Flashcards in Cholinergic/Adrenergic Pharmacology Deck (34):
In which parts of the peripheral nervous system does ACh act?
Somatic, and parasympathetic branch of the autonomic nervous system
Name the principal neurotransmitter in the body
What are the two types of cholinergic receptor?
What type of receptor works in the somatic branch of peripheral nervous system?
Nicotinic receptors (NMJ)
Parasympathetic nerves consist of pre ganglionic fibres and post ganglionic fibres. What are the receptors at each of these synapses?
Pre ganglionic = nicotinic
Post ganglionic = muscarinic
How does botulinum toxin prevent release of ACh at synaptic cleft?
Botulinum toxin is a protease and so degrades vesicle proteins and prevents vesicle fusion with the presynaptic membrane
Name 4 ways in which ACh is modulated at junctions
1) Botulinum toxin
3) Depolarising blockade (agonist)
What are the two main effects of ACh in the eye?
Constricts constrictor muscle and ciliary muscle leading to constriction of pupil (miosis).
Lowers intraocular pressure due to improved filtration of aqueous fluid (useful in glaucoma)
Name an agonist and antagonist of ACh in the eye
Agonist = pilocarpine
Antagonist = atropine cyclopentolate or tropicamide
What affect does ACh have in the lung?
Name one short acting antagonist (bronchodilator) of ACh in the lung and one long acting antagonist
Short acting - Ipratropium
Long acting - Tiotropium
What affect does ACh have in the bladder
Contracts detrusor muscle so will cause urination
What affect will both an agonist and antagonist of ACh have on the bladder and give an example of each
Agonist = prevents urinary retention (bethanechol)
Antagonist = can reduce urinary frequency (oxybutinin)
What affect does ACh have on GI motility and name two antagonists of ACh that work in the GI system
ACh increases gastric motility
Examples of antagonists: Mebeverine, scopolamine
Give the mnemonic for the adverse effects of muscarinic agents
What is hexomethonium?
A competitive agonist for ACh at nicotinic receptors in the autonomic nervous system (so affects both sympathetic and parasympathetic divisions)
Name two antagonists that work in the CNS
Scopolamine - anti muscarinic and prevents motion sickness
Benzatropine - blocks reuptake of dopamine in synaptic cleft - treats Parkinsons
Name one cholinesterase inhibitor that works in the CNS
Donepezil - works for Alzheimers and inhibits cholinesterase. Alzheimers is often caused by lacking cholinergic neurones so less ACh.
In what part of the nervous system does NAd work?
Sympathetic division of autonomic nervous system
What activates NAd to be released from post synaptic neurone?
ACh binding to nicotinic receptors, which creates an AP in pre-synaptic neurone. This allows influx of calcium which fuses dopamine vesicles with pre-synaptic membrane.
Give the 5 stages of catecholamine synthesis
Tyrosine --> DOPA --> Dopamine --> Noradrenaline --> Adrenaline
Which G proteins are coupled to alpha and beta adrenoreceptors?
Alpha 1 = Gq
Alpha 2 = Gi
Beta = Gs
What significant molecules are produced in alpha and beta adrenoreceptor stimulation and what do these molecules do?
Alpha = IP3, which stimulates opening of calcium ion channels meaning smooth muscle contraction
Beta = PKA* which causes heart muscle contraction, smooth muscle relaxation and glycogenolysis
What effect does α1 stimulation have on the body?
Vasoconstriction, mydriasis, contraction of bladder neck (urinary retention)
What effect does NAd binding to α2 receptors have on the body?
Inhibits the release of NAd into the cleft, and reduces insulin produced from pancreas
What effect does NAd binding to β1 receptors have on the body?
Positive inotropic effect on heart, increased renin from kidney, increased BP
What effect does NAd binding to β2 receptors have on the body?
Bronchodilation, vasodilation, decreased GI motility
What effect does NAd binding to β3 receptors have on the body?
Increased lipolysis and relaxation of the bladder
What 3 ways can drugs target adrenergic responses in an attempt to alter them?
1. NAd transporter
2. Enzymes (MAO and COMT)
3. Adrenoreceptor directly
How does adrenaline target adrenoreceptors?
Is a non-selective agonist for α1 (vasoconstriction), β1 (positive inotropic effect), and β2 (bronchodilation)
Would you give beta-blockers to an asthmatic?
No, because their inhaler salbutamol is a β2 agonist, so by giving a β antagonist, it would mean their inhaler was ineffective
Give an example of a β2 agonist that would be used as an anti-hypertensive
How do amphetamine and cocaine effect adrenoreceptors?
They block the NAd transporter so that NAd remains in the synaptic cleft which increases arousal and alertness in the brain