Term
| Parkinson's is probably due to a loss of ___, which shifts the balance towards ___, which excites ___ and thereby ___ |
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Definition
Loss of inhibitory DA
Shift towards ACh-mediated excitation
Excites GABA neurons
Thereby inhibits movement |
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Term
| General mechanisms for Parkinson's drug therapy (2) |
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Definition
Increase DA function: DA precursor, DA agonist, DA degradative-enzyme inhibitors
Decrease ACh activity: antiACh |
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Term
| Muscarinic cholinergic antagonist Parkinson's drug: MOA, drug |
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Definition
Decrease ACh dominance which shifts the balance back towards DA
Benztropine |
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Term
| Antihistamine Parkinson's drug: MOA, drug |
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Definition
Increases central muscarinic blockade
Diphenhydramine |
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Term
| DA precursors: MOA, drugs (2) |
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Definition
Levodopa: precursor of DA converted to active form in the body
Carbidopa: inhibits peripheral DOPA decarboxylase conversion of L-dopa to inactive form, thereby allowing L-dopa to get to the CNS |
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Term
| DA agonists: MOA, drugs (2) |
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Definition
Directly stimulates DA-R
Bromocriptine
Pramipexole |
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Term
| MOA-B inhibitor Parkinson's drug: MOA, drug |
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Definition
Prevents degradation of DA, thereby increasing DA levels (neuroprotective?)
Selegiline |
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Term
| COMT inhibitor Parkinson's drug: MOA, indication, drug |
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Definition
| Inhibitors catechol-o-methyltransferase conversion of L-dopa to O-methyl dopa, thereby allowing L-dopa to get to the CNS Adjunct to levodopa/carbidopa therapy in patients who aren't adequately managed with levo/carbi alone or who experience "end-of-dose wearing off" Entacapone |
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Term
| Drug therapy is ___ not ___ |
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Definition
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Term
| Muscarinic cholinergic antagonist Parkinson's drug: indications (3) |
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Definition
Mild-moderate parkinsonism
Severe parkinsonism if combined with levodopa/carbidopa
Drug-induced parkinsonism in schizos on antipsychotics |
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Term
| Anticholinergics can often be used to treat ___ initially and can improve ___ but have little effect on ___ |
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Definition
Mild Parkinson's consisting of resting tremor
Improve rigidity
Little effect on Bradykinesia |
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Term
| Anticholinergic Parkinson's drug: S/E (4) |
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Definition
All due to muscarinicR blockade
-Dry mouth
-Blurry vision
-Constipation and urinary retention
-Sedation, mental confusion, hallucinations |
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Term
| Anticholinergic Parkinson's drug: contraindications (4) |
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Definition
Bladder/bowel function issues
Memory/cognitive disturbances (especially elderly)
Narrow angle glaucoma
Patients taking antihistamines, DA-R blockers, amantidine, alcohol |
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Term
| Starting with L-tyrosine, name the enzymes and intermediates necessary to come to DA |
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Definition
L-tyrosine + tyrosine hydroxylase = L-dopa
L-dopa + dopa decarboxylase = DA |
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Term
| Why give L-dopa instead of DA? |
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Definition
L-dopa can cross the BBB
DA can't |
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Term
| Aside from the usual S/E of levodopa, what other issues are you worried about that might cause you to use something else as initial therapy? |
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Definition
| Levodopa conversion to DA can produce oxidative stress and hasten the degeneration of the striatal neurons |
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Term
| Levodopa: pharmacokinetic issues |
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Definition
Most of it is decarboxylated in the periphery to DA (leading to the S/E)
This means you need large doses in order to get a sufficient amount of levodopa to the brain |
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Term
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Definition
Due to the peripheral synthesis of DA/NE:
-Anorexia
-n/v (DA on area postrema): occur early in therapy, decrease with time, can avoid with carbidopa
-Orthostatic hypotension: occurs early in therapy and decreases with time
-Arrhythmia, transient tachycardia (DA onto B-adrenergic): especially if have pre-existing heart issues, can avoid with carbidopa or B-blocker
Dyskinesia: can develop with long-term therapy, DOSE-LIMITING!
Hallucinations, confusion, delirium, depression, suicidal thoughts: DOSE-LIMITING!
Insomnia, agitation, anxiety: occur early in therapy
Exacerbate Huntington's chorea
Usually have improved mood and mental function, increased interest in people and things |
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Term
| Levodopa + carbidopa: why it's better than levodopa alone (4) |
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Definition
Can decrease the dose of levodopa
Can get effective doses of levodopa more quickly
Avoid pyridoxine/B6 antagonism (enhances decarboxylase activity)
Get rid of n/v and arrhythmias |
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Term
| Levodopa: indications for decreasing dosage or adding another drug |
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Definition
Dyskinesia
Psychotic reactions |
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Term
| Describe how levodopa works in the progression of Parkinson's. (4) |
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Definition
Works best early in the course of PD, with the beneficial effects exceeding plasma lifetime (nigrostriatal DA system seems to be able to store/release DA)
Time + degeneration causes the nigrostriatal DA system to lose its ability to store/release DA = "wearing off"
Later stages: patients may fluctuate between "off" (no benefits) and "on" (dyskinesias)
Progression: body seems to become resistant and so symptoms come out more |
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Term
| What are the steps to avoid levodopa fluctuation responses? (3) |
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Definition
Smaller doses more frequently
Sustained release formulations
Add DA agonist, cholinergic antagonist, MOA-B inhibitor, or COMT inhibitor |
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Term
| Why are DA-R agonists good? (2) |
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Definition
Don't require enzymatic conversion = don't depend on functionality of nigostriatal system = can be more effective in later stages
Maybe more selective for D2-R |
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Term
| Bromocriptine: pharmacokinetics (2), indications (3) |
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Definition
Prefers D2-R
Longer duration of action
Adjunct to levo/carbi in patients who aren't adequately managed with levo/carbi alone or who experience "end-of-dose wearing off"
Tx hyperPRL: associated with DA-blockers and ant. pit. tumors; causes amenorrhea, infertility (women), galactorrhea (men and women)
Tx neuroleptic malignant syndrome in patients treated with antipsychotics (life-threatening rapid blockage of DA-R) |
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Term
| Pramiprexole: pharmacokinetics, indications (2) |
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Definition
Prefers D3 > D2-R
Early PD monotherapy
Later PD adjunct to levo/carbi in patients who aren't adequately managed with levo/carbi alone or who experience "end-of-dose wearing off" |
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Term
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Definition
Low-dose orthostatic hypotension (more common than levo)
Psychotic reactions (more common and more severe than levo)
Dyskinesia
n/v/constipation: occur early in treatment |
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Term
| How are MAO-B inhibitors different from non-selective MAOI? (2) |
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Definition
Don't inhibit peripheral metab of NE or 5HT
Don't interact with tyramine-containing foods |
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Term
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Definition
| Adjunct therapy in patients with declining/fluctuating response to levo (attentuate akinesias, on-off phenomenon) |
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Term
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Definition
Exacerbate levo-induced dyskinesias and psychosis
Metabolized to amphetamine = anxiety, insomnia |
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Term
| What do you need to watch out for with entacapone? |
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Definition
COMT and MAO are the major systems involved in catecholamine metabolism
Inhibition of both with entacapone and non-selective MAOI is bad news bears |
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Term
| Tourette's drug therapy (2) |
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Definition
Haloperidol: watch out for tardive dyskinesia
Clonidine (a-adrenergic agonist): good for pedi population to avoid tardive dyskinesia |
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