Levodopa

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Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 More General Terms 10 Additional Terms 11 Internet Database 12 References

Introduction

• Tradenames: Dopar, Larodopa.

Indications

• symptomatic treatment of Parkinson's disease
• used to provide relief from Herpes zoster pain
• fibromyalgia
• restless legs syndrome

Contraindications

• narrow-angle glaucoma
• concurrent MAO inhibitor therapy
• melanoma or undiagnosed skin lesion

• Caution:

• patients with history of myocardial infarction
• arrhythmias
• asthma
• glaucoma
• peptic ulcer disease
• sudden discontinuation of L-dopa can worsen symptoms of parkinsonism
  

• pregnancy category = c
• safety in lactation = -

Dosage

• start 250-500 mg PO BID, max 8 g/day
• take all doses with food
• avoid vitamin B6 ( pyridoxine)

• Tabs: 100, 250 500 mg.

Pharmacokinetics

• good oral bioavailability
• metabolized by peripheral decarboxylation unless given concurrently with carbidopa
• metabolized in the liver
• excreted in the urine
• plasma 1/2life is 1-3 hours
• a significant therapeutic response may occur in 2-3 weeks, but may not be seen for up to 6 months
  

• elimination via liver
• 1/2life = 1-3 hours

Adverse-effects

• common (> 10%)

• dyskinesia, choreiform & involuntary movements, orthostatic hypotension, blepharospasm, anorexia, nausea/vomiting, difficult urination, arrhythmias, anxiety, confusion, constipation, nightmares

• less common (1-10%)

• eyelid spasms, anorexia, diarrhea, dry mouth, headache, muscle twitching, discoloration of urine/ sweat

• uncommon (< 1%)

• duodenal ulcer, hypertension, hemolytic anemia, GI bleeding, blurred vision

• other:

• bradykinetic episodes
• '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

• dark color of body fluids
• transient elevation of serum transaminases

Drug-interactions

• pyridoxine ( vitamin B6) enhances decarboxylation of L-dopa
• hydantoins decrease effect of L-dopa
• MAO inhibitor used in combination may result in hypertensive reactions
• carbidopa increases the concentration of L-dopa in the CNS by inhibiting peripheral decarboxylation
• antipsychotic agents ( phenothiazines, haloperidol) & metoclopramide antagonize the effects of L-dopa
• benzodiazepines
• reserpine
• methyldopa
• antihypertensive agents
• antacids

Mechanism-of-action

• penetrates the CNS
• converted to dopamine in the basal ganglia
• increases dopamine concentrations in the CNS

More General Terms

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

Additional Terms

• carbidopa (Lodosyn)

Internet Database

PubChem: 6047
PubChem: 836

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: [1]
   - Vingerhoets FJG. Dyskinesia in Parkinson disease: Back for the future? Neurology 2009 Apr 7; 72:1202. PMID: [2]

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