ATROPINE

Drugs in Pregnancy and Lactation.

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Name: ATROPINE
Class: Parasympatholytic
Risk Factor:    C

Fetal Risk Summary

Atropine, an anticholinergic, rapidly crosses the placenta (1,2,3 and 4). Atropine exposure in the 1st, 2nd, and 3rd trimesters was estimated in one study to be 11.3, 6.7, and 6.3/1,000 women, respectively (5). The drug has been used to test placental function in high-risk obstetric patients by producing fetal vagal blockade and subsequent tachycardia (6).

Intravenous atropine (0.5 mg) caused a decrease of 10 to 100% in fetal breathing in 13 of 15 fetuses, an increase of 300% in one fetus, and no effect in another (7). The decrease in fetal breathing occurred approximately 2 minutes after administration of the drug and lasted 5–10 minutes. No fetal hypoxia was observed, nor was there an effect on fetal heart rate or beat-to-beat variability.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 401 of whom used atropine in the 1st trimester (8, pp. 346–353). For use anytime during pregnancy, 1,198 exposures were recorded (8, p. 439). In neither group was evidence found for an association with malformations. However, when the group of parasympatholytics was taken as a whole (2,323 exposures), a possible association with minor malformations was found (8, pp. 346–353).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 381 newborns had been exposed to atropine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 18 (4.7%) major birth defects were observed (16 expected). Specific data were available for six defect categories, including (observed/expected) 4/4 cardiovascular defects, 0/0.5 oral clefts, 1/0 spina bifida, 2/0 polydactyly, 1/1 hypospadias, and 2/0 limb reduction defects. Only with the latter defect is there a suggestion of a possible association, but other factors, such as the mother's disease, concurrent drug use, and chance may be involved.

Atropine has been used to reduce gastric secretions before cesarean section without producing fetal or neonatal effects (9,10). In a study comparing atropine and glycopyrrolate, 10 women in labor received 0.01 mg/kg of atropine IV (11). No statistically significant changes were noted in fetal heart rate or variability nor was there any effect on uterine activity.

A single case of a female infant born at 36 weeks' gestation with multiple defects, including Ebstein's anomaly, was described in a 1989 report (12). In addition to the cardiac defect, other abnormalities noted were hypertelorism, epicanthal folds, low-set posteriorly rotated ears, a cleft uvula, medially rotated hands, deafness, and blindness. The mother had taken Lomotil (diphenoxylate and atropine) for diarrhea during the 10th week of gestation. Because exposure was beyond the susceptible stages of development for these defects, the drug combination was not considered causative. However, a possible viremia in the mother as a cause of the diarrhea could not be excluded as playing a role in the infant's anomalies.

Breast Feeding Summary

The passage of atropine into breast milk is controversial (13). It has not been adequately documented whether measurable amounts are excreted or, if excretion does occur, whether it may affect the nursing infant. Although neonates are particularly sensitive to anticholinergic agents, no adverse effects have been reported in nursing infants whose mothers were taking atropine and the American Academy of Pediatrics considers the agent to be compatible with breast feeding (14).

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References

  1. Nishimura H, Tanimura T. Clinical Aspects of The Teratogenicity of Drugs. New York, NY:American Elsevier, 1976:63.
  2. Kivalo I, Saarikoski S. Placental transmission of atropine at full-term pregnancy. Br J Anaesth 1977;49:1017–21.
  3. Kanto J, Virtanen R, Iisalo E, Maenpaa K, Liukko P. Placental transfer and pharmacokinetics of atropine after a single maternal intravenous and intramuscular administration. Acta Anaesth Scand 1981;25:85–8.
  4. Onnen I, Barrier G, d'Athis Ph, Sureau C, Olive G. Placental transfer of atropine at the end of pregnancy. Eur J Clin Pharmacol 1979;15:443–6.
  5. Piper JM, Baum C, Kennedy DL, Price P. Maternal use of prescribed drugs associated with recognized fetal adverse drug reactions. Am J Obstet Gynecol 1988;159:1173–7.
  6. Hellman LM, Fillisti LP. Analysis of the atropine test for placental transfer in gravidas with toxemia and diabetes. Am J Obstet Gynecol 1965;91:797–805.
  7. Roodenburg PJ, Wladimiroff JW, Van Weering HK. Effect of maternal intravenous administration of atropine (0.5 mg) on fetal breathing and heart pattern. Contrib Gynecol Obstet 1979;6:92–7.
  8. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
  9. Diaz DM, Diaz SF, Marx GF. Cardiovascular effects of glycopyrrolate and belladonna derivatives in obstetric patients. Bull NY Acad Med 1980;56:245–8.
  10. Roper RE, Salem MG. Effects of glycopyrrolate and atropine combined with antacid on gastric acidity. Br J Anaesth 1981;53:1277–80.
  11. Abboud T, Raya J, Sadri S, Grobler N, Stine L, Miller F. Fetal and maternal cardiovascular effects of atropine and glycopyrrolate. Anesth Analg 1983;62:426–30.
  12. Siebert JR, Barr M Jr, Jackson JG, Benjamin DR. Ebstein's anomaly and extracardiac defects. Am J Dis Child 1989;143:570–2.
  13. Stewart JJ. Gastrointestinal drugs. In Wilson JT, ed. Drugs in Breast Milk. Australia (Balgowlah):ADIS Press, 1981:65–71.
  14. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.

