Doxylamine Pharmacology

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. 

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Show notes provided by Chong Yol G Kim, PharmD Student.

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Melatonin Pharmacology

I cover melatonin pharmacology on this episode of the Real Life Pharmacology Podcast.

Melatonin, commonly taken by patients for insomnia, is an endogenous hormone produced by the pineal gland. It is an over-the-counter supplement available in dosage forms such as liquid drops, gummies, and tablets. The pharmacology of melatonin is primarily through the activation of melatonin receptors in the suprachiasmatic nucleus; it is also a derivative of L-tryptophan. The production and secretion of melatonin is stimulated by darkness and is inhibited by light. Melatonin concentrations are also shown to vary with age. Its production primarily begins between months 3-4 post-birth, and it peaks between years 1-3. The production and secretion decrease with age and can play a role in insomnia in adults. The doses of melatonin can vary but is commonly found in 1 mg, 3 mg, 5 mg, and 10 mg. Although it is usually taken in higher doses, doses between 0.1-0.5 mg may be adequate. 

Certain things need to be taken into consideration when a patient is taking melatonin. Some of the things that should be taken into consideration are if it works as it’s expected to or if the patient is already on stimulating medications that can cause insomnia. If the patient is taking other medications like zolpidem, trazodone, or mirtazapine, melatonin may not be needed. Other things that should be taken into consideration are if the patient tolerates melatonin well and if a lower dose of melatonin can be used. Melatonin is commonly well-tolerated, but it can occasionally cause CNS issues at higher doses such as oversedation, cognitive impairment. It can even cause hyperprolactinemia that can cause sexual dysfunction, fertility risk, lactation, and is associated with lower bone mineral density. 

Common adverse drug reactions associated with the pharmacology of melatonin are headache, CNS depression, irritability, and daytime sedation. With long-term use, melatonin can cause suppression of the hypothalamic-pituitary axis. Melatonin is primarily metabolized by CYP1A2, CYP2C9, and CYP2C19. The concentration and efficacy of melatonin can potentially be impacted by medications that induce or inhibit the CYP enzyme system, such as propranolol, calcium-channel blockers, and others. Interactions of melatonin that are not CYP mediated are additive effects when taken with other sedatives, caffeine, and ethanol that can reduce the efficacy of melatonin, or other medications that can increase the risk of adverse drug reactions. 

Melatonin is regulated by the FDA as a dietary supplement, and not as a medication. Toxicology studies are limited.

Show notes provided by Chong Yol G Kim, PharmD Student.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!

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Resources

  1. Information is taken directly from the podcast episode
  2. Light/dark melatonin levels, concentrations with age paragraph 1: 10.1016/s0531-5565(98)00054-0 , podcast
  3. ADRs paragraph 2: Lexicomp, podcast
  4. CYP interactions paragraph 3: Lexicomp
  5. Toxicity paragraph 4: Lexicomp

Zolpidem Pharmacology

Zolpidem enhances the action of GABA which is an inhibitor neurotransmitter.

Zolpidem metabolism can be impacted by the use of CYP3A4 inhibitors. Concentrations can rise on account of this potential interaction.

It is important to remember to go slowly when tapering off zolpidem. Particularly in patients who have been on the drug for a long time or those who are on higher doses.

Abnormal sleeping behaviors like sleep-walking, eating, or driving have been reported with zolpidem.

Remember that CNS depressant drug interactions can happen with zolpidem. Take note of any other sedating medications prior to starting zolpidem.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

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Trazodone Pharmacology

Trazodone pharmacology is complex. It can inhibit serotonin reuptake, block histamine receptors, and possibly have alpha-blocking activity.

Side effects of trazodone include sedation, dizziness, and dry mouth. Rarely, priapism may occur. I’ve seen this nugget come up on pharmacology exams!

While trazodone is classified as antidepressant, it is often used to help manage insomnia.

Trazodone can possibly prolong the QT interval. Risk of other medications and patient specific parameters should be considered.

Trazodone concentrations can be increased with the use of CYP3A4 inhibitors and reduced with 3A4 inducers.

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