Pharmaco

20, others likely

• 1 million Americans
• •Neurodegenerative disorder

• –Loss
• of dopaminergic neurons in Basal Ganglion

• –Decreased
• dopamine

• –Movement
• requires balance between dopamine and ACh

• •Rigidity,
• tremor, instability, bradykinesia…akinesia

•Therapeutic goal

• –Improve
• activities of daily living (ADL)

• –Drug
• selection and dosages are determined by ADL performance

•Catecholamine

–Must be given IV

–Very short half-life

–

–Can’t cross blood brain barrier

–Only 2% gets into brain

•Need active transport

–Metabolized to dopamine in the brain

–Initially highly effective, then diminish over time

–Wearing off-near dose time-(CR)

–On/off-at any time maybe r/t protein

•Adverse reactions

•N/V, dyskinesias, dysrhythmias, hypotension

•20% develop psychosis-clozapine is best choice

•Contraindicated


    •malignant melanoma-can activate                  neoplasm

    •MAO inhibitors-hypertensive crisis

Taking up to 10 days off treatment can increase drug effectiveness.

But it’s no picnic.

Levodopa  +  Carbidopa

• –Blocksthe metabolizing of levodopa to dopamine in the gut 
• –Increaseslevodopa in the brain
• –Decreasesdopamine metabolism in periphery, so decreases cardiovascular effects
• –Abnormalmovements and psychoses may occur sooner

•Increase activation of dopamine receptors

•Less effective than dopamine

–Best for mild symptoms

–Not affected by proteins

•Adverse effects: hallucinations, sedation, postural hypotension

• Promote activation of dopamine receptors
•                                     •Selegiline/Carbex

•Prevention of dopamine degradation

• •Promotion of dopamine release, inhibits  reuptake              
•              •Amantadine/Symmetrel–Anti-viral

• •Direct activation of dopamine receptors
•                                     •Ropinorole/Requip

Prevent activation of cholinergic receptors

•Benztropine (Cogentin)



•Blockade of cholinergic receptors

•Decrease tremors and rigidity, not bradykinesias

•Side effects:

• limbic system
• memory, emotion, motivation  
• spatial navigation

5.1 million Americans

•Degeneration of cholinergic neurons

–neuritic plaques, neurofibrillary tangles

•Progressive memory loss

•Neuropsychiatric symptoms

•Neuromotor decline

•Prognosis-4-8 years

•10,000 die annually

–Mild to moderate symptoms

–Prevent breakdown of Ach

•Improve availability

•Only 20-30% of patients respond



–Donepezil (Aricept)-less side effects

–Cholinergic side effects 

•??

memantin/namenda

–N-methly-D-aspartate

•For moderate to severe

•Better tolerated than C I

•Decreases and can reverse symptoms

•Modulates action of glutamate

Blocks extracellular influx of calcium in memory cells

Possible benefit:

•Mediterranean Diet

•Folic Acid

•Statins



Minimal protection

•Physical Activity

•Cognitive training

• No
• benefit:

• •Gingko
• Biloba

•Vitamins

•Omega-3

• •Beta
• carotene

•Estrogens

•NSAIDS

•ASA

• •C
• I

•Antihypertensive

•Homocysteine