anaesthesia and neuromuscular blocking agents

Question 1

what are the requirements of anaesthetics ?

Answer 1

abolition of sensations and pain and must have the triad of general anaesthetics

Question 2

what is the triad of general anaesthetics ?

Answer 2

must cause unconscious
must cause analgesia
and must cause muscle relaxation
- no drug does all 3 so need a combination

Question 3

where are the sites of action of anaesthetics ?

Answer 3

• thalamus- causes -unconsciousness
• prefrontal cortex, hippocampus and amaydala - causes amnesia
• spinal cord causes muscle relaxation

Question 4

what is stage of one of anaesthetics?

Answer 4

analgesia 
- conscious 
- drowsy 
- noicereception 
and amnesia

Question 5

what is sage two of anaesthetics ?

Answer 5

excitement 
- loss of consciousness but delirium 
-irregular cardio respiration
gagging and vomiting 
apnea and spasticity

Question 6

what is stage three of anaesthetics?

Answer 6

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

Question 7

what is stage four of anesthetics?

Answer 7

Medullary paralysis

• depression of cardiovasular respiratory system until death
• death occurs unless the respiratory and circulation are maintained.

Question 8

what are some of the ideal GA characteristics?

Answer 8

- non toxic 
non irritant 
- stable 
- large therapeutic window 
- non cardio depressant 
- not respiratory depressant 
- - adjustable 
- rapid on and off

Question 9

which GA is ideal and why isn’t it used?

Answer 9

xenon is ideal but is expensive so not widely used

Question 10

what is induction ?

Answer 10

• 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

Question 11

what should children be given for induction?

Answer 11

halothane or sevoflurane

Question 12

what is the maintenance ?

Answer 12

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

Question 13

what is recovery ?

Answer 13

withdrawal of aesthetic and wait for the patient to recover and monitor the patient for a return to consciousness

Question 14

what is the lipid theory of general anaesthesia ?

Answer 14

• 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

Question 15

what is the protein theory of general anaesthesia?

Answer 15

luciferase inhibiton correlates with aesthetic potency.

so the anaesthetics interact with the membrane proteins to alter function

Question 16

what is the MOA of general anaesthetics?

for example propofol and barbiturates

Answer 16

• 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

Question 17

what are local anaesthetics ?

Answer 17

they cause anaesthesia with out causing unconsciousness

Question 18

what are topical local anaesthetics?

Answer 18

applied to the skin or mucus membranes
benzocaine lidocaine and tetracine
used to relive or prevent pain form minor burns , irritation or itching
adverse

Question 19

what is the purpose of neuromuscular blocking agents?

Answer 19

• to paralyse the neuroskeletal muscles being investigated

Question 20

what is the route of administration and why?

Answer 20

IV and IM because they have poor oral absorption

Question 21

what receptor and NT does the neuroskeletal muscle use?

Answer 21

it has a single neurone from the CNS to the skeletal muscle and uses a nicotinic receptor and so the NT is ACH

Question 22

Define a motor unit?

Answer 22

the motor neurone and the muscle fibre it innervates

Question 23

what is the mechanism which releases Ach at the NMJ?

Answer 23

1. AP is conducted along the motor neurone causing depolarisation.
2. Causing Ca2+ voltage-gated ion channels open and an influx of Ca2+ into the motor neurone.
3. The influx of Ca2+ causes vesicles containing Ach to detach from their binding site and Ach is released into the synaptic cleft.
4. The Ach diffuses across the synaptic cleft and binds to Nicotinic receptors on the neuromuscular endplate causing Na+ voltage-gated ion channels to open.
5. In the neuromuscular end plate Na + causes depolarisation and further AP.

Question 24

what is a nicotinic receptor?

Answer 24

it is a ligand-gated ion channel, the ligand which binds is Ach and it’s a heterodimer as it has 5 subunits

Question 25

what are the 5 subunits of a skeletal muscle nicotinic receptor?

Answer 25

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

Question 26

how does Ach bind to a skeletal muscle nicotinic receptor?

Answer 26

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

Question 27

How do neuromuscular blocking agents work?

Answer 27

they work by interfering with the postsynaptic transmission of Ach.
There are two types based on the MOA
Non-deploarising agents and depolarizing agents

Question 28

What is the mechanism of action of non-depolarising agents?

Answer 28

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