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Need loss of what % of neurons to see symptoms in Parkinson's?
70-80
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Compensation of DA loss
Decreased reuptake due to loss of boutons, increased synthesis of DA, increased release of DA per bouton, increased receptors
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What is responsible for the release and removal of DA
Boutons
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Do we use DA directly for tx? Why ?
No-doesn’t cross BBB
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Do we use anticholinergics? Why?
No- too many S/E
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Standard drug of choice for Parkinsons? Why?
L-dopa-it is after the rate limiting step of TH
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How much L-dopa originally makes it to the brain? Why
1/3- AAAD in the gut and blood
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What S/E are seen with L-dopa and why
DA is precursor to NE and Epi- see those s/e
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What drug is ALWAYS given in combo with L-dopa. How does it work?
Carbidopa. It is a peripheral AAAD inhibitor that cannot penetrate the BBB
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What combo drug is usually given
Sinemet
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Dietary consideration with L-dopa
High protein food can interfere with absorption. Take with full glass of water, don’t take with meals. Most use XR anyway
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What is on-off phenomena?
- Is drug holiday useful
- No
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Best results of drug use?
First 5-7 yrs. Range 2-15 yrs
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Drug interactions with L-dopa
Don’t give with MAOis or MAO-As (lead to hypertensive crisis). Don’t give to psychotic patients (can make them worse) anticholinergics can decrease absorption
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Sleep attacks can occur without warning
Ropinerole and Paramipexole
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Rescue therapy for the on-off phenomena and mechanism of drug
Apomorphine- D1 and D2 agonist
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2nd generation agonists that work on the D3-Da receptors
Ropinerole and Paramipexole
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Tolcapone and Entacapone: what type of drug? Which one is longer-acting? Which one must you monitor liver enzymes for and why? Which one has orange urine?
- COMT-inhibitors.
- Tolcapone.
- Tolcapone.
- Entacapone.
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Antiviral drug for PD
Amantadine
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Which one can cause red/purple skin blotches
Amantadine
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MAO-B Inhibitors
Rasagiline, Deprenyl
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Used in young patients with severe tremor
Anticholinergics
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Other drug that can be used to treat resting tremor
Histamine
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3 types of tremors
Resting, postural, kinetic/intentional
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Medications for postural tremors, Other meds for postural tremor
- Beta-blockers
- Pregabalin, wine, benzos, botox
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Medication for postural hand tremor
Primidone
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Pathophys of Huntington's
Selective degeneration of the neurons of the basal ganglia esp GABA and Ach. Loss of the basal ganglia
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Are DA neurons affected in Huntington's
No
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In general what type of drugs do you want for Huntington's
Ones that decrease DA levels
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What drug must you monitor depression in. what drug do you also give because of this?
- Reserpine, tetrabenazine.
- Fluoxetine(Prozac)
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Drugs that deplete vesicle storage levels of DA
Reserpine, Tetrabenazine
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Drugs that block DA receptors
Haloperidol, Chloropromazine
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Drug to treat the early rigid signs
Clozapine
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Treats the spastic effects of Huntington's
Benzo-Diazepam
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What can you give in the late stages
L-dopa
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Disorder of copper metabolism
Wilsons
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What happens if D/O or copper metabolism is left untreated
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Drugs to treat D/O of copper metabolism
- (Wilsons)
- Penacillamine, Potassium disulfide, Zinc acetate
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Which med to treat D/O of copper metabolism is a chelating agent
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What can you give is resistant to Penicillamine
Trientine
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What can you give with Penicillin to decrease absorption of copper
Potassium disulfide
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Can you give potassium disulfide alone
No
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Explain mechanism of Zinc acetate
It increases the production of a metabolite that binds with copper to prevent it from being absorbed
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Which medication can you use for long term maintenance tx
Zinc acetate
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Can you start with zinc acetate right away?
No- give it in combo with a chelating agent and slow go to just this drug
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How do you treat the other hyperkinetic disorders
DA depleting drugs-reserpine, tetrabenazine. Or neuroleptic drugs-Haloperidol, chloropromazine. Or benzos. Or anti-seizure (carbamazepine). And anticholinergics in kids
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Tx for Tourettes
DA receptor blockers- Haloperidol or clonidine
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Tx for focal dystonia
Botox
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Tx plan for Parkinsons
Start with amantadine, ropinerole, paramipexole. Then go to L-dopa when needed. When L-dopa becomes less effective decrease the dose and supplement with DA agonists
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