Alzheimers/Parkinson's

Question 1

Dementia

Answer 1

Dementia and Alzheimers
- decrease cholinergic neuron activity-> die or destroyed
changes in brain: glutamate, dopamine, norepinephrine, serotonin, somatostatin

tx: increase amount of acetylcholine in synapse by inhibiting in the breakdown of acetylcholine

NON OF THE DRUGS ALTER THE UNDERLYING PATHO-> PRODUCE ONLY MARGINAL IMPROVEMENTS IN SYMPTOMS

Question 2

Alzheimer’s disease- Acetylcholinesterase Inhibitors

Answer 2

Donepezil (Aricept)
MOA: increases acetylcholine conc in the synaptic cleft by blocking acetylcholinesterase -> prevents it from getting broken down
High selectivity for brain enzyme= fewer systemic effects
OFF LABEL USE FOR DEMENTIA
ae: gi, brady, bronchospasm, QT PROLONGATION, TORSADES DE POINTES

other class members: Tacrine, RIVASTIGMINE (Exelon) GALANTAMINE (Razadyne ER)

Question 3

AD- N-Methyl-D-Aspartate Receptor Antagonist (NMDA)

Answer 3

Memantine (Namenda)
MOA: not well understood
AE: dizzy, hypo/hypertn, syncope
Combo with Donepezil
used in mild to mod disease

Question 4

Parkinson Disease

Answer 4

Decreased dopamine release-> Cholinergic overexpression
Loss of dopamine-> neurons to fire out of control

Question 5

classes for parkinson’s

Answer 5

1. Dopamine replacement therapy> never dopamine alone bc doesn’t cross BBB
   -Levodopa (L-dopa) with carbidopa
2. Dopamine agonist therapy
   -Ergot: Bromocriptine
   -Nonergot: pramipexole (Mirapex), Ropinirole (Requip)
   -Amantadine - dopamine agonist
3. Anticholinergic therapy
   -Benztropine, trihexyphenidyl, diphenhydramine
4. Catecholamine inhibitors
   -Monoamine Oxidase type-B Inhibitors (MAOI-B): selegiline
   -Catechol-O-Methyltransferase Inhibitors (COMT-I)- tolcapone

Question 6

Levodopa aka L-dopa

Answer 6

Carbidopa/levodopa (Sinemet)= MOST EFFECTIVE DRUG FOR PD

MOA:
L-dopa= precursor to dopamine-> cross BBB
Carbidopa= stops L-dopa breakdown -> so more can cross BBB

Benefits: allev symptoms- bot Akinesia though-> better tolerated by elderly

Disadvant:
-“on-Off” phenomenon- bc short halflife ie On= good relief at peaks-> OFF= no symptom relief at trough levels

Contra: NARROW ANGLE GLAUCOMA, MELANOMA, UNDIAGNOSED SKIN LESIONS, PSYCHOSES, DEMENTIA

AE: confusion, dizzy, dyskinesias, nausea, hypoTn, HA, cardiac dysrhythmias, psychosis

Question 7

Amantadine (Symmetrel)

Answer 7

Dopamine Agonist
MOA: release stored dopamine and catecholamines from presynaptic fibers of nerve cells: some anticholinergic properties

Benefits: Good for pts w. glaucoma or urinary retention
-early dz= effective 6-12 mo
-later= helps w. levodopa dyskinesia

AE: edema, Livedo reticularis (patchy blue/red net underskin), confusion, insomnia, nightmares, hallucinations
Drug interactions: anticholinergics

Question 8

Dopamine Receptor Agonists DRAs

Answer 8

MOA: stimulate remaining dopamine receptors
Benefits:
1. neuroprotective
2. Delays development of L-dopa dyskinesia
3. Decreases dyskinesia, musc rigidity, gait problems

AE: dyskinesia, postural hypoTN, hallucinations, psychosis, compulsive behaviors

Drug interactions: adrenergic drugs

AVOID IN ELDERLY BC CONFUSION AND HALLUCINATIONS

Question 9

Types of Dopamine receptor agonists

Answer 9

Ergot: Older -> lack sensitivity-> More AE
-Bromocriptine (Parlodel)
-moa: stim D2 recept
-more SE
-CONTRA IN ISCHEMIC DZ (PERIPHERAL VASCULAR DZ)

Nonergot: Newer-> high affinity for D2 and 3 but stim 2-4
Pramipexole (Mirapex)= D2,3
Ropinirole (Requip)= D3>D2>D4-> really likes D3
-MOA: stim D2-4
Activating dopamine receptors in pituitary gland INHIBITS PROLACTIN RELEASE-> ALTER REPROD FXN

Question 10

Anticholinergics

Answer 10

Benztropine (Cogentin)
MOA: blocks cholinergic activity (muscarinic antagonists)
Benefits: reduces akinesia, rigidity, tremor
AE: memory impairment, confusion, hallucinations, sedation, dysphoria, tachy, blurred vision, constipation, urinary retention
Contra: GLAUCOMA AND URINARY RETENTION

Question 11

MAOI-Bs

Answer 11

Selegiline (Eldepryl, Zelapar ODT aka deprenyl)
Rasagiline (Azilect)
MOA: Prevents dopamine breakdown through IRREVERSIBLE inhibition of monoamine oxidase
Benefits:
1. neuroprotective prop
2. improves “wearing off” effect of levodopa
3. may allow for decreased levodopa dose
AE: insomnia, hallucinations, nausea
Drug interactions: SSRI!!!! and mepridine

Question 12

Catechol-O-Methyltransferase Inhibitors (COMT-I)

Answer 12

MOA: prevents L-dopa breakdown through selective inhibition of catechol-O-methyltransferase
Benefits: increase bioavailability and halflife of L-dopa & improves “wearing off” of L-dopa
AE: Tolcapone (Tasma)= FULMINANT HEPATOTOXICITY (sudden and bad onset), gi upset, urine discoloration, dyskinesia
Drug interactions: many but espec nonselective MAOIs

Question 13

Drug induced Parkinsonism

Answer 13

1. ANTIPSYCHOTICS= 1ST GEN WORSE THAN 2ND
   -phenothiazines
   butyrophenones
2. Antiemetics
   -Metoclopramide, prochlorperazine, promethazine
3. Antihypertensives (older ones)
   -Reserpine, Alpha-methyldopa
4. Antidepressants
5. Calcium channel blockers
6. Lithium
7. Valproic acid (rare)