Dopamine Agonists in PD
Unlike the dopamine replacement group of medications, these medications aren’t converted into dopamine in the brain. Instead these drugs mimic the effects of dopamine by binding to the same receptors of the brain – essentially tricking the brain into thinking dopamine is at work.
Dopamine agonists may be used on their own as an initial treatment or may be combined with other Parkinson’s medications. There are a few advantages when used in combination with levodopa. For example if dopamine replacement such as levodopa becomes less effective at controlling symptoms and the dose cannot be comfortably increased due to side effects, then adding a dopamine agonist may be helpful in controlling symptoms. Or by adding in a dopamine agonist, the dose of levodopa can be reduced which then also reduces the severity of dyskinesias, an uncomfortable, involuntary movement side effect that occurs with levodopa use. Overall, dopamine agonists can improve motor functioning and reduce the motor fluctuations that occur as a result of the wearing-off effect of levodopa.
An advantage to the dopamine agonists is that they tend to cause less dyskinesias compared to dopamine replacement. But once again, they only treat the motor symptoms of Parkinson’s (although perhaps not as well), not the nonmotor manifestations of this disease.
Like all medications, there are some potential side effects. The most common ones are nausea, vomiting and a drop in blood pressure particularly with a change in position (sitting to standing for example).
There is also concern regarding other impactful side effects which may include hallucinations, sudden episodes of sleep (without preceding drowsiness to serve as a warning) and compulsive, risk-taking behaviors such as gambling and sexual hyperactivity. Estimates are that these compulsive behaviors take place in about 14% of those taking dopamine agonists, with sometimes devastating consequences. This may limit their use in some cases and as is the case with all medications, the advantages must be weighed against the disadvantages.
If a decision is made to discontinue dopamine agonist therapy, then it is important to taper off the medication slowly under the care of a physician. Gradually tapering the drug may help avoid dopamine agonist withdrawal syndrome (DAWS) which can cause significant distress if it occurs. The symptoms of DAWS include anxiety, panic attacks, depression, agitation, nausea, pain and irritability. Usually these symptoms are transient but in some individuals can run a longer course.
Bromocriptine (Parlodel) is an older medication that is somewhat limited in its use secondary to its side effects of nausea, low blood pressure, dry mouth, headaches, swelling and depression. And because of its chemical structure, it may rarely cause scarring or fibrosis around the lung, heart and kidney.
Pramiprexoleand ropinirole (Mirapex and Requip respectively) are considered newer dopamine agonists. They are better tolerated than bromocriptine and also come in long acting formulations (Mirapex ER and Requip XL)
Apomorphine injection (Apokyn) is a powerful, fast-acting injectable compound is used as a type of rescue medication to treat “off” periods. It usually takes effect within 10 to 20 minutes after it is administered and wears off fairly quickly as well. If “off” periods occur despite efforts to avoid them through standard medications, apomorphine can be given occasionally or several times a day as needed. The significant nausea that can occur must also be treated, usually prior to the injection, with an antinausea medication.
The rotigotine transdermal system (Neupro patch) uses a different delivery system to get the dopamine agonist into the body. Through a patch that is applied once daily, the medication is absorbed through the skin in a steady fashion, maintaining a constant level of the medication as possible throughout the day. This results in a reduction in “off” time that is experienced normally when oral medications begin to wear off. Because of its delivery method the rigotine transdermal system may also cause local skin reactions (rash, swelling etc.) along with the other side effects seen with dopamine agonist use.
Although like so many other medications, dopamine agonists fail to treat the complete myriad of symptoms that are manifested in Parkinson’s disease, they do provide another option when trying to manage this complex illness.