DrugZ (movement disorders)
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- What transmitters are released via volume transmission?
- Dopamine and catecholamines, Vt is associated with the raising of extracellular levels
- By what mechanism are Glutamate and Gaba released?
- Within the synapse (classical neurotransmission)
- What is the source of dopaminergic input to the basal ganglia?
- Nirgal-striatal pathway. Cell bodis in the substantia nigra project through the medial forebrain bundle (MFB) to the basal ganglia
- What is the basal ganglia comprised of?
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1. The striatum which consists of the caudate and the putamen
2. The internal/external Globus Pallidus - What neural pathway is responsible for motor movements?
- Pyramidal/corticospinal tract
- What is the extrapyramidal system?
- Pathway including basal ganglia, recticular formation, vestibular nuclei and red nucleis responsible for starting and stopping movement and maintenance of tone and posture
- What are pathways important in modification/correction of motor movement?
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1. Extrapyramidal system
2. Cerebellar output- coordinates msls of skilled movement - What compensatory mechanisms occur in Parkinsons?
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1. Increased synthesis of DA
2. Increased synaptic release of DA
3. Upregulation of DA receptors when lesion is > then 90% - What is Sinemet?
- Treatment for Parkinsons. L-Dopa and carbidopa (peripheral aromatic amino acid decarboxylase Inhibitor that cannot cross BBB)
- Discuss side effects of L-dopa.
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1. anorexia, nausea and vomitting
2. Also some tacchycardia, hypertension - What are some dietary considerations neccessary for utilization of L-dopa?
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1. Foods high in protein may interfere with L-Dopa absorption
2. Take 30 min before eating - What are problems associated with L-dopa/sinemet use?
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1. Short half-life
2. Cab cause hypertensive crisis if given to patient on MAO or MAO-I
3. On-off phenomenon after 5 years
4. Peak dose dyskinesia - Discuss the use of Bromocriptine and Pergolide.
- Ergot derivatives and Dopamine agonists typically used in conjunction with L-Dopa to decrease dosage and concomitatnt bouts of dyskinesia. Bromo-D2/D1 ag/antagonist and Pergolide is a DI and D2 agonist.
- What is the advantage to using Bromocriptine and Pergolide to L-dopa?
- No dependence on dying neurons, bypass presynaptic part to directly excite D2...etc. Disadvantage is that there is no regulation of release.
- Discuss the action and cliniclal utility of Ropinirole and Paramipexole.
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Newer D3>D2 dopamine agonists useful as monodrug therapy.
used to reduce off time when used with L-dopa - Discuss the utility of apomorphine.
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An emetic inhalant....cannot be taken orally
2. Rapid onste and short duration for emergency use in "off" pahse situations. - Discuss the clinical utility of COMT-Inhibitors.
- Used to block metabolism of L-dopa in the periphery by Catechol-O-Methyl Transferase after Aromatic Amino Acid Decarboxylase is blocked by Carbidopa in Sinemet. Allows decrease in dosage and side efx
- Name two COMT-Inhibitors?
- Tolcapone....off the market and enacapone which turns urine bright orange.
- Characterize the utilization and classification of Amantidine.
- Amantidine is an antivral agens which enhances DA releause and inhibits its uptake...useful as a first line therapy
- For what type of patient are anticholinergics typically used?
- Young patients...they have too many side efx
- What is the recommendation for treatment of Parkinsons?
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1. Initiate with amantadine, ropinirole or pramipexole
2. Low does L-dopa
3. Combine with COMT or DA agonists - What is the treatment for tremor?
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1. Beta-blockers- propanolol, indorol
2. Anticonvulsants- gabapentin, topiramate
3. Benzodiazepines- Alprazolam - Characterize Huntingtons DZ.
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Imbalance between Ach, GABA, and dopamine secondary to destruction of Gabaergic/cholinergic neurons in the striatum resulting in slightly increased to normal dopamine...chorea and dementia
SSRI for depression- fluoxetine - How is Wilsons Dz treated?
- Pencillamine- copper chelating agent or ZInc acetate- interferes with copper absorption
- True/False. Chorea responds to anticholinergics.
- False. But other hyperkinetic disorders do.
- Give an example of a dopamine depleting drug.
- Reserprine or tetrabenazine
- What is the characteristic treatment for TIC?
- Haloperidol, DA receptor blocker (neuroleptic) can cause tardive dyskinesia
- For what dz are their good pharmalogical treatments? Poor?
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Good!
1. Wilson
2. Parkisnons
3. Focal dystonia
Bad.
1. Huntington
2. Tremor