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Modes of drug delivery used to manage Parkinson's disease

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VOL: 102, ISSUE: 32, PAGE NO: 30

Carolyn Noble, MST, RN, is Parkinson's disease nurse specialist/neuro rehab coordinator, Greater Peterborough Primary Care Partnership

Parkinson's disease is a life-changing, progressive, neurological condition affecting movement, speech, swallowing ...

Parkinson's disease is a life-changing, progressive, neurological condition affecting movement, speech, swallowing and self-expression. Parkinson's develops following degeneration and loss of dopaminergic cells, resulting in the subsequent depletion of the neurotransmitter dopamine.

Dopamine is produced in the substantia nigra (SN), deep within the basal ganglia, a group of structures that are crucial to the normal control of voluntary and involuntary movement. Lewy bodies, neuronal inclusions that comprise a variety of proteins, can be found in the areas of degeneration in both the SN and the olfactory nucleus.

It is now well established that people with Parkinson's have a disorder of olfactory function. Loss of taste or the ability to smell can be a predictive factor for the development of Parkinson's and this may correlate with the presence of Lewy bodies in the anterior olfactory nucleus (Chaudhuri, 2004). Other premorbid or prodromal signs include depression, shoulder pain or dysautonomia.

Epidemiology

An epidemiological survey carried out in London estimated that approximately 170 per 100,000 of the population have Parkinson's, consistent with the results of other UK studies (Schrag et al, 2000). A GP with 1,900 patients may expect to have approximately three people with Parkinson's and therefore may have relatively limited experience of managing the problems associated with the condition. An estimated 120,000 people in the UK have Parkinson's (von Campenhausen et al, 2005) but many more live with the condition and are affected by it, such as carers and relatives.

Aetiology

Mechanisms underlying the degeneration and death of dopaminergic cells are not fully understood. But evidence suggests that genetic factors can influence susceptibility to the condition. Foltynie et al (2002) proposed that the inheritance of certain genes may lead to the clinical and pathological features of Parkinson's, whereas other genes may require exposure to environmental agents or multiple mutations of other genes before the disease can progress. The researchers identified subgroups based on age of onset and motor presentation, which may reflect the distribution of Lewy body deposition within areas of the brain. It is thought that subgroup identification may be useful in predicting disease progression (Foltynie et al, 2002).

Symptoms

The condition is characterised by slowness of movement (bradykinesia), rigidity (stiffness) of the muscles and resting tremor. Presentation of symptoms and the degree of disability varies with each individual.

The tremor initially affects one side of the body, may increase with stress and usually disappears during sleep.

Bradykinesia refers to both slowness of movement and difficulty in performing and initiating movement. For example, fine motor movements requiring manual dexterity for carrying out dressing and personal hygiene activities are restricted, and handwriting becomes smaller, a symptom known as micrographia. Walking can be compromised, and there is loss of arm swing, particularly on the affected side. There may be hesitation in initiation of movement, resulting in shorter steps or a shuffling gait and turning can be unsteady.

Rigidity of the muscles can cause stiffness and pain, localised to one limb or occurring throughout the body. Turning over in bed and transfers can be problematic. Facial muscles may become stiff and expressions appear restricted, giving the face a 'mask-like' appearance. This can contribute to difficulties with communication, as the face appears less animated and less responsive. Lack of expression and slowness in initiation of speech may be misinterpreted and this can affect social interactions.

Early access to physiotherapy and speech and language therapy can help. However, management with medication is a vital component of treatment.

Non-motor symptoms

Dysphagia may contribute to difficulties swallowing medication, food or fluids, and often results in drooling as the saliva is not swallowed effectively. Bladder and bowel function may be affected. Constipation is common and may have an impact on absorption of oral medication. Sleep problems, which may be related to side-effects of medication, can occur at any stage or during the premorbid phase. Sleep deprivation can impact on daytime symptom control, and it may be beneficial to treat the sleep disturbance before considering alterations to antiparkinsonian medication.

