In
general, dopaminergic medicines share similar side effects.
It is first important to
understand the general side effects caused as a dopamine class effect. Dopaminergic
medication includes any type or class of medication that enhances the
dopamine availability in the brain. Levodopa containing medications such as carbidopa/levadopa
(Sinemet, Stalevo, and Parcopa) improve the symptoms of PD by directly
supplementing our brain reserves of dopamine.
The dopamine agonists are a
group of medications that have a molecular structure similar to dopamine, yet
have longer lasting action in the brain than levodopa and include
ropinirole (Requip), pramipexole (Mirapex) and rotigotine (Neupro).
Medications that block or delay the breakdown of dopamine in the brain are
called enzyme inhibitors and include rasagiline (Azilect), selegeline (Eldepryl
and Zelapar), entacapone (Comtan and Stalevo) and tolcapone (Tasmar).
Amantadine (Symmetrel) is a commonly used medication to reduce dyskinesia
or provide mild symptomatic benefit, however the mechanism of how this drug
works isn't fully understood. Each of these medicines has a different mechanism
of action (See Figure 1) but each effectively enhances function of the
dopaminergic system.
Therefore, they
share many side effects attributed to dopamine. All of these medications can
cause similar side effects related to the enhancement of our dopamine system
and include sleepiness, nausea, dizziness, low blood pressure, mental
fogginess, fatigue, vivid dreams, confusion and hallucinations and impulsivity
control problems.
Side
effects can be avoided or reduced. Side effects can be
anticipated if any dopaminergic medication is increased too quickly or when
given at high doses. Dopaminergic medications are better tolerated if given in
smaller doses and increasing gradually over several weeks. This applies to
starting your first dopaminergic medication or adding on additional
medications. Giving the brain and body time to adjust can help avoid side
effects that may limit medication options.
Other tips to avoiding or
limiting side effects are to take dopaminergic medication initially with food
to limit nausea and plenty of water to fully swallow the medication. Once the
body has adjusted, nausea and dizziness are not typically persistent side
effects but can linger with the higher doses of any dopaminergic medication.
Caffeine or exercise may be helpful if daytime sleepiness or fatigue persists
as a lot of daytime napping will disrupt nighttime sleep. The first step to
improving lightheadedness due to orthostatic hypotension is to be sure an
individual is drinking the appropriate volume of fluids daily.
The cognitive or emotional
side effects of confusion, hallucinations or impulse control problems are best
mitigated by early and open conversations with your health care provider before
these problems spin out of control. Psychosis is a condition where the person
can lose insight while experiencing a quick decline in mentation or rational
thought and can be precipitated by medication interactions or combined side
effects and can be reversed with proper medical care.
Many times, medication
adjustments can eliminate or improve any of the side effects mentioned above.
In general amantadine, selegeline and dopamine agonists have a higher risk of
causing confusion, hallucinations than levodopa. If
these problems exist, it may be necessary to reduce these agents and use
levodopa in there place if possible.
More information on medical treatment of these problems will be
addressed the next edition of the Nurses Navigator.
There
are side effects that are unique to individual medicines. Leg swelling or even body swelling can occur
with dopamine agonists and amantadine and may require smaller more frequent
dosing or adding on additional dopaminergic medications to keep all the
individual doses lower. The pressure from increased fluids in the legs can
increase the risk of blood clot formation in the legs.
Low blood pressure can
occur after taking any dopaminergic medication, however, dopamine agonists are
longer lasting and may need to be reduced if dizziness with standing
is occurring due to blood pressure drops.
Diarrhea can occur with agents that
contain COMT inhibitors such as carbidopa/Ldopa/entacapone (Stalevo), entacapone
(Comtan) or entacapone (Tasmar) and should be avoided if diarrhea is moderate
to severe due to the risk of dehydration and malnutrition. Liver enzyme
monitoring by a blood test is required when taking tolcapone due to past
reports of life threatening liver failure.
Dry mouth, dry eyes, blurred
vision, urinary retention, constipation, memory problems, leg rash and
swelling can occur specifically with use of amantadine and may limit the
dose. Selegeline is converted to an amphetamine like compound in the body
and can be associated with insomnia, anxiety and hallucinations.
In addition, the MAO B
inhibitors, selegeline and rasagiline, can cause fatal interactions if
given with, pain or psychiatric medications and should be reviewed with the pharmacist
before taking with any over the counter medications. Selegeline and rasagiline
can also cause a type of drug interaction called serotonin toxicity that
can affect blood pressure, body temperature, muscles stiffness and mentation if
taken with some types of antidepressants, namely selective serotonin
re-uptake inhibitors so caution is used with this combination of therapy.
Side effects
associated with specific Parkinson's medicines:
General Dopaminergic side
effects:
Sedation
Confusion
Lightheadedness
Nausea
Hallucinations
Specific drug side effects:
Dopamine
agonist (ropinirole, pramipexole)- sedation, sleep attacks, confusion,
hallucinations, impulsivity control
COMT
inhibitors(entacapone)- diarrhea
COMT
inhibitor (Tolcapone)-diarrhea, liver toxicity
MAOB
inhibitor (Rasagiline and Selegeline)- drug interactions, possible serotonin
syndrome when used in combination with SSRIs.
MAOB
inhibitor (Selegeline)- amphetamine effects- insomnia, hallucinations, anxiety
Amantadine -
levido reticulation, leg swelling. anticholinergic side effects of constipation,
urinary retention, dry eyes, blurry vision, and memory loss.
Clinical
pearl: Last medicine added may not be the first to stop if your patient
experiences a side effect. Many patients are on multiple medicines to treat
their disease. It is important to review all of the medicines, especially those
with CNS activity to determine which one is the most appropriate to change.