AD & Dementia & HD Flashcards
protein tau
neural thread protein, which binds and helps stabilize microtubules which form the cell transport and skeleton system
Deposition of extracellular amyloid plaques:
- •Most specific, change in the brain of patients with AD.
- •It is not known whether amyloid plaques cause AD or result from it.
- •But, the number of senile plaques seems to correlate with the severity of disease.
Risk Factors for AD
- Presenilin 1 & 2
- APP genes
- APOe4
AD treatment
- Acetylcholinesterase Inhibitors
- Tacrine (Cognex)
- Donepezil ( Aricept)
- Rivastigmine (exelon)
- Galantamine ( Reminyl)
- NMDA Receptor Antagonist
- Memantine ( Namenda)
AChEI’s
- MOA: enhance cholinertic activity in Dementia patients by inhibiting hydrolysis of acetylcholine through reversible inhibition of cholinesterase
- SE: Nausea, vomitting, anorexia, flatulence, loose stools, diarrhea and abdominal cramping, vivid dreams, insomnia, cadiac arrythmia
- CI: Severe cardiac disease, recurrent syncope, uncontrolled epilepsy, active PUD
- Avoid combining anticholinergic medications with these inhibitors
- Abrupt discontinuation leads to worsening behaviors
Tacrine ( COGNEX)
- First Drug
- Hepatotoxicity (QID)
- No longer avai
*
Donepezil ( Aricept )
- Longest half life
- Specific & reversible MOA
- mild, moderate & severe AD
Galantamine ( Reminyl)
- Short Half life ( 7 hrs)
- Selective, competitive, reversible MOA
- Alloesteric potentiating ligang at nocotinic receptors ( enhances action of Ach)
Rivastigmine ( Exelon)
- Shortest half life ( 1.5 hours)
- BID oral, QD transdermal
- Inhibits butyryl- & acetylcholinesterase
- Pseudoinhibitor : forms a labile carbamoylate complex with the enzymes
- indicated in AD & dementia associate with PD
Memantine (Namenda)
- Block glutamate (exci. )
- Indicated in moderate to severe AD
- Not metabolized by the liver and does not inhibit CYP 450 ⇒ safe for polypharmacy
- Excreted unchanged in urine (half life 60-80 hours)
HD Risk Factors
- Autosomal Dominant Familial Disease
- Chromosome 4, where large number of triplet repeats (CAG) are noted
- protein htt has a long segment of glutamine AA ( coded by CAG triplet repeat)
HD symptoms
A.Hyperkinetic Motor features of HD:
i)Abnormal involuntary movements of arms & legs (chorea, dystonia, ballism, myoclonus & tics) -> Huntington chorea
B.Non-Motor features of HD:
i) Behavioral disturbance,
ii) Cognitive dysfunction.
iii) psychiatric disease
C.HypokineticMotorfeatures: (Dystonia,bradykinesia&mutism)&dementia->predominatesinadvanceddisease.
Tetrabenazine(TBZ) (Xenazine®)
TBZ is a dopamine-depleting agent.
- TBZ reversibly inhibits the central vesicular monoamine transporter type 2.
- TBZ more selectively depletes dopamine than norepinephrine
-Specific side effects & Contra-indications (CI):
- Drowsiness,somnolence,insomnia,oragitation.
- Akathisia&hyperkinesia.
- Dizziness,GIDistress.
- Fatigue,orparkinsonism
- AllpatientstakingTBZneedtobemonitoredforsignsofdepressionandsuicidalideation
Other Pharmacological Treatment Options for HD
- Dopamine antagonists (neuroleptics):
- -Specific side effects & CIs:
- Tardivedyskinesia(higherriskwithTypicalneuroleptics).
- Apathyandakathisia.
- Amantadine: (NMDA-antagonist)
- -Specific side effects & CIs:
•Mayincreaseirritability&aggressiveness
- Benzodiazepines: (enhances the action of GABA at the GABAAreceptor,)
- -Specific side effects & CIs:
•Sedation becomes a potential adverse effect.
- Riluzole (Retards striatal glutamate release) (Rilutek®and Teglutik®)
- Is used to treat amyotrophic lateral sclerosis.
Pharmacological Treatment Options for Parkinsonism
For patients with the akineticform of HD (Westphalvariant):
- Antiparkinsonian medications, such as: levodopa, dopamine agonists, and amantadine, may be beneficial.
- Botulinum toxin injections:
- Can also be considered for focal dystonia associated with HD, of both typical presentation & Westphalvariant.
General Considerations when treating chorea pharmacologically
