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levodopa; L-3-hydroxytyrosine; L-3,4-dihydroxyphenylalanine; L-dopa (Dopar, Larodopa, Inbrija)

Tradenames: Dopar, Larodopa. Indications: 1) symptomatic treatment of Parkinson's disease 2) used to provide relief from Herpes zoster pain 3) fibromyalgia 4) restless legs syndrome Contraindications: 1) narrow-angle glaucoma 2) concurrent MAO inhibitor therapy 3) melanoma or undiagnosed skin lesion Caution: 1) patients with history of myocardial infarction 2) arrhythmias 3) asthma 4) glaucoma 5) peptic ulcer disease 6) sudden discontinuation of L-dopa can worsen symptoms of parkinsonism Dosage: 1) start 250-500 mg PO BID, max 8 g/day 2) take all doses with food 3) avoid vitamin B6 (pyridoxine) Tabs: 100, 250 500 mg. * inhalation powder (Inbrija) [5] - inhlation powder bypasses liver metabolism moving from lungs to the bloodstream [5] Pharmacokinetics: 1) good oral bioavailability 2) metabolized by peripheral decarboxylation unless given concurrently with carbidopa 3) metabolized in the liver 4) excreted in the urine 5) plasma 1/2life is 1-3 hours 6) a significant therapeutic response may occur in 2-3 weeks, but may not be seen for up to 6 months Adverse effects: 1) common (> 10%) - dyskinesia, choreiform & involuntary movements, orthostatic hypotension, blepharospasm, anorexia, nausea/vomiting, difficult urination, arrhythmias, anxiety, confusion, constipation, nightmares 2) less common (1-10%) - eyelid spasms, anorexia, diarrhea, dry mouth, headache, muscle twitching, discoloration of urine/sweat 3) uncommon (< 1%) duodenal ulcer, hypertension, hemolytic anemia, GI bleeding, blurred vision 4) other: a) bradykinetic episodes b) 'on-off' phenomenon - sudden loss of pharmacologic action - abrupt onset of akinesia - due to shortening of levodopa's 1/2 life in the striatum, without a measurable change in peripheral pharmacokinetics [4] - the down-regulation of dopamine transporters that occurs in response to loss of dopaminergic terminals is mitigated by exogenous dopamine (from levodopa), thus the shorter duration of levodopa action [4] - minimized by increasing the number or doses/day c) dark color of body fluids d) transient elevation of serum transaminases Drug interactions: 1) pyridoxine (vitamin B6) enhances decarboxylation of L-dopa 2) hydantoins decrease effect of L-dopa 3) MAO inhibitor used in combination may result in hypertensive reactions 4) carbidopa increases the concentration of L-dopa in the CNS by inhibiting peripheral decarboxylation 5) antipsychotic agents (phenothiazines, haloperidol) & metoclopramide antagonize the effects of L-dopa 6) benzodiazepines 7) reserpine 8) methyldopa 9) antihypertensive agents 10) antacids Laboratory: - levodopa in CSF - levodopa in serum/plasma - levodopa/creatinine in urine Mechanism of action: 1) penetrates the CNS 2) converted to dopamine in the basal ganglia 3) increases dopamine concentrations in the CNS

Interactions

molecular events

Related

carbidopa (Lodosyn)

Specific

foslevodopa; levodopa phosphate inhaled levodopa (CVT-301)

General

aromatic amino acid catecholamine pharmacologic agents for treatment of Parkinson's disease

Properties

MISC-INFO: elimination route LIVER 1/2life 1-3 HOURS pregnancy-category C safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Troiano AR et al. PET demonstrates reduced dopamine transporter expression in PD with dyskinesias. Neurology 2009 Apr 7; 72:1211. PMID: 19020294 - Vingerhoets FJG. Dyskinesia in Parkinson disease: Back for the future? Neurology 2009 Apr 7; 72:1202. PMID: 19349599
  5. George J, FDA Approves Inhaled Levodopa for Parkinson's. Improved motor function when taken during 'off' episodes. MedPage Today. Dec. 26, 2018 https://www.medpagetoday.com/neurology/parkinsonsdisease/77104

Component-of

carbidopa/entacapone/levodopa (Stalevo) carbidopa/levodopa (Sinemet, Parcopa, Atamet, Crexont)