My doctor says there are some other drugs called dopamine agonists which can help. How do they work?
Dopamine agonists (sometimes called dopa-agonists) work in a different way from the replacement drugs like Sinemet and Madopar. They do not provide extra dopamine; instead they stimulate the parts of the brain where the dopamine works (agonist is a term used for drugs which have a positive stimulating effect on particular cells in the body).
Table 3.2 lists the dopamine agonists that are currently available in tablet or capsule form. Bromocriptine (Parlodel) has been around for many years; the others, all of which seem to work equally well, have been developed more recently. Cabergoline (Cabaser) does not need to be taken as often as the other tablets, so may be more convenient for some people. Apomorphine (discussed later in this section) is also a dopamine agonist but is currently only available as an injection.
What are the main advantages and disadvantages of dopamine agonists?
There are two main advantages. First, dopamine agonists rarely cause involuntary movements (there is more information about involuntary movements in Chapter 2 and in the section on Long-term problemslater in this chapter) in people who have never been on any form of levodopa. Because of this advantage, some doctors are already preferring to prescribe an agonist to newly diagnosed people and then adding levodopa later if necessary. By
doing this they hope to manage with lower doses of the levodopa drug and therefore to reduce the risk of later problems such as involuntary movements and fluctuating responses to medication.
Secondly, because these drugs remain in the bloodstream and in the brain for longer than Madopar and Sinemet, they can be tried for people who are having a fluctuating or unpredictable response to those medicines.
The disadvantages of the tablet/capsule forms of dopamine agonists are that:
• most people find them less effective in removing their symptoms than Madopar or Sinemet;
• they have to be introduced slowly;
• they may make the drug regimes of elderly patients with other illnesses too complicated;
• some side effects such as sleepiness and hallucinations may be slightly commoner;
• rare, but serious, side effects such as fibrosis (a thickening and scarring of connective tissue) occur with some of them.
Because of this complex mix of advantages and disadvantages, dopamine agonists are rarely used on their own in the long term.
Table 3.2 Dopamine agonists available as tablets or capsules
Trade name Generic name Sizes available (mg)
Parlodel bromocriptine 1.0, 2.5, 5.0, 10.0
Revanil lysuride 0.2
Celance pergolide 0.05, 0.25, 1.0
Requip ropinirole 0.25, 1.0, 2.0, 5.0
Cabaser cabergoline 1.0, 2.0, 4.0
Mirapexin pramipexole 0.125, 0.25, 1.0
(containing pramipexole 0.088, 0.18, 0.7 substance)
Many people who try them will finish up on a combination of a dopamine agonist and a reduced dose of Madopar or Sinemet.
Are the newer dopamine agonists less likely to cause side effects?
We cannot give a direct answer to this question, because a trial that directly compares the main dopamine agonists has never been done. However, there is little evidence that any one dopamine agonist has any advantage over the others – they all appear to work equally well and to have much the same side effects with the exception of the ergot derivative drugs, e.g. pergolide/cabergoline/
lisuride/bromocriptine that can rarely cause fibrosis in the abdomen or lung. If these drugs are to be used, blood tests and a chest X-ray are advised; sometimes lung function tests are recommended and advice on symptoms to look out for given.
What type of person can benefit from apomorphine?
The people who seem to benefit most are those who have bad
‘off’ periods but who are reasonably well when ‘on’. It does not help everyone, but it is now often tried with people who have ‘off’
periods of half an hour or more and who have not improved after adjustments to their ordinary medication. As apomorphine (Apo-go) currently has to be given by injection, the person with Parkinson’s and his or her carer have to be able to cope with this and to learn how to do it. This sometimes involves staying in hospital for a few days, although an increasing number of potential users are now being assessed and trained on a day care or domiciliary (home) care basis.
What are the main advantages of apomorphine?
Apomorphine is a dopamine agonist which is given by injection rather than as a tablet. The main advantage of apomorphine is that it can act as a ‘rescue treatment’ when tablets or capsules fail to take effect. For people who are assessed as suitable, it will work within 10–15 minutes – much more quickly than tablets or
capsules. Because of this predictable response, it can sometimes help people with Parkinson’s to go on working for longer than would otherwise be possible.
Does apomorphine have disadvantages too?
Yes. Its main disadvantage is that at the moment it can only be given by injection (other methods of delivery have been tried but have so far proved ineffective). This means that both the person with Parkinson’s and their main carer need to be willing and able to give the injections. The technique and the confidence to use it can be taught (as we explain later in this section), but there are people who feel unable to face the prospect of having or giving regular injections. It is important to involve the main carer (who may be a partner or a close friend or relative) because there may be times when the person with Parkinson’s is too rigid or immobile to give the injection.
