Autonomic Nervous System Flashcards
What is a ganglion?
A group of cell bodies outside the central nervous system
Where do pre-ganglionic fibres originate from?
The central nervous system
Where do post-ganglionic fibres originate from?
Autonomic ganglia
Describe the pre-ganglionic outflow of each system of the ANS
Sympathetic - Thoracolumbar (leaves spinal cord at thoracic and upper lumbar region)
Parasympathetic - Craniosacral (leaves from brain stem and sacro-spinal cord)
Where does the sympathetic nervous system synapse?
Paravertebral chain (close to spinal cord) or prevertebral ganglia (just in front of vertebra)
Where does the parasympathetic nervous system synapse?
In or near target organ
What is nicknamed the fight or flight system?
Sympathetic nervous system
What is nicknamed the fight or flight system?
Sympathetic nervous system
What is nicknamed the rest and digest system?
Parasympathetic nervous system
What is the parasympathetic effect on the heart?
Decreased heart rate
What is the sympathetic effect on the heart?
Increased heart rate
Increased force of contraction
What is the parasympathetic effect on the digestive tract?
Increased motility and secretion
What is the sympathetic effect on the digestive tract?
Decreased motility and secretion
What is the parasympathetic effect on the lungs?
Bronchoconstriction
What is the sympathetic effect on the lungs?
Bronchodilation
What is the parasympathetic effect on the urinary bladder?
Release of urine
What is the sympathetic effect on the urinary bladder?
Urinary retention
What is the parasympathetic effect on the pupil of the eye?
Constricts
What is the sympathetic effect on the pupil of the eye?
Dilates
What is the sympathetic effect on the pupil of the eye?
Dilates
What is the parasympathetic effect on the males sexual organs?
Erection
What is the parasympathetic effect on the males sexual organs?
Erection
What is the sympathetic effect on the male sexual organs?
Ejaculation
What is the parasympathetic effect on the blood vessels?
No effect (apart from those related to sexual organs)
What is the sympathetic effect on the blood vessels?
Constriction (apart from some skeletal muscle situations)
What is the parasympathetic effect on the salivary glands?
Increased secretion
What is the sympathetic effect on the salivary glands?
Increased secretion
What is the parasympathetic effect on the sweat glands?
No effect
What is the sympathetic effect on the sweat glands?
Increased secretion
What is the parasympathetic effect on the liver?
No effect
What is the sympathetic effect on the liver?
Glycogenolysis and gluconeogenesis
What is the parasympathetic effect on the pilomotor?
No effect
What is the sympathetic effect on the pilomotor?
Piloerection
What is mydriasis?
Dilation of the pupil (sympathetic)
What is miosis?
Constriction of the pupil (parasympathetic)
What is the purpose of the canal of Schlemm?
Drain excess fluid out of the eye
What effect would a sympathetic agonist have on the eye?
Mydriasis (dilation)
What effect would a parasympathetic antagonist have on the eye?
Mydriasis (dilation)
How does the ANS work when the bladder is filling?
Sympathetic control predominates
- Relaxation of detrusor muscle
- Contraction of internal sphincter muscles
How does the ANS work when the bladder is full?
Parasympathetic control predominates
- Contraction of detrusor muscle
- Relaxation of internal sphincter muscle
Describe sympathetic innervation of the adrenal gland
- Preganglionic sympathetic fibres synapse on chromaffin cells
- Chromaffin cells release adrenaline (roughly 80%) and noradrenaline (roughly 20%) into systemic circulation
- Results in widespread tissue response
Features of neurotransmitters of the ANS
- All pre-ganglionic neurons in the parasympathetic and sympathetic systems release ACh - nicotinic receptors
- All post ganglionic parasympathetic neurons release ACh - muscarinic receptors
- Most postganglionic sympathetic neurons release noradrenaline - some release ACh (i.e sweat glands)
What type of nicotinic receptors are found in muscle?
(alpha-1)2beta-1-delta-epsilon
What type of nicotinic receptors are found in ganglia?
(alpha-3)2(beta-2)3
What are predominate locations of nicotinic ACh receptors?