Index

Q&A about Atropine

airforce...
How effective is an atropine injection after a chemical attack?
Also, is it true that in severe cases you must inject it into the heart? The ones they issue us in the AF are too short to do so, though.
Scott B
Atropine is very effective and no, it does not ever need to be injected into the heart, that would be very dangerous and serve no purpose. Injecting it into the heart would only serve to get it into the bloodstream very quickly(if hypothetically you could do it safely) but the same thing could be done by a normal IV injection.
Missy
What is the nebulizer dose for Atropine?
Trying to find the dosage for Atropine for a SVN. Thanks
Harmony
For bronchospasm the inhaled dose is 0.03 - 0.05 mg/kg/dose 3 -4 times/day. Maximum 2.5 mg
Micho L
Does anyone know a optician practitioner in Sydney, Australia who uses atropine drops to treat myopia?
i am 15 years old and have high myopia and i am hoping to use atropine to retard my prescription from getting worse
Susan S
I am in the US, and here, opticians only deal with glasses, and do not handle medications. Optometrists could give you atropine, provided the benefits of this pharmaceutical vision therapy outweigh the risks. At present, studies are underway to assess the validity of the hypothesis. You would not want to endanger your future vision while trying to avoid future vision problems. "Out of the frying pan and into the fire."
KK
Anybody out there using Atropine eye drops by mouth to dry up saliva?
How many drops are you using, and how often?
killfoot...
I don't think I would do that. Put atropine in your mouth and it might go systemic.
student_...
About the effect of atropine on histamine?
Could anyone tell me more about the effect of atropine and histamine together on smooth muscle? Would both of the drugs exert contractile force on smooth muscle or have relaxing effect? If possible, could you include the reference? Thanks
i~hope~u...
Histamine prevents bronchiolar or gastrointestinal smooth muscle constriction. Atropine also relaxes smooth muscle tissue.

http://www.pharmacology2000.com/Autonomi...
Johnny
Would you ever need to use Atropine instead of Epinephrine to speed up the heart?
conusgyp...
Yes, Atropine is usually your FIRST line of defense in speeding up the heart rate. Atropine blocks the parasympathetic stimulus to the SA node. Epi is not intended to speed up the heart, it's to increase irritability so that you can have a rhythm to convert in V. fib. Increased heart rate is a side effect
dn
How does atropine counteract the effects of nerve gas?
Yes
So: we've got a fairly important neurotransmitter called acetylcholine (ACh). ACh is responsible for signaling all skeletal muscle contraction (your voluntary muscles, in general) and controlling a number of glands and central nervous system (CNS) pathways. ACh is released from the end of a neuron into the synaptic space between either two neurons or a neuron and muscle fiber (in skeletal muscle). It binds to that neuron or muscle fiber on the other side of the synapse, causing it to depolarize, which either accomplishes neurotransmission (if the target is a neuron) or muscle contraction (if the target is a muscle fiber). Because these signals can come very quickly, the system must be shut off very quickly, resetting it so the next signal can come and exert its effect - this is accomplished by acetylcholine esterase (AChE) which lie in that synaptic space and degrade ACh extremely rapidly, so each neurotransmission event has very short duration.

Nerve agents, mainly classified as organophosphates, bind to AChE and irreversibly inhibit them (i.e. once bound, they will never work again). With all the AChEs in a synapse knocked out, ACh builds up and constantly stimulates the neuron/muscle on the other side. In muscles, this leads to constant contraction and convulsions; in autonomic pathways, this leads to lacrimation (tears), salivation (salivary gland overstimulation), urination and defecation (sphincter tone loss), and sweating. Action in the CNS eventually causes respiratory arrest and death.

Atropine comes into play because it is an ACh antagonist - it blocks ACh from binding to the neuron/muscle fiber on the other side of the synapse. This counters the effect of the nerve agent, which causes massive amounts of ACh to be left in the synapse - that ACh is still present, but atropine prevents it from having any effect. Eventually, the AChEs inactivated by the nerve agent are degraded and removed, new AChEs are produced, and the system begins to work again - atropine sustains life while that process takes place.
Beth V
Has anyone had the atropine/scopolamine injections from the stop smoking clinic?
My husband just had the atropine/scopolamine injections by Dr. Gugga. The purpose is to stop smoking. He is now on Belladona, he still has a scopolamine patch, and he has a new Rx for ativan prn. The side effects of these drugs can cause blurred vision, hallucinations, drowsiness. The Dr said he would be ok to work by day 2 which was Wednesday, but he has been acting very loopy. Has anyone had this injection? Did it make you somewhat tired, or did you not remember the events of the day? I had to get my parents to watch our kids while I go to work, because I don't think he would wake up for them. Does anyone have any experience with this?

Thanks
Alice K
Is this a legitimate clinic?? Did you google these drugs to see what they really do? Atropine dilates your eyes and speeds up your heart; belladonna is a poison; ativan is an anti-anxiety drug; and the CIA used to use scopolamine (a depressant) when they interrogated suspects. A small overdose of any ONE of these drugs can be fatal. This sounds like a very dangerous combination. How on earth are they supposed to help you quit smoking? I doubt seriously that any of them should be prescribed for that purpose. Have you spoken to your regular doctor about this?
oliviast...
Tricyclic Antidepressant + Atropine? What are the side effects on eyes?
An optometrist put the dilating drops called Atropine in my eyes when I was taking Doxepin (a tricyclic antidepressant). I am on week 10 of long term dilation of the eyes (which is getting better, but is not 100%). This long term of a dliation is freaking me out.

Any consoling words of wisdom?

In theory, if I am still experiencing problems, does that mean the drug is still in my blood/body? Can I flush the drug out quicker?
hasafer
I had a case with interaction between the same drugs , since when did you stop doxepin ?
aks
why are drugs prepared in salt form? as atropine sulphate?
morphine is also dispensed in salt form.why it is not only morphine or atropine?
dmc
they are more stable in that form and less likely to degrade.