Levodopa - Parkinson's: Difference between revisions

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Levodopa (L-dopa) is a common drug administered during the progressive stages of PD.  L-dopa is considered a prodrug, meaning it is not activated until after it crosses the blood brain barrier via active transport<ref>Standaert DG, Roberson ED. Chapter 22: Treatment of Central Nervous System Degenerative Disorders. In: Goodman & Gilman's: The Pharmacological Basis of Therapeutics. Vol 1. 12th ed. New York, NY: The McGraw-Hill Companies, Inc. ; 2011.1.  </ref>.  The primary use of Levodopa is to restore depleted levels of dopamine at the presynaptic terminal of the substantia nigra, which restores functional movement<ref name=":0">Lewitt MD, PA. Levodopa therapy for Parkinsons disease: Pharmacokinetics and pharmacodynamics. Movement Disorders. 2014;30(1):65-67. doi:10.1002/mds.26082.</ref>. This replacement can relieve symptoms of PD, such as freezing and rigidity<ref name=":1">Connolly MD, BS, Lang MD, AE. Pharmacological Treatment of Parkinson Disease. Jama. 2014;311(16):1670. doi:10.1001/jama.2014.3654.</ref>. If a tolerance is built up to L-dopa, or adverse motor effects become present with this drug alone, partner drugs Benserazide and Carbidopa (LD-CD) can be supplemented to prevent the further premature breakdown in the periphery<ref>del Amo EM, Urtti A, Yliperttula M. Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2. European Journal of Pharmaceutical Sciences. 2008;35(3):161-174. doi:10.1016/j.ejps.2008.06.015</ref>.
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Optimal oral dosing of LD-CD is typically between 97.5 mg-390 mg for a single dose, and 25mg-100mg bi-daily/tri-daily for either sustained release or immediate release<ref>Hsu PhD, A, Yao PhD, H-M, Gupta PhD, S, Modi PhD, NB. Comparison of the pharmacokinetics of an oral extended-release capsule formulation of carbidopa-levodopa (IPX066) with immediate-release carbidopa-levodopa (Sinemet®), sustained-release carbidopa-levodopa (Sinemet® CR), and carbidopa-levodopa-entacapone. The Journal of Clinical Pharmacology. 2015;55(9):996. doi:10.1002/jcph.514.</ref>. The volume of distribution is typically around 28.5 L and the plasma half-life clearance is 1.8 hours. Therefore, frequent dosage is required.  The renal clearance of L-dopa is approximately 72 ml/min<ref name=":0" />.


Many of the adverse effects that are present with Levodopa are due to the fact that it is not combined with a partner drug. Some of the most common adverse effects to be aware of during a physical therapy visit include gastrointestinal distress due to the enteral administration, cardiac difficulties, gait disturbances due to dyskinesias, end of dose akinesia, and a tolerance after around 3-4 years. Administering physical therapy treatment during the peak time of this drug helps to avoid these end of dose side effects.<ref name=":1" />
==Introduction==
The mainstay of current PD treatment are levodopa-based preparations, designed to replace the [[dopamine]] in the depleted striatum. Dopamine itself is unable to cross the  [[Blood-Brain Barrier|blood brain barrier]] (BBB) and cannot be used to treat PD. In contrast, the dopamine precursor levodopa is able to cross the BBB and can be administered as a therapy. After absorption and transit across the BBB, it is converted into the neurotransmitter dopamine by DOPA decarboxylase 


'''<u>References:</u>'''
The primary use of Levodopa is to restore depleted levels of dopamine at the presynaptic terminal of the [[Basal Ganglia|substantia nigra]], which restores functional movement<ref name=":0">Lewitt MD, PA. Levodopa therapy for Parkinsons disease: Pharmacokinetics and pharmacodynamics. Movement Disorders. 2014;30(1):65-67. doi:10.1002/mds.26082.</ref>. This replacement can relieve symptoms of PD, such as freezing and rigidity<ref name=":1">Connolly MD, BS, Lang MD, AE. Pharmacological Treatment of Parkinson Disease. Jama. 2014;311(16):1670. doi:10.1001/jama.2014.3654.</ref>. 
 
