general anaesthetics

Question 1

what are stages of anaesthesia

Answer 1

stage 1: analgesia, still conscious

stage 2: excitement, delirium and respiration becomes irregular

stage 3: surgical anaesthesia: unconscious, respiration and reflexes become progressively depressed as anaesthesia deepens

stage 4: medullary depression, no spontaneous respirator and depressed vasomotor centres, coma and death follow in absence of artificial respiration and circulatory support

Question 2

what are 2 main categories of general anaesthetics

Answer 2

those that are inhaled as vapour or gas (volatile anaesthetics)

intravenous anaesthetics

Question 3

what are examples of volatile anaesthetics

Answer 3

neither ether (explosive) or chloroform (damages liver) are used any longer

N20, nitrous oxide is used

most are volatile liquids such as halothane, enflurane and isoflurane

Question 4

what are examples of intravenous anaesthetics

Answer 4

thiopentone is most common, it is a thiobarbiturate

other agents are used such as propofol

Question 5

how are volatile anaesthetics absorbed and excreted

Answer 5

both absorption and excretion is via lungs

Question 6

how is potency of volatile anaesthetics expressed, what determines potency

Answer 6

potency is expressed as minimum alveolar concentration (MAC) of anaesthetic which will, when equilibrium has been attained, prevent movement in response to surgical incision in 50% of individuals (essentially an ED50)

MAC is expressed by %volume in the alveoli, measure in percentage atmospheres

mmHg= percentage atmx760

higher solubility in blood will cause an anaesthetic to be more potent

potency is also correlated with lipid solubility

Question 7

how is solubility of volatile anaesthetics expressed

Answer 7

the blood: air partition coefficient, termed lamda

this is ratio of concentration of anaesthetic in blood:air at equilibrium, an anaesthetic which has a concentration of n times higher in blood than air at equilibrium will have a lamda value of n

Question 8

what is the product of MAC and lamda value directly proportional to

Answer 8

blood concentration of anaesthetic at equilibrium when 1 MAC is administered

Question 9

how do solubility/potency of anaesthetics compare

Answer 9

nitrous oxide is least potent, is far less potent than halogenated hydrocarbons such as halothane and enflurane

MAC of nitrous oxide is 105%, which is not achievable at atmospheric conditions, considering a patient needs at least 15% oxygen

out of halothane, enflurane and N2O: halothane has lowest MAC (0.75), then enflurane (1.6) then N2O (105)

Question 10

how blood: air partition coefficients relate of some anaesthetics

Answer 10

highest in halothane (2.3) then enflurane is 1.8, and 0.47 for nitrous oxide

Question 11

how is MAC related to lamda value

Answer 11

generally an inverse relationship

Question 12

what is rate of onset and rate of recovery of an anaesthetic dependent on

Answer 12

rate of onset is faster in anaesthetics with a high MAC, since there is a larger concentration gradient between air in lungs and blood at time of administration, thus less soluble anaesthetics are faster

rate of recovery is faster is anaesthetics with low solubility as well so have low lamda values

Question 13

what properties would an ideal anaesthetic have

Answer 13

high MAC (quick onset) and low lamda (quick recovery), thus low solubility anaesthetics

Question 14

why is methoxyflurane no longer used

Answer 14

large lamda value so had long recovery rate

Question 15

how does rate of elimination relate to onset, what may effect this

Answer 15

rate of elimination is inverse rate of onset

rate of elimination may be slower in patients which large fat depots

high lipid solubility causes slower recovery as it accumulates in fat

Question 16

what is mechanism of volatile anaesthetics

Answer 16

although potency is correlated with lipid solubility mode of action does not involve insertion into lipid bilayer

they bind to hydrophobic regions of proteins, selective effects on certain ion channels have been demonstrated

halogenated hydrocarbons at anaesthetic doses selectively effect synapses between neurones over axons

GABAa receptors and 2 pore (leak) potassium channels that control neuronal excitability are shown to be important targets

effect of glycine at glycine receptors is also enhanced

ketamine, nitrous oxide and xenon are examples of anaesthetics which block NMDA receptors

Question 17

what are side effects of volatile anaesthetics

Answer 17

all agents produce respiratory depression (especially halothane) and fall in blood pressure caused by myocardial depression and vasodilation

incidence of serious toxic effects is quite low, however therapeutic index for general anaesthetics is quite low; dose does not need to be increased much to move from surgical anaesthesia to respiratory paralysis

safety depends on skill of the anaesthetist

use of a mixture of halogenated hydrocarbon with nitrous oxide may minimise vasomotor depression

Question 18

describe metabolism of volatile anaesthetics

Answer 18

halogenated agents are to some extent metabolised

about 60-80% of halothane is exhaled unchanged during first 24 hours after administration, up to 20% of halothane broken down into compounds such as trifluoroacetic acid

other volatile anaesthetics are broken down to a smaller extent (up to 3%)

Question 19

what is an example of an intravenous anaesthetic, what are they usually used for

Answer 19

thiopentone, very commonly used to induce anaesthesia as they have very high speed of action

Question 20

what are pharmacokinetics of thiopentone

Answer 20

often reffered to as ultra short acting barbiturate, however not actually short lasting

metabolised quite slowly in the liver, half life for catabolism is 4.6 hours

it has very rapid onset and recovery after a single dose

Question 21

how does thiopentone concentrations in various tissues relate to time

Answer 21

very lipid soluble and can cross cellular barriers including blood brain barrier very quickly; therfore concentration in brain along with other tissues with large blood supply peaks soon after peak in blood concentration

blood peak is very short for thipentone as it redistributes to other less well perfused tissues quite quickly, drop in blood concentration causes drop in brain concentration, causing quick recovery

lean tissues and fat are last tissues to peak

if repeated doses of thiopentone are given, the blood and hence the braine concentration will remain high and thiopentone will be quite long lasting and slowly metabolised

Question 22

what are pharmacokinetics of most intravenous anaesthetics and how does this relate to their use

Answer 22

quick onset, slow metabolism

normally only used for induction since anaesthetist needs to be able to control level of anaesthesia from moment to moment and best control is obtained with anaesthetics

Question 23

how does mode of action of thiopentone compare to volatile anaesthetics

Answer 23

mode of action is very similar

however it has no analgesic effects and respiratory depression is profound

effects are via GABAa receptors

Question 24

what is main hazard of thiopentone

Answer 24

solution of thiopentone is very alkaline, can cause serious tissue damage if it is not injected properly

Question 25

how is propafol used

Answer 25

iv anaesthetic

fast onset and recovery

administration via continuous slow intravenous infusion, controlled by computer to avoid overdose

is an irritant at site of injection, causing pain

Question 26

how is ketamine used

Answer 26

is a dissociative anaesthetic

disadvantages: slow recovery and causes hallucinations (less in children)

used in pediatric surgery and as pediatric sedative after trauma

widely used in vetinary practice

widely abused and can cause bladder damage with chronic use

produced incomplete anaesthesia, however very good analgesic

causes dissociation from surrounding and light sleep, for when co-operation is needed

lethal overdose is rare

can be used in combat zones or acute trauma outside hospital settings such as in bombings

orally active

Question 27

how is epidural anaesthesia used

Answer 27

use of local anaesthetic such as bupivacaine (long duration), in combination with narcotic analgesic such as fentanyl

only gives pain control below site of epidural

uses of epidural: childbirth, minor surgery, lower limb surgery, post operative pain control

Question 28

how are drugs used peri-operatively

Answer 28

premedacation for surgery: analgesics, anxiolytics, anti-emetics and anti-muscarinics

induction of anaesthesia: intravenous anaesthetic

maintenance: inhaled anaesthetic

muscle relaxants are also used to reduce amount of anaesthetic needed