drugs and the nervous system L10 Flashcards
What does the nervous system allow
A system which allows an organism :
to sense information about its environment (internal & external)
to respond rapidly and accordingly.
whats the difference between efferent and afferent peripheral nervous system
afferent is nerves going to the brain and spinal cord, efferent are those going away
what is the autonomic nervous system
controls the smooth muscle and glands
autonomic responses which are outside the influence of voluntary control
what is the autonomic nervous system split into
Divided into sympathetic (increase) and parasympathetic (return to normal level)
what is the somatic nervous system
motor innervation of skeletal muscles.
Voluntary control
describe the organisation of sympathetic autonomic nervous system
short preganglionic fibre that terminates onto autonomic ganglion
long post ganglionic fibre that terminates on to target tissue
what neuro transmitter is released from pre and post ganglionic neuron in sympathetic autonomic nervous system
pre: acetylcholine
post: noradrenaline
what neuro transmitter is released from pre and post ganglionic neuron in parasympathetic autonomic nervous system
both release acetylcholine
what are the exceptions to Sympathetic system
- sweat glands
- both post and pre release ACH - Adrenaline release from adrenal glands
give the name of a efferent somatic nervous system, describe its structure and what neurotransmitter does it release
neuromuscular junctions
one long fibre - no autonomic ganglion
releases acetylcholine
what are the fundamentals of neurotransmission
Synthesis
Storage
Release
Receptor interaction
Termination.
describe Synthesis, Storage, Release , Receptor interaction
and Termination of ACH.
- ACH is made from choline and AcCoA and catalysed by cholineacetyl transferase
- ACH is stored in vesicles
- calcium comes in causing vesicles to fuse with membrane causing release of ACH into synaptic cleft - exocytotic
- ACH binds to nicotinic or muscarinic receptors
- acetylcholinesterase breaks down ACH in to choline and acetate
- choline is recycled
what are the two types of cholinergic receptors that ACH binds to
Muscarinic receptors and Nicotinic receptors
Muscarinic receptors
how many types are there
where are they found
what type of receptors are they
there are 3 subtypes M1,2 and 3
Located at postganglionic parasympathetic synapses
G-protein coupled receptor - slow receptor
Nicotinic receptors
how many types are there
where are they found
what type of receptors are they
2 subtypes: neuronal and muscle
neuronal- brain and autonomic ganglia (both sympathetic and parasympathetic (excitatory)
muscle- neuromuscular junction (NMJ) (excitatory)
Ligand gated ion channels (or ionotropic receptor)
- 4 or 5 subunits structure
- coupled directly to a ion channel
- fast
what do Muscarinic receptors mainly effect
parasympathetic effects
what are the effects of muscarinic agonists
- increase pupil constriction (contraction of constrictor pupillary muscle)
- decrease focal length of the lens (contraction of ciliary muscle)
- Bronchoconstriction
- decrease cardiac output, (rate & force
- increase GI motility
- increase exocrine gland secretion (sweating salivation, bronchiol secretion)
what are muscarinic agonists known as
parasympathomimetics
what are the Effect of muscarinic antagonist
- pupil dilate (relaxation of constrictor pupillary muscle) (blurred vision)
- increase focal length of the lens (relaxation of ciliary muscle)
- Bronchodilation
- increase cardiac output, rate & force
- decrease GI motility
- decrease exocrine gland secretion (dry mouth decreased sweating)
what are muscarinic antagonists known as
parasympatholytics
what muscarinic agonist cause increased pupil constriction and decreased focal length of lens
Pilocarpine, Carbachol
what is the clinical use of Pilocarpine
and other muscarinic agonist
- used to treat Glaucoma
- Local application causes ciliary muscle contraction –
focus on near vision + also allows increase drainage of aqueous humour
- Contraction of sphincter muscle causes pupil constriction - Treatment of xerostomia: Dry mouth/reduced saliva secretions
- Pilocarpine stimulates saliva secretions
- Taken systemically
- Side effects: muscarinic-sweating, nausea, minimal cardiovascascular side effect (due to low dose)
what is the clinical use of muscarinic antagonists such as Atropine like drugs
- Pupil dilation in eye surgery (causes pupil dilation)
- Tropicamide - Decrease oral/respiratory secretions before oral procedures and as an adjunct to anaesthesia,
- Atropine (belladonna, deadly nightshade)
- Glycopyrronium - Resuscitation in bradycardia (causes increase heart rate)
- Atropine - Asthma (causes bronchodilation)
- Ipratropium - Motion sickness- Orally it decreases gastric motility - Hyoscine
what are the 2 subtypes of nicotinic receptors and where are they found
neuronal type- brain and autonomic ganglia (excitatory)
- Located on both sympathetic and parasympathetic ganglia
muscle-type: neuromuscular junction (NMJ) (excitatory)
- located at NMJ
what do agonists to neuronal nicotinic receptors do
Agonists (nicotine) activates both systems
- sympathetic: vasoconstriction, tachycardia, hypertension
- parasympathetic: bradycardia, hypotension, increase GIT motility, increase secretions
what is the effect of having neuronal nicotinic receptors activating both pathways
autonomic confusion
- one pathway tries to increase, the other tries to decrease rate
- not of clinical use
what do antagonists to neuronal nicotinic receptors do
hexamethonium
- loss of sympathetic & parasympathetic reflexes, especially cardiac
what happens when muscarinic nicotinic receptors cause
Stimulation of these receptors by ACh causes depolarisation (in muscle fibre this is known as an end plate potential (EPP)) and contraction of the skeletal muscle fibre
what is the Effect of nicotinic agonists at neuromuscular junction
Agonist (suxemethonium)
- Initial depolarisation/EPP and muscle fibre contraction (muscle twitch)
- Because the synthetic agonist is not metabolised rapidly by acetylcholinesterase, the fibre is persistently depolarised resulting in loss of further electrical excitability-known as depolarising block
- after a muscle twitch, paralysis happens
- Induce paralysis for surgery
what is the Effect of nicotinic antagonist at neuromuscular junction
tubocurarine
- Hyperpolarisation, inhibition of EPPs
Muscle fibre relaxation
- Paralysis (for surgery)
- Non-depolarising blocker
- Induce paralysis for surgery
describe Drugs affecting synthesis of ACH
Hemicholinium
- blocks the choline uptake, inhibits synthesis and blocks ACh transmission.
- no clinical use
describe Drugs affecting release of ACH
botulinum toxin, & bungarotoxin
- inhibit ACh release
- Causes parasympathetic, and motor paralysis if ingested.
how can break down of ACH be inhibited
anticholinesterases inhibits Acetylcholinesterase
- This will increase ACh transmission
give examples of anticholinesterase and their effects on autonomic NS and NMJ
neostigmine, organophosphates
Effects on autonomic nervous system:
- Reflect increased transmission at parasympathetic postganglionic synapses- increase secretions, bradycardia, hypotension, pupil constriction
Effects on neuromuscular junctions:
- Increased muscle tension and twitching, at large doses can cause a depolarising block.
Neostigmine used to treat myasthenia gravis (autoimmune disease, circulating antibodies against muscle nicotinic receptors)
