Dementia_Rajib

DementiaA group of thinking and social symptoms that

interferes with daily functioning.

Presented By : Rajib Barua

Key points :Impairment of multiple domains of cognitive functions:

Memory impairment – (Must)1. New material learning2. Forget previous learning

With at least one of the following cognitive disturbance:1. Aphasia : Language disturbance2. Apraxia : Impaired ability to carry out motor activities despit

intact motor function3. Agnosia: Failure to recognize/ identify familiar object

despite intact sensory function4. Disturbance in executive functions

Significant impairment of social & occupational functioning decline from previous level


Types Of Dementia


The global “prevalence” of dementia

• 46.8 million people worldwide are living with dementia in 2015.

• This number will almost double every 20 years.

• Reaching 74.7 million in 2030 and 131.5 million in 2050.

• These new estimates are 12-13% higher than those made for the World Alzheimer Report 2009.

Ref : www.alz.co.uk/worldreport2015


“Prevalence” in Bangladesh

According to the study of Alzheimer Society of Bangladesh :

• There are about 4,60,000 people with dementia in Bangladesh in 2015.

• While the number will rise to 8,34,000 in 2030 and 21,93,000 in 2050 respectively.

Ref : http://alzheimerbd.com/dementia-statistics/


Risk Factors


Alzheimer’s Dementia (AD)

Alzheimer's is the most common form of dementia,

a general term for memory loss and other intellectual abilities serious enough to

interfere with daily life. Alzheimer's disease accounts

for 60 to 80 percent of dementia cases.

Ref: http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp


1. Recent memory loss that affects job skills.

2. Difficulty performing familiar tasks.3. Problem with language.4. Disorientation of time and place.5. Poor or decreased judgment.6. Problem with abstract thinking.7. Misplacing things.8. Changes in personality.9. Changes in mood or behavior.10. Loss of initiative.

“10 warning signs” ofAlzheimer’s Disease


Memory, Language & Judgment centreof human brain.


Healthy brainVs

Alzheimer's brain


What a normal brain loses in AD?

The cholinergic deficit in AD underlies the clinical symptom :

Progressive loss of Cholinergic neurons

Progressive decrease in available Ach*.

Impairment in ADL*, behavior & cognition.

*Ach = Acetylcholine*ADL = Activity of daily living


Strategies for Medical Treatmentof Dementia

• Prevention of disease• Delay of onset• Slow rate of progression• Treat primary symptoms (cognitive)• Treat secondary symptoms (behavioural)


Management of Dementia

• Supportive treatment (Non-pharmacological)

• Treatment of complications& co-morbidities

• Symptomatic treatment


Supportive treatment(Non-pharmacological)

• Advice, support and a sensible explanation are important for the caregiver.

• Reduce excessive stimulation.• Divide tasks into small, simple

steps; allow ample time.• Eliminate caffeine and alcohol.• Take their concern seriously.


Treatment of complications and co-morbidities

Like AD other diseases rise with advancing age :-

• Hypertension• Diabetes mellitus• IHD• Heart failure• Arthritis• Infections


Symptomatic treatment

Symptomatic treatment of mild to moderate forms of Alzheimer's dementia is “Cholinesterase inhibitor”.

• It increases acetylcholine in the brain, &• Slowing down of the disease's progression.


Overview of AChE inhibitors

– Obsolete because, very short lasting (half life 30 mints) necessitating frequent oral administration

– Potentially serious dose-limiting S/E

– Again S/E; 50% of the patients treated with tacrine discontinued treatment because of adverse events especially hepatotoxicity.

Oldest (probably most extensively tested): “Physostigmine”

In the past : “Tacrine”


Overview of AChE inhibitors(cont’d.)

– Launched in the USA in January 1997 and in the UK in March 1997

– Modest benefits in terms of cognition– Most common S/E are similar to those seen with tacrine

– Launched in the USA in April 2000; received approval for use in 60 countries including all member states of EU and USA

– Improvements were seen in cognition, ADL & severity of dementia

– Dose of 6-12 mg/day– Lower risk of adverse effects

Recent past : “Donepezil”

Recent : “Rivastigmine”


What is “Rivastigmine” ?

• Rivastigmine is Acetyl Cholinesterase (AChE) as well as Butyl Cholinesterase (BChE) inhibitor.

• Rivastigmine treats Alzheimer’s disease as well as other dementias.


Cholinergic function in AD:from pathology to therapy – summary

• In AD brains BuChE activity increases significantly; BuChE as well as AChE regulates ACh levels.

