Let's talk about a special topic which is nicotine. Nicotine
actually can cause cholinomimetic toxicity. First time smokers
when you first start smoking can often become nauseous and
that's because of excitation of nicotine receptors in the brain.
And that's very high level of nicotine excitation. Sometimes
with occasional smokers of cigars they will also get nauseous
when they smoke especially a large stoge. What about malathion
and parathion. Malathion and parathion are very common herbicides
and pesticides. These are prodrugs and they are metabolized to
an active form in insects but not humans. So generally speaking
it does'nt affect humans but if you ingest it as in drink it
you can sometimes have significant side effects. We're gonna
speak more malathion and parathion in our toxicology lectures.
What about overdoses with certain types of drugs. Pyridostigmine,
neostigmine and physostigmine which is pictured here are
typical drugs that can cause a parasympathetic crisis.
Let's talk about terrorism. In 1995, there is an attack in
a subway in Tokyo. Members of a cult released sarin gas
into the Tokyo subway system and it caused a large number of
deaths. Now a few people survived and the reason why they survived
was because the physicians who were working at the hospitals
were alert enough to realise that these patients had
acetylcholine toxicity. Now, sarin is an organophosphate.
It is very very potent. Death can occur within minutes.
And they have death because of asphyxia. They can also develop
permanent neurological damage. Now the antidote to sarin or any
drug that increases acetylcholine activity excessively is
atropine. Now atropine is available in pretty much every single
crash cart. And it's probably the least used drug in the crash
cart. So it's usually the one that is kind of at the back
of the drawer. But if you see a patient who you suspect has
been poisoned by something like sarin and you have a lot of
people coming in at the same time, think about using atropine.
So what do these patients look like? They look exactly like
those patients who have pesticide toxicity. So pesticide
ingestion from say malathion or parathion or even an excess
dosage of the medicines pyridostigmine, neostigmine and
physostigmine. Now let's compare a cholinergic crisis or a
parasympathetic crisis to a disease called myasthenia gravis
and myasthenia crisis. Now in the case of myasthenia, there is
destruction of the acetylcholine receptor. In the case of
cholinergic crisis there is excess acetylcholine. For example,
when you are exposed to sarin gas. In myasthenia crisis,
you have an increase in heart rate and blood pressure,
and bowel and bladder incontinence. In cholinergic crisis,
there is a decrease in blood pressure and you have abdominal
cramps, nausea, vomiting and diarrhoea. In myasthenic crisis
they're very weak, so they will an absent cough reflex
and an absent swallow reflex. One of the tricks we sometimes
do is we give them a little bit of water in a spoon and put
them in the mouth and see if they swallow and responds to it. A
cholinergic crisis is blurred vision, pallor and facial muscle twitching.
In terms of the effect of edrophonium, edrophonium will give
temporary relief in myasthenic crisis. Remember that edrophonium
is an acetylcholinesterase inhibitor so it actually causes
more acetylcholine in the synaptic cleft which does'nt
necessarily overcome the lack of receptors in the post synaptic
nerve, but at least it helps stimulate more of the receptors
because of increased concentration. In cholinergic crisis,
edrophonium has no effect because the receptors are already
saturated. However, edrophonium given to a person who is'nt
in full blown cholinergic crisis can actually precipitate
a cholinergic crisis because now you have really done it and
caused an increase in ACH levels. Atropine will not help
myasthenic crisis. But in cholinergic crisis, atropine will
improve symptoms. So there you have it. Those are very
complicated especially the differentiation of myasthenic versus
cholinergic crisis. We are going to have questions on them
so that you can review them in detail.
Thank you very much.