Medication
Currently there are four medications (three acetylcholinesterase inhibitors and one NMDA receptor antagonist) and one medical food. Approved for the management of dementia caused by Alzheimer’s Disease.
Emerging disease modifying monoclonal antibodies may change the management of Alzheimer’s Disease substantially
Fortasyn Connect ( Souvinaid) is a medical food that has been shown in one study to slow cognitive decline. It has been recommended these study results be discussed with patients with MCI. [1]
Psychotropic drugs are sometimes indicated for the treatment of psychological and behavioural symptoms of dementia (BPSD).
Tolerability and safety issues and the medications relationship to side effects for cholinesterase inhibitors are listed in the below tables.
Tolerability and safety issues
|
Exelon |
Aricept |
Reminyl |
|
|---|---|---|---|
|
Metabolism |
By AChE and Minimal CP450 metabolism No drug interactions |
Liver Metabolism Leads to drug interactions: SSRIs, tegretol, phenytoin, antibiotics, anti-hypertensives |
Liver metabolism (CP450, 2D6, 3A4) Potential for drug interactions |
|
Half-life |
1-2 hrs in periphery Extended action in brain (10 hrs) No accumulation |
3 day extended Problems if GA needed |
4-6 hrs Little accumulation |
|
Protein binding |
Low (40%) Will not displace highly protein bound drugs Few drug interactions |
High (96%) Displaces protein bound drugs Leads to drug interactions |
Low (20%) Few drug interactions |
|
Selectivity for brain over periphery |
Yes Central – cortex |
No Central, with |
No 10x more |
|
Isoform selectivity |
G1 selective |
Inhibits G1, G2, G4 |
Inhibit G1, G2, G4 |
|
Up regulation of AChE gene expression |
No Low potential for tolerance with |
Yes Long term Potential for tolerance |
Yes Long-term treatment increase AChE in CSF. Potential for tolerance with long-term treatment |
Relationship of cholinergic activity to side effects
|
Area of cholinergic |
Side effects |
Exelon |
Aricept |
Reminyl |
|---|---|---|---|---|
|
Central |
||||
|
Hypothalamus |
Gastrointestinal (nausea |
+++ |
++ |
++ |
|
Caudate nucleus |
Extra pyramidal |
+/- |
++ |
+/- |
|
Brainstem (pons) |
Sleep disturbances |
+/- |
++ |
+/- |
|
Medulla (cardio |
Cardiovascular |
+/- |
+ |
+ |
|
Frontal / temporal |
Agitation |
+ |
++ |
++ |
|
Peripheral |
||||
|
Peripheral inhibition |
Bradycardia and |
+/- |
+ |
+ |
|
Peripheral |
Muscle cramps |
+/- |
++ |
+/- |
|
Bladder |
Urinary incontinence |
+/- |
+ |
+/- |
Cholinergic activity:
+/- little or none;
+ mild;
++ moderate;
+++ strong
Tables courtesy of Associate Professer Mark Yates combined Director of Clinical studies Deakin University and University of Melbourne: Medication in Dementia education resource 2010
1. Woodward M, Brodaty H, McCabe M, Masters CL, Naismith SL, Morris P, et al. Nationally Informed Recommendations on Approaching the Detection, Assessment, and Management of Mild Cognitive Impairment. J Alzheimers Dis. 2022;89(3):803-9.