On this episode, I discuss the pharmacology of zaleplon including side effects, drug interactions, and important clinical pearls.
Zaleplon is a non-benzodiazepine sleep aide commonly known as Sonata. It is commonly used for sedation and the management of insomnia. Zaleplon is a controlled medication, with a high risk for dependence, and because of that, it is best used to treat short-term insomnia. The pharmacology of zaleplon is similar to other sleep aids like Ambien, and Lunesta; they all have an impact on GABA. Specifically, zaleplon regulates the GABABZ receptor. The GABABZ receptor has been shown to be responsible for the pharmacological properties of benzodiazepines which produce sedative, anxiolytic, relaxant, and anticonvulsive effects. For pharmacokinetics, zaleplon has a general onset of action around 30-60 minutes, because of that it is best dosed closer to bedtime.
For sedatives, and other drugs similar to zaleplon, it is generally better to start at lower doses in geriatrics and smaller patients. The commonly accepted dosing is between 5-20 mg, but it is best to use non-pharmacological therapies, instead of pharmacological whenever possible. The most common side effect that may be experienced with zaleplon is next-day sedation, also known as hangover sedation. Loss of mental clarity, dizziness, and confusion may also be present. Serious side effects of taking zaleplon are abnormal sleep behaviors, which it carries a US boxed warning for, and risk of dependence. Zaleplon is also on Beer’s list because of the increased risk of falls, delirium, and increased complications while driving due to sedation and lethargy.
When a sedative is first prescribed, it’s important to first look at the other medications a patient may be taking to see if that’s what may be causing insomnia. For example, a diuretic administered at night can cause excessive urination that can lead to insomnia. The addition of stimulants too late in the day can also cause that, and similarly, lifestyle changes like increased intake of caffeine can increase the risk for insomnia as well.
Most of the drug-drug interactions that zaleplon has are due to additive depressive effects. Examples include alcohol, opioids, older antihistamines, trazodone, or any medication that can cause sedation. There is also a smaller risk for CYP3A4 interaction. Concurrent administration of an inducer, like St. John’s Wort, or carbamazepine, can lower the concentrations of zaleplon. Likewise, inhibitors may increase concentrations.
In cases of overdose, the signs and symptoms that will most likely precipitate are exaggerations of zaleplon’s adverse effects. The manifestations of CNS depression can range from drowsiness to coma. More mild cases might have drowsiness, confusion, and lethargy; while more serious cases may have ataxia, hypotonia, hypotension, respiratory depression, coma, and death. To treat a zaleplon overdose, symptomatic and supportive measures are necessary along with gastric lavage. Animal studies suggest that flumazenil is an antidote as an antagonist to zaleplon, but there is no human data. With proper treatment, recoveries have been made with overdoses greater than 200 mg. In instances where the outcome was fatal, it was most often associated with the use of additional CNS depressants.
Show notes provided by Chong Yol G Kim, PharmD Student.
In the podcast this week, I talk about doxylamine pharmacology. Doxylamine is a first-generation antihistamine; it is commonly an active ingredient in night-time medications like Unisom, Nyquil, and Mucinex. The pharmacology of doxylamine is similar to other first-generation antihistamines, it competitively inhibits the binding of histamine at H1 receptors. Its main uses are as sleep aides, in cough-and-cold medications, but doxylamine has also been given with pyridoxine to treat nausea and vomiting during pregnancy.
Doxylamine’s adverse reactions are related to its anticholinergic properties, they include dry eyes, dry mouth, increased fall risk, sedation, urinary retention, constipation, and confusion. Contraindications include concurrent use with a monoamine oxidase inhibitor, known hypersensitivities, concomitant alcohol use, and if the patient has the following conditions: elevated intraocular pressure, narrow-angle glaucoma, asthma, peptic ulcer disease, urinary bladder neck obstruction, or gastric outlet obstruction. It is also a Beer’s list drug due to its anticholinergic effects. The normal dose in adults is 25 mg. In cases of overdosage, the most common manifestation is exacerbations of its anticholinergic effects. The major complications of an overdose include arrhythmia, respiratory failure, seizures, hyperthermia, rhabdomyolysis, and coma.
When you know a patient is taking doxylamine, it’s important to be cognizant of their occupation, as well as what other conditions they may have. For example, doxylamine should be used with caution in patients that drive heavy machinery due to its sedating properties. You might be able to tell if a patient’s experiencing an adverse reaction exacerbation if they begin having worsening dementia symptoms or increased urinary retention. Other indications include the use of artificial tears, or saliva, or increased complaints of constipation. To monitor for doxylamine, it’s important to monitor the patient’s tolerability. The onset of doxylamine is relatively quick as well, with a peak concentration within 2-4 hours.
For drug-drug interactions, CYP interactions aren’t as concerning as usual. The main interaction to consider when a patient is taking doxylamine is additive anticholinergic effects. Sedative effects can increase when benzodiazepines, skeletal muscle relaxants, opioids, or antihistamines are concurrently taken. Doxylamine can also counteract the usefulness of dementia or BPH medications due to its anticholinergic properties. There is also a risk of increased anticholinergic burden when taken with skeletal muscle relaxants or tricyclic antidepressants.