2. Pharmacology of Dementia

Question 1

Therapeutic uses of agents that stimulate AChRs are for diseases of the eye, GI and urinary tracts, NMJ, the heart and alzheimers disease. Pts with progressive dementia of the alzheimer type have a def of intact cholingeric neurons, pts with dementia assoc w parkinson disease also benefit from AChE inhibitors, the amount of benefit is modest and does NOT prevent?

Answer 1

Disease progression

Question 2

Pts w alzheimers disease have reduced cerebral content of choline acetyl transferase which leads to a decrease in acetylcholine synthesis and impaired cortical cholingeric function. Cholinesterase inhibitors increase cholinergic transmission by inhibiting cholinesterase at the?

Answer 2

synaptic cleft- allowing symptomatic benefit

Question 3

Cholinesterase inhibitors and Memantine are the only symptomatic medications for cognition and global functioning in pts with dementia. They target the acetylcholine deficit arising from loss of neurons in the nucleus basalis of meynert and its?

Answer 3

projections in patients with dementia

***SYMPTOMATIC relief only… not neuroprotective/ does not alter underlying disease trajectory

Question 4

Degree of expected benefit is modest, and therapy should not be continued indefinitely in patients who do not appear to be benefiting or have significant side effects. Three cholinesterase inhibitors are used, including donepezil, galantamine, and?

Answer 4

Rivastigmine

Question 5

Donepezil is availible as one/day tablet and once daily disintegrating sublingual tabelt, galantamine is a 2x daily tablet or solution and extended release once a day capsule and rivastigmine comes as 2x/day capsule or solution, and or a 24 hour?

Answer 5

Transdermal Patch*

Question 6

Cholinesterase inhibitors enhance vagal tone and are contraindicated in patients with baseline bradycardia or known cardiac conduction system disease due to syncope, falls and fractures, use with caution with any drugs that induce bradycardia or alter AV nodal conduction. Which drug should NOT be used in pts w end stage kidney disease or severe hepatic impairment?

Answer 6

Galantamine

Question 7

What drug requires dose adjustments for hepatic impairment and low body weight ? (NOTE**: all can cause weight loss and decreased body weight- make sure to monitor and adjust dosing)

Answer 7

Rivastigmine Patch

Question 8

Donepezil is the oldest Cholinesterase inhibitor still in use and remains preferred and widely prescribed due to its once daily, indicated for tx of Alzheimers dementia, efficacy demonstrated in pts with mild mod and severe AD. Cholinesterase inhibitors are likely to exaggerate succinylcholine type muscle relaxation during anesthesia and also may have vagotonic effects on the sinoatrial and AV nodes manifesting as? (2)

Answer 8

bradycardia or heart block

Question 9

The MC adverse reactions in clinical studies of Aricept (Donepezil) are nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue and?**

Answer 9

Anorexia * important to monitor weight and adjust dosing*

Question 10

Galantamine is a Cholinesterase inhibitor indicated for mild to mod alzheimers dementia, it can cause serious skin reactions, same SE of cardiac conduction, active or occult GI bleeding is seen, may cause bladder outflow obstruction, may cause breathing problems in patients with?

Answer 10

Severe asthma or COPD

Question 11

Galantamine has MC SE (>5% of the time) including nausea, vomiting, diarrhea (all Cholinesterase inhibitors cause these) along with dizziness, headache, decreased appetite and?

Answer 11

Weight decrease

Question 12

Rivastigmine is used for mild to moderate alzheimer dementia AND* mild to mod dementia associated with parkinsons disease, AND it is a transdermal patch. SE include nausea and vomiting which becomes more significant at higher doses, what should be monitored especially during patch treatment?

Answer 12

Weight*

if pt forgets to take dosing- titrate as prescribed and REINITIATE at the LOWEST* dose

Question 13

The following are what kind of drugs used (?) for dementia?
Ambenonium
Echothiophate
Edrophonium
Neostigmine
Physostigmine
Pyridostigmine

Answer 13

Other Cholinesterase inhibitors with INC adverse effects because they have less specific actions

Question 14

There are also antimuscarinic meds such as atropine and cholinesterase reactivators such as pralidoxime. Atropine is used in combo with maintenance of vital signs (respirations) and decontamination, it is ineffective against peripheral neuromuscular stimulation (nAChRs), so to regenerate AChE at the NMJ cholinesterase regenerators can be administered, such as?

Answer 14

Pralidoxime, they regenerate AChE enzyme by removing the phosphorus group from the active site of the enzyme

Question 15

What drug has a MOA as an antagonist of the NmethylDasparatate (NMDA) type of glutamate receptor (glutamate may contribute to path of Alz disease by overstimulating glutamate receptors), which binds to the intra-pore magnesium site - functioning as an effective receptor blocker only under conditions of excessive stimulation?

Answer 15

Memantine (fewer SE than cholinergic meds)

(note: normal unstimulated NMDA receptor ion channel is blocked by magnesium ioins, which are displaced after agonist induce depolarization)

Question 16

What is the only agent listed for mild dementia and whose drug delivery is by a patch matrix formulation?

Answer 16

Rivastigmine

Question 17

What drug is approved for use to treat dementia associated with alzheimers or parkinsons disease, the remaining drugs are NOT FDA approved to treat dementia assocaited with parkinson’s disease?

Answer 17

Rivastigmine