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Where is the basal ganglia and what is its function?
In the forebrain; motor response and habitual action selection
_____________ receives input from the substantia nigra pars compacta and is the primary input of the substantia nigra.
From where does the substantia nigra pars compacta receive its name?
The high concentration of melanin within its dopaminergic neurons.
What two neuromodulators act on the caudate putamen?
DA and ACh
_____ is an inhibitory NT;
_____ is an excitatory NT
- GABA - inhibitory
- Glutamate - excitatory
The basal ganglia has two efferent neurons. One goes to the 'go' pathway (which is the _____), and the other goes to the 'no go' pathway (which is the _____)
- globus pallidus/substantia nigra reticulata [GO]
- external globus pallidus [NO GO]
What is the function of the direct/GO pathway?
Leads to movement through binding of D1 receptors
What is the function of the indirect/NO GO pathway?
Activate the D2 receptor; NO MOVEMENT
What will ACh do to the DA neurons in the caudate putamen?
ACh tends to excite the indirect pathway and inhibit the direct pathway.
What is the primary deficit of PD?
Loss of melanic DA neurons in the substantia nigra pars compacta
Why are DA reuptake inhibitors not effective in treating PD?
PD is a loss of dopaminergic neruons.
Why is L-DOPA co-administered with carbidopa?
Carbidopa is a peripheral decarboxylase inhibitor, which prevents the L-dopa in the periphery from being synthesized into DA
What is the major side effect of L-DOPA being synthesized into DA in the gut?
Nausea, because of activation of DA receptors in the chemoreceptor zone.
What are the two major contraindications for L-DOPA?
1. MAO inhibitors - a major enzyme used in the metabolism of DA, inhibiting this may lead to a build of DA, which could be life threatening and/or result in psychosis/hallucinations
2. Patients with closed-angle glaucoma. DA becomes NE in the eye and can result in even less outflow of aqueous humor.
Name 2 COMT inhibitors.
- Entacapone (Comtan)
- Stalevo (carbidopa+levodopa+entacapone)
What is the most frequently prescribed DA agonist?
Name a direct acting DA agonist that is formulated as a transdermal system.
What are the general class features of DA agonists?
- 1. Selective for D2
- 2. Effective as monotherapy, or adjunct therapy with L-DOPA
- 3. Longer duration of action than L-DOPA
- 4. May reduce on-off fluctuations or "wearing off" effect
- 5. May help more in late disease stages
- 6. Significantly lower rates of motor side effects (dyskinesias)
- 7. Possibly slows disease progression
Name three DA agonists.
What are three common adverse effects associated with DA agonists?
- Increased sedation
- Impulse control disorders
Which pathway to DA agonists target? Direct, indirect, or both?
Name the "other" DA agonist.
What makes apomorphine special?
- D2 agonist
- Administered s.c. via pen
- Used to treat sudden on/off periods
- Significant N/V
- Contraindicated in patients taking 5HT3 agonists because of exacerbated hypotension
Name 2 anticholinergic agents used for PD.
- Benztropine mesylate
What is amantadine?
An antiviral agent
What are the three classes of Anti-Parkinsonian drugs?