Apomorphine also causes nausea and vomiting but this problem has been largely overcome by giving another drug called domperidone (Motilium) beforehand. Some people can even manage without the domperidone after a few months.
Domperidone is a safe drug and, although it makes the drug regime a little more complicated, this is not really a disadvantage.
Another disadvantage is that the site of the injections can become rather sore and irritated, especially when a syringe driver is used. This problem can be reduced by diluting the apomorphine with an equal amount of saline (a sterile salt solution).
Is apomorphine addictive?
No.
I have been told that I may need to use a syringe driver for my apomorphine injections. What is a syringe driver?
A syringe driver (one type is shown in Figure 3.1) is a small, battery driven pump, which can deliver continuous medication through a needle inserted under the skin of your lower abdomen
or outer, upper thigh. The medication is then absorbed into your bloodstream and goes from there to your brain. The dose can be adjusted to suit you, and the pump itself is carried in your pocket or in a small pouch round your waist. You need to change the needle and its position each day to reduce the risk of your skin getting sore. A small number of people use their syringe drivers continuously day and night. If this is essential, the needle site must be changed every 12 hours.
The proportion of people using a syringe driver rather than separate injections (see next question) varies with local and individual circumstances, but mainly they are people who need more than six injections a day. For them, the provision of a syringe driver can greatly improve the quality of life.
What are the alternatives to a syringe driver and how do they work?
There are two alternatives available at the moment. The first is a syringe of the type that people with diabetes use to give themselves their insulin. Some people who use apomorphine begin with this and many find it quite simple and easy to use. The
Figure 3.1 One of the two main types of syringe driver in use
syringe can be carried in a toothbrush container and fits easily into pockets and handbags.
The disadvantage of a syringe is that it can only hold one dose.
For this and other reasons, some people prefer to use an injection pen, a special type of multidose syringe. Until recently the only pen available was the Hypoguard Penject which has to be loaded from the ampoules of apomorphine (Apo-go) prescribed by the pharmacist. This created a problem for some people, especially those living alone or with carers who were unable to carry out this task. Now Britannia Pharmaceuticals (see Appendix 1) has produced a ready-loaded, disposable Apo-go pen (see Figure 3.2), which overcomes this difficulty. It holds 30 mg of apomorphine and the individual dose (anything from 1 to 10 mg) is set by turning the dial. Britannia has issued clear and easy-to-follow booklets for patients and professionals.
The disadvantage of the Apo-go Pen is that it costs the Health Service considerably more than other methods, so clear evidence of the need for this particular method of injection should be provided by the consultant or Parkinson’s Disease Nurse Specialist.
Both syringes and pens deposit the apomorphine (Apo-go) just under your skin, and have the advantage of not irritating it as much as a syringe driver. They do not, of course, give you continuous medication, but you can repeat your apomorphine injection several times a day as necessary.
How will I know which injection system is best for me?
Once the specialist has decided that you might benefit from apomorphine, the hospital team or Parkinson’s Disease Nurse Specialist will decide which is the most appropriate system for
Figure 3.2 The ready-loaded, disposable Apo-go pen
you and will train you in its use. No one delivery system is right for everyone – the choice depends on many different factors like frequency of dose, manual dexterity, lifestyle and availability of help.
Can syringe drivers, syringes and injection pens be prescribed on the National Health Service?
There is little problem with prescribing the syringes as they are also widely used for diabetes. Apo-go pens can be prescribed but the needles come separately. These can be obtained free of charge by the pharmacist from Britannia Pharmaceuticals (who make apomorphine) as long as they are requested when you are ordering Apo-go pens.
Syringe drivers are available on loan from Britannia Pharma-ceuticals free of charge. The syringes and fine infusion lines used with the syringe drivers are not obtainable on prescription.
However, the syringes can be obtained free of charge from Britannia Pharmaceuticals as requested. The District Nursing Service pays for and provides the fine infusion lines. Your GP surgery can put you in touch with your local service.
Are there some special centres providing training and support to apomorphine users?
In several areas of the UK there are now neurologists or geriatricians (doctors who care for the elderly) with a particular interest in Parkinson’s. In the hospitals or clinics where they work, there will generally be a special service for people who need apomorphine.
Many of these doctors work with Parkinson’s Nurse Specialists (see Chapter 4 for more information on their role) and, if there is one, their role will include helping and supporting anyone who is trying apomorphine.
Are there any new developments in the pipeline which will make apomorphine easier to use?
Many people hope that a different method of delivering apomorphine (i.e. other than by injection) will be found. The most promising research is nasal delivery of apomorphine.
Clinical trials of nasal sprays are currently taking place and there is a reasonable chance that they will become available in the foreseeable future. There are also other developments which could lead to delivery by mouth or via a skin patch. However, it is not clear yet whether such systems will offer the major advantage of injected apomorphine, which is its rapid action.