Pharmacology Of Cholinergic Transmission Flashcards
What neurotransmitter is released at most autonomic synapses?
What is the exception?
Acetylcholine
Sympathetic (eg.blood vessels)
What is ACh formed from?
Choline
Acetyl coenzyme A
What enzyme catalyses the formation of ACh?
Choline acetyl transferase (CAT)
What is ACh stored in?
Pre-synaptic vesicles
By what process are the contents of pre-synaptic vesicles released?
Exocytosis
What causes the release of ACh?
Increased intracellular calcium ion concentration within nerve terminal
What are the two types of cholinergic receptor?
Muscarinic
Nicotinic
What enzyme catalyses the breakdown of ACh?
Acetylcholine-esterase (AChE)
Where is acetylcholine-esterase found?
In synaptic cleft tethered to post-synaptic membrane
What type of receptor is present at neuromuscular junctions?
Cholinergic nicotinic
What is the small brief depolarisation that occurs in the muscle fibre to trigger an action potential?
End plate potential
What causes sustained muscle fibre contraction?
Frequent action potentials
Causing twitch summation
What three pre-synaptic processes could be targeted to modify synaptic transmission?
Synthesis
Storage
Release
What drugs inhibit ACh synthesis?
Hemicholiniums
What enzyme do hemicholiniums inhibit?
Choline acetyl transferase (CAT)
What drug inhibits storage of ACh?
Vesamicol
What does vesamicol inhibit?
ACh storage
What inhibits the release of ACh?
Botulinum toxin
What is the (only) clinical use of nicotinic agonists?
Nicotine patches
What type of drug are muscle relaxants?
Reversible competitive antagonists of cholinergic nicotinic receptors
What are the properties of antagonists?
Have affinity but no efficacy
What do muscle relaxants do?
Bind to cholinergic nicotinic receptors on muscle fibres
Prevents ACh binding/activating receptor
What is an example of a skeletal muscle relaxant?
Vecuronium
Atracurium
Pancuronium
TUBOCURARINE
Why are ganglion blockers not used clinically (often)?
Many side effects
What is the major effect caused by ganglion blockers?
Reduction in blood pressure
What is an example of a ganglion blocker?
Hexamethonium
Trimetaphan
What is trimetaphan used for clinically?
Reduces bleeding during brain surgery
Reduces blood pressure
What is botulism?
Paralysis (of respiratory muscles)
What does botulinum toxin do?
Destroys key proteins involved in exocytosis (inhibiting release of ACh)
What are some key proteins involved in exocytosis?
SNAP-25
Synaptobrevin
Syntaxin
How many serotypes of botulinum toxin are there?
Which is most commonly used clinically?
7
Serotype A
What is botulinum toxin used to treat?
Bletharospasm (involuntary tight closure of eyelids)
Bladder hyperreactivity
Why is botulinum toxin injected locally?
Toxic in blood —> botulism
What type of receptor alters ANS (especially parasympathetic) activity?
Muscarinic
What are parasympathomimetics?
Muscarinic agonists that mimic effects of parasympathetic NS
What are parasympatholytics?
Muscarinic antagonists that block effects of parasympathetic NS
Why do drugs acting on muscarinic receptors tend to have side effects when given systemically?
Difficult to distinguish between subtypes
Which glands are typically innervated by the sympathetic and parasympathetic NS?
S = sweat
P = salivary and others
What are some effects of activating M3 receptors?
Pupil constriction/miosis
Ciliary muscle contraction
Lacrimal gland secretion
Airway smooth muscle constriction
Increased peristalsis
Detrusor contraction
Increased bronchial secretions
Where is the M2 receptor found?
Heart/SAN
What does activation of M2 cause?
Decreased heart rate
What does M1 activation cause?
Gastric acid secretion
What is bethanacol used for?
Stimulant laxative
Prevent constipation after surgery
What are pilocarpine eye drops used to treat?
How?
Glaucoma
(Miosis and) contraction of ciliary muscle so suspensory ligaments lose tension
Lens becomes more spherical
Improves aqueous humour flow to reduce intraocular pressure (canal of Schlemm)
What was the ‘pilocarpine sweat test’ used to diagnose in the past?
Cystic fibrosis
What can atropine be used for? (2)
Sinus bradycardia (M2)
Preparing patients for surgery by reducing bronchial secretions (M3)
What type of drug is atropine?
Muscarinic antagonist
What drugs may be used to dilate the pupil?
Tropicamide
Cyclopentolate
What drugs (parasympathetic) may be used to treat asthma (and other chronic obstructive pulmonary diseases)?
Ipratropium
Tiotropium
What drug is used to treat motion sickness?
Hyoscine
What drugs may be used to treat Parkinson’s disease?
Benzhexol
Benztropine
What drug may be used to treat urinary incontinence?*
Tolterodine
Oxybutynin
What is an example of an AChE inhibitor?
Neostigmine
Edrophonium
Dyflos
How do AChE inhibitors affect transmission?
Prevent breakdown of ACh so increased ACh concentration in synaptic cleft
Enhances transmission in all autonomic ganglia and at parasympathetic neuroeffector junctions
What are some physical effects of AChE inhibitors? (5)
Increased secretions (saliva, sweat, gastric acid, mucus, lacrimal)
Increased smooth muscle tone (bronchoconstriction, increased peristalsis)
Miosis (decreased intraocular pressure)
Bradycardia
Hypotension
What drug is used to reverse the effects of muscle relaxants?
Neostigmine
What is neostigmine used to treat?
Myasthenia gravis (autoimmune disease where autoAbs destroy nicotinic receptors)/neuromuscular weakness
