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Dementia Pathways Tool

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Medication

Currently there are four medications used in the treatment of Alzheimer's Disease. Tolerability and safety issues and the medications relationship to side effects are listed in the below tables. Further information on how these medications work can be found at the NPS MEDICINEWISE links:

Tolerability and Safety Issues

 

Exelon

Aricept

Reminyl

Metabolism

By AChE and
BuChE

  • Minimal CP450 metabolism
  • No drug interactions
  • Confirmed in trials

Liver Metabolism
(CP2D6, and 3A4)

  • leads to drug interactions: SSRIs, Tegretol, phenytoin , antibiotics, antihypertensives

Liver metabolism (CP450, 2D6, 3A4)

  • potential for drug interactions, (as opposite)

Half-life
  • 1-2 hrs in periphery
  • Extended action in brain (10hrs)
  • 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. 10 X 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 vomitting)

+++

++

++

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