Scopolamine

Mechanism of Action

Scopolamine derives from the plants of Datura stramonium (Jimsonweed), Scopolia carniolica, and Hyoscyamus niger (henbane). These plants produce toxic compounds called belladonna alkaloids as a protective mechanism.[7] Scopolamine competitively inhibits G-protein coupled post-ganglionic muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects.[8] It is structurally very similar to atropine and is useful in conditions requiring decreased parasympathetic activity. Peripherally this results in smooth muscle relaxation and reduced gland secretion. Centrally, unlike atropine, scopolamine causes mostly sedation, but over-excitement and restlessness can occur at higher doses.[7]

The vomiting center of the brain is located in the medulla oblongata and contains a high amount of M1 muscarinic acetylcholine, H1 histamine, NK1, and 5-HT3 serotonin receptors. Thus, any agent that antagonizes these receptors will have antiemetic properties. Scopolamine exerts its action by primarily affecting the M1 receptor. However, some research has reported H1 receptor activity.[7]

Administration

The most commonly used dose form of scopolamine in the United States is a transdermal patch. Each patch is a circular shape of about 2.5 cm in diameter and 0.2 mm in thickness. Its design is in four layers for step-wise delivery of a priming dose of 140 micrograms of scopolamine initially, followed by a steady 1.5 mg release over 72 hours.[9] The onset of action of scopolamine is four hours, and the peak effect of the patch occurs at 24 hours. Per package labeling, the recommendation is to apply scopolamine the night before surgery if used to prevent postoperative nausea and vomiting or four hours before exposure if used for motion sickness. For cesarean sections, apply one hour before surgery to limit exposure to the baby. The manufacturer also recommends discontinuation of the patch 24 hours after surgery because there was no significant antiemetic effect of scopolamine for PONV between 24 and 48 hours. For motion sickness, reapplication can be every 72 hours.[7][10][11]

Patch placement should be on the postauricular area (the hairless area behind the ear). The stratum corneum, which acts as a significant barrier to percutaneous absorption, is the thinnest at this location. Patients should not cut the scopolamine patch, as it will alter the delivery system, and blood levels become less controlled. There are two other scopolamine products available outside the USA: scopolamine hydrobromide and scopolamine butylbromide. Both are useable in parenteral, intramuscular, intravenous, and subcutaneous forms. The short duration of action, less predictable blood levels, and common side effects resulted in the exclusion of these products from U.S. markets.[9]

Adverse Effects

The most commonly reported side effects of scopolamine patch use are blurred vision, dilated pupils, and dry mouth. The vision disturbances are most often due to inadequate handwashing techniques after the application of the patch.[1] Less frequently reported side effects are related to anticholinergic toxidrome: flushed skin, tachycardia, agitation, and confusion. These side effects are usually mild and quick to resolve after patch removal. If needed, the clinician can administer a reversal agent like physostigmine if a side effect persists.[8][12] 

Contraindications

The FDA currently lists two contraindications for scopolamine: allergy to belladonna alkaloids and angle-closure glaucoma. Patients with angle-closure glaucoma should not be prescribed scopolamine. Scopolamine causes mydriasis or pupillary dilation. A dilated iris prohibits proper drainage of fluid from the anterior chamber, creating a further increase in anterior chamber pressure and precipitating acute angle-closure glaucoma.[13]

Monitoring

There are several conditions in which scopolamine use requires caution or its effects monitored more frequently.

There are reports of scopolamine worsening psychosis. Reports also exist of acute toxic psychosis, agitation, speech disorder, hallucinations, paranoia, and delusions.[14][15] Patients need monitoring for new or worsening psychiatric symptoms during treatment.

Use caution in using scopolamine for patients with myasthenia gravis. Myasthenia gravis is caused by a lack of proper nerve impulse transmission due to antibodies to acetylcholine receptors, resulting in muscle fatigue. Although myasthenia gravis primarily affects skeletal muscle, the use of anticholinergic agents, like scopolamine, causes unpredictable results.[16]

There has been some concern about the use of scopolamine in patients with a seizure history. The speculated reason is that scopolamine might lower seizure threshold potential. However, further examination of medical records showed this not to be true. This false claim was primarily attributable to the coding of reported cases as "dizziness, rule out seizures." Patients in these cases did not experience an actual seizure or had it before the application of scopolamine.[17] Nonetheless, there is a valid concern for seizure induction with the use of scopolamine in patients with severe preeclampsia. Currently, the understanding of preeclampsia has its basis in a vasospasm theory, and the use of anticholinergic agents may leave the sympathetic system unopposed, further deteriorating the condition of preeclampsia into eclampsia and HELLP syndrome.[18]

Patients should also discontinue using a scopolamine patch before MRI. One of the four layers contains metal and can burn the skin during MRI imaging.[7]

Due to scopolamine's anticholinergic properties, its use can decrease gastrointestinal motility and cause urinary retention.[19] In patients suspected of having intestinal obstruction, pyloric obstruction, urinary bladder neck obstruction, or patients receiving other anticholinergic drugs, consider more frequent monitoring during treatment. Discontinue scopolamine in patients who develop difficulty urinating.

Scopolamine use also merits caution in special populations. Children, pregnant or lactating mothers, patients with hepatic or renal impairment, and the elderly should be monitored earlier for more severe side effects.

There is no formal laboratory testing of scopolamine levels currently available.

Toxicity

Toxicity does not happen as frequently with the transdermal form of scopolamine due to its extended-release nature. Data on the toxic dose of scopolamine in the tablet form is scattered. Reports exist that 10 mg a day can be lethal for children. In adults, consumption of more than 100 mg a day did not result in death. The other feared toxidrome of scopolamine overdose is an anticholinergic syndrome resulting in tachycardia, hallucinations, hyperthermia, and dry membranes. Physostigmine 1 to 4 mg IV can serve as an antidote in such severe cases. However, with the transdermal application, only minor side effects are most commonly observed.[12][9]

Enhancing Healthcare Team Outcomes

Scopolamine is used extensively to prevent PONV in the hospital setting and motion sickness outside of the hospital, and its use and administration should have the involvement of an interprofessional team. Nursing staff should be knowledgeable about proper placement and side effects of scopolamine. The most commonly occurring are mucosal dryness and visual disturbances. The latter is usually due to touching the patch and rubbing the eyes or not properly washing hands after patch administration. Patch formulation prevents systemic toxicity, but one should be aware of the side effects of a possible overdose and monitor closely in specific populations. Nursing can monitor the patient's progress with therapy and check for adverse events in both inpatient and outpatient settings. Pharmacists should check for drug-drug interactions and educate patients and team members regarding the proper use and potential side effects. With an interprofessional team paradigm, scopolamine can achieve maximum therapeutic benefit with minimal adverse events. [Level 5]