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Medication

Currently there are four medications used in the treatment of Alzheimer's disease. These include cholinesterase inhibitors or memantine which treat the cognitive impairment caused by Alzheimer's disease. 

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
BuChE

Minimal CP450 metabolism

No drug interactions

Liver Metabolism
(CP2D6, and 3A4)

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
elimination half-life

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
and hippocampus

No

Central, with
peripheral AChE
inhibition

No

10x more
selective for
periphery than
brain

Isoform selectivity

G1 selective

Inhibits G1, G2, G4

Inhibit G1, G2, G4

Up regulation of AChE gene expression

No

Low potential for tolerance with
long-term treatment

Yes

Long term
treatment increase
AChE in CSF

Potential for tolerance
with long-term
treatment

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
activity

Side effects

Exelon

Aricept

Reminyl

Central

Hypothalamus
(area postremus)

Gastrointestinal (nausea
and vomiting)

+++

++

++

Caudate nucleus

Extra pyramidal
symptoms

+/-

++

+/-

Brainstem (pons)

Sleep disturbances

+/-

++

+/-

Medulla (cardio
respiratory centres)

Cardiovascular
and respiratory

+/-

+

+

Frontal / temporal
lobe

Agitation

+

++

++

Peripheral

Peripheral inhibition

Bradycardia and
ECG abnormalities

+/-

+

+

Peripheral
neuromuscular
junction

Muscle cramps
and weakness

+/-

++

+/-

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