General Anaesthetics

Question 1

Describe the history of general anaesthetics

Answer 1

PRe 1800s amputation was a popular form of surgery but no anaesthesia was invented (ow). In 1800s Humprey davies discovered nitrous oxide produced euphoria, analgesia and loss of conciousness. Later ether become popular in surgery and dental treatment but it wasnt until queen victoria used cholorform to relief the pain of child birth that it been widely accepted to use general anaesthetics.

Question 2

What are the stages of general anaesthesia?

Answer 2

1. analgesia (pain supression)
2. Excitability (dangerous stage)
3. Unconciousness (operative state) and memory loss
4. Overdose (due to medullary paralysis causing cardiorespiratory depression)

Question 3

What are the sites of action of general anaesthetics and what effects do actions at these sites produce?

Answer 3

1. Analgesia (pain supression) is due to action in the substnatia gelantenosa
2. Unconciousness is due to action primarily in the reticular formation and thalamocortical tract,
   Memory loss is due to action in the hippocampus
3. Supression of skeletal muscle reflexes and tone are as a consequence of action in the spinal interneurones
4. Also have sites of action in the liver where they can cause liver toxicity
5. Also can cause respiratory and blood pressure depression

Question 4

What are the three theories for the way general anaesthetics work?

Answer 4

1. Unitary theory - they all work in the same way - discredited
2. Lipid theory - there is a correlation between the potency of a GA and its size (i.e. the bigger the size the more lipophillic it is the better it can get into the cell) but after a certain point this isnt true. Also thought that they expand the cell volume and this leads to the effects seen but has been shown that the volume change is only about 0.5%
3. Protein theory
   GAs bind to ion channels and inhibit the action of glutamate or potentiate the action of GABA

Question 5

What are the teo types of general anaesthetics and give a secription of them?

Answer 5

1. Intravenous general anaesthetics normally given to induce anaesthesia but do not maintain it - they are short acting and less easily reversible
2. Inhalantional anaesthetics are used to maintain anaesthesia they are more easily reversible and longer acting

Question 6

Thiopental

Answer 6

A barbiurate that acts inside the open chloride channel of the GABA receptor to increase duration of channel opening leading to hyperpolarisation of the cell. Problems with barbiturates in that they cause cardiorespiratory depression and also induce p450 hepatic enzymes that leads to increased breakdown of other drugs e.g. anticoagulants

Question 7

Etomidate

Answer 7

Similar to thipental but has cardiorespiratory depression

Question 8

Propofol

Answer 8

Used in day surgery

Question 9

Diazapam

Answer 9

A benzodiazepine, highly lipphillic so can cross the BBB, which binds between the gamma and alpha subunit on the GABA receptor cholirde channel to increase the frequency of the channel openingin and leads to hyperpolarisation of the neurons. Has varying effects depending on dose e.g. low dose is used to treat anxiety, higher dose is used as a sleep tablet and even higher is used as anaesthesia.

Question 10

Nitrous Oxide

Answer 10

An inhalational anaesthetic that is used as laughing gas but isnt very potent

Question 11

Halothane

Answer 11

Potentiates GABA as well as opening a potassium channel leading to further depolarisation.

Question 12

Ether

Answer 12

There are several variations of the classical ether used back in the 1840s but they all come with their problems. Enflurance has a chance of causing epilepsy while isoflurance is irritant to the respiratory tract - sevoflurance has been developed to give to asthma sufferers that is not so irritant but has a chance to cause kidney damage.