Dopamine Agonist Drugs in the treatment of Parkinson's Disease

Dopamine agonists are another commonly used class of drugs implemented during the treatment of PD[1][2]. Dopamine agonists work by actively influencing dopamine receptors in the brain to produce more in-vivo dopamine, thus making it the preferential treatment early on in the disease process. Apomorphine is considered the premier drug in this category, due to its powerful motor fluctuation modulating capabilities, such as those seen in end of dose dyskinesias generated by some anti-parkinsonian medications (i.e. LD)[3]. Apomorphine is typically administered subcutaneously on a continuous cycle for an average of 16 hours per day at a rate of 3-6 mg/hr[4]. Further pharmacokinetics of apomorphine, include the drug taking approximately 15-20 minutes to reach its maximum bioavailability within the bloodstream[5][6]. Once in the blood, the drug takes about 30-40 minutes to reach its half life[4][5][6]. This is fairly quick and the reason for the drug being given on a constant basis throughout the day[4]. Apomorphine’s clearance in the system is close to 3-4 L/h/kg, meaning that it leaves the plasma at a rapid rate[7]. After the drug has been metabolized, it is then excreted through urine by the kidneys[4].

The main adverse effects seen after the intake of this medication include somnolence, withdrawal, and psychiatric disorders, such as confusion and hallucinations[3][4]. It is vital that the physical therapist is aware of such side effects to dictate the treatment.

References:
  1. Bonuccelli U, D. D. Role of dopamine receptor agonist in the treatment of early Parkinson's disease. Parkinsonism Related Disorders, 2009;(4): S44-53.doi: 10.1016/S1353-8020(09)70835-1.
  2. Harris PE ,C. K. Prevalence of complementary and alternative medicine (CAM) used by the general population: a systematic review and update. Int J Clin Pract, 2012; 66(10): 924-939. doi: 10.1111/j.1742-1241.2012.02945.x.
  3. 3.0 3.1 Regina Katzenschlager MD, W. P. Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet Neurology, 2018;(9):749-759. doi: 10.1016/S1474-4422(18)30239-4
  4. 4.0 4.1 4.2 4.3 4.4 Auffret M, D. S. (2018) Pharmacological Insights into the Use of Apomorphine in Parkinson's Disease: Clinical Relevance. Clinical Drug Investigation, 2018; 38(4) 287-312. doi: 10.1007/s40261-018-0619-3.
  5. 5.0 5.1 Nomoto M, K. S., & Group, P. S. A Randomized Controlled Trial of Subcutaneous Apomorphine for Parkinson's Disease: A Repeat Dose and Pharmacokinetic Study. Clinical Neuropharmacology, 2015; 38(6): 241-247. doi: 10.1097/WNF.0000000000000111.
  6. 6.0 6.1 Elisa Unti, R. C. Apomorphine hydrochloride for the treatment of Parkinson's disease . Expert Review of Neurotherapeutics, 2015; 15(7): 723-732. doi: 10.1586/14737175.2015.1051468.
  7. Argiolas A, H. H. (2001). The pharmacology and clinical pharmacokinetics of apomorphine. BJU international, 2001; 88(3): 18-21. https://doi.org/10.1046/j.1464-4096.2001.00124.x