In practice Parkinson’s disease it treated using monamine oxidase type B inhibitors as first-line therapy in young patients who cannot tolerate dopamine agonists but who wish to delay treatment with levodopa (Allcock, 2007). By inhibiting the enzyme monamine oxidase type B, selegiline increases the dopamine levels in the substantia nigra. Dopamine concentration is increased in the brain as selegiline also blocks dopamine re-uptake from the synaptic cleft (Allcock, 2007).
However, due to by-products of selegiline metabolism, neuropsychiatric side-effects can occur (Allcock, 2007). However it may be difficult to decide if these side affects are due to the drugs or the progression of the disease (Laurance, Bennett and Brown, 1997). It is not yet known “if the lack of amphetamine metabolites with rasagiline confers any clinical benefit over selegiline. These agents are effective for reducing motor symptoms in Parkinson’s disease, and can delay the need for treatment with levodopa” (Allcock, 2007).
The pharmacokinetics of selegiline are highly variable. After the administration of an oral dose of selegiline, it is rapidly absorbed and metabolised to desmethylselegiline, levoamphetamine and levomethamphetamine (Selegiline data sheet, 2011). This metabolism is mainly in the liver (Delue et al, 2002). It is distributed into tissues including the brain. The drug is highly lipid-soluble, which is why it rapidly penetrates the central nervous system (Delue et al, 2002).
Plasma protein binding is ninety nine point five percent (Drug bank, 2011). The absolute bioavailability of selegiline is approximately 10% (Medafe, 2000). Which means a lot of the drug is wasted before it reaches the systemic circulation. Selegiline bioavailability can be substantially increased however by up to threefold if it is administered with food high in fat (Medsafe, 2000 and Drugs.com, 2011). Selegiline is mainly excreted as metabolites in the urine, about fifteen percent is excreted in the faeces. The half life of selegiline is between one to two hours (Drug bank, 2011) or about ten hours (Medsafe, 2000).
Selegiline’s benefits in Parkinson’s disease has only been recorded as an addition to levodopa. Drug.com (2011) documented selegiline’s effectiveness as a monotherapy was unknown, but past attempts to treat Parkinson’s disease with non-selective monamine oxidase inhibitors as a sole treatment are reported to have been unsuccessful. However, Heinonen and Myllyla (1998) stated in all studies where selegiline has been used as monotherapy in the treatment of Parkinson’s disease the drug has been well tolerated if it is compared with, for example, dopamine agonists. Attempts to treat Parkinson’s disease with combinations of levodopa and currently marketed non-selective monamine oxidase inhibitors were stopped because of multiple side effects including hypertension, increase in involuntary movement, and toxic delirium (Drugs.com, 2011).
Serious drug interactions can occur with monamine oxidase type B inhibitors. An interaction of monamine oxidase type B inhibitors with antidepressants such as tricyclics and selective serotonin reuptake inhibitors is particularly important as this can result in a fatal serotonin syndrome (Allcock, 2007). A daily dose of selegiline is ten milligrams either as one dose or five milligrams twice daily (BNF, 2007).
As selegiline is a irreversible monoamine oxidase B inhibition, the duration of clinical effect does not depend on the elimination time, and therefore once daily dosing can be applied (Medsafe, 2000). Selegiline can also be used in conjunction with levodopa in the later stages of the diseases (Craig and Stitzel 2004). The main adverse reactions caused by selegiline is due to the increased levels of dopamine (Craig and Stitzel, 2004).
A new preparation for selegiline has recently been tested. Zydis selegiline is a tablet that dissolves on the tounge and undergoes pregastric absorption. This provides high plasma concentrations of selegiline missing the first-pass metabolism. In this study, Zydis selegiline was assessed in patients who were experiencing motor fluctuations with levodopa for safety and its effects. “Zydis selegiline safely reduces daily offtime when used as adjunctive therapy with levodopa in patients with Parkinson’s disease” (Movement Disorder Society 2004).
Co-beneldopa is a mixture of benserazide and levodopa (BNF, 2007). Levodopa is the metabolic precursor of dopamine (Roche products, 2010). It is considered that giving levodopa raises the level of available dopamine (Roche products, 2010). Most of the levodopa dose is decarboxlated in the tissues outside the brain and as a result of this the full therapeutic effect of the drug may not be obtained which could lead to adverse reactions (Roche products, 2010). A prodrug is a drug which is inactive until metabolised in the body to the active drug. Dopamine is supplied as the pro-drug levodopa to dopamine in the brain, where it relieves the symptoms of Parkinson’s disease in the early stages.
The amino acid levodopa is used to substitute the dopamine deficiency in Parkinson’s disease (TEVA UK Ltd, 2009). This is due to the fact that at least ninety five percent of orally administered levodopa is decarboxylated in extracerebral organs such as the intestines, liver, kidneys, heart and stomach. Only small amounts reach the central nervous system after administration of levodopa monotherapy. Many gastrointestinal and cardiovascular adverse reactions can occur with a build up of dopamine with levodopa monotherapy (TEVA UK Ltd, 2009). There are two problems with levodopa (McGovock, 2005).
