Let's start off with the monoamine oxidase inhibitors.
Monoamine oxidase reduce the breakdown of norepinephrine
and serotonin in the pre-synaptic neuron. So you can see
there that the MAO inhibitors are acting at the level
of the pre-synaptic neuron to reduce the breakdown of those
drugs before they are even released. The increased amounts of
norepinephrine and serotonin are then stored in the vesicles.
So vesicles is Latin for bag. So they have little bags of
hormone at the end of these nerve terminals and they become
ready for use. When the nerve fibers are firing, the increased
amount of transmitter is then released into the synaptic cleft
and so you have more post-synaptic stimulation. That's how MAO's
work. Monoamine oxidase inhibitors can be selective and non-
selective. The non-selective monoamine oxidase inhibitors
include a large list of drugs including phenelzine and
tranylcypromine. These are the two that I want you to remember.
You don't have to remember obviously the 21 others for your
exam. The more selective MAO-A inhibitors include Mannerix
or moclobemide. Now this is a prototypical drug. This is the
one that you will probably be tested on. The selective MAO-B
inhibitor is selegiline and it's also used in Parkinson's
disease. This is a prototypical drug. There are many many
MAO-B inhibitors that are selective and you don't need to
know them all. Side effects to MAO-A's and MAO-B's are
usually due to increased norepinephrine in the nerve terminals.
So this means peripheral autonomic sympathomimetic effects
that we covered before in our autonomic nervous system lectures.
It may actually lower blood pressure and it may reduce the
seizure threshold. Which means that you have an increased risk
of seizures with MAO's. Why is it that MAO's can cause
a reduction in blood pressure. Well you have to remember that
MAO's are being given in the absence of indirect sympathomimetics.
And that's how they cause a drop in blood pressure. So it's
not just about sympathomimetic activity, it's about which type
of sympathomimetic activity you are endangering. Now in the
presence of an indirect sympathomimetic, MAO's cause a large
rise in blood pressure. MAO's in fact may cause severe
hypertension in patients taking tyramine. So tyramine is a
precursor to adrenaline and it is metabolized by monoamine
oxidase. Now, tyramine is found in aged cheeses, in soybean,
in beers and in red wine. And it's also found in
cured and processed meats. So a meal like this
to a patient who is taking a monoamine oxidase
inhibitor can be quite deadly because it can cause
severe hypertension. This is
the great drawback of MAO's.