Alzheimer’s Disease

This is the presentation for B. Pharm. students under subject Medicinal Chemistry.

1. ALZHEIMER’S DISEASE Ms. Pradnya Gondane Assistant Professor Gurunanak College of Pharmacy Nagpur

2. LEARNING OBJECTIVES After watching this video, you will be able to Understand the disease. Apply the basic pharmacological knowledge in the treatment of disease. Understand the chemistry of drugs with respect to their pharmacological activity.

3. INTRODUCTION Alzheimer's disease (AD), also known as Senile Dementia of the Alzheimer Type (SDAT) or simply Alzheimer’ s is the most common form of dementia . This incurable, degenerative, terminal disease was first described by a German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him.

4. INTRODUCTION Alzheimer's disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of memory eventually by disturbances in reasoning, planning, language, and perception. Generally, it is diagnosed in people over 65 years of age , although the less-prevalent early onset of Alzheimer’s can occur much earlier.

5. MANISFESTATIONS AND CAUSES Loss of memory. Senile dementia. Intraneuronal neurofibrillary tangle formation. Genetic patters. Beta-amyloid plague development. The role of estrogen in the brain. Inflammatory and oxidative stress processes.

6. AMYLOID PLAQUES

7. SIGNS AND SYMPTOMS MILD Disorientation to date Impaired recall Diminished insight Irritability MODERATE Increased disorientation Difficulties with comprehension Poor judgments Aggression

8. SIGNS AND SYMPTOMS. Restlessness Psychosis Sleep disturbances SEVERE Unable to use language appropriately Urinary and fecal incontinence

9. COMPLICATIONS Pneumonia Malnutrition and dehydration Aspiration Injury from wandering, violent behavior , or unsupervised activity.

10. REFLECTION SPOT At what age Alzehemier’s Disease usually begins? Is it genetically transmitted?

11. TREATMENT Behavioral therapy. Nonsteroidal anti-inflammatory drugs Cholesterol lowering drugs Estrogen NMDA antagonists like Memantine Cholinesterase inhibitors such as Tacrine, Donepezil,Galantamine,Rivastigmine

12. DRUGS USED IN AD NMDA Antagonist Glutamate is the principal excitatory NT in brain which acts on post synaptic NMDA receptors. Glutaminergic overstimulation may result in neuronal damage ( excitotoxicity ) implicates in dementia. Eg . Memantine

13. DRUGS USED IN AD MEMANTINE (COGNEX) It is a novel NMDA receptor antagonist , and has been shown to be moderately clinically efficacious . It acts on the glutaminergic system by blocking NMDA glutamate receptors.

14. DRUGS USED IN AD AchE inhibitors ( AchEIs ) These agents prevent the breakdown of Ach in brain. Ach plays a major role in memory & learning ; higher level in the brain help nerve cell communicate more efficiently. Eg . Donzepil , galantamine and rivastigmine .

15. DRUGS USED IN AD DONEPEZIL (ARICEPT) Acetylcholinesterase inhibitor It also used to increase cortical Ach

16. DRUGS USED IN AD GALANTAMINE Used in the symptomatic treatment of polio Was later developed into an Alzheimer medication. It also stimulate N-receptors to release more Ach in the brain .

17. DRUGS USED IN AD RIVASTIGMINE (ELEXON) It is used for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson’s disease.

18. Newer Drugs Caprylidene ( axona ) (1-Octyne) MOA :- Brain-imaging scans of older adults & those with Alzheimer’s disease reveal a dramatically decreases uptake of glucose , the brain’s preferred source of energy. It is being developed to replace these depleted glucose levels to treat age-associated memory impairment ( AAMI ) & Alzheimer's disease. Caprylic triglyceride is converted by the liver into ketone bodies , which provide an alternative fuel for brain cells . Ketone bodies are naturally occurring compounds that are mainly by the liver from fatty acids during periods of extended fasting. The formed ketone bodies have the property to protect neuron cells.

19. REFERENCES Textbook of Medicial Chemistry by Algarswamy Volume I Foye’s Principle of Medicinal Chemistry Willson & Giswold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry