Anaesthesia

Question 1

Sodium Thiopental

largely been replaced with propofol

Answer 1

IV general anaesthetic - barbiturate

Onset - <10 secs

Duration - 15 mins - after which drug redistributed to other tissues e.g. muscle and fat.

No analgesic effects, causes resp. despression - intubation may be needed. May depress the heart, irritatant effects, laryngospasm (difficult intubation).

Question 2

Propofol

may be given in combination with N2O

Answer 2

IV general anasthetic

Responsive at GABAa receptors

Onset - approx 10-30 seconds

Rapid metabolism - recovery very quick (around 5 mins)

Similar effects to CNS and resp. to barbiturates with the exception of it lowering BP and no irritant effects.

Anti-emetic effect (beneficial during recovery).

Question 3

Alphaxone

Answer 3

Prototype neurosteroid

Responsive at the GABAa receptors

Not used anymore - replaced with etomidate

CNS & Resp. depression

Question 4

Etomidate

Answer 4

I.V anaesthetic
Used for induction of anasethesis or relocation of joints
Short acting - hypnotic drug without analgesic effect (usually given alongside analgesic drug)
Onset - usually around 1 minute
Duration - around 3 mins
Little CVS and resp. depression

Question 5

Ketamine

Answer 5

IM/IV form of general anaesthetia
Non-competitive NMDA receptor antagonist

Causes dissociative (loss of conscious perception) anaesthesia - characterised by catalepsy (trance/seizure like state with loss of sensation and rigidity of the body), analgesia and amnesia - doesn’t result in complete unconciousness.

No resp. depression
Bronchodilator so clinically used in patients with COPD
Not widely prescribed due to its hallucinogenic effect in adults (20%) - hallucinogenic effects not seen in children.

Question 6

Ethanol

Answer 6

Used prior to general anasethesia - effects depend on concentration

Responsive at GABAa receptors

Metabolised mainly in the liver by alchohol dehydrogenase into aldehyde (toxic). Aldehyde is then metabolised into acetic acid by aldehyde dehydrogenase.

Disulfiram inhibits action of aldehyde dehydrogenase

Question 7

Disulfarim

Answer 7

Inhibits aldehyde dehydrogenase from metabolising aldehyde into acetic acid in alcohol metabolism.

Leads to aldehyde syndrome (accumulation of toxic acetaldehyde in the body - causes facial flush, nausea, vomiting, tachycardia, hypotension)

Used for deterring alcoholics from relapsing during recovery.

Question 8

Phenol

Answer 8

Used pre-anaesthetic

Causes loss of sensation by chemically lysing nerve cells.

Question 9

Benzocaine

Answer 9

Ester local anaesthetic

Inhibits voltage gated sodium channels on the neuronal membrane - stops propagation of an action potention.

Topical anaesthetic used in cough drops or oral medications (ulcers) - Anbesol & Tyrozets

Short duration of action, metabolised rapidly by pseudocholinesterases in plasma.

Can induce severe side effect such as methemglobinemia (iron in haemoglobin is oxidized into fe3 (ferric) from Fe2 (ferrous) leading to elevated methemglobin levels (form of haemoglobin that cannot bind oxygen) - results in poor tissue perfusion.

Question 10

Local Anaesthetic

Answer 10

MOA - main mechanism of local anaesthetics is inhibition of Na+ channels through preferentially binding to them when they are in the active or inactive state.

Binding is mostly at the s6 part of domain 4 of the na+ channel (Na+ channels are usually 4 homologous domains each with 6 subunits).

Blocks the pore of the channel - stabilising it and thus increases the refractory period.

Inhibition decreases the likelyhood of A.P propogation.

Question 11

Lidocaine/Lignocaine

Answer 11

Amide local anaesthetic
Na+ channel blocker
Metabolised slower than ester anaesthetics by microsomal liver enzymes so have a longer duration of action.
Can induce methaemoglobinaemia

Question 12

Diethyl ether

Answer 12

Prototype general anaesthetic - inhalable
Colourless, volatile, flammable liquid
Good anaesthetic which maintains stable CVS and relaxes skeletal muscle, however has a slow onset of action, bronchial irritation and long term exposure leads to liver damage.

Use discontinued to flammability causing safety issues in the presence of an O2 rich environment.

Question 13

Inhaled Anaesthetics

Answer 13

Volatile liquids/gases

Responsive at GABAa receptors - xenon may block glycine site of NMDA receptors

Notes:
Large proportion inhaled is rapidly exhaled
Lung conc. = brain conc. - once carried in blood
Agents comparted via minimum alveolar conc. (MAC) - partial pressure/conc. of vapour in the alveoli that is needed to prevent motor response in 50% of subjects in response to surgical stimulus - compares the potency
brain:blood co-efficient varies between drugs, e.g not all drugs bind plasma proteins
Giving the drug at very high partial pressure may affect the partial pressure of O2 in the blood and cause diffusion anoxia (absence of O2 in alveolar gas).

Question 14

Nitrous Oxide

Answer 14

Inhaled analgesic and low potency anaesthesia
Not used alone for surgery due to low potency.
Rapid onset - used for short procedures (risk of O2 tension and hypoxia with long duration)

Prolonged exposure >6 hours can lead to megaloblastic anaemia (decreases the activity of methionine synthase)

Question 15

Isoflurane

Answer 15

Halogenated ether
Likely binds to GABAa receptor

Depth of anaesthesia is easily controlled, induction is easy, BP is lowered and the excitatory spikes are not typically seen during induction.

Disadvantages: Slow onset (5ish mins), increases the hearts sensitivity to catecholamines (arrhythmias, liver damage).

Question 16

Sevoflurane

Answer 16

Halogenated ether
Positive-allosteric inhibitory of GABAa - actual MOA not fully determined

Depth of anaesthesia is easily controlled, induction is easy, BP is lowered and the excitatory spikes are not typically seen during induction.

Disadvantages: Slow onset (5ish mins), increases the hearts sensitivity to catecholamines (arrhythmias, liver damage, also kidney damage (unproven).