MnR S10 - Autonomic Nervous system Flashcards
Outline the general structure of how neurones are arranged in the ANS
Myelinated pre-ganglionic neurone in the CNS and unmylinated post-ganglionic neurone in the PNS
Where does the parasympathetic outflow originate from?
Lateral horn of the medulla and sacral regions
Where does the sympathetic outflow originate?
Lateral horn of the thoracic and lumbar regions
Name two exceptions in the sympathetic nervous system where post-ganglionic neurones release ACh opposed to NA and act on muscarinic receptors
Sweat glands and hair follicles
What are the other transmitters of the ANS and when would they be released?
Non-adrenergic, non-cholinergic transmitter (NANC)
Often co-released with NA or ACh
Give some examples of NANC transmitters
ATP, Serotonin, Neuropeptides and nitric oxide
How do sensory receptors in the carotid body and carotid artery, such as chemoreceptors, relay information to the CNS?
Via the glossopharyngeal nerve
The primary sensory nerves project onto second order sensory nerves located in the medulla oblongata, what structure does this system form?
Nucleus tractus solitarius (nTS)
Where else does the nucleus tractus solitarius nTS receive information from, other than primary sensory neurones?
The area postrema which is responsible for detecting toxins present in the blood and cerebrospinal fluid
How are chromaffin cells stimulated and what do they behave as?
Stimulated by sympathetic input from pre-ganglionic neurones and then behave as specialised post-ganglionic neurones of the sympathetic NS by secreting adrenaline into the bloodstream
How does the parasympathetic nervous system stimulate erection?
Release of Ach causes the release of NO which causes dilation of the trabecular arteries of the penis and subsequently the filling of the corpora cavernosa with blood
What effect does the parasympathetic nervous system have on glands?
Stimulates secretion from sweat, salivary and lacrimal glands via M1 and M3 receptors
What effect does the sympathetic nervous system have on the kidneys?
Stimulates renin secretion
What is the autonomic input to the prostate gland and outline the effects
Parasympathetic- generation of secretions in epithelial cells
Sympathetic- contraction and secretion of the smooth muscle cells
What are the most common targets for drug action in the neurotransmission pathway?
- Degradation of transmitter in the pre-synaptic neurone before release
- Interaction with post-synaptic receptors
- Inactivation of the transmitter
- Re-uptake of the transmitter
- Interaction with pre-synaptic receptors
Which enzyme is involved in synthesis of Ach?
Choline acteyltransferase
Describe the structure of sympathetic post-ganglionic neurones
Highly branching axonal network with numerous varicosities which are specialised sites for Ca2+ dependent noradrenaline release
What is the function of pre-synaptic adrenoreceptors on the nerve terminal in the sympathetic NS?
Regulate NA release by acting as a feedback system
NA is release from the post-ganglionic nerve terminal and most binds to post-synaptic receptors whereas some binds to pre-synaptic receptors
Which adrenoreceptors is involved in modulating the release of NA?
Alpha 2
- NA binding to receptors activates Gi which stimulates the beta-gamma sub-unit to block VOCC
- This decreases Ca2+ influx into the nerve terminal which decreases the release of NA via Ca2+ mediated exocytosis
Which receptors do ganglion-blocking drugs act at and give an example of a drug of this class
Nicotinic Ach Receptors
Trimethaphan- used in hypertensive emergencies or to create controlled hypotension in surgery
Which class of drugs would be used to treat overactive bladder?
Muscarinic antagonists e.g. tolterodine/ oxybutynin
Give two examples of diseases treated with acteylcholinesterase inhibitors
Myasenthia gravis, Alzheimer’s
List the common unwanted side effects of muscarinic agonists
Heart- decrease heart rate and cardiac output
Smooth muscle - increase bronchoconstriction and GI peristalsis
Exocrine glands- increase sweating and salivation
What are the two methods of noradrenaline uptake?
Uptake 1- taken up into pre-synaptic terminal through the Na+ dependent high affinity transporter. Located on a neuronal membrane.
Uptake 2- takes up escaped NA, low affinity system that uses a non-neuronal mechanism. Located on non-neuronal membrane (smooth muscle cell, cardiac muscle, endothelium)
What drugs can be used to inhibit uptake 1?
- Cocaine
- ## Tricyclic antidepressants
What drugs can be used to inhibit uptake 2?
Steroids
What are indirectly acting sympathiomimetic agents?
Drugs that are taken up into noradrenergic synaptic vesicles and displace NA causing it to leak out into the synaptic cleft independent of Ca2+ mediated exocytosis e.g. amphetamine
What are the most commonly used beta adrenoreceptor antagonists in the treatment of heart failure?
Bisoprolol, metoprolol, carvedilol
What are the different types of response brought about by ligand binding to a receptor?
Change in membrane permeability to ions
Generation of second messengers
Define tachyphylaxis
Excessive exposure to an agonist leads to reduced sensitivity meaning more agonist is needed for the same response
What leads to suprasensitivity?
Agonist deprivation
Excessive exposure to an antagonist
List the possible causes of a change in tissue responsiveness
- Change in receptor number
- Change in receptor coupling to second messengers
- Change in availability of second messengers
- Change in cell responsiveness
Where do opioids act?
Opioid receptors in the CNS and PNS
What changes occur in the process of opioid withdrawel with an addict?
- Opiod levels fall
- As the opioid leaves the receptor it is less likely to be replaced
- Second messenger activity falls
- Patient begins to perceive pain
How does angina treatment affect the number of beta adrenoreceptors?
Beta blockers cause an up-regulation of beta adrenoreceptors
Give two possible causes of bronchoconstriction in asthmatics
Increased parasympathetic stimulation
Decreased sympathetic stimulations
List four possible treatments for asthma
- Muscarinic antagonists
- Beta 2 adrenoreceptor agonists
- Glucocorticosteroids
- Leukotriene modifiers
- Xanthine
What is the advantage of patient controlled analgesia?
Decrease chances of tachyphylaxis as patient administers the drug intermittently opposed to regularly as a doctor would so less likely to become opioid dependent
Why are adrenoreceptors not up regulated in phaeochromocytoma?
Intermittent release of noradrenaline means there is no tachyphylaxis
How does increasing age, so elderly patients compared to young, affect catecholamine sensitivity?
Decreased sensitivity to endogenous catecholamines
Reduced heart rate responsiveness to exogenous catecholamines
Potential excess pharmacological efficacy of administered drugs