- Neuromuscular junction
- Sympathetic ganglia
- Parasympathetic ganglia
- Central nervous system
What are predominate locations of muscarinic ACh receptors?
- Parasympathetic target organs
- Sweat glands (sympathetic)
- Vascular smooth muscle
- Central nervous system
Can we differentiate muscarinic from nicotinic?
- Nicotinic and muscarinic ACh receptors share 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 is the muscarinic and nicotinic receptor specificity for acetylcholine?
Muscarinic - Very strong
Nicotinic - Very strong
What is the muscarinic and nicotinic receptor specificity for nicotine?
Muscarinic - very little/none
Nicotinic - very strong
What is the muscarinic and nicotinic receptor specificity for Muscarine?
Muscarinic - very strong
Nicotinic - very weak/none
What is the muscarinic and nicotinic receptor specificity for bethanecol?
Muscarinic - very strong
Nicotinic - very weak/none
What is the muscarinic and nicotinic receptor specificity for pilocarpine?
Muscarinic - Quite strong
Nicotinic - very weak/none
What are the main locations of M1 (neural) muscarinic ACh receptors?
- Autonomic ganglia
- Glands: gastric, salivary, lacrimal
What are the main locations of M2 (cardiac) muscarinic ACh receptors?
Heart: atria
What are the main locations of M3 (glandular/smooth muscle) muscarinic ACh receptors?
- Exocrine glands: gastric, salivary
- Smooth muscle: GI tract, eye, airways, bladder
- Blood vessels: endothelium
What is the cellular response of M1 receptors?
-Increase in IP3 and DAG
What is the cellular response of M2 receptors?
Decrease in cAMP
What is the cellular response of M3 receptors?
Increase in IP3 and DAG
What is the functional response of M1 receptors?
Gastric secretion
What is the functional response of M2 receptors?
Cardiac inhibition
What are the functional responses of M3 receptors?
- Gastric, salivary secretion
- GI smooth muscle contraction
- Ocular accommodation
- Vasodilation
Are all muscarinic receptors in the ANS?
- No
- M1,2,4 and 5 also found in CNS
- M3 found on vascular endothelial and smooth muscle cells
Are all muscarinic receptors in the ANS?
- No
- M1,2,4 and 5 also found in CNS
- M3 found on vascular endothelial and smooth muscle cells
What is pilocarpine?
Non-selective muscarinic agonist
What are some clinical uses of pilocarpine?
- Constriction of pupils (miosis)
- Glaucoma (to decrease IOP)
- Xerostomia (following head/neck radiotherapy)
What is bethanechol?
Non-selective muscarinic agonist
What are some clinical uses of bethanechol?
Bladder and gastrointestinal hypotonia
What are some pharmacological properties of atropine?
- Non-selective muscarinic antagonist
- Well absorbed orally
- CNS effects
What are some pharmacological properties of glycopyrronium?
- Similar to atropine
- Does not cross blood brain barrier
What are some pharmacological properties of hyoscine hydrobromide?
- Similar to atropine
- CNS effects
What are some pharmacological properties of hyoscine butylbromide?
- Similar to atropine but poorly absorbed
- Does not cross blood brain barrier
What are some pharmacological properties of ipratropium?
- Delivered via inhaler or nebuliser
- Does not cross blood brain barrier
What are some pharmacological properties of tropicamide?
-Similar to atropine but shorter acting
What are some clinical uses of atropine?
- Adjunct for anaesthesia
- Anticholinesterase poisoning
- Bradycardia/cardiac arrest
What are some clinical uses of glycopyrronium?
Similar to atropine
What are some clinical uses of hyoscine hydrobromide?
- Hypersalivation
- Motion sickness
What are some clinical uses of hyoscine butylbromide?
Gastrointestinal spasms
What are some clinical uses of ipratropium?
Maintenance treatment of COPD
What are some clinical uses of tropicamide?
Opthalmic use (mydriasis)
What facilitates release of noradrenaline?
Calcium ions
How does noradrenaline carry out negative feedback?
- alpha-2 adrenoreceptors on the presynaptic terminal
- Noradrenaline binds to these receptors inhibiting adenylyl cyclase which regulates calcium flow across membrane
- Results in a decrease in calcium influx and therefore a decrease in noradrenaline release
Is noradrenaline degraded outside the neuron?
