anaesthesia and neuromuscular blocking agents Flashcards
what are the requirements of anaesthetics ?
abolition of sensations and pain and must have the triad of general anaesthetics
what is the triad of general anaesthetics ?
must cause unconscious
must cause analgesia
and must cause muscle relaxation
- no drug does all 3 so need a combination
where are the sites of action of anaesthetics ?
- thalamus- causes -unconsciousness
- prefrontal cortex, hippocampus and amaydala - causes amnesia
- spinal cord causes muscle relaxation
what is stage of one of anaesthetics?
analgesia - conscious - drowsy - noicereception and amnesia
what is sage two of anaesthetics ?
excitement - loss of consciousness but delirium -irregular cardio respiration gagging and vomiting apnea and spasticity
what is stage three of anaesthetics?
Anaesthesia
- regular respiration loss of muscle movement
- want this stage on surgery and must monitor the patient to keep them at this stage during surgery
- has subdivisions as its used commonly for surgery
- diaphragm muscles are affected so the patient has to be ventilated
- pupil dilation can be used to help determine what stage the patient is in
what is stage four of anesthetics?
Medullary paralysis
- depression of cardiovasular respiratory system until death
- death occurs unless the respiratory and circulation are maintained.
what are some of the ideal GA characteristics?
- non toxic non irritant - stable - large therapeutic window - non cardio depressant - not respiratory depressant - - adjustable - rapid on and off
which GA is ideal and why isn’t it used?
xenon is ideal but is expensive so not widely used
what is induction ?
- period leading to the loss of consciousness
- use IV profol or thiopentone
- can be given additional inhalation or IV anaesthesia to get desired depth
- Use IV skeletal relaxant to facilitate intubation and muscle relaxation
what should children be given for induction?
halothane or sevoflurane
what is the maintenance ?
to provide sustained anaesthesia fo the surgery
they do this by maintaining with inhalation agents e.g N20 and halothane
to prevent patients falling into stage 4
what is recovery ?
withdrawal of aesthetic and wait for the patient to recover and monitor the patient for a return to consciousness
what is the lipid theory of general anaesthesia ?
- the fluidity changes due to changes in the lipids which causes a conformational change of the proteins in the membrane so no ions pass through
BUT not all lipophilic compounds cause anaesthesia
what is the protein theory of general anaesthesia?
luciferase inhibiton correlates with aesthetic potency.
so the anaesthetics interact with the membrane proteins to alter function
what is the MOA of general anaesthetics?
for example propofol and barbiturates
- affects ion channels
- increases the sensitivity of GABA receptors to the NT GABA
- prolonging yer inhibitory chloride ion current after Gaba release
- reducing post synaptic neurone excitability.
- NMDA receptors cause analgesic effects but not anaesthesia
what are local anaesthetics ?
they cause anaesthesia with out causing unconsciousness
what are topical local anaesthetics?
applied to the skin or mucus membranes
benzocaine lidocaine and tetracine
used to relive or prevent pain form minor burns , irritation or itching
adverse
what is the purpose of neuromuscular blocking agents?
- to paralyse the neuroskeletal muscles being investigated
what is the route of administration and why?
IV and IM because they have poor oral absorption
what receptor and NT does the neuroskeletal muscle use?
it has a single neurone from the CNS to the skeletal muscle and uses a nicotinic receptor and so the NT is ACH
Define a motor unit?
the motor neurone and the muscle fibre it innervates
what is the mechanism which releases Ach at the NMJ?
- AP is conducted along the motor neurone causing depolarisation.
- Causing Ca2+ voltage-gated ion channels open and an influx of Ca2+ into the motor neurone.
- The influx of Ca2+ causes vesicles containing Ach to detach from their binding site and Ach is released into the synaptic cleft.
- The Ach diffuses across the synaptic cleft and binds to Nicotinic receptors on the neuromuscular endplate causing Na+ voltage-gated ion channels to open.
- In the neuromuscular end plate Na + causes depolarisation and further AP.
what is a nicotinic receptor?
it is a ligand-gated ion channel, the ligand which binds is Ach and it’s a heterodimer as it has 5 subunits
what are the 5 subunits of a skeletal muscle nicotinic receptor?
skeletal muscle nicotinic receptors are specific and the subunits of nicotic receptors are different in the CNS.
the subunits are 2 alpha, 1 beta , 1 gama and 1 sigma
how does Ach bind to a skeletal muscle nicotinic receptor?
1 Ach binds to one alpha1 receptor causing a conformational change at the second subunit allowing another Ach to bind at the second alpha subunit.
So 1 nicotinic receptor has 2 Ach binding sites
How do neuromuscular blocking agents work?
they work by interfering with the postsynaptic transmission of Ach.
There are two types based on the MOA
Non-deploarising agents and depolarizing agents
What is the mechanism of action of non-depolarising agents?
it is a competitive nicotinic receptor antagonist which binds to the nicotinic receptors on the endplate.
It binds and does not produce an effect. It blocks neuromuscular transmission but not nerve conduction or muscle contractility
