Anaesthetics – Principles and Pharmacology

Question 1

define anaesthesia?

Answer 1

without feeling or perception

Question 2

types of drugs used in anaesthesia

Answer 2

o Inhalational anaesthetics
o IV anaesthetics
o Muscle relaxants
o Local anaesthetics
o Analgesics

Question 3

techniques and equipment used in anaesthesia

Answer 3

o Tracheal intubation
o Ventilation
o Fluid therapy
o Regional anaesthesia
o Monitoring
o Main areas of progress
o Use of improved technology e.g. USS, fibre optics, CPUs, BIS, sensors etc

Question 4

name the componenets of the triad of anaestheisa

Answer 4

analgesia
hypnosis
relaxation

Question 5

what kind of drugs produce relaxation

Answer 5

muscle relaxations
local anaesthetics
GAs

Question 6

what kind of drugs produce hyponosis

Answer 6

GAs

Opiates

Question 7

what kind of drugs produce analgesia

Answer 7

local anaesthetics
opiates
(GAs)

Question 8

with a patient under GA why is pain relief still needed?

Answer 8

Pain relief, can also be taken in this context to mean “removal of perception of unpleasant stimulus” since not all unpleasant stimuli patients need protected from are necessarily painful. E.g. handling of gut. If patient is unconscious and therefore unaware of pain, analgesia usually still required to suppress reflex autonomic responses to painful stimulus.

Question 9

what kind of operations require relaxation of skeletal muscle?

Answer 9

body cavity access

permit artificial ventilation

Question 10

advantages of balanced anaesthesia

Answer 10

Big advantage of balanced anaesthesia is that it allows a great degree of control over the individual components of the triad. And allows different drugs and techniques to be used to achieve each of the individual “targets” as it were while tailoring the technique to each patient and procedure. Helps keep doses of individual drugs down. Balanced anaesthesia allows you to titrate doses separately and therefore more accurately to requirements. This avoids over dosage and allows enormous flexibility. E.g. we can use much less general anaesthetic agent to provide hypnosis for abdominal surgery if we use a muscle relaxant to provide the muscle relaxation needed for access and immobility. Additionally, we could use less of each of these if we added in an epidural anaesthetic (regional local anaesthesia) to provide additional analgesia and muscle relaxation.

Question 11

issues with balanced anaesthesia

Answer 11

polypharmacy - reactions + allergy

muscle relaxants and airway, awareness

Question 12

how do GAs work?

Answer 12

All general anaesthetic agents work by suppressing neuronal activity in a dose dependant fashion. This is largely done by opening chloride channels which hyperpolarise the neurones or suppressing excitatory synaptic activity. They interfere with neuronal ion channels causing them to hyperpolarise and thus less likely to fire. Inhalational agents dissolve in membranes causing a direct physical effect. IV agents have allosteric binding through GABA receptors opening chloride channels.

Question 13

describe loss of function with administration of GAs

Answer 13

Cerebral function is lost from the top down. The most complex processes are interrupted first – LOC early and hearing later. More primitive functions are lost later. Reflexes are relatively spared as they are primitive and involve a small number of synapses. Not surprisingly the most complex processes which rely on the greatest and most complex neuronal activity are the most susceptible to inhibition in this way and therefore cerebral function is lost “from the top down” with relative sparing of the simpler more primitive functions including reflexes (i.e. spinal reflexes) and other automatic functions.

Question 14

name two IV GAs

Answer 14

thiopentone

propofol

Question 15

advantages of IV GAs

Answer 15

• Rapid onset of unconsciousness
o 1 arm-brain circulation time
• Rapid recovery
o Due to disappearance of drug from circulation
o Redistribution vs metabolism

Question 16

how do IV GAs work so quickly and wear off rapidly?

Answer 16

They are highly fat-soluble drugs and cross membranes extremely
quickly. They also leave the circulation very quickly indeed and if given as a once off “bolus” dose will
cause only temporary unconsciousness as they disappear very rapidly from the circulation and
consequently the brain. This rapid fall in blood concentration is due mainly to the drug leaving the
circulation and moving to other parts of the body (compartments). Metabolism of the drug (i.e. the
Figure 3 Ion Channels
process of the drug being destroyed and removed from the body) actually contributes very little to
the termination of action of an intravenous anaesthetic agent given as a bolus.

Question 17

how do you measure inhalational anaesthetics

Answer 17

• Uptake and excretion via lungs
o Concentration gradient – lungs > blood > brain
o Cross alveolar BM easily
o Arterial concentration equates closely to alveolar partial pressure
• MAC = minimum alveolar concentration
o Measure of potency
o Low number = high potency

Question 18

induction with inhalational agents

Answer 18

Inhalational anaesthetic agents are all halogenated hydrocarbons and are taken up and almost
exclusively excreted via the lungs. At induction the patient is given a relatively high concentration of
the agent to breath. The gas then moves down the concentration gradient in to the patients’ blood
and finally brain to achieve a high enough partial pressure there to produce unconsciousness.

Question 19

what is MAC?

