Lec 5- ANS 2 Flashcards
1
Q
Cholinergic transmission
A
- Neurotransmitter ACh acts at: autonomic ganglia; neuroeffector junction in the parasympathetic nervous system; and neuromuscular junctions (NMJ)
- Action terminated by action of AChE (ACh esterase)
- There are 2 different receptor subtypes: nicotinic and muscarinic (sweat glands)
2
Q
Nicotinic Cholinergic receptors
A
- Effects of ACh mimicked by nicotine
- Ligand-gated ion channels (Na+, K+)
- Composed of 5 subunits
- 2 ACh binding sites
- Occurrence: Neuromuscular junction; Autonomic ganglia; CNS
- Stimulate adrenaline secretion from adrenal medulla
3
Q
Muscarinic cholinergic receptors
A
- Effects of ACh mimicked by muscarine
- Effects blocked by atropine
- G-protein coupled receptors
- Occurrence: neuroeffector junction of parasympathetic nervous system ( also cholinergic sympathetic sweat glands and CNS)
4
Q
Muscarinic cholinergic receptors m1
A
- M1 (neural)
- Activate phospholipase C (increase is IP3, DAG)
- Gastric secretion
- Slow excitatory effect at ganglia (due to dec K+ conductance)
- CNS excitation
- Specifically inhibited by pirenzepine
5
Q
Muscarinic cholinergic receptors M2
A
- Cardiac (Bradycardia)
- Inhibit adenylate cyclase (decrease in cAMP)
- Mainly inhibitory effects due to increase in K+ (hyper polarise harder to respond as more -ve) and decrease in Ca2+ conductance so less excitable
- Cardiac inhibition
- Autoinhibition of ACh release from peripheral nerve terminals
- Specifically inhibited by gallamine
6
Q
Muscarinic cholinergic receptors M3
A
- Glandular/ smooth muscle
- Activate phospholipase C (increase in IP3/ DAG)
- Mainly excitatory effects
- Contraction of smooth muscle in GU and urinary tracts
- Stimulation of glandular secretions (digestive enzymes)
7
Q
Drugs affecting cholinergic transmission
A
- Muscarinic agonist/antagonists
- Ganglion stimulating or blocking drugs
- Depolarising or non-depolarising neuromuscular blocking agents
- Inhibitors of ACh synthesis or release (blocking of receptors)
- Cholinesterase inhibitors or stimulants of ACh release
8
Q
Acetylcholine
A
- Choline is taken into nerve terminal by specific carrier (Blocked by hemicholinium)
- Choline acetyltransferase (CAT) catalyses formation of ACh
- Transporters move ACh into synaptic vesicles (inhibited by vesamicol)
- Released by exocytosis (Ca2+ dependent)- blocked by botulinum toxin –> progressive inhibition of parasympathetic function and motor paralysis
9
Q
Types of inhibiting agents
A
- Non-depolarising blocking agents; e.g. tubocurarine
- Pre-synaptic toxins; Botox
- Inhibits ACh into vesicles; vesamicol
- Anti-cholinesterase; neostigmine
- Depolarising blocking agents; suxamethonium
10
Q
Muscarinic agonists
A
- Parasympathomimetics- effects resemble stimulation of parasympathetic nervous systems
- Cardiovascular effects: Decrease HR and CO; vasodilation (endothelium-derived NO)
- Smooth muscle: contraction in GI tract, bladder, lung; Bethanechol formerly used in bladder or GI hypotonia
- Exocrine glands: sweating; lacrimation; salivation; bronchial secretions
- Central effects: tremor; hypothermia; improved cognition; increased locomotor activity
11
Q
Muscarinic antagonists
A
- Atropine and hyoscine are naturally occurring antagonists
- Cardiovascular effects: tachycardia; vascular smooth muscle has no parasympathetic innervation –> no effect on BP
- Smooth muscle: relaxation of bronchial, biliary and urinary tract smooth muscle (urinary retention; oxybutynin and tolterodine treats incontinence; Ipratropium used in asthma)
- GI tract: partially inhibition of GI motility (hyoscine and derivatives of atropine used as antispasmodics
- Exocrine glands: inhibition of sweating, lacrimation, salivation and bronchial secretion
- Central effects: Tremor, hypothermia, improved cognition (dementia), increased locomotor activity
12
Q
Muscarinic antagonists; EYE
A
-Dilution of pupils (mydriasis); cyclopentolate and tropicamide used in eye examinations
-Relaxation of ciliary muscle: Cycloplegia –> impaired vision
- Increased intraocular pressure (cautions in patients with glaucoma)
-Constriction of constrictor papillae muscle, pupil constricts
+Increased drainage of aqueous humour; decreased intra-occular pressure (Pilocarpine used in glaucoma)
13
Q
Muscarinic antagonist- central effects
A
- Excitation
- Anti-emetic action; hyoscine used in motion sickness
- Antiparkinson action
- NB atropine poisoning treated with anticholinesterase e.g. physostigmine
14
Q
Drugs acting at autonomic ganglia; Ganglion stimulants
A
- Most nicotinic agonist act as ganglia and neuromuscular junction (NMJ)
- Nicotine and dimethylphenylpiperazinium (DMPP) preferential for ganglia
- Complex responses due to stimulation of sympathetic and parasympathetic pathways
- Not used clinically
15
Q
Drugs acting on autonomic ganglia: Ganglion blockers
A
- Block neuronal nicotinic receptors or associated ion channels
- Complex effects due to inhibition of sympathetic and parasympathetic pathways (decreased arterial BP; block CV reflexes)
- hexamethonium was first effective anti-hypertensive
- Trimetaphan only agent still used clinically
- Nicotine can cause depolarising block
- Botox blocks transmitter release at ganglia as well as NMJ
