Pharm: Dementia Meds Flashcards
Donepezil
- tertiary uncharged AChE inhibitor, for dementia
PK: rapid absorption, once dailiy dosing, CYP metabolism
USE: mild to moderate AD, severe AD dementia
ADR’s:
- GI: nausea, vomiting, diarrhea
- urinary incontinence, vivid dreams**, bradycardia, syncope
types of AChE inhibitors
- Alcohol (edrophonium) - noncovalent, reversible, short lived binding - quaternary charged
- Carbamates - have tertiary and quaternary ammonium groups, can be positively charged or neutral (neostigmine, pryidostigmine, physostigmine, carbaryl)
- Organophosphates: charge neutral, highly lipid soluble –> CNS toxicity, binding is covalent and irreversible (echothiophate, sarin gas)
* quaternary/charged AChE inhibitors are insoluble in lipids and have poor absorption w/ NO CNS distribution ex - neo, pyrido, edrophonium, echothiophate, ambenoium - act mostly at NMJ
- tertiary/uncharged AChE inhibitors are well absorbed w/ CNS distribution ex - physo, donepezil, galntamine, rivastigmine, tacrine
- well absorbed after oral administration
systemic effects of AChE inhibitors?
PS innervation often dominates:
eye- miosis
heart- net CV effects: modest bradycardia, fall in CO, increase in BP (toxic doses can cause decreased CO and hypotension!)
NMJ - increased strength of contraction, fibrillation of mm. fibers, fasciculations when concnetration too high
- sustained elevated doses can result in depolarizing NM blockade
succinylcholine + AChE inhibitor?
may increase serum concnetration of succinylcholine- prolonging NM blockade
beta blockers + AChE inhibitor?
enhanced bradycardia
systemic corticosteroids + AChE inhibitor?
enhanced mm. weakness seen in pts. w/ MG
Pralidoxime
Cholinesterase Re-activator - used to tx AChE inhibitor toxicity!
systemic corticosteroids + AChE inhibitor?
enhanced mm. weakness seen in pts. w/ MG
AChE intoxication?
miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea, mm. fasciculations
CNS toxicity: confusion, ataxia, convulsions, coma, resp. paralysis
antidote? atropine + pralidoxime (to regenerate AChE)
which approved for tx of parkinsons related dementia?
rivastigmine
Galantamine
- tertiary uncharged AChE inhibitor, for dementia
PK: rapid abosprtion, multiple daily doses, CYP metabolism
USE: mild to moderate AD
ADR’s:
- GI - nausea, vomiting, diarrhea, anorexia
- dizziness, w/l, bradycardia, syncope
- depression, fatigue, somnolence
Rivastigmine
- tertiary, uncharged AChE inhibitor, for dementia
PK: oral form rapidly absorbed, metabolized via esterase hydrolysis
USE: mild/moderate AD, severe AD dementia (transdermal patch), Parkinsons related dementia!!!
ADR’s: high incidence of nausea and vomiting, diarrhea
- GI effects much less w/ transdermal patch!
- bradycardia, syncope
Tacrine
- tertiary uncharged AChE inhibitor, for dementia
Memantine
MOA: antagonist of NMDA glutamate receptors (glutamate overstimulation might results in neuronal cell death in AD)
- Under normal physiologic conditions, the (unstimulated) NMDA receptor ion channel is blocked by magnesium ions, which are displaced after agonist-induced depolarization
- Pathologic or excessive receptor activation, as postulated to occur during AD, prevents magnesium from reentering and blocking the channel pore resulting in a chronically open state and excessive calcium influx
- Memantine binds intra-pore Mg site, w/ longer timing, thus functions as a receptor block only under conditions of excessive stimulation
- does not affect normal neurotransmission
PK: t1/2 is 60-80 hours, excreted in urine
USE: moderate to severe AD
ADR’s: usually well tolerated; fewer side effects than cholinergic medications
- Dizziness is the most common side effect; confusion and hallucinations are reported to occur at a low frequency; may increase agitation and delusional behaviors in some patients