Answer 19

MAC is the concept of the concentration of the drug required in the alveoli which is required to produce anaesthesia with any particular agent. Therefore, a low MAC value means an agent is potent. E.g. Halothane (MAC = 0.8%) is more potent than Desflurane (MAC = 6%) because it takes a lesser concentration of the agent to produce the same effect

Question 20

when is inhalational induction useful?

Answer 20

potentially obstructing airway

Question 21

main role for inhalational anaesthetics

Answer 21

maintainence

Question 22

physiology of GA: CVS

Answer 22

• Central
o Depress CV centre
§ Reduce sympathetic outflow
§ Negative inotropic/chronotropic effect on heart
§ Reduced vasoconstrictor toon à vasodilation
• Direct
o Negatively inotropic
o Vasodilation
§ Decreased peripheral resistance
o Venodilation
§ Decreased venous return
§ Decrease CO

Question 23

how do the CVS effects of GA occur?

Answer 23

All general anaesthetic agents IV or inhalational have adverse effects on the cardiovascular system and are almost universally depressant (Ketamine is the exception). Central effects arise due to the depressant effects of the agent on the CNS and, more specifically, the cardiovascular centres and nuclei in the brainstem. They reduce sympathetic nerve activity and have direct negative chronotropic and inotropic effects on the heart and cause venous and arterial vasodilatation. Effects also arise from the direct effects of anaesthetic agents on vascular smooth muscle and myocardium. They compound the effects of the reduced sympathetic activity. By causing vasodilatation general anaesthetic agents reduce the venous return to the heart and the cardiac output (CO) therefore falls. This is compounded by the negative inotropic effects of the general anaesthetic agent which worsen the fall in the CO. The arterial vasodilatation leads to a reduction in the systemic vascular resistance (SVR). As you can see from the equation Mean arterial pressure (MAP) = CO x SVR. Therefore, any reductions in CO and SVR are multiplicative. e.g. if both CO and SVR are reduced by 1/3 this results in the MAP being more than halved! (Because 2/3 x 2/3 = 4/9).

Question 24

respiratory effects of GA

Answer 24

• All anaesthetic agents are respiratory depressants
o Reduce hypoxic and hypercarbic drive
o Decreased tidal volume and increased rate
• Paralyse cilia
• Decrease FRC
o Lower lung volumes
o VQ mismatch
o May be prolonged effect

Question 25

how do the respiratory effects of GAs come about

Answer 25

In addition to being CVS depressants – all GA agents (again largely excepting Ketamine) are respiratory depressants. The respiratory depression due to anaesthetic agents is characterised by reduced tidal volumes (often greatly so) and a high respiratory rate. Contrast with opiate respiratory depression which largely preserves tidal volume and is characterised by a low respiratory rate. They produce the respiratory depression by reducing hypoxic and hypercarbic drive via the depression of the brainstem respiratory centres. Perhaps the most important effect of general anaesthetic agents however is their effect on lung volumes. These are often greatly reduced and this fall in lung volumes interferes with ventilation perfusion matching in the lungs. This effect persists into the postoperative period and is the main reason anaesthetists are so keen patients are given postoperative oxygen. Because this effect can persist for several days patients therefore often need postoperative oxygen for several days.

Question 26

what kind of muscle do relaxants work on?

Answer 26

skeletal

Question 27

indications for muscle relaxants

Answer 27

o Ventilation and intubation
o When immobility is essential
§ Microscopic surgery, neurosurgery
o Body cavity surgery (access

Question 28

problems with muscle relaxants

Answer 28

o Awareness
o Incomplete reversal à
§ Airway obstruction, ventilatory insufficiency in immediate post op period
o Apnoea = dependence on airway and ventilatory support

Question 29

why the need for intra operative analgesia?

Answer 29

o Prevention of arousal
o Opiates contribute to hypnotic effects of GA
o Suppression of reflex responses to painful stimuli
§ Tachycardia, hypertension

Question 30

why regional anaesthesia

Answer 30

Intense/complete analgesia

o No direct hypnotic effects

Question 31

examples of local anaesthetics

Answer 31

lignocaine, bupivacaine and ropivacaine

Question 32

how do local anaesthetics work?

Answer 32

Work by blocking Na+ channels and preventing axonal action potential from propagating.
Pharmacologically filthy with effects on every tissue so toxic if delivered wrongly (intravenously!!).
Much progress in ability to deliver analgesia with regional techniques, either alone or in conjunction
with GA. Biggest benefit is avoidance of reliance on opioid analgesics.

Question 33

limiting factors for use of local anaesthetics

Answer 33

o High plasma levels
o IV injection
o Absorption > rate of metabolism = high plasma levels
o Therefore vasoconstrictors – reduce blood flow, reduce absorption

Question 34

what does LA toxicitiy depend on

Answer 34

o Dose used
o Rate of absorption (site dependant)
o Patient weight
o Drug (bupivacaine > lignocaine > prilocaine

Question 35

signs and symptoms of local anaesthetic toxicity

Answer 35

• Circumoral and lingual numbness and tingling
• Light-headedness
• Tinnitus, visual disturbances
• Muscular twitching
• Drowsiness
• Cardiovascular depression
• Convulsions
• Coma
• Cardiorespiratