Autonomic Nervous System 2 Flashcards
Where do afferent sensory fibres carry information to?
Back to autonomic processing centres (hypothalamus and medulla)
Which clinically used drug activates muscarinic cholinoceptors?
Pilocarpine
Which clinically used drug(s) act to block muscarinic cholinoceptors?
Atropine, ipratropium, tiotropium
Where are muscarinic-M3 receptors found? What is their function?
Smooth muscle and glands, causing contraction and mucous secretion
Why do we use pilocarpine?
- Activates M3 cholinoceptors of constrictor pupillae muscle causing constriction
- Promotes aqueous humour drainage and reduces intraocular pressure
- Given topically, reducing systemic side effects
- Sometimes used for glaucoma
Why do we use atropine? What are some of its limitations of use?
- First line therapy for poisening with anticholinesterase agents
- Blocks all muscarinic receptors, so inhibiting gland secretion and smooth muscle contraction, as well as decreasing heart rate. Because it crosses into the CNS to block muscarinic receptors, it also produces excitatory effects like restlessness, hyperactivity and increased body temperature.
- Has no organ selectivity (limitation)
What type of patient would use tiotropium?
Patients with COPD
- Dilates airways and reduces mucus secretion
- For maintenance, not immediate relief of symptoms
How would a drug “indirectly” affect the autonomic nervous system?
By increasing or decreasing the level of neurotransmitter - it’s indirect because the drugs do not bind directly to receptors
What is the purpose of noradrenaline transporter (NAT)?
Stimulated nerves will release noradrenaline, most of this undergoes neuronal reuptake via NAT - this reduces the amount of noradrenaline at the synapses. This is an important regulatory process through which the CNS controls the activity of postsynaptic cells.
After reuptake, noradrenaline is transported back into vesicules through the VMAT (vesicular monoamine transporter) or it is inactivated via MAO (monoamine oxidase)
Describe the mechanism of action of amphetamine.
Amphetamine uses NAT to enter the adrenergic nerve terminal. It inhibits both VMAT (vesicular monoamine transporter) and MAO (monoamine oxidase). It reverses NAT (noradrenaline transporter). All of these actions increases the level of noradrenaline at the nerve synapse. Some effects are increased HR & contractility, and vasoconstriction.
Describe the neurotransmission of cholinergic nerves.
- Cholinergic nerves synthesis and store acetylcholine (ACh)
- When nerve is stimulated, ACh released onto post-synaptic cells thus activating receptors
- Released ACh metabolised by Acetylcholinesterase enzyme - reducing [ACh]
What is the mechanism of action of an acetylcholinesterase inhibitor?
Inhibits acetylcholinesterase so ACh is not broken down to choline and acetate (inactive forms). Therefore, [ACh] increases causing activation of receptors inducing a greater response (glandular secretion, SM contraction and slowing of HR). E.g. ACh-E inhibitors = organophosphate pesticides and war gases
Why would we use anticholinesterase inhibitors in medicine?
To treat myasthenia gravis characterised by skeletal muscle weakness (due to autoantibodies against nicotinic receptors). The muscles have lost sensitivity to ACh. ACh-E inhbitors will increase the amount of ACh at the neuromuscular junction therefore increase binding to receptors.
What is the effect of anticholinesterase on the ANS?
Mimics stimulation of the PNS: glandular secretion, smooth muscle contraction and slowing of the heart rate
What are the symptoms of a cholinergic overdose?
DUMBBELSS Diarrhoea Urination Muscle weakness Bronchorrhea/bronchoconstriction Bradycardia Emesis Lacrimation Salivation/sweating Seizures
