Term
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Definition
| progressive, degenerative disease with onset usually after 50 yrs of age; Symptoms: tremor (resting tremor, "pill rolling" movement), muscular rigidity ("cogwheel" rigidity, "masked" facial expression), bradykinesia, akinesia (slowed purposeful movements, difficulty in initiating or stopping movements), postural & gait defects ("simian posture", "downhill walk") |
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Term
| Reason for Parkinsonian symptoms |
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Definition
| alteration of dopamine-ACh balance in striatum; a relative deficiency of dopaminergic activity in relation to ACh; due to death of dopaminergic neurons in nigrostriatal dopamine pathway |
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Term
| Drugs that enhance dopaminergic activity - raise levels of dopamine |
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Definition
| l-DOPA (Larodopa; Sinemet, Stalevo) - dopamine precursors converted to DA; selegiline/deprenyl (Eldepryl) & rasalagine (Azilect) - inhibit metabolism of DA by MAO-B; entacapone (Comtan) - inhibits metabolism (breakdown) of DA by COMT; |
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Term
| Drugs that enhance dopaminergic activity - stimulate post-synaptic dopamine receptors |
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Definition
| bromocryptine (Parlodel) & pergolide (Permax) - ergot derivatives; pramipexole (Mirapex) & ropinirole (Requip) - newer, non-ergot dopaminergic agonists |
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Term
| Drugs that enhance dopaminergic activity - stimulate release of dopamine |
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Definition
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Term
| Drugs that reduce cholinergic activity - centrally acting antimuscarinics |
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Definition
| benztropine (Cogentin), trihexiphenidyl (Artane), & diphenhydramine (Benadryl) |
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Term
| Chemistry & Mode of Action of l-DOPA (Larodopa, Sinemet) |
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Definition
| amino-acid precursor of dopamine that is transported to brain & converted to dopamine |
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Term
| Pharmacokinetics of l-DOPA (Larodopa, Sinemet) |
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Definition
| variable absorption in GI; enters brain by active transport amino acid pump; metabolized to form DA by DOPA decarboxylase in brain & periphery; addition of a peripheral DOPA-decarboxylase inhibitor (Carbidopa) significantly reduces metabolism of DOPA to DA in periphery (reduction in dose of l-DOPA by 75% & greatly decreases severity of peripheral side effects) |
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Term
| Therapeutic Effects of l-DOPA (Larodopa, Sinemet) |
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Definition
| takes 3-4 wks to see full effect; 15% of pts are symptom free, 60% will be significantly improved, 25% show no improvement; therapeutic effects become less pronounced as disease progresses; does not halt the progression of disease, but becomes less effective as disease progresses |
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Term
| Side Effects of l-DOPA (Laradopa, Sinemet) |
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Definition
| nausea & vomiting (occurs in 80% of patients); cardiovascular effects: postural hypotension, tachycardia, arrhythmias; behavioral effects: depression, psychotic reactions, hallucinations, nightmares, euphoria, mood & personality changes, increased libido, release of inhibitions, compulsive behavior; Extrapyramidal Motor Symptoms: choreiform movements; Endocrine Effects: decreased levels of prolactin; |
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Term
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Definition
| atypical antipsychotic that is preferred in managing psychiatric effects of l-DOPA; unfortunately, it is also associated with agranulocytosis |
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Term
| Ways to minimize nausea & vomiting side effects of l-DOPA |
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Definition
| minimize incidence of this side effect by giving l-DOPA in divided doses after meals or by building up total daily dose gradually; since CRTZ is located outside of the BBB, concurrent administration of carbibidopa (Sinemet) significantly reduces incidence & severity |
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Term
| Concurrent administration of carbidopa with l-DOPA |
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Definition
| decreases significantly the frequency & severity of side effects caused by just l-DOPA |
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Term
| Miscellaneous Effects of l-DOPA |
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Definition
| precipitation of glaucoma, precipitation of gout, hot flashes, taste & smell disturbances, elevation of liver enzymes, positive Coomb's test, blood dyscrasias, exacerbation of malignant melanoma |
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Term
| Contraindications of taking l-DOPA |
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Definition
| cardiac arrhythmias, psychosis, melanoma, glaucoma, active peptic ulcer disease |
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Term
| Major Drug Interactions with l-DOPA |
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Definition
| interacts with: pyridoxine - enhancement of extracerebral metabolism decreases therapeutic effects; antipsychotics (DA antagonists) - inhibit effects; MAO inhibitors - hypertensive crisis; tricyclic antidepressants - hypertensive crises |
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Term
| carbidopa (Lodosyn, Sinemt [+ l-DOPA]) |
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Definition
| inhibits DOPA decarboxylase in periphery but does not enter brain, permits reduction in dose of l-DOPA, thus reducing some of its side effects |
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Term
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Definition
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Term
| bromocryptine (Parlodel) & pergolide (Permax) |
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Definition
| ergot derivatives that act as relatively nonspecific DA receptor agonists; less effective than l-DOPA in treatment of Parkinson's disease; use in pts who do not tolerate or respond to l-DOPA, also used as therapeutic effects of l-DOPA diminish; |
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Term
| Side Effects of bromocryptine (Parlodel) & pergolide (Permax) |
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Definition
| nausea & vomiting, postural hypotension, mental disturbances (confusion, agitation, hallucinations, seizures), choreiform movements, endocrine disturbances (due to inhibition of prolactin) |
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Term
| ropinirole (Requip) & pramipexole (Mirapex) |
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Definition
| newer non-ergot dopaminergic agonists; approved for use in both early & late stage parkinsonism, used increasingly as first line drugs; also used in treatment of "restless leg syndrome" |
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Term
| Side Effects of ropinirole (Requip) & pramipexole (Mirapex) |
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Definition
| choreiform & dyskinetic movements, nausea, dizziness, confusion, sedation, behavioral changes, hallucinations |
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Term
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Definition
| newer non-ergot dopaminergic agonist that may have antioxidant & neuroprotective effects which may be beneficial in slowing progression of Parkinson's Disease |
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Term
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Definition
| originally used as an antiviral agent; stimulates release of DA from nerve endings; less effective than l-DOPA but more effective than anticholinergic drugs; may potentiate actions of l-DOPA |
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Term
| Side Effects & Toxicities of amantadine (Symmetrel) |
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Definition
| mental disturbances, hyperexcitability, ataxia, confusion, convulsions, choreiform movements, excreted by kidney - may require dosage adjustments in pts with impaired renal function |
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Term
| selegiline/deprenyl (Eldepryl) |
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Definition
| selectively inhibits MAO-B & prevents breakdown of dopamine in CNS; used as a supplement to l-DOPA, particularly in latter stages of Parkinsons; initial reports indicated it may slow progression of Parkinson's possibly inhibiting conversion of MPTP to neurotoxic metabolites but recent studies have not confirmed the earlier results |
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Term
| Side Effects of selegiline/deprenyl (Eldepryl) |
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Definition
| tremor, dyskinesias, choreiform movements, hallucinations, agitation, behavior & mood changes, nausea, weight loss, "Cheese toxicity" with tyramine seen at high doses |
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Term
| entacapone (Comtan) & tolcopone (Tasmar) |
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Definition
| newer drugs that inhibit metabolism of DA & l-DOPA by COMT; approved for use in conjunction with l-DOPA & l-DOPA + carbidopa for treatment of parkinson's disease; main side effects are due to increased levels of dopamine (hallucinations, nausea, hypertension) |
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Term
| Stalevo (l-DOPA + carbidopa + entacapone) |
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Definition
| new combination product used in treatment of Parkinson's Disease; has l-DOPA + carbidopa + entacapone |
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Term
| benztropine (Cogentin) & trihexyphenidyl (Artane) |
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Definition
| anticholinergics that may be effective in mild parkinsonism, usually more effective against tremor than rigidity; drugs of choice for treatment of iatrogenic Parkinsonism from DA antagonists |
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Term
| Side Effects of benztropine (Cogentin) & trihexyphenidyl (Artane) |
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Definition
| automatic - dry mouth, dry hot skin, hyperthermia, constipation, urine retention, loss of visual accomodation, tachycardia; behavioral - sedation, confusion, memory impairment; drug interactions with CNS depressants - alcohol, sedatives, opioids, muscle relaxants |
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Term
| diphenhydramine (Benadryl) |
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Definition
| antihistamine used to treat Parkinsonism primarily due to its anticholinergic activity |
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Term
| Treatment of Mild to Moderate Symptoms of Parkinson's Disease |
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Definition
| amantadine, dopamine agonists, MAO-B inhibitors, or anticholinergics may be adequate; pramipexole (Mirapex) and ropinirole (Requip) are becoming increasingly popular first line drugs |
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Term
| Treatment of Moderate to Severe Symptoms of Parkinson's Disease |
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Definition
| l-DOPA and carbidopa with or without entacapone |
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Term
| Treatment of non-responsive patients with Parkinson's |
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Definition
| add a dopamine agonist, selegiline, amantadine, or anticholinergics |
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Term
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Definition
| autosomal dominant with onset in middle-age; progressive deterioration; many of extrapyridal motor symptoms are similar to those seen in tardive dyskinesia; effects of treatment have focused on: decreasing dopaminergic activity (antipsychotics), enhancing effects of GABA (benzodiazepines), or ACh (physostigmine, rivastigmine) |
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