DMA intended to lighten its burden on society and help enhance national health by establishing and implementing comprehensive policies on preventing dementia, support for dementia patients, and research of finding a cure for dementia. Life expectancy between AD and AAD group 1, 2 were significantly observed (Fig. 1. between 2018 and 2019). It is because the DMA was strengthened on June 12 2018.
However, the neurological side effects of donepezil among AAD are similar to those of dementia 1. Few people can distinguish whether they are side effects caused by dementia or donepezil drugs: Dizziness, delusions, dream abnormalities, ataxia, convulsive seizures, hemiplegia, hypertonia, salivation 2 3. Four FDA-approved therapeutics for the management of cognitive impairment diseases and symptomatic AD include three cholinesterase inhibitors (ChEIs; donepezil, rivastigmine, and galantamine) and memantine, an uncompetitive NMDA receptor modulator. Three ChEIs are approved for use in mild-to-moderate AD, and their symptomatic benefit in AD has been confirmed via meta-analyses assessing both cognitive performance and global functioning 4. However, the data analysis on the number of people who took donepezil and the number of fatalities among the three ChEIs revealed that the number of deaths increased as the number of prescriptions increased (Fig. 5).
All studies from many countries already confirmed that antipsychotic drugs should not be administered for dementia patients because they increase the risk of seizures and all-cause mortality. Deprescribing psychotropic medications are feasible to most people experiencing no withdrawal symptoms in long-term care 5 6.
However, many toxins are cholinesterase inhibitors, and these toxins can cause death if given in high enough dosages. There is no known cumulative effect when taken consistently like humans. Botulinum toxin blocks the release of acetylcholine hormone from the presynaptic terminal by preventing acetylcholine release 7. Black widow spider venom is thought to be associated with a wide release of neurotransmitters, especially norepinephrine and acetylcholine, due to spider envenomation. If the widow venom exhausted all acetylcholine supplies as the opposite effect of botulinum toxin, paralysis occurs 8 9.
Acetylcholine performs various physiologic functions through cholinergic muscarinic receptors, five different types of muscarinic receptors, M1, M2, M3, M4, and M5. The muscarinic receptor M1 is in the cerebral cortex, salivary, and gastric glands. The muscarinic receptor M2 are present in smooth muscle as well as cardiac tissue. The muscarinic receptor M3 are in smooth muscle cells, particularly of the bronchioles, iris, bladder, and small intestines. The muscarinic receptor M4 and M5 have a less clear distribution but have been found in the hippocampus, substantia nigra, and other locations within the brain 10 11.
The non-neuronal cholinergic system is involved in the pathophysiology of diseases 12. On the cardiovascular system, it determines generalized vasodilation, negative chronotropic effect, negative inotropic effect. It is a less pronounced negative dromotropic effect in the specialized tissue of the sinoatrial and atrioventricular nodes at the ventricular level than other organs. Muscarinic receptor 2 is not the only functional subtype found within the heart, and muscarinic receptors 1 and 3 mediate both dilation and constriction in the vasculature 13.
When a patient who had been taking dapsone, which is mainly used in clinical studies on inflammasome competitors 3 14 15, stopped dapsone for stroke treatment and administered acetylcholine precursors, it rapidly progressed to rapid hypertension and pulmonary hypertension 2. Patients life expectancy at Sorokdo National Hospital, which is known to live longer 16, is gradually decreasing (Fig. 1).
AADs administered to the elderly are closely related to health insurance policies. If the elderly die early, health insurance companies will benefit. However, health insurance policies have been operated to improve the health of the elderly 17. Long-term administration of ChEIs to patients with dementia has increased mortality. The effects of ChEIs on cardiovascular systems should be analyzed and studied.