Pharmacology of Alzheimer's Disease Cheat Sheet by Bailey_Rickett

It is a prominent part of Alzhei­mer's disease.

Dementia gets progre­ssively worse.

Antips­ych­otics

Buspirone

The hippoc­ampus is respon­sible for spacial and recent memory. This is where Alzhei­mer's starts.

Indica­tions: better for mild cognitive impair­ment, you must have cholin­ergic neurons left. NO disease modifying effects seen

Contra­ind­ica­tions: Pregnancy, liver disease, peptic ulcer

Rule of Thirds: 1/3 of patients will improve on these, 1/3 of patients will stabilize (slow progre­ssion tempor­arily), 1/3 of patients will experience no improv­ement.

Galant­amine (Razad­yne): Tablet (Razad­yne), ER capsule (Razadyne ER), oral soultion

Indica­tions: used for anxiety and mild/m­oderate agitation

Well tolerated.

Has addictive potential.

Vascular dementia- this type of dementia is caused by damage to the vessels that supply blood to you brain. Is caused by athero­scl­erosis in the carotid arteries, and other arteries serving the brain.

Fronto­tem­poral dementia- atrophy of neurons that die off in the fronto­tem­poral region.

It occurs in up to 20% of patients over 85 (5th leading cause of death 65+)

There is also an inflam­matory process.

The alpha and beta tubulin dimers are wrapped around in a spiral to hold the microt­ubule together. Normally the tau protein holds microt­ubules together. But the hyperp­hos­pho­ryl­ation of tau causes a disass­oci­ation of the microt­ubules, forming a "­clu­mp" that tangles.

Increased glutamate activity may also play a role (NMDA receptor)

This typically starts out in the hippoc­ampus, it spreads out from there.

Decreasing glutamate is another focus of therapy due to excess glutamate excitation being present in this disease.

MOA: by blocking NMDA receptor, decreases the activity of glutamate

Formul­ation: comes in a titration pak until goal dose achieved

Contra­ind­ica­tions: Gastric ulcers, lung disease, heart disease, kidney disease.

Other notes: has a long half life 60-80 hours, 100% absorbed orally. Memantine in combin­ation therapy with a cholin­est­erase inhibitor is recomm­ended in moderate to severe disease (efficacy not shown in mild disease) Memantine comes in combo with Donepezil (Namza­ric)**

Indica­tions: Used for agitation in Alzhei­mer's disease, FDA approved for pseudo­bulbar effects (uncon­trolled laughi­ng/­crying due to neurol­ogical condition)

They start having: learning problems, trouble with problem solving, poor judgement making, trouble commun­ica­ting, depression and mood swings

Finally there is a loss of self care.

Lewy bodies are made up of brain proteins that are misfolded and forms aggreg­ates. The protein aggregates causes cell death.

Quetiapine and Clozapine are used off-label. Can also use Achase inhibi­tors.

Lewy Body vs. Alzhei­mer's: lewy body has reduces DA uptake vs Alzhei­mer's. Lewy body has less temporal lobe atrophy it can be confirmed on MRI. Lewy body has less occipital lobe glucose metabolism per PET scan. (this may be the reason for increased visual halluc­ina­tions in Lewy body because of occipital lobe hypome­tab­olism)

It is involved in memory, motiva­tion, arousal, and attention.

1/3 of cases are inherited.

MOA: a monoclonal antibody against amyloid beta plaque

Formul­ation: given as a 1 hour infusion every 4 weeks

Consid­era­tions: $56,000, serious side effects, benefits unknown. Has been shown to reduce plaques.

Only used in patients with severe agitation or psychosis that are distre­ssing to the patients or makes them act in a way that they are dangerous to themselves or others. This is a last resort.

There are not a lot of benefit seen in these drugs in the popula­tions, LOTS of side effects. Most evidence with aripip­razole, olanza­pine, risper­idone. Halope­ridol is reserved for emergency use.

Labeled waring for antips­ychotic use in patients with dementia- increased risk of death and cerebr­ova­scular events

Donepezil or Rivast­igmine recomm­ended as first line options.

Last line: antips­ych­otics- unlikely effective and may worsen motor symptoms

Nuplazid (pimav­ans­erin): FDA approved for halluc­ina­tio­ns/­del­usions associated with Parkin­son's disease (positive diseases)

It blocks the 5HT2A and C receptors, NOT DA receptors so less effects on motor symptoms. High risk of side effects or death (almost 10%). QT prolon­gation. Also helps with anxiety.