NS is a 78-year-old male admitted to the hospital with idiopathic pancreatitis and severe nausea. He has no serious comorbidities and is a generally healthy person.

During morning rounds, your team discusses NS’s case. The nurse says that NS is having trouble sleeping at night and he has become severely confused and agitated over the past several days. It’s like he has restless leg syndrome all over his body. He thinks he’s at home, he keeps trying to use his cellphone to change the tv stations, and he’s very unsteady when he walks.

The primary care physician says that the pancreatitis has resolved and, medically speaking, NS can be released from the hospital. The social worker asks if she should start making arraignments to have NS placed in a nursing home since he has developed signs of dementia. The physicians mentions it is curious that NS was previously living independently at home prior to his hospitalization. NS has no family history of Alzheimer disease or any other type of cognitive impairment. 

You are the team pharmacist and you look at the drug list for NS with your laptop computer. You see that he is on the following medications.
  • Natural tears, 1 drop each eye bid
  • Bimatoprost, 1gtt each eye qhs.
  • Warfarin, 2 mg qhs with sips of water
  • Finasteride, 5mg qhs with sips of water
  • Promethazine, 25 to 50 mg IV q6h prn severe nausea and vomiting
  • Acetaminophen, 650mg suppository q4h prn mild pain or fever
  • Morphine, 2 mg IV q4 hours prn severe pain

You ask the team to hold off on a nursing home placement and suggest changing 1 of his medications to see if his dementia resolves. What you really want to say is, “He’s fine, he’s just having adverse effects from one particular medication. He’ll be able to go back to his normal life after 48 hours if we stop this 1 drug.”

Mystery: Which medication is causing cognitive changes in NS?

Solution: Promethazine 25 mg orally or iv q8 hours as needed for nausea.

Promethazine is an antinausea drug with anticholinergic properties. It opposes acetylcholine. Acetylcholine is an essential brain neurotransmitter that is also located in various nerve endings throughout the body. As we age, all our neurochemicals can diminish in production. Anticholinergic drugs diminish this neurochemical even more, and if it diminishes too much, cognitive impairment can set in. If these drugs are given for too long, years, the changes can become permanent. 

There is a new study that discovered these drugs cause problems in healthy people who do not have risk factors or family members with dementia. This study found that people taking at least 1 anticholinergic drug were 47% more likely to develop mild cognitive impairment, which can be a precursor to dementia.1

This finding is supported by another study, published in 2019.2 This earlier investigation was a case controlled study that looked at 58,769 patients with a diagnosis of dementia and 225,574 controls who did not have dementia. It specifically evaluated people aged 55 years and older, and who had exposure to anticholinergic drugs.

The 2019 study found that approximately 10% of dementia diagnoses are attributable to anticholinergic drugs. There was nearly a 50% increased odds of dementia with the use of a strong anticholinergic drug consumed daily for 3 years.

Acetylcholine plays a role in the brain regarding cognitive function, learning and attention. It also plays a major role throughout the body in the junctions between nerves and muscles, specifically at the neuromuscular junction.

Many anticholinergic drugs work in the body to improve the lives of patients suffering from severe nausea, muscle spasms, overactive bladder, and intestinal cramping. These drugs are also used to treat depression, mood disorders, Parkinson disease, and epilepsy because they also exert an effect in the brain.

These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older adults.


REFERENCES
  1. Weigand AJ, Bondi MW, Thomas KR, et al. Association of anticholinergic medication and AD biomarkers with incidence of MCI among cognitively normal older adults. Neurology. Published online September 2, 2020. DOI: https://doi.org/10.1212/WNL.0000000000010643
  2. Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. Published online June 24, 2019. doi:10.1001/jamainternmed.2019.0677