6. Cholinomimetics Flashcards
(45 cards)
What are cholinomimetics?
- Drugs that mimic the action of ACh in the body
* Parasympathomimetic drugs
What is muscarine?
- Selective muscarinic agonist
* Can replicate muscarinic effects
How can muscarinic effects be abolished?
Low doses of atropine
- a muscarinic antagonist
What happens after an atropine blockade?
• Muscarinic actions blocked
• Large dose of ACh produced
• Induce effects similar to those caused by nicotine
(• Nictonic receptors are in all autonomic ganglia/motor neurones)
What are the 3 main muscarinic receptors and what do they do?
M1
• CNS - excitation
• Salivary glands
• Stomach - stimulates HCl release
M2
• Heart (atria and in both nodes) - decreases heart rate
M3 • Salivary glands • Bronchial/Visceral smooth muscle • Swear glands • Eye
Where are M4 and M5 found?
CNS
Are muscarinic receptors generally excitatory or inhibitory?
Excitatory (apart from M2 on heart)
What type of receptor are muscarinic receptors?
Type 2 (G-protein coupled)
• M1, M3, M5: Gq => stimulates PLC to increase IP3 and DAG
• M2, M4: Gi => inhibitory - reduces cAMP
Describe the structure and types of nicotinic receptors
- Ligand gated ion channels
- 5 subunits (α, β, γ, δ, ε)
- Combination of subunits determines ligand binding properties
- Muscle - 2α, β, δ, ε
- Ganglion - 2α, 3β
How does the effect of ACh on nictonic receptors compare to that of muscarinic receptors?
Relatively weak on nicotinic
What are the 3 main muscarinic effects on the eye?
- Contraction of the ciliary muscle (near vision)
- Contraction of sphincter pupillae (circular muscles) - constriction of pupil (miosis) - increased drainage of intraocular fluid
- Lacrimation
What is glaucoma?
- Increase in intraocular pressure
* Can damage the optic nerves and retina => blindness
Where is the aqueous humour generated and what does it do?
- Generated by capillaries of ciliary body
- Flows into anterior chamber of the eye
- Supplies oxygen and nutrients to the lens and cornea as they don’t have a blood supply
How does the aqueous humour drain?
- Diffuses forwards across the lens then across the cornea
* Drains through the canals of Schlemm back into the venous system
What is Angle-closure glaucoma?
- Angle between cornea and iris becomes narrowed
* Reduced drainage of intraocular fluid via canals of Schlemm
How can you increase drainage of intraocular fluid in a aptient with glaucoma?
• Administer muscarinic agonist
- contraction of iris - opens up angle
• Increased drainage through the canals of Schlemm
Describe how ACh achieves its muscarinic effect on the heart
- ACh on M2 AChR
- Decrease in cAMP
- Decreased Ca2+ entry => decreased CO
- Increased K+ efflux => decreased heart rate
- Drop in BP
Describe the muscarinic effects on vasculature
- Although most blood vessles have no parasympathetic innervation, they do have receptors
- ACh acts on vascular endothelial cells (M3) => NO release => VSMC relaxation
- Decreased TPR
Describe the muscarinic effects on non-vascular smooth muscle
- Responds in opposite way to VSMCs
- Contracts
- Lungs - bronchoconstriction
- Gut - increased peristalsis/motility
- Bladder - increased emptying
What are the muscarinic effects on exocrine glands
- Salivation
- Increased bronchial secretions
- Increased GI secretions (HCl production)
- Increased sweating
Summarise the muscarinic effects in the body
- Decreased heart rate
- Decreased BP
- Increased sweating
- Difficulty breathing
- Bladder emptying
- GI pain
- Increased salivation and tears
What are the 2 types of cholinomimetics?
- Directly acting (usually muscarinic receptor agonists)
* Indirectly acting
What are the 2 types of muscarinic receptor agonists?
- Choline esters (bethanechol)
* Alkaloids (pilocarpine)
Explain the use of pilocarpine
• Derived from leaves of the plant Pilocarpus
- Non-selective muscarinic agonist (stimulates ALL muscarinic receptors)
- Good lipid solubility and half life of 3-4 hours
- Useful to treat glaucoma - constricts sphincter pupillae and opens up canals of Schlemm
