Autonomic Nervous System (2) Flashcards
Location of ACh receptors in the ANS
Parasympathetic System
Adrenal Medulla of Sympathetic System
Location of Nicotinic ACh receptors
NMJ
Sympathetic Ganglia
Parasympathetic ganglia
Central Nervous system
Location of Muscarinic ACh receptors
Parasympathetic target organs
Sweat glands (sympathetic)
Vascular smooth muscle
CNS
Nicotinic ACh receptor
Ionotropic
Muscle - (alpha1)2 Beta1 Delta(3backwards)
Ganglia - (alpha3)2(beta2)3
Muscarinic ACh receptor
G-protein linked receptor (metabotropic)
Gq - M1 and M3 –> Increase IP3 and DAG
Gi - M2 –> decrease cAMP
Can we differentiate muscle from ganglion Nicotinic ACh receptors ?
Differences in subunits may allows for some specificity
Predominate Tone
Tissues innervated by both branches of the ANS
Effects of anti-cholinesterase on the ANS
(SLUDGE)
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal upset
Emesis
Effects of anti-cholinesterase on ANS
Parasympathetic
Bradycardia
Hypotension
Broncho-constriction
Pupillary constriction (MIOSIS)
How can nicotinic and muscarinic receptors be differentiated ?
Nicotine binds to Nicotinic receptors
Muscarine binds to Muscarinic receptors
What affects both nicotinic and muscarinic receptors ?
Anything that influences storage and release of ACh will affect both receptor types.
How can muscarinic receptors be classified ?
Classified by their tissue distribution and their cellular response.
Not all muscarinic receptors are in the ANS
What muscarinic receptors are found in the CNS ?
M1,2,4,5
Where is M3 found ?
On vascular endothelial and smooth muscle cells
State the 3 muscarinic receptors that are under parasympathetic control
M1(neural)
M2 (cardiac)
M3 (glandular / smooth muscle)
M1
GLANDS : gastric, salivary, lacrimal
Autonomic ganglia
Gastric secretion
M2
HEART: Atria
Cardiac inhibition
M3
Gastric, salivary secretion
GI smooth muscle contraction
Ocular accommodation
Vasodilation
What is atropine ?
Muscarinic Antagonist
Muscarine receptor mediated effects
SLUDGE + Sweating
Nicotinic receptors effects
Changing between sympathetic and parasympathetic effects
Muscle weakness
Atropine effects
CNS mediated effects
Inhibition of muscarinic receptors
Describe :
-pilocarpine
-bethanechol
Non-selective muscarinic agonists
Show little or no selectivity between the subtypes of muscarinic receptor
Clinical uses of Pilocarpine
Constriction of pupils (Miosis)
Glaucoma (decrease IOP)
Xerostomia (following head/neck radiotherapy)
Clinical uses of Bethanechol
Bladder and GI hypotonia
How is selectivity of action with muscarinic agonists achieved ?
Achieved by a combination of choice of route of administration and the ionised state of the drug.
State the muscarinic ACh receptor antagonists
Atropine
Glycopyrronium
Hyoscine Hydrobromide
Hyoscine butyl bromide
Ipratropium
Tropicamide
Pharmacological properties of : Atropine
Non-selective antagonist
Well absorbed orally
CNS effects
Pharmacological properties of : Glycopyrronium
Simliar to atropine
Doesn’t cross blood-brain barrier
Pharmacological properties of : Hyoscine hydrobromide
Similar to atropine
CNS effects
Pharmacological properties of : Hyoscine butyl bromide
Similar to Atropine but poorly absorbed
Doesn’t cross blood-brain barrier
Pharmacological properties of : Ipratropium
Delivered via inhaler or nebuliser
Doesn’t cross blood-brain barrier
Pharmacological properties of : Tropicamide
Similar to atropine but shorter acting
Clinical uses of : Atropine
Adjunct for anaesthesia
Anticholinesterase poisoning
Bradycardia
Clinical uses of : Glycopyrronium
Similar to atropine
Clinical uses of : Hyoscine hydrobromide
Hyper-salivation
Motion sickness
Clinical uses of : Hyoscine butyl bromide
GI spasms
Clinical uses of : Ipratropium
Maintenance treatment of COPD
Clinical uses of : Tropicamide
Ophthalmic use
(Mydriasis)
Diseases cause muscarinic ACh
Increased PSNS activity
- Little therapeutic uses for antagonists
Problems of selectivity with antagonists
Few differentiate between subtypes effectively
Muscarinic ACh receptors widespread - side effects
Control by route of administration and distribution.
Atropine use
Treats bradycardia
