Autonomic Nervous System 2 Flashcards
Describe sympathetic innervation of the adrenal gland
Preganglionic sympathetic fibers synapse on chromaffin cells
Chromaffin cells release adrenaline (~80%) and noradrenaline (~20%) into systemic circulation
-> widespread tissue response
Where are the locations of all acetylcholine receptors in ANS?
Eye Lacrimal gland Salivary gland Heart Lungs Upper GI tract Lower GI tract Genitalia Adrenal medulla Sweat glands All ganglia including pelvic ganglia to lower GI tract and paravertabral sympathetic chain
What are the two types of acetylcholine receptors?
Nicotinic (Inotropic) and Muscarinic (G-protein linked receptor)
Can we differentiate muscle from ganglion NAChr?
Kinda:
Differences in subunits may allow for some specificity
Therapeutically, what’s the benefit of differentiating muscle NAChr from ganglion NAChr?
What would the effect of stimulating or blocking all ganglia be?
Tissues innervated by both branches of the ANS generally have a predominate tone
What is predominate tone?
In “most” organ systems, the parasympathetic nervous system displays a “predominant tone”, meaning it has a stronger influence on tissue function when the body is at rest, as compared to the sympathetic nervous system
What kind of drugs act on ACh with implications for the ANS?
Presynaptic toxins like botulinum
Anticholinesterases like neostigmine
What are the effects of anticholinesterases?
SLUDGE – Salivation – Lacrimation – Urination – Defecation – Gastrointestinal upset – Emesis – Bradycardia – Hypotension – Bronchoconstriction – Pupillary constriction (miosis)
Where are the predominate locations of nicotinic ACh receptors?
Neuromuscular junction Sympathetic ganglia Parasympathetic ganglia
Central nervous system
Where are the predominate locations of muscarinic ACh receptors?
Parasympathetic target organs Sweat glands (sympathetic) Vascular smooth muscle
Central nervous system
What complication may the presence of nicotinic ACh receptors being present at the neuromuscular junction cause?
Differences in the receptor types or subtypes may allow for specificity of drug action
Drugs that affect ACh at the NMJ may affect the ANS! Side effects of suxamethonium? Anticholinesterases?
How are muscarinic and nicotinic ACh receptors differentiated?
Nicotinic andmuscarinicAChreceptorsshare some agonists, but can be differentiated by others
Drugs that affect the synthesis, storage, release and termination of ACh will affect both receptor types
Drugs that affect ACh at the Sk. NMJ may affect the ANS
What drugs affect both muscarinic and nicotinic ACh receptors?
Acetylcholine
What drugs affect only muscarinic and not nicotinic ACh receptors?
Muscarine
Bethanechol
Pilocarpine
What drugs affect only nicotinic and not muscarinic ACh receptors?
Nicotine
How are muscarinic ACh receptors classified?
Muscarinic receptors can be classified by their tissue distribution and their cellular response.
What are the classifications of muscarinic ACh receptors?
M1 (neural)
M2 (cardiac)
M3 (glandular/smooth muscle)
Where are the main locations of the M1 (neural) muscarinic ACh receptors?
Autonomic ganglia Glands: gastric, salivary, lacrimal, etc.
What are the functions of M1 (neural) muscarinic ACh receptors?
↑ IP3, DAG
Which leads to
Gastric secretion
Where are the main locations of the M2 (cardiac) muscarinic ACh receptors?
Heart: atria
What are the functions of M2 (cardiac) muscarinic ACh receptors?
↓ cAMP
Which leads to
Cardiac inhibition
Where are the main locations of the M3 (glandular/smooth muscle) muscarinic ACh receptors?
Exocrine glands: gastric, salivary, etc. Smooth muscle: GI tract, eye, airways, bladder
Blood vessels: endothelium
What are the functions of M3 (glandular/smooth muscle) muscarinic ACh receptors?
↑ IP3, DAG
Gastric, salivary secretion
GI smooth muscle contraction Ocular accommodation Vasodilation
Are all muscarinic receptors found in the ANS?
Not all muscarinic receptors are in the ANS
– M1, M2, M4 and M5 also found in CNS
– M3 found on vascular endothelial and smooth muscle cells
What factors should be considered when discussing parasympathetic directed therapies?
There are several types of muscarinic ACh receptors
– Some are excitatory
– Some are inhibitory
Can differences be exploited therapeutically?
– Receptor subtype specificity?
– Receptor tissue distribution?
What type of drug would be required?
– Agonist?
– Antagonist?
Name some muscarinic ACh receptor agonists
- Pilocarpine
Constriction of pupils (miosis) Non-selective muscarinic agonist Glaucoma (to decrease IOP)
Xerostomia (following head/neck radiotherapy) - Bethanechol
Non-selective muscarinic agonist Bladder and gastrointestinal hypotonia
Name some muscarinic ACh receptor antagonists
-Atropine
Non-selective antagonist Well absorbed orally CNS effects
Adjunct for anaesthesia Anticholinesterase poisoning Bradycardia / cardiac arrest
-Glycopyrronium
Similar to atropine
Does not cross blood brain barrier
Similar to atropine
-Hyoscine hydrobromide
Similar to atropine CNS effects
Hypersalivation Motion sickness
-Hyoscine butylbromide
Similar to atropine but poorly absorbed Does not cross blood brain barrier
Gastrointestinal spasms
-Ipratropium
Delivered via inhaler or nebuliser Does not cross blood brain barrier
Maintenance treatment of COPD
-Tropicamide Similar to atropine but shorter acting Ophthalmic use (mydriasis)
What are the muscles innervated by the ANS in the eye?
Pupillary dilator muscle – Sympathetic innervation only
• Mydriasis
Pupillary constrictor muscle – Parasympathetic innervation
• Miosis
Discuss muscarinic ACh receptor pharmacology
Very few diseases of ↓parasympathetic activity, moredueto↑ac vity
– Little therapeutic use for agonists
General problem of selectivity with antagonists
– Few differentiate between subtypes effectively
– Muscarinic ACh receptors widespread side effects
– Control by route of administration and distribution
How should one approach pharmacology questions?
During surgery, a patient becomes bradycardic as a result of a muscle relaxant.
What pharmacological agent could be used to counter this?