Firstly, less then ten percent of an oral dose reaches the brain the reminder is metabolised in many body tissues giving many intolerable adverse effects such as insomnia, nausea and vomiting and anorexia. The second is that levodopa does not replace lost nerve cells or stop the progression of the disease. So to overcome this problem drug companies combined levodopa with one of two drugs, one of which is benserazide, which inhibits the peripheral breakdown of dopamine and ensures that sufficient reaches the central nervous system (McGavock, 2005). Benserazide is a decarboxylase inhibitor and at the therapeutic dose it does not cross the blood-brain barrier however at a higher dose it may entre the central nervous system (Roche products, 2010).
Levodopa is readily absorbed from the upper small intestine by active amino acid and has a half life of one and a half hours (Laurance, Bennett and Brown, 1997). Levodopa crosses the blood-brain barrier by means of a saturable transport mechanism. It is not bound to plasma protein. Half life in increased in the elderly by twenty five percent (TEVA UK Ltd, 2009). Co-beneldopa has a bioavailability of sixty percent, this is not reduced by food but can be reduced by antacids (Roche products, 2010).
Ten to thirty percent of the drug binds to plasma protein (Drugsupdate, 2011). Co-beneldopa is said to be the best treatment for patients over the age of seventy five, or for younger patients with evidence of neuropsychiatric involvement cognitive impairment or hallucinations. For night-time hours the slow release preparation can be used, but it has reduced and more unpredictable bioavailability than standard-release preparations and so is recommended not to be used through the day time (Allcock, 2007).
Benserazide is almost entirely eliminated by metabolism. Sixty four percent of metabolites are excreted in the urine and twenty four percent is in faeces (Roche products, 2010). Problems with long term treatment can begin after five years, some patients will have a gradual reoccurrence of parkinsonian akinesia (Neal, 1992). Various kinsesias may appear and in time many patients start to get increasingly severe and rapid oscillations in mobility and dyskinesias (Neal, 1992)
Selegiline and co-beneldopa have some of the same adverse reactions; the main ones are hypotension, nausea and sleep disorders (BNF, 2007). Nausea is caused by the stimulation of the chemoreceptor trigger zone which lies behind the blood brain barrier (Neal, 1992). Sleep disorder is due to stimulation of mesolimbic dopamine receptors and hypotension is common but often asymptomatic (Neal, 1992).
To maximise the effect in the early stages of the condition, some specialists advocate early treatment, whereas others who think delaying the treatment will lower the risk of long-term motor complications (Noble, 2006). Risks and benefits will need to be considered by the individual before a decision can be reached about their treatment. Noble (2006) states research has suggested fifty percent of patients do not comply with their prescription, which resulting in high financial costs wasted medicines and serious health and lifestyle consequences for patients and their families.
It is important that the nurse is aware of their role when it comes to anti Parkinson medication. Sudden withdrawal of Parkinson’s disease medication should be avoided, as there can be serious adverse reactions or allowed to become ineffective due to problems with absorption. Sudden withdrawal can result in acute akinesia and neuroleptic malignant syndrome. Drug holidays should also be avoided (NICE, 2006).
Rigid medication rounds in hospital and nursing homes may not suit a person with Parkinson’s (NICE, 2006). Nurses should ensure that patients have their medication at the right time for them, which may require self-medication and that any changes in medication should be overseen by a Parkinson’s disease specialist (Bedford-Bell, 2006). If drugs are not available or a patient is nil by mouth it is to remember as a nurse that an abrupt stop of this type of medication is potentially life threatening. If a person is due for surgery, they should take their medications as normally as possible and be nil by mouth for as little time as possible around the time of the operation. Occasionally people may need to be nil by mouth for some time in which case the advice of a Parkinson’s specialist nurse or doctor is crucial (Lindhal and MacMahon, 2011)
To manage Parkinson’s disease a nurse is required to assisting the patient with the symptoms as well as the adverse effects of the drug therapy can also help to improve motor function, prevent injury, and maintain autonomy. (Cranwell-Bruce, 2010).
“Despite the introduction of several new drugs to the antiparkinsonian armamentarium, no single best treatment exists for an individual patient with PD. Particularly in the advanced stage of the disease, treatment should be individually tailored”. (Deleu, Northway and Hanssens, 2002)
The most effective and common treatment for most people with Parkinson’s disease is with medication. However, it is important to remember that the medication is only a treat for the symptoms of the condition but may not slow down the progression of the disease. Each patient will have their own treatment and medication carefully balanced so that it suits them as an individual. As every person with Parkinson’s disease is different, it’s essential that the nurses takes a holistic approach to treatment, including therapies and consult patients’ Parkinson’s specialists before making any changes to their treatment programmes.
ADAM (2011) Substantia nigra and Parkinson’s disease. Available at: http://www.nlm.nih.gov/medlineplus/ency/imagepages/19515.htm (Accessed 1 December 2011).
Allcock, L. (2007) Managing patients with Parkinson’s disease. Available at: http://www.pulsetoday.co.uk/article-content/-/article_display_list/10957176/may-2007-managing-patients-with-parkinson-s-disease (Accessed 2nd December 2011)
Beckford-Bell (2006) ‘Implications of the latest NICE Parkinson’s disease guidance’, Nursing times, 102 (29) pg 26
British National Formulary (2007). London: RPS Publishing
Campbell, J. (2011) Campbell’s Physiology Notes. Glasgow: Bell and Bain Ltd