Module 4.4.1 (Pharmacology of Drugs for Alzheimers)

Question 1

What is alzheimers disease?

Answer 1

Alzheimer’s disease (AD) is a progressive dementia

• It results from the destruction of cholinergic and other neurons
• Alzheimer’s disease is associated with brain shrinkage and loss of neurons in many brain regions but especially the hippocampus and basal forebrain. The loss of cholinergic neurons in the hippocampus and frontal cortex is a feature of the disease and is thought to underlie the cognitive deficit and loss of short-term memory that occur.

> Extracellular amyloid plaques, consisting of amorphous extracellular deposits of betaamyloid protein (known as (Aβ)

> Interneuronal neurofibrillary tangles comprising filaments of a phosphorylated form of a microtubule associated protein (tau)

Question 2

what are the FOUR drugs used in alzheimers disease?

Answer 2

• Donepezil
• Galantamine
• Rivastigmine
• Memantine

Question 3

What are THREE anticholinesterases used in alzheimers? What is the MOA

Answer 3

1. Donepezil
2. Galantamine
3. Rivastigmine

Mechanism of action

• ↓ Breakdown of ACh reducing the apparent deficiency of cholinergic neurotransmitter activity

Question 4

AE (CI) of Donepezil „ Galantamine „ Rivastigmine?

Answer 4

Common

• GI effects - N, V, D, anorexia, abdominal pain, dyspepsia
• Insomnia „
• Vivid dreams „
• Urinary incontinence „
• ↑ sweating „
• Rivastigmine – skin reaction to patch at application site

Infrequent

• Bradycardia „
• Heart block „
• Seizures „
• GI haemorrhage

Question 5

What are precuations and contraindications for anticholinesterases?

Answer 5

GI or uretic obstruction

Active peptic ulcer disease

Drugs with anticholinergic effects antagonize therapeutic effect

Question 6

What are some drug interactions for anticholinesterases?

Answer 6

Anticholinesterases can cause bradycardia – interact with other drugs that cause bradycardia e.g. diltiazem

Question 7

What is the MOA of memantine?

Answer 7

AD is thought to be associated with excess glutamate

• Memantine acts as a N-methyl-D-aspartate (NMDA) antagonist which may reduce glutamate-induced neuronal degradation.

Question 8

AE (CIR) of memantine?

Answer 8

Common

• Headache, insomnia, drowsiness, confusion, dizziness, agitation, hallucinations

Infrequent

• Vomiting, anxiety

Rare’

• Seizures, bradycardia, renal failure, HF

Question 9

What is a contraindication for memantine?

Answer 9

Hx of seizures