Generally, the clinical effect of levodopa is noticed quickly, and may last for several hours, particularly in the early stages of disease. However, as disease becomes more advanced, the effect of the drug usually wears off after shorter durations, and an increased frequency of dosing is often required.
 
Levodopa comes with significant side effects that constitute an important part of the illness experienced by the patient, particularly in advanced disease. Some of its associated side effects result from the conversion of levodopa to dopamine outside the CNS (peripheral conversion) by DOPA decarboxylase. To reduce these side effects, levodopa is administered in combination with DOPA decarboxylase inhibitors such as benserazide and carbidopa. These compounds do not cross the BBB, but selectively prevent the peripheral conversion of levodopa to dopamine, thereby reducing the peripheral side effects. The most frequently prescribed combination drugs are carbidopa/levodopa (co-careldopa [trade names Sinemet, Pharmacopa, Atamet]) and benserazide/levodopa (co-beneldopa [trade name Madopar])<ref name=":2">Zahoor I, Shafi A, Haq E. [https://www.ncbi.nlm.nih.gov/books/NBK536726/ Pharmacological treatment of Parkinson’s disease.] Exon Publications. 2018 Dec 21:129-44. Available:https://www.ncbi.nlm.nih.gov/books/NBK536726/ (accessed 14.4.2022)</ref>
 
Researchers continue to focus on the development of other long-acting oral preparations as well as other modes of drug delivery, which may allow for improved clinical efficacy and side-effect profiles in the future.<ref name=":2" />
 
==References==
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[[Category:Parkinson's]]
[[Category:Pharmacology]]

Latest revision as of 16:28, 6 August 2022

Original Editor - Andrew Bennett Lee Price Top Contributors - Kim Jackson, Lucinda hampton, Andrew Bennett Lee Price and Lauren Greeson


Introduction[edit | edit source]

The mainstay of current PD treatment are levodopa-based preparations, designed to replace the dopamine in the depleted striatum. Dopamine itself is unable to cross the blood brain barrier (BBB) and cannot be used to treat PD. In contrast, the dopamine precursor levodopa is able to cross the BBB and can be administered as a therapy. After absorption and transit across the BBB, it is converted into the neurotransmitter dopamine by DOPA decarboxylase

The primary use of Levodopa is to restore depleted levels of dopamine at the presynaptic terminal of the substantia nigra, which restores functional movement[1]. This replacement can relieve symptoms of PD, such as freezing and rigidity[2].

Generally, the clinical effect of levodopa is noticed quickly, and may last for several hours, particularly in the early stages of disease. However, as disease becomes more advanced, the effect of the drug usually wears off after shorter durations, and an increased frequency of dosing is often required.

Levodopa comes with significant side effects that constitute an important part of the illness experienced by the patient, particularly in advanced disease. Some of its associated side effects result from the conversion of levodopa to dopamine outside the CNS (peripheral conversion) by DOPA decarboxylase. To reduce these side effects, levodopa is administered in combination with DOPA decarboxylase inhibitors such as benserazide and carbidopa. These compounds do not cross the BBB, but selectively prevent the peripheral conversion of levodopa to dopamine, thereby reducing the peripheral side effects. The most frequently prescribed combination drugs are carbidopa/levodopa (co-careldopa [trade names Sinemet, Pharmacopa, Atamet]) and benserazide/levodopa (co-beneldopa [trade name Madopar])[3]

Researchers continue to focus on the development of other long-acting oral preparations as well as other modes of drug delivery, which may allow for improved clinical efficacy and side-effect profiles in the future.[3]

References[edit | edit source]

  1. ↑ Lewitt MD, PA. Levodopa therapy for Parkinsons disease: Pharmacokinetics and pharmacodynamics. Movement Disorders. 2014;30(1):65-67. doi:10.1002/mds.26082.
  2. ↑ Connolly MD, BS, Lang MD, AE. Pharmacological Treatment of Parkinson Disease. Jama. 2014;311(16):1670. doi:10.1001/jama.2014.3654.
  3. ↑ 3.0 3.1 Zahoor I, Shafi A, Haq E. Pharmacological treatment of Parkinson’s disease. Exon Publications. 2018 Dec 21:129-44. Available:https://www.ncbi.nlm.nih.gov/books/NBK536726/ (accessed 14.4.2022)
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