds or have a stent put in to open the artery back up.

Is there any way to do a safe lab demonstration of nitroglycerin?, I wanted to do a research project for chemistry on nitroglycerin, and the teacher said it'd be really cool to do a demonstration, but only if its safe. So is there any way to demonstrate it effectively, efficiently, safely, and "cool" too? I'm just a high school kid, so it's not like I'm a pro at this.

You should find another project. Nitro is extremely dangerous and even experienced chemists should not handle or make it without vast experience in the field. Even extremely dilute solutions are controlled.

What is the chemical name of nitroglycerin?, What is the most common scientific name for nitroglycerin? I have seen many listings, including glyceryl nitrate and 1, 2, 3 propanetriol trinitrate. Which of these two (if either) is correct?

It is known as many things but the scientific name is 1-2-3-trinitroxypropane because it is a 3-carbon chain (propane) with the 'trinitroxy' groups on each of the 3 carbons giving the 1-2-3-.

How do I find the bond angles of nitroglycerin? Because I have to make a molecular model of it?, have to make a molecular model of nitroglycerin. How do I go about finding the bond angles? I am very confused. Any help would be greatly appreciated! The chemical formula is C3 H5 N3 O9.

Thanks!!!

bond... James Bond!>???

how to preserve nitroglycerin and the risk factor of preservation?, Dear friends,

I have a question on nitroglycerin. First is, how to preserve nitroglycerin and the risk factor of preservation, and second is, how to shift nitroglycerin here to there I mean is there any risk if it would be shacked?

Thanking U

Using a refrigerator is the basics for elements like that.




Peace ☣
^_^

How can I make nitroglycerin at home? How do you plasticize the substance?, I have heard that it is done by mixing glycerin and nitric acid.

"Mixing" is not a good word when talking about Nitro Glycerin. The temperature has to be just right. The ingredients are combined by placing a stirring rod into the glass container, and letting them slide together. One false motion, and you'll see God real quick. Sometimes I hear of people mixing it with saw dust to stablize it, but I do not know about this. I recommend to find something else to make. Something legal, also. And you are missing an ingredient in your question. I will not share that info.