Parkinsons

Question 0

Nigrostriatial

Answer 0

integrates sensory information with movement, initiate motor command (to cortex), integrates thoughts and emotions with motor activity, modulates simple execution of emotion

Question 1

3 dopamine systems

Answer 1

Nigrostriatal, tuberinfundibular, mesocortical/mesolimbic

Question 2

TRAP

Answer 2

Tremor (3-5 hz), rigidity (cogwheel resistance), akinesia (mask like facial expression), postural stability (hunched festinating gait)

Question 3

Etiology of Parkinson’s

Answer 3

Loss of DA cells: (stroke, atherosclerosis, MTPT, et al)
ACh/DA imbalance: creates non-specific motor output that interferes with voluntary movement
iatrogenic is reversible (phenothiazines and metoclopramine)

Question 4

Receptor supersensitivity

Answer 4

• prevents symptoms until 80% of receptors are gone

Question 5

Anticholinergics

Answer 5

DMAs: benztropine, trihexphenadyl

- ACh activates the inhibitory GABA neurons, which DA neurons typically block

Question 6

Trt with DA

Answer 6

Cannot give tyrosine or dopamine

• L-DOPA: crosses BBB
• hypotension can be a problem with trt
• eventuall can contribute to dystonia

Question 7

DA trt contraindications

Answer 7

Narrow angle glaucoma 
Peptic ulcers
Melanoma
Pulmonary disorders
Severe CVD and other heart issues

Question 8

Carbidopa: function, interactions, contraindications

Answer 8

• AAAD
• improves on 1-5% entering CNS
• interactions: MAOI (lethal), antipsychotics (APsy block AAAD actions) anti-ACh potentiation
• Cind: closed angle glaucoma, melanoma

Question 9

Bromocryptine et al

Answer 9

• DA agonist (ropinirole; least dyskinetic, carbergoline, pramipexole; a-2 agonist)
• used as agonist without increasing dystonia

Question 10

MAOBI

Answer 10

• selebiline, rasagiline
• does not alter NE, 5-HT
• potentiates release of DA
• prolongs DA action
• first monotherapy

Question 11

DA- COMT

Answer 11

• tolcapone entacapone used with I-DOPA
• inhibits COMT
• normal DA side effects
• tolcapone can be hepatotoxic
• must avoid non-specific MAOI
• rare hallucinations

Question 12

Amantadine

Answer 12

• indirect DA agonist (possibly blocks NMDA receptor)
• A2 flu prophylaxis
• lower efficacy that I-DOPA

Question 13

Late treatment

Answer 13

• acute onset of immobility

- add direct agonist; selegeline or entacapone

Question 14

Pipeline

Answer 14

Pallidotomy reduces dyskinesia

• A2A adenosine receptor antagonists modulate GABA
• DBS of subthalamic nucleus (paradoxical)

Question 15

Cyclobenzaprine and metoxalone

Answer 15

• (flexoril)
• sedating
• anticholinergic SE
• better for strains/sprains that true spasticity

Question 16

Benzodiazepines

Answer 16

• GABA - A agonist
• higher dose - antianxiety
• muscle spasms/muscle trauma

Question 17

Baclofen

Answer 17

• increases K conductance, reducing Ca influx following an A/P
• used for spinal cord injury/MS and potentially ALS
• sedation, weakness, lassitude, confusion, withdrawal syndrome of anxieties and hallucinations
• overdose danger

Question 18

Tizanidine

Answer 18

• a-2 agonist
• preferentially acts on a-2 NER on boutons
• MS, stroke, spinal cord injuries
• sedation, dry mouth, dizziness

Question 19

Dantrolene: MOA, SE, indications

Answer 19

• antispastic
• Decrease calcium release from SER
• dizziness, muscle weakness, fatigue
• potential hepatotoxity
• useful for malignant hyperthermia and neuromalignant syndrome