• Dual AChE/BuChE inhibition may result in cholinergic function being effectively maintained along the continuum of AD.

• Rivastigmine is a dual AChE/BuChE inhibitor.

• Inhibition of CSF AChE and BuChE with Rivastigmine correlates with clinical benefits in AD patients.

Ref : Perry et al.,1978, 1984;Giacobini, 1997, Cutler et al; 1998, Costa et al., 1999


What is Exelon?• Exelon is rivastigmine.• Exelon is Acetyl Cholinesterase (AChE) as well as (BChE) inhibitor.• Exelon treats Alzheimer’s dementia as well as other dementias.

Rivastigmine Brand :-

HISTORY : Rivastigmine was developed by Marta Weinstock-Rosin of the

Department of Pharmacology at the Hebrew University of Jerusalem and sold to Novartis by Yissum for commercial development. It is a semi-synthetic derivative of physostigmine.

It has been available in capsule and liquid formulations since 1997. In 2006, it became the first product approved globally for the

treatment of mild to moderate dementia associated with Parkinson's disease and in 2007 the rivastigmine transdermal patch became the first

patch treatment for dementia.

Ref : https://en.wikipedia.org/wiki/RivastigminePresented By : Rajib Barua

Available Dosage Forms

CapsuleCapsule Transdermal PatchTransdermal Patch

1.5 mg =

3.0 mg =

4.5 mg =

6.0 mg =

Exelon Patch 5 cm2 = 4.6 mg/24 h

Exelon Patch 10 cm2=9.5 mg/24 h


Aim to achieve maximum tolerated individual dose

Start with 1.5mg, BID.

Increase by 3mg/day at intervals of minimum 02 weeks, up to maximum 12mg/day.

Omit dose(s) in response to adverse events.

Reduce dose if problems persist.

Exelon Capsule Dosage Guideline


Exelon Patch Dosage Guideline

1. “Exelon Patch is once daily”.

2. Target dose is Exelon Patch-10 (9.5mg/ 24h).

3. Only one patch should be worn at a time.

4. Patch should be replaced by a new one after 24 hours.

5. It is recommended that location for new patch be rotated.


Exelon Patch: How Delicately it is made

Coloured backing layer

Acrylic (drug) matrix

Silicone (adhesive) matrix

Release liner (peeled off just before patch application)

Designed with new generation matrix technology


Exelon Patch: How drug is Delivered Across the Skin

Epidermis

PatchDermis

Subcutis

Blood Vessels


Dosage Guideline for newly diagnosed patient

Exelon 4.6 mg/24 h

Patch

Exelon 9.5 mg/24 h

Patch

Starting dose

Target dose

4 weeks

One-step dose increase

Exelon Patch-5 Exelon Patch-10


Algorithm for Starting or Switching to Exelon Patch

< 6 mg/day*Start on Exelon

4.6 mg/24 hours patch

4 weeks

Switch directly to target dose Exelon 9.5 mg/24 hours patch

Is the patient already receiving oral Exelon?

NO YES

What dose of oral Exelon is the patient receiving?

Increase to Exelon 9.5 mg/24 hours patch

6–12 mg/day*


Smooth and continuous drug delivery over 24 hours

Graphic representation (not ‘real’ data) Imbimbo 2001

Increased side effects

Poor activity

“Optimal therapeutic

window”

Dru

g le

vel i

n th

e bl

ood

Peak

Oral Dose

Trough

Patch Time


Exelon Patch: How to apply

1. The patch should be removed from the pouch,

2. Remove one side of the protective liner,

3. Place the patch at the selected application site,

4. Remove the other side of the protective liner,

5. Press the patch firmly into place for 20–30 seconds.


Exelon Patch: Where to apply• Exelon Patch can be applied to:

– Upper or lower back– Upper arm– Chest

• When replacing the patch, the new patch should be applied to a different spot of skin.

– Do not use the same spot more than once every 14 days

• Normal daily activities, such as bathing are permitted.


Advantage of Exelon Patch


1. Easy to apply.2. Reduce patients’ pill burden.3. Reduce care giver’s distress.4. Achieve optimal therapeutic dose.5. Dramatically improved GI Tolerability.6. Ensures Continuous & Consistent drug

delivery that results fewer side effects & Improved efficacy.

Conclusion : The time to act


• Promoting a dementia-friendly society.• National public health and social care priority.• Improving public and professional attitudes and

understanding of dementia.• Investing to improve care and services for

dementia affected people.• Priority given to dementia in the

public health research agenda.

““Love them while they are with you”Love them while they are with you”

Dementia_Rajib

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