- No, there is no equivalent to acetylcholinesterases for noradrenaline
- ~75% recaptured by neurons
- Using norepinephrine transporter (NET)
- Repackaged by vesicular monoamine transporter (VMAT)
What are drugs that affect noradrenergic neurons?
Drugs that affect catecholamine synthesis
-e.g. methyldopa
Drugs that affect catecholamine release
- indirectly acting sympathomimetics e.g. amphetamines
- by acting on alpha-2 adrenoreceptors e.g. clondine
Inhibitors of catecholamine uptake
-NET inhibitors e.g. cocaine, tricylic antidepressants
Inhibitors of catecholamine metabolic degradation
-monoamine oxidase inhibitors used in depression
What are the three main catecholamines?
- Dopamine
- Noradrenaline
- Adrenaline
Define metabotropic receptors and give an example
- G-protein coupled receptors
- e.g adrenergic receptors
What are the two main groups of adrenoreceptors?
- Alpha - alpha-1, alpha-2
- Beta - beta-1, beta-2, beta-3
What are some features of alpha-1 adrenoreceptors?
Main ANS locations:
- cardiovascular
- GI tract
- genitourinary
Cellular response:
-Increase IP3 and DAG
Functional ANS response:
- Vasoconstriction
- Smooth muscle contraction (GI sphincters and genitourinary)
What are some features of alpha-2 adrenoreceptors?
Main ANS locations:
-Neuronal
Cellular response:
-decrease cAMP
Functional ANS response:
-decrease transmitter release
What are some features of beta-1 adrenoreceptors?
Main ANS locations:
- Heart
- Kidneys
Cellular response:
-Increase cAMP
Functional ANS response:
- Increase cardiac rate
- Increase cardiac force
- Renin release
What are some features of beta-2 adrenoreceptors?
Main ANS locations:
- Lungs
- Smooth muscle
- Skeletal muscle
Cellular response:
-Increase cAMP
Functional ANS response:
- Bronchodilation
- Relaxation of visceral smooth muscle
- Vasodilation (sk. muscle)
- Tremor
What does phenylephrine do?
- Constriction of airway blood vessels (alpha-1)
- Used to reduce nasal congestion
What drugs can be used to cause bronchodilation via the beta-2 adrenoreceptors when treating asthma?
- Salbutamol
- Salmeterol
- Terbutaline
What is the main difference between salbuatmol and salmeterol?
Salbutamol is short-acting whereas salmeterol is long-acting
What side effects can salbutamol and salmeterol cause?
Muscle tremor and cardiac arrhythmias
How can salbutamol aid in premature labour?
Relaxation of uterine smooth muscle allowing delay in delivery
What is the basic equation to determine mean arterial blood pressure?
Mean arterial blood pressure = cardiac output multiplied by total peripheral resistance
How does the sympathetic nervous system increase cardiac output?
- By increasing the heart rate
- By increasing the volume pumped on each stroke
- Both mediated by beta-1 receptors
How does the sympathetic nervous system increase total peripheral resistance?
- By constricting blood vessels (mainly small arteries/arterioles)
- Mediated by alpha-1 receptors
What is the purpose of dobutamine?
- Increase heart rate and force (beta-1)
- Can be used to treat cardiogenic shock
What drugs are used to treat hypertension and how do they work?
- Prazosin - Vasodilation by blocking alpha-1 receptors
- Propranolol - decrease heart rate and force by blocking beta-1 receptors, decrease renin release by kidneys (beta-1)
- Atenolol - decrease heart rate by blocking beta-1 receptors, decrease renin release by kidneys (beta-1)
- Clonidine - stimulation of pre-synaptic alpha-2 receptors to decrease NA release, also has central effect
What drugs are used to treat cardiac dysrhythmias and how do they work?
- Propanolol - decrease heart rate and force by blocking beta-1 receptors, decrease renin release by kidneys (beta-1)
- Atenolol - decrease heart rate and force by blocking beta-1 receptors, decrease renin release by kidneys (beta-1)
