SEMINAR ON PHARMACOTHERAPY OF ALZHEIMER’S DISEASE

FACILITATED BY:DR.RAJU KONERI SIRHOD of Pharmacology department

SUBMITTED BY:Dipankar acharjeeM.Pharmacy 1st yearDepartment pharmacology

1. INTRODUCTION2. ITEOLOGY3. SYMPTOMS4. STAGES OF DEVELOPMENT5. DIAGNOSIS6. PHARMACOTHERAPY

CONTENTS

Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. A neurodegenerative type of dementia, the disease starts mild and gets progressively worse.

INTRODUCTION:

Several competing hypotheses:

Amyloid hypothesis Tau hypothesis Cholinergic hypothesis Other neurotransmitter abnormilities. Genetic Environmental and other factor

ITEOLOGY

EARLY STAGE:-

oThis is considered as a mild/early stage and the duration period is 2-4 years.

oFrequent recent memory loss, particularly of recent conversations and events.

oDrastic personality changes may accompany functional decline.

oNeed reminders for daily activities and difficulties with sequencing impact driving early in this stage.

SYMPTOMS OF DEVELOPING A.D

Second stageoThis is considered as a middle/moderate

stage and the duration is 2-10 years.

oPotential to become lost in familiar settings, sleep disturbances, and mood or behavioral symptoms accelerate

oNearly 8O% of patients exhibit emotional and behavioral problems which are aggravated by stress and change.

Moderate stage

o Increased memory loss and confusion.

o Problems recognizing family and friends.

o Inability to learn new things.

o Difficulty carrying out tasks that involve multiple steps (such as getting dressed).

o Delusions and paranoia.

Last stageo This is considered as the severe stage and the

duration is 1-3 years.

o Confused about past and present. Loss of recognition of familiar people and places.

o Generally incapacitated with severe to total loss of verbal skills.

o Problems with swallowing, incontinence, and illness.

Stages of Alzheimer’s Disease

Mild (MMSE score 26–18)--------Patient has difficulty remembering recent events.

Ability to manage finances, prepare food, and carry out other household activities declines.

  Moderate (MMSE score 17–10)Patient requires assistance with activities of daily

living. Frequently disoriented with regard to time (date, year, season).

Severe (MMSE score 9–0)Patient loses ability to speak, walk, and feed self.

Incontinent of urine and feces. Requires care 24 hours a day, 7 days a week.

Alzheimer's disease is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions.

DIAGNOSIS OF ALZHEIMER’S DISEASE

Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single photon emission computer tomography (SPECT) or positron emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of dementia.

The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examined histologically.

Obesity High blood pressure Head trauma High cholesterol Being American!

Higher rates in Japanese-Americans than Japanese African-Americans than Africans

Depression Lower rates in highly educated

Beneficial consequences of learning and memory

RISK FACTORS

Cholinesterase inhibitors

increase the levels of acetylcholine in the brain, which plays a key role in memory and learning.

This kind of drug postpones the worsening of symptoms for 6 to 12 months in about half of the people who take it.

Cholinesterase inhibitors most commonly prescribed for mild to moderate Alzheimer's disease

Include Aricept (donepezil HCL), Exelon (rivastigmine), and Razadyne (galantamine).

Cholinesterase inhibitor(donepezil , revastigmine) Inhibits hydrolysis of Achetylcholine

Through reversible inhibition of cholinesterase

Increased level of Acetylcholine

MECHANISM OF ACTION

Exelon ( Rivastigmine )

Exelon is FDA approved for mild and moderate stages of the disease; it is also approved for the treatment of mild to moderate dementia due to Parkinson's disease.

Exelon is available as a capsule, liquid, and patch.

Mild to moderate gastrointestinal symptoms (nausea, vomiting, and diarrhea ).

Other cholinergic side effects are generally dose-related and include urinary incontinence, dizziness, headache, syncope, bradycardia, muscle weakness, salivation, and sweating .

ADVERSE REACTIONS

Glutamate is the major excitatory neurotransmitter in the cortex and hippocampus

Glutamate have been implicated as potential neurotoxins in AD.

If glutamate is allowed to remain in the synapse for extended periods of time, it can destroy nerve cells.

Memantine is the only (N-methyl-D-aspartate) NMDA antagonist currently available.

Memantine has been studied in patients with moderate and severe AD as monotherapy and in combination with donepezil

ANTIGLUTAMATERGIC THERAPY

Memantine

Antagonize NMDA receptor

Decreases activity of glutamate in synapses

Reduce risk of AD

MECHANISM OF ACTION

Constipation, Confusion. Dizziness.Headache. Hallucinations. Coughing Hypertension

ADVERSE REACTIONS

Estrogen replacement has been studied extensively for the treatment and prevention for AD.

Antiinflammatory Agents Epidemiologic studies suggest a protective effect against AD in patients who have taken NSAID’s. Treatment for less than 2 years is associated with a lower relative risk of AD; however, longer treatment duration lowered this risk further

OTHER POTENTIAL TREATMENT APPROACHES

Lipid-Lowering Agents(LOVASTATIN) Interest in the potential protective effects in AD patients of lipid-lowering agents.

Vitamin E(antioxidant) is a adjunctive treatment for AD patients. Ginkgo Biloba Ginkgo is one of the most popular dietary supplements used in AD. Hypothesized mechanisms of action in AD include increasing blood flow, decreasing the viscosity of blood, antagonizing platelet activating factor receptors, increasing tolerance to anoxia, inhibiting monoamine oxidase, antiinfective properties, and preventing the damage of membranes caused by free radicals.

Ginkgo biloba may also inhibit catecholamine-O-methyl transferase.

Side effects are rare and usually mild, and may include nausea, vomiting, diarrhea, headaches, dizziness, palpitations, restlessness, and weakness. Because EGb also has a potent antiplatelet effect

MEDICINES USED TO TREAT A.D AND ITS SYMPTOMS

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