Pharmacology of the ANS Flashcards
What do both parasympathetic and sympathetic system both use
- Acetylcholine and nicotinic receptors between pre and post synaptic neurones
- Excitatory
what does the parasympathetic post ganglionic neurone use
- Acetylcholine and muscarinic receptors on target organs
- Excitatory or inhibitory
Sympathetic post-ganglionic neurones use:
• Noradrenaline and α or β adrenoreceptors
• Sweat glands - acetylcholine and muscarinic receptors
• Kidney - dopamine and dopamine receptors
• Adrenaline and noradrenaline secreted by adrenal gland
• Excitatory and inhibitor
- they use noradrenaline at post ganglionic synapse except for sweat glands which use ACh
what does ganglionic transmission use
Ach
what does NANC stand for
NON adrenergic and non cholinergic
what does NANC
- it is cotransmitters with ACh or noradrenaline o Nitric oxide o Vasoactive intestinal peptide o Neuropeptide Y o 5-hydroxtryptamine o ATP
where is NANC
- widely distributed in peripheral tissues
describe acetylcholine
- Choline + acetyl CoA using choline transferase = acetylcholine
- Packaged into vesicles
- Broken down into choline and acetate by acetylcholinesterase
- Choline then transferred back into pre-synaptic terminal fro recycling
what do Parasympathomimeticdo
- These mimick the parasympathetic activation
what is a parasympathetic agonist
- Produce similar response to acetylcholine
- Can be substances that activate the muscarinic receptors
- Prevent normal ACh breakdown so more endogenous neurotransmitter
what activates a nicotinic receptor
- Selectively activated by alkaloid nicotine
what activates a muscarinic receptor
- Selectively activated by alkaloid muscarinic such as fly agaric
what are the nicotinic agnostic
Nictotine
- for ganglionic and CNS
- Smoking cessation
Suxamethonium
- for neuromuscular junction
- Short term neuromuscular block – depolarising blockade
what are the nitoctirnic antagonist
Hexamethonium –
• for ganglionic nicotinic receptors
• 1st effective antihypertensive treatment – it casues vascodilation, activates the sympathetic system to cause vascodilation
Pancuronium
• for neuromuscular junction receptors
• Longer neuromuscular block – prevents sodium from entering, cuases long term blockage
• Used in lethal injections
Tubocurarine
• Causes skeletal muscle relaxation / paralysis
what is the structure of the nicotinic receptor
Found in ganglions 2 alpha subunits and 3 beta subunits Different subtypes have different affinities for nicotine (more in ganglionic and CNS than neuromuscular) Alpha 3 – autonomic ganglia Alpha 1 – neuromuscular junction
what is the nicotinic receptor in the ganglia
alpha 3
what is the nicotinic receptor in the neurmuscular junction
alpha 1
where are the muscarinic receptors found
Found on postganglionic parasympathetic fibres
what are the 5 types of muscarinic receptors
- M1 – excitatory – increases gastic acid secretion
- M2 – inhibitory – decreases heart rate and force
- M3 – excitatory – increase GI motility, bladder contraction, bronchiocontriction, constricts pupil
- M4&5 – CNS
what are the muscarinic agonists
carbachol • Work at both nicotinic and muscarinic Bethanechol • Selective for muscarinic receptors • Not hydrolysed by cholinesterase so has long duration of action • Increases bladder and gastrointestinal contraction Pilocarpine • Selective for muscarinic receptors • Eye drops for glaucoma
what are the antagonist for muscarinic receptor non selective for muscarine receptors
Atropine- opposite of carbachol • Reduced bronchial secretions • Pupil dilation • Treats bradycardia • Used in organophosphate poisoning – causes the neuromuscular junction to become depolarised • Can be given locally • M2 causes inhibitory • Problem – if you only want to open the eye up you don’t want to affect the heart but will do so anyway as it is non selective
Scopolamine
• GI Antispasmodic
• Motion sickness
• Can be given as a patch which can be absorbed across the skin
Ipratropium
• Inhaled for asthma (bronchodilator)
what are the antagonists selective for muscarnic receptors
Pirenzepine / Telenzepine
• M1 selective antagonist
• Reduces gastric acid secretions
Gallamine
• M2 selective antagonist binds to M2 so M1 is more active causes tachycardia
• Causes tachycardia
Darifenacin / Solifenacin
• M3 selective antagonist
• Urinary incontinence – urge this is where they feel that they need to go but they don’t their bladder has just expanded more
• Used for people with Overactive bladder
what do cholinestrase inhibitors do
- Stimulate GI function - prokinetics
- Cognitive enhancers – used in Alzheimer’s patients
- Skeletal muscle activity
- Neostigmine used for myasthenia gravis – this is so that the remaining nicotinic acetylcholine receptors have more of a chance of being activated/ works on both nicotinic and muscarinic receptors
what does botulinum toxin do
Clostridium botulinum bacteria
- Prevents acetylcholine release
- Irreversible
- Excessive sweating
- Overactive bladder
- Muscle spasm
- No SNARE proteins to cause vesicles to move to the membranes so no acetylcholine is released
what are sympathomimetrics
• Agents that produce a similar response as noradrenaline and adrenaline on the sympathetic nervous system
what are the sympathomimetics
Monoamine – neurotransmitters
• Noradrenaline, adrenaline, dopamine, histamine, 5-hydroxytryptamine, melatonin
• Amine group connected to an aromatic ring
Catecholamine
• Noradrenaline, adrenaline, dopamine isoprenaline
• Catechol group (benzene + 2 hydroxyl) and amine side chain
how is noradrenaline synthesised and broken down
- Synthesised in the cell body and then transported down
- Amino acid is tyrosine this si the starting point, this gets converted to L-dopa which is made into dopamine which is made into noradrenaline
- After noradrenaline is released into the synaptic cleft it needs to be switched of, this happens by monoamine oxidase - Catechol-O-methyltransferase (COMT)
what does the noradrenaline receptors do
- Alpha 1 stimulation = vasoconstriction and inhibition of GI and bladder
- Beta 1 stimulation = increase heart rate and force
- Beta 2 stimulation = bronchodilation, vasodilation, inhibits GI and bladder
what is the clinical use of noradrenaline receptors
o Alpha 1 antagonists for hypertension
o Beta 1 antagonists for angina and hypertension (beta blockers) - atenolol
o Beta 1 agonists for cardiac arrest and shock, increase cardiac contractility and heart rate and is used in cardiac arrest and shock
o Beta 2 agonists for asthma – salbutamol causes bronchodilation
- B3 solabegron - begin developed for overactive bladder and iBS
what does a2 clonidine do
o Antihypertensive (inhibits noradrenaline release) o Analgesic and sedation used in combination with ketamine
what does a1 do
prazosin, doxazosin, tramsulosin
• Anti-hypertensive- cause vascodilation
• Benign prostatic hyperplasia
what is a non selective isoprenaline
Beta receptors agonists
• Non selective isoprenaline
• No longer used for asthma because of effects on heart
• Now only used to reverse overdose by β-blockers
what are the beta receptor antagonists
Non selective
Propranolol
• Timolol used to decrease aqueous humour production
β1 atenolol
• Decreases heart rate and force of contractility used in angina, hypertension, cardiac dysrhythmias, tremor
β2 butoxamine
• Has no medical use
