Cholinomimetics Flashcards
Describe the synthesis of acetylcholine.
Acetylcholine is synthesised from Acetyl CoA and choline via choline acetyltransferase (CAT)
Why are the receptors described as nicotinic and muscarinic?
Muscarinic effects are those that can be replicated by muscarine + abolished by atropine. Correspond to parasympathetic stimulation.
Nicotinic effects are those that an be replicated by nicotine
State where you would find the different types of muscarinic receptor.
M1: salivary glands, CNS, stomach
M2: heart
M3: salivary glands, bronchial/ visceral smooth muscle, eyes, + sweat glands
M4 and M5 are found in the CNS
NOTE: generally excitatory except for on the heart
What type of receptor are all muscarinic receptors?
G-protein coupled receptors
What is the difference in the G-protein receptors of M1, M3 and M5 compared to M2 and M4?
M1, M3 and M5 = Gq protein linked receptors: they stimulate PLC which increases IP3 and DAG
M2 and M4 = Gi protein linked receptors (inhibitory) – they decrease the production of cAMP
Describe the structure of nicotinic receptors. What determines its ligand binding properties?
Ligand gated ion channels- consist of 5 subunits (alpha, beta, gamma, delta or epsilon)
Combination of subunits determines ligand binding properties.
What are the 2 main types of nicotinic receptor? Describe their subunit composition.
Muscle = 2 alpha + beta + delta + epsilon Ganglion = 2 alpha + 3 beta
How do the effects of acetylcholine on nicotinic receptors compare to its effects on muscarinic receptors?
Effects of ACh are relatively weak on nicotinic compared to muscarinic
What 3 effects does muscarinic stimulation have on the eye?
Contraction of the ciliary muscle (accommodates near vision)
Constriction of sphincter pupillae (circular muscle of iris) – this constricts the pupil + increases drainage of intraocular fluid
Lacrimation
What is glaucoma?
Sustained raised intraocular pressure
Can cause damage to the optic nerves + retina
Can lead to blindness
Where is aqueous humour produced? Describe its passage through the eye.
Capillaries in the ciliary body produce aqueous humour
which flows anteriorly into the anterior chamber and is then drained through the canals of Schlemm into the venous system
What is the role of aqueous humour?
Provides oxygen and nutrients to the cornea and lens because they don’t have a blood supply
What happens in Angle-closure glaucoma?
Angle between cornea + iris is narrowed, which decreases the drainage of intraocular fluid through the canals of Schlemm, thus intraocular pressure increases
What are the effects of giving a muscarinic agonist to people with Angle-closure glaucoma?
Causes constriction of sphincter pupillae and opens up the angle to increase the drainage of intraocular fluid
Describe the muscarinic effects on the heart.
Binding of ACh to M2 receptors causes a decrease in cAMP production
This triggers a decrease in Ca2+ influx, which leads to a decrease in CO
It also triggers an increase in K+ efflux, which leads to a decrease in HR
Describe the muscarinic effects on the vasculature.
No direct parasympathetic innervation of blood vessels
However, there are muscarinic receptors on the endothelial cells
ACh stimulates production of NO from the endothelial cells, which causes vasodilation and a decrease in TPR and BP
Summarise the muscarinic effects on the cardiovascular system.
Decrease in HR
Decrease in CO (due to decreased atrial contraction)
Decrease in TPR (due to vasodilation)
Decrease in BP
Describe the muscarinic effects on non-vascular smooth muscle.
Opposite of muscarinic effects on vascular smooth muscle
It causes CONTRACTION of non-vascular smooth muscle
Lungs = bronchoconstriction (difficulty breathing)
GI tract = increased motility (GI pain)
Bladder = increased bladder emptying
Describe the muscarinic effects on exocrine glands.
Salivation
Increased bronchial secretions
Increased GI secretions (including gastric HCl production)
Increased sweating (sympathetic-mediated)
What are the 2 types of cholinomimetic drug?
Directly Acting: muscarinic agonists
Indirectly Acting: acetylcholinesterase inhibitors -> increase the synaptic concentration of ACh
State 2 types of muscarinic receptor agonists and give an example of each.
Choline Esters e.g. Bethanechol
Alkaloids e.g. Pilocarpine
Describe the selectivity of pilocarpine.
Non-selective muscarinic receptor agonist
It stimulates ALL muscarinic receptors
What is pilocarpine used to treat?
Glaucoma (stimulates muscarinic receptors of iris, flattening iris + improving drainage)
State 5 side-effects of pilocarpine.
Blurred vision Hypotension Sweating Respiratory difficulty GI disturbance and pain
