Pharmacotherapy of Alzheimer's disease Introduction History Risk factors Pathophysiology Symptoms Diagnosis Non pharmacological treatment Drugs used in treatment of Alzheimer`s Recent advances Screening methods Summary References

1. PHARMACOTHERAPY FOR ALZHEIMER’S
DISEASE
HALL TICKET NUMBER -

2. CASE STUDY
A 75-year-old man was brought with a h/o misplacing
his daily need articles, forgets what he said few
minutes ago, is unable to perform simple calculations,
mixes up what happened today and what happened
yesterday, has poor control of emotions, but vision,
hearing and other sensations are well preserved.

3. LEARNING OBJECTIVES
 Introduction
 History
 Pathophysiology
 Pharmacotherapy
 Recent advances
 Summary

4. INTRODUCTION
 Alzheimer's disease (AD) is a progressive, neurodegenerative disorder in elderly (≥
60 years)
 Characterized by
 Memory loss (92%)
 Confusion (71%)
 Short attention span (63%)
Personality changes (31%)
 Prevalence – 46.8 million (worldwide)
 20% in individuals over 85
 China > U.S > India

5. Alzheimer`s Disease
TOM FEARS BETTY ROBINSON BILL QUACKENBUSH RONALD REAGAN
β

6. HISTORY
Alzheimer's disease was first described by
German Physician Dr. Alois Alzheimer in 1906
Alois Alzheimer Auguste Deter

7. Pathogenesis of Alzheimer’s Disease
 Amyloid beta (Aβ)
 Tau protein
 Progressive loss of cholinergic neurons
 Excitotoxic activation of glutamate via NMDA receptors neuronal death.
 Early onset
Trisomy 21
Mutation of gene for Presenilin-1
Abnormal allele, ε4, for the lipid-associated protein, ApoE

8. TREATMENT OF AD
• Donepezil
• Rivastigmine
• Galantamine
Cholinesterase
inhibitors
• MemantineNMDA Antagonist
• Antipsychotics
• Antidepressant
Treatment of
Neuropsychatric
Symptoms

9. CHOLINESTERASE INHIBITORS
* Competitive
inhibitor
* 4 - 12 mg BD
GALANTAMINE
• Non competitive
inhibitor
• 5-mg -10 mg
• Long acting
• Once daily doses
DONEPEZIL
Non competitive
inhibitor
oral(1.5-6 mg BD)
skin patch forms
RIVASTIGMINE

10. CHOLINESTERASE INHIBITORS
• Orally active
• Cerebroselective AChE inhibitor.
• Less toxic than Tacrine.
• Should be used with caution in patients receiving
drugs that inhibit CYP P450 enzymes.

11. Dual Mechanism of Action
Postsynaptic
nerve terminal
M receptor N receptor
Presynaptic nerve
terminal
Galantamine
 ACh and other
neurotransmitters
M receptor N receptor
ACh
• Choline
• Acetic acid
Galantamine
N = nicotinic
M = muscarinic
ACh = acetylcholine

12. NMDA receptor antagonists
5 mg OD  20 mg/day
Noncompetitive blockade
moderate-to-severe AD

13. Treatment of Behavioral Symptoms
Behavioral and psychiatric symptoms in dementia (BPSD)
SSRI:
• Citalopram
Atypical antipsychotics:
• Risperidone,
• Olanzapine,
• Quetiapine
for Agitation & Psychosis in AD
Benzodiazepine Occasional control of acute Agitation
Typical antipsychotic:
• Haloperidol
Aggression

14. CHOLINESTERASE
INHIBITORS
MEMANTINE
CURRENT
MODES OF
THERAPY

15. RECENT ADVANCES
 Gamma secretase inhibitor – Semagacestat [Withdrawn]
- Skin cancer, rash, hair discolouration
 Pyrintinol - 100-200 mg TDS - Disulphide bond connecting two pyridoxine
 Piracetam - 0.8-1.6 gm TDS PO - 1st Nootropic, Inhibit AChE
 Antioxidants – Curcumin, Gingko biloba, Green tea
 Vitamins - A, E, C, B12
 PPAR gamma agonist – Pioglitazone 15-30 mg
- Amyloid beta phagocytosis
 BACE – Verubecestat

16. SUMMARY
 AD - Most debilitating diseases affecting the old age.
 Pathology - Amyloid beta protein & Tau protein.
 No cure – Delay preogression
 Approved drugs – AChE & NMDA receptor inhibitors.

17. “Even though helpful
medication exists, there’s
still no cure,
and we have to keep
fighting
to find one.”
WORLD ALZHEIMER’S DAY
SEPTEMBER 21ST
THANK YOU...