Common asked questions about
ChEIs – Where is the answer?
Switching ChEIs – What is the
rationale?
How long does ChEls get
prescribed?
When to stop? What would happen
afterward?
When to do an ECG?
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ChEIs: Common Questions and Studies on Switching, Indications, and Discontinuation, Slides of Geriatrics
An overview of commonly asked questions regarding cheis (cholinesterase inhibitors) including reasons for switching, indications, discontinuation, and results from various studies. Topics covered include intolerance, adverse events, and practical guidelines for discontinuation.
Typology: Slides
2011/2012
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Common asked questions about
ChEIs – Where is the answer?
Switching ChEIs – What is the
rationale?
How long does ChEls get
prescribed?
When to stop? What would happen
afterward?
When to do an ECG?
Pharmacological Properties of ChEIs
Cognitive and functional measure – dose response Behavioural manifestations – variable
Summary of the Studies
Majority did not include individuals
switched for lack of response after
several years of treatment.
Global evaluation, cognitive and
functional measures show stabilization
or improvement in >50% of switched
patients for unsatisfactory response
>50% switched for intolerance were
able to tolerate the second agent
(being Exelon or Reminyl +/- Ebixa)
No specific recommendations could be
drawn as to whom, when and how to
switch.
How Common is Switching ChELs?
Study (Yr of Publish)
Place Population (Yr of Study)
Result
Herrmann (2002)
Ontario Comm/NH
28961 (2000-2)
6%
Herrmann (2007)
Ontario Community only
5622 (2006)
Aricept 21.9% Exelon 32.3% Reminyl 32.3%
Massoud (2010)
Quebec Community based
18748 (2001-3)
Aricept 10% Exelon 11.7% Reminyl 5%
Dybicz (2006)
US Nationwide Nursing Home
2873 (2001-3)
Aricept 3.3% Exelon 4.7% Reminyl 2%
Mucha (2008)
Medicare Beneficiaries
3177 (2001-3)
Aricept 14.5% Exelon 21.5% Reminyl 15%
Discontinuing ChLs - Survey from C5R
Patient/caregiver preference
- Competent patient (78%) or substitute decision maker (63%) requested it.
Administration
- Disagree for simply admission to LTC (93%)
- Would not discontinue after only 1 year (96%)
- Disagree that ChLs be stopped if the patient no longer qualified for drug benefit coverage (96%)
- Specific length of time (?) beyond which doubt in efficacy should prompt discontinuation (74%)
- Should not be D/C when MMSE < 10 (93%)*
Survey of Canadian Dementia Experts
Effectiveness
- If the patient initially demonstrated obvious clinical improvement, ChEI should not be discontinued regardless of subsequent deterioration (46 vs 38%)
- If the patient did not clearly improve after initiating ChEI, but appeared to be clinically stable for 6-12 months, ChEI should not be discontinued regardless of subsequent deterioration. (no consensus)
- A trial of switching to another ChEI in each scenario for subsequent decline.+
- if a patient begins to deteriorate at a rate that would be ‘greater than expected’, ChEI should be discontinued. (35 vs 46%)*
Survey Results (con’t)
Adverse Events
- On-going side effects could be considered reasons to discontinue: loose stools (92%), N/V (85%), and unexplained syncope (54%)
- Weight loss and anorexia - > 5% IBW (1 to 6 months)
- Bradycardia < 60 beats / min (12%) < 50 beats / min (42%)
Others to consider
- Non-adherent, new onset seizures, exacerbation of COPD, muscle cramps, new sleep disturbance, emergence of worsening BDSP, pailliative care.
Practical Guidelines for Discontinuation
Ensure compliance and dose adjustments.
Concomitant medical conditions, such as delirium or depression, and the initiation of inappropriate drugs should be ruled out.
In the case of intolerance , switching to a second ChEI should not be tried before complete resolution of side-effects after discontinuation of the initial agent.*
The second ChEI can then be initiated at the usual starting dose and increased according to the recommended titration scheme, or titrate up more rapidly (two-week intervals) until the minimal therapeutic dose.
When considered for lack of benefit , switching ChEIs can be done overnight.
Switching for loss of benefit after taking the initial ChEI for several years is not suggested. Add Memantine.
Case Studies in ChEIs
Bordier (2006) – 7 cases of new-onset
bradycardia related syncope – 4 had
carotid sinus hypersensitivity and 3 sinus
node disease
Newby (2004) – one case of 2nd^ degree
and complete HB after 1 week
Brembilla-Perrot (2004) – atriaventricular
rhythm disturbances on galantamine
Walsh (2002) – Case report of QT
prolongation complicated by medical
comorbidity, electrolyte disturance and
polypharmacy
What can be learnt from studies?
Incidence is very low.
Rarely, they cause or unmask
parasympathetically mediated bradycardia except in significant overdose.
People with SSS or other cardiac conduction
defects may be at a theoretically greater risk
Before beginning treatment with an AChE
inhibitor, it is necessary to:
a. carry out an ECG
b. take a pulse check
c. take blood samples to check
serum electrolytes
d. monitor cardiac activity for 24
h continuously
e. measure blood pressure.
If a patient on an AChE inhibitor presents with syncope, one should:
a. investigate further
b. continue the drug
c. measure pulse and blood
pressure
d. consider restarting the drug after
a pacemaker has been fitted
e. change to a different AChE
inhibitor.
Cardiac conduction problems related
to AChE inhibitors: