Let's start with the drug levodopa. Why do we call it levodopa?
Well, dopamine doesn't cross the blood brain barrier unfortunately.
So we have to use the L-enantiomer of dopa, L-DOPA, or
levodopa. L-DOPA enters the brain via L-amino acid transporters.
So they are very specific transporters that actually actively
move L-DOPA from outside the cell or outside the brain
into the brain area. Toxicity of levodopa include anorexia,
nausea and emesis. That just make sense because it's affecting
the chemoreceptor trigger zone. Other symptoms include postural
hypotension and tachycardia. And remember, that levodopa is
contraindicated in patients who have psychosis because you are
going to worsen the psychotic symptoms. What is carbidopa
and why do we give it with levodopa? Well let's take a look
at this reaction and interaction between drug and barrier.
L-DOPA is broken down by tissue decarboxylases in the peripheral
tissues. This causes side effects. So when you have breakdown
of L-DOPA into dopamine, it causes side effects in the peripheral
tissue. Carbidopa blocks DOPA decarboxylase. You get prolonged
activity of action and more transmission and movement of
L-DOPA into the brain. You also have fewer side effects peripherally.
That's why we give carbidopa in association with levodopa.
Let's talk about dopamine agonist, bromocriptine and pramipexole.
Bromocriptine and other analogues are ergot alkaloids. They are
partial D2 agonist, and they increase the activity of dopamine pathways.
They may be used in combination with L-DOPA. The side effects
of drugs like bromocriptine include nausea and vomiting
through the CTZ, dyskinesia and confusion, and postural
hypotension which I had mentioned before with L-DOPA.
The ergot alkaloid related side effects that are specific
to bromocriptine is pulmonary infiltrates and erythromelalgia.
Erythromelalgia is a very unique kind of a skin reaction and
you can see a women and her daughter. You can see the woman's
hand is very swollen, very red, very inflammed. You can take
a look at the feet as well, and they are thickened and red
and inflammed. And they can be very very painful. Let's
move on to the other dopamine agonist, called Mirapex
which has just come on to the market recently in Canada, has
been in the United States for a couple of years. It's a high
affinity D3 receptor agent. Now remember that most of the
agents are D2 receptor agents. So when we say that this is a
D3 receptor agent, that makes it kind of unique. We can use it
as monotherapy or we can use it in combination with levodopa.
Adverse events are same as bromocriptine. Anorexia, nausea,
vomiting. Remember it's working on the CTZ. Postural hypotension
and dyskinesia. The major adverse events. Confusion, hallucination
and impulsivity almost like a psychosis but not quite.
One of the unique things that you see with this particular
drug is something called narcolepsy or the tendency to fall asleep
very quickly. It's a unique situation. It's something that
you want to recognise and it will be on exams. This particular
drug is contraindicated in peptic ulcer disease, in acute
psychotic illnesses and in patients who have had recent
myocardial infarctions. Dopamine agonist also include new
drugs like ReQuip. It is high affinity for once again the D2
receptor just like bromocriptine. Remember pramipexole is
D3 agent, it makes it unique. The other agents are all D2.
It can be used for monotherapy or combined with levodopa. It
is metabolized by the cytochrome P450 system so it will interact
with warfarin and even caffeine. Adverse events, the same.
Anorexia, nausea, vomiting, postural hypotension and dyskinesias.
Mental confusion can also occur. Confusion, hallucination,
impulsivity. Once again you will see narcolepsy with these agents.
ReQuip is contraindicated in peptic ulcer disease just like
pramipexole. It is also contraindicated psychotic illness
and in recent myocardial infarction. Parkinson's disease is
treated with many dopamine agonist. So this one quite an
interesting one from a historical perspective. Apomorphine is
an injectable high potency dopamine receptor agonist. In the 1920's
it was initially used misguidedly to treat homosexuality
because at that time we used to think homosexuality was a disease.
It provided temporary relief of akinesia.
effects of this drug include anorexia, nausea and vomiting
and postural hypotension with dyskinesia. We often pre-treat
with antinauseants before we use this medication. This is a
medication I think that is important for your exams in terms
of knowing that this is a parenteral drug, it is not given
orally. And it is a very high potency drug.