Examining the treatment options
Examining the treatment options
Now let's look at the three main first-line treatments in a little more depth.
The treatments:
Levodopa is a precursor to dopamine, usually given with a dopa decarboxylase inhibitor (benserazide hydrochloride or carbidopa) as co-beneldopa or co-careldopa. The dopa decarboxylase inhibitor blocks the peripheral conversion of levodopa to dopamine to allow levodopa to cross the blood brain barrier and be converted to dopamine. If levodopa is broken down into dopamine in the peripheral system it activates other dopamine receptors, commonly causing nausea. Domperidone is often the anti-emetic of choice prescribed at the start of levodopa therapy. There are various preparations of levodopa available – immediate/modified release preparations, hard or dispersible capsules, liquid or gel.
Although levodopa is one of the most common and widely used first-line treatments, it is often associated with motor complications, including response fluctuations and dyskinesias:
- Response fluctuations are characterised by large variation in motor performance, with normal function during the ‘on’ period, and weakness and restricted mobility during the ‘off’ period
- ‘End-of-dose’ deterioration with shorter duration of benefit can also occur – modified release preparations may help with this and with nocturnal immobility
- Hallucinations/delusions, sleep disturbance and nausea are all common side-effects of levodopa treatment and may be intermittent or last throughout treatment. A key aim of pharmacy input from the start of treatment is to try to ensure that these side-effects do not affect adherence.
Dopamine agonists stimulate dopamine receptors both post- and pre-synaptically and have a similar but less potent effect than levodopa. They are classified as ergot derived (bromocriptine, pergolide and cabergoline) or non-ergot derived (apomorphine, pramipexole, rotigotine and ropinirole). Ergot derived dopamine agonists are often associated with a risk of moderate to severe cardiac valvulopathy and serosal fibrosis, so are not first-line treatments.
For some people, dopamine agonists have been linked with the development of compulsive behaviours (addictive gambling and an excessive increased libido), especially at high doses. Sudden onset of sleep also occurs more frequently, particularly when the dose is being increased, so patients should avoid driving and/or operating machinery while the dose is being increased if this side-effect occurs.
The MAO-B inhibitors, such as selegiline and rasagiline, prevent the breakdown of dopamine so they have a levodopa-sparing effect. They typically provide less improvement than levodopa in motor symptoms and daily functioning and can be used in the early stages of the disease as monotherapy or as an adjunct to other medications. If used adjunctly, MAO-B inhibitors help to reduce ‘off’, and to extend ‘on’, periods.
Triptans or selective serotonin reuptake inhibitors should not be used concurrently due to the increased risk of potentially fatal serotonin syndrome. When advising on over the counter decongestants or cold remedies, people who are on MAO-B inhibitors should be advised to not take medications that contain pseudoephedrine due to the increased risk of a hypertensive crisis.
There are also some prescribed medications that people with PD should avoid. Any medication that inhibits a dopamine receptor could worsen symptoms of PD. For example, typical antipsychotic medications (e.g. phenothiazines and haloperidol) exacerbate the motor symptoms of PD as do anti-emetics such as prochlorperazine and metoclopramide.
Reflective exercise
- Find out what local resources are available to PD patients and make a note of the most useful.
- Look into how your patients could join Parkinson’s UK and bookmark the website.