Neuropsychiatric complications may also be present, and acute psychosis can occur as an adverse effect of medication that may be delusional in nature. This is usually precipitated by non-distressing hallucinations, which are mainly visual (Lauterbach, 2004). As the condition progresses, cognitive function may deteriorate, and dementia occurs in 15-20% of those affected (Mayeux et al, 1990).

There is a relatively normal life-expectancy, as the condition is better understood and treatments are utilised more effectively (Findley and Bowman, 2004).

The impact of the diagnosis

The diagnosis can have a major effect on the person. Younger people may have concerns regarding body image, self-esteem, career or work, financial security and the impact on relationships or family members. Older people may have fears concerning increasing disability and dependency on others.

Some people will be relieved at finally having the diagnosis after a period of uncertainty and fear of the unknown. For others, the diagnosis can be devastating, producing many different emotions. Individual expectations may vary, particularly between the individual with Parkinson's and her or his carer.

Accepting the diagnosis can be difficult and so it must be conveyed in a sensitive manner, accompanied by guidance regarding help, support and education. MacCarthy and Brown (1989) found that self-esteem, coping style and practical support contributed significantly to the variance in psychological adjustment.

Parkinson's disease nurse specialists (PDNSs) are a valuable resource and, where available, may offer emotional support and education. The PDNS is often the first point of contact for the individual and the family, and can offer specialist assessment, often in the person's own environment. Acting as a case manager, the PDNS can involve other health and social care professionals to ensure that the individual receives a wide range of access to therapeutic interventions to improve quality of life and maintain independence.

Long-term complications

As the condition progresses, treatment response varies and may be exacerbated by motor fluctuations and neuropsychiatric complications. Motor complications occur in 50-90% of people who have taken levodopa for 5-10 years (Olanow et al, 2001) and can be a problem for those who have young-onset Parkinson's.

Motor fluctuations comprise variations in periods of good mobility, determined as 'on' periods, and periods of impaired motor function, or 'off' periods, during which response to medication is poor. As the condition progresses, the medication effects wear off sooner and result in shorter 'on' times. Eventually, the 'on' and 'off' periods alternate unpredictably and lead to anxiety and distress for the individual and family.

Dyskinesias are involuntary writhing movements that occur in response to medication for Parkinson's as the condition progresses. Any part of the body may be involved, and this side-effect of medication can cause more distress than the condition itself. When the dyskinesias are associated with 'on' time and are mild, they may cause little distress. But when they are more severe or associated with 'off' time, they can be disabling and may be associated with an increased risk of falling, pain and problems with breathing. This is a major cause of disability and can be difficult to treat (Obeso et al, 2000). It is important to determine if the individual is distressed by the dyskinesias and not to make an assumption that the dyskinesias should be eliminated by reducing or stopping medication.

Freezing episodes, autonomic dysfunction and postural instability with falling can develop. These problems affect confidence and may result in increased anxiety and social withdrawal (Obeso et al, 2000).

Medication management

Levodopa

Levodopa is a precursor of dopamine, and is administered in capsule or dispersible tablet. It has been referred to as the 'gold standard' treatment, providing effective symptom control and reducing mortality (Poewe and Wenning, 1996). Levodopa is combined with a decarboxylase inhibitor in the form of carbidopa or benserazide. Common side-effects include nausea, constipation and hypotension (Nutt and Wooten, 2005). Neuropsychiatric complications, including depression, anxiety and psychosis, are also associated with it. The most distressing effects occur with prolonged use and include motor complications, such as dyskinesias, fluctuating 'on'/'off' and the drug wearing off before the next dose (Obeso et al, 2000).

Motor complications have been associated with fluctuations in the plasma concentration of levodopa, which in turn affects the levodopa/dopamine levels in the brain, exposing the dopamine receptors to alternating high and low concentrations of dopamine (pulsatile stimulation). Therefore, drugs that provide more continuous dopamine receptor stimulation may provide symptom relief with a reduced risk of motor complications (Thanvi and Lo, 2004).

Dopamine agonists

Dopamine agonists (DAs) act directly on dopamine receptors, independently of the dopaminergic neurons. DAs have a longer half-life than levodopa and have the potential to provide more-sustained stimulation of the striatal dopamine receptors. For this reason, DAs may be the preferred first-line treatment in Parkinson's (Obeso et al, 2000).

Side-effects include hypotension, dizziness, nausea, sudden somnolence and neuropsychiatric effects, including hallucinations and psychosis (Nutt and Wooten, 2005). Ergot-derived DAs (such as cabergoline) have been associated with pulmonary, retroperitoneal and pericardial fibrotic reactions; therefore, patients receiving these DAs should be subject to regular monitoring.

Catechol-O-methyltransferase (COMT) inhibitors

COMT inhibitors, such as entacapone and tolcapone, may be useful adjuncts to levodopa therapy and may reduce the risk of motor complications. COMT inhibitors are only licensed for patients with advanced Parkinson's.

Discolouration of urine can occur and this must not be confused with the dark colouring associated with urinary tract infection. Common side-effects are similar to those observed with levodopa (Deane et al, 2004).

A combination therapy that contains levodopa/carbidopa and the COMT inhibitor entacapone has demonstrated therapeutic improvements in motor function and activities of daily living (Bonifati and Meco, 1999). However, although this combination means that patients take fewer tablets, individual titration of doses and timings may be necessary.

Monoamine oxidase (MAO)-B inhibitors

Selegiline is an MAO-B inhibitor that slows the breakdown of dopamine. It is likely to cause insomnia, hallucinations and vivid dreaming if taken after midday (Nutt and Wooten, 2005). Rasagiline is an MAO-B inhibitor that does not produce the metabolites that cause parasomnias (Macleod et al, 2005).

Other agents

Amantadine is an antiviral agent with antiparkinsonian activity. It is thought to increase the release of dopamine, and may be beneficial in treatment of drug-induced dyskinesias (Goetz et al, 2005). If administered after midday, it can precipitate sleep disturbance. Common side-effects include peripheral oedema, livedo reticularis, confusion and hallucinations (Nutt and Wooten, 2005).

Anticholinergic drugs are used less frequently due to the increased risk of adverse effects, including cognitive impairment, confusion, hallucinations, urinary retention, dry mouth (which may affect swallowing), constipation and nausea (Nutt and Wooten, 2005).

Neuropsychiatric problems associated with the condition, including cognitive impairment, confusion and psychosis, can be aggravated by levodopa and other antiparkinsonian medication (Lauterbach, 2004).

When to start treatment

The decision about when to treat the symptoms is controversial (Olanow et al, 2000). Some specialists advocate early treatment to provide the maximum clinical effect in the early stages of the condition, whereas others delay treatment to minimise the risk of long-term motor complications. Many factors must be considered before the decision is reached and the individual will need to consider the benefits and the risks.

Research suggests that 50% of patients fail to comply with the terms of their prescription, resulting in wasted medicines, associated high financial costs and serious health and lifestyle consequences for patients and their families (Department of Health, 2000). For those unlikely to follow medication regimens, there is a new, non-ergolinic dopamine agonist (rotigotine), delivered over 24 hours by a once-daily transdermal patch, which may be a more acceptable option.

- This article has been double-blind peer-reviewed.

For related articles on this subject and links to relevant websites see www.nursingtimes.net

Learning objectives

Each week Nursing Times publishes a guided learning article with reflection points to help you with your CPD. After reading the article you should be able to:

- Recognise the symptoms of Parkinson's disease

- Appreciate the impact of the diagnosis and the role of the Parkinson's disease nurse specialist

- Demonstrate awareness of the long-term motor complications

- Discuss pharmacological management, including new drug delivery systems

Guided reflection

Use the following points to write a reflection for your PREP portfolio:

- Outline where you work and why you were interested in reading this article

- Discuss the last time you came across a patient with Parkinson's disease

- Highlight a piece of information you have learnt that could have helped you

- Discuss how you would disseminate this to your colleagues

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