Cholinergic pharmacology I Flashcards
What are the three main peripheral cholinergic pathways ?
- Spinal cord –> muscle (nAChR) (Somatic system)
- Sp cord –> ganglion (nAChR) –> target e.g. bl vessel (Symp NS)
- Sp cord –> ganglion (nAChR)
What kinds of receptors are found the post-ganglionic neurons of the parasympathetic nervous system ?
- Preganglionic neurones synapse in the ganglion onto postganglionic neurones.
- Postsynaptic receptors at this synapse are (mostly) nicotinic
In Dale’s famous experiment, what effect did he observe on heart pressure after injecting a small dose of ACh (1ug) ?
What about when atropine (1ug) was added ?
And when a larger dose of ACh (1mg) was added ?
What about when finally hexamethonium was was added ?
Small dose of ACh = vasodilation (muscarinic)
This was blocked by atropine
Larger dose of ACh (in the presence of atropine) stimulates ganglia and adrenal medulla (nicotinic), causing vasoconstriction and tachycardia. This is all blocked by hexamethonium, even if 1mg of ACh is added after.
Which structure of the parasympathetic system are not innervated ?
Most blood vessels.
What effect does muscarinic stimulation have on :
- smooth muscle of the eye, bronchi, GIT + bladder
- most blood vessels
- arterioles in genitals
- glands : lacrymal, salivary, GIT, bronchial, sweat glands
- heart
Smooth muscle of the eye, bronchi, GIT + bladder –> contraction
Most blood vessels –> relaxation (not innervated)
Arterioles in genitals –> relaxation
Glands : lacrymal, salivary, GIT, bronchial, sweat glands –> secretion
Heart –> slow rate + conduction
Name 6 muscarinic agonists you know.
Specify to which receptor(s) they bind and how quickly they are metabolized/broken down.
ACh –> both N and M, quickly hydrolysed by ChE
Methacholine –> M, slowly hydrolysed by ChE
Carbachol, CCh –> both N and M, resistant
pilocarpine –> M, resistant
muscarine (Fly agaric, amanita muscaria ) –> M, resistant
bethanechol –> M, resistant
What is atropine and what effects does it have ?
What does it reveal ?
Atropine (from atropa belladonna, Deadly nightshade ) = a muscarinic antagonist, its effect reveal the tonic activity of the parasympathetic NS
Its effects include :
- CNS: antiemetic (motion sickness); less tremor in Parkinson’s; excitation (toxic doses); cognitive impairment in elderly
- Eye: pupil dilatation (mydriasis); paralysis of accommodation, intra-ocular pressure may rise
- Secretions reduced: saliva, tears, sweat, bronchi, GI
- Smooth muscle relaxed (bronchi, GI tract)
- Heart: may increase heart rate; no effect on blood vessels
- Urinary retention
What effects do muscarinic stimulation have on the eye ?
ACh activates M receptors : pupils constrict (miosis), ciliary muscle contracts, releasing the lens, which relaxes into a “fat” shape, good for near vision (accommodation)
What happens during glaucoma ?
How can it be treated ?
In glaucoma an increased intraocular pressure leads to retinal damage.
Muscarinic agonist are helpful because pinpoint pupils (miosis) and ciliary spasm improve the drainage of aqueous humour.
Which areas of the heart does the parasympathetic system innervate ?
What effect does cholinergic stimulation of the heart have ?
The parasympathetic system (via vagus nerves) innervates mostly the sino-atrial and atrio-ventricular nodes and the atria.
M receptor activation slows heart rate by slowing the spontaneous depolarization of pacemaker cells.
What are the therapeutic uses of muscarinic agonists ?
1) Glaucoma (pilocarpine eye drops; not first choice)
2) Relieve dry mouth (xerostomia; pilocarpine)
3) Relieve paralytic ileus after abdominal surgery (oral bethanechol)
4) Relieve urinary retention (bethanechol; catheterisation more common)
What are the therapeutic uses of muscarinic antagonists ?
- Anaesthesia: pre-medication (sedation, less secretions) or to reduce effects of ChE inhibitors and vagus stimulation induced by surgery of visceral organs (hyoscine = scopolamine).
- Eye: eye drops to induce mydriasis and ciliary muscle paralysis for retinal examination (tropicamide) or after surgery (atropine).
- Intraocular pressure may rise
- In anticholinesterase poisoning
- Symptomatic relief of smooth muscle spasm (eg bronchi, in chronic obstructive pulmonary disease or asthma resistant to first-line drugs; ipratropium, tiotropium inhalation)
- Parkinson’s disease
- Motion sickness (hyoscine)
- Urinary urgency & incontinence (oxybutynin, tolteroldine, trospium)
What kinds of drugs can block muscarinic receptors ?
Many common drugs (antipsychotics, antidepressants,
antihistamines) can block muscarinic receptors.
