Hi, welcome to pharmacology by Lecturio. We're going to
continue our discovery of the autonomic nervous system
and the drugs that we use to control various aspects of it.
I'm Dr.Pravin Shukle. Let's start by taking a look
at all of the direct activators of the cholinergic system.
What we mention before in a previous lecture was that
there were two types of cholinergic receptors. The muscarinic
receptors and the nicotinic receptors. Now in order to have
activity at the muscarinic or nicotinic receptors, we
sometimes use choline esters to activate them. Acetylcholine,
methacholine and carbachol will act at both muscarinic and
cholinergic receptors. So these three drugs are drugs worth
remembering but remember that they are not necessarily
specific between the two. The alkaloids, in particular
pilocarpine is a very specific muscarinic cholinergic agent.
Obviously muscarine, which is a chemical that we use sometimes
is a muscarinic agent. And nicotine which is available in any
cigarette that you want to smoke is active at the nicotinic
receptor which is where they both got their names. So now, we
have acetylcholine in the synaptic cleft. There is one of
two things that can happen with acetylcholine. The first thing
is that it will get broken down by acetylcholinesterase into
choline and acetate. That's what we call metabolism of
acetylcholine. The second thing that can happen is
it will actually act on the cholinergic receptor. Now, if you
activate acetylcholinesterase or give it a chance to work
the activity of the cholinergic receptor is going to be reduced.
So acetylcholinesterase stimulators will actually reduce the
effect of that particular choline postsynaptic agent. Let's
take a look at indirect activators. So edrophonium
is a very short acting acetylcholinesterase inhibitor.
Organophosphates are intermediate acting so they act for about
2 to 8 hours. Malathion, parathion or pesticides and sarin is
a terrorist drug if you will, that was used in the 1995
Tokyo attack. So these are acetylcholinesterase inhibitors which
means that the amount of acetylcholine is increased in the
synaptic cleft because you are inhibiting the breakdown.
Carbamates are long acting acetylcholinesterase inhibitors.
They will act anywhere in between 5 and 21 days. So there is
neostigmine and physostigmine. And these are often used
in the treatment of a disease called myasthenia gravis.
We are going to talk about that in a later lecture.