Cholinergic pharmacology II Flashcards
How can ganglion nAChRs be blocked ?
W/ hexamethonium.
How we muscle nAChRs be blocked ?
W/ decamethonium/tubocurarine.
What are the 7 steps in cholinergic transmission ?
How can various drugs interfere w/ these different steps ?
- Uptake (- hemicholinium)
- Synthesis
- Packaging (- vesamicol)
- Release (presynaptic toxins e.g. botulinum)
- Receptors (agonists, antagonists)
- Postsynaptic response
a) channel opens
b) postsynaptic cell depolarises
c) and fires an action potential - AChE destroys ACh (ChE inhibitors e.g. neostigmine)
What is suxamethonium ?
Suxamethonium = depolarizing blocking agent, acts post-synaptically
What is tubocurarine ?
Tubocurarine = a non-depolarizing, competitive blocking agent, acts pre- and post-synaptically on nAChRs
What did Dr Giles Everard have to say about tabacco in 1659 ?
“. . .to strengthen the memory the smoke is excellent taken by the nostrils, for it is properly belonging to the brain, and it is easily conveyed into the cels of it and it cleanseth that from all the filth (for the brain is the Metropolis of flegme, as Hippocrates teacheth us . . .)”
What are the characteristics of nicotine, from the nicotiana tabacum plant (and which is preent in tobacco) ?
A volatile compound, absorbed through mucous membranes (smoking!) and skin (patches)
Activates and desensitises nicotinic receptors
Stimulation of autonomic ganglia: vasoconstriction, increases in blood pressure & heart rate
CNS stimulation: reward (limbic areas), appetite suppression (hypothalamus POMC neurones)
What are the effects of ganglion blockers ?
Effects depend on whether autonomic tone in the
target organ is Sympathetic or Parasympathetic :
- sweat secretions reduced
- nasopharyngeal and salivary secretions reduced
- eyes : paralysis of accomodation and reaction to light; secretions reduced
- face : vasodilation
- heart : modest tachycardia
- stomach/gut : mvnts imaired; constipation
- pelvic region : difficulty in micronutrition; impotence
- hands : vasodilation
- lower legs/feet : vasodilation
What is autoimmune autonomic ganglionopathy (AAG)
Autoimmune autonomic ganglionopathy (AAG) is an extremely rare form of dysautonomia in which the patients immune system produces ganglionic AChR antibodies, inhibiting ganglionic AChR currents and impairing transmission in autonomic ganglia (leading to “hexamethonium man” symptoms).
What is trimetaphan ?
How is it used ?
A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.
What is curare ?
Curare is an example of a non-depolarizing muscle relaxant that blocks the nAChR at the neuromuscular junction.
How does tubocurarine work ?
Tubocurarine reduces the number of available receptors and decreases the amplitude of the postsynaptic current at the NMJ.
The postsynaptic current is now too small to evoke an action potential.
What is suxamethonium/succinylcholine ?
How does it work ?
Suxamethonium (do NOT confuse w/ hexamethonium!) is an agonist of muscle nicotinic receptors and is resistant to the local ChE (AChE). At first, the depolarisation produced by the agonist effect of suxamethonium causes an action potential, but as depolarisation continues the surrounding voltage dependent sodium channels inactivate, and action potentials cease.
Name three nicotinic competitive blockers.
What are their characteristics and why are they used ?
Tubocurarine, pancuronium, atracurium Large molecules Paralysis without initial contraction Reversed by ChE inhibitors Relatively long-acting Used to obtain muscle relaxation at lower depth of general anaesthesia (faster recovery) and for mechanical ventilation
Name one nicotinic depolarizing blocker.
What are its characteristics and why is it used ?
Suxamethonium Small molecule Fasciculations Not reversed by ChE inhibitors Short-acting (2-6 min) if plasma ChE is normal Used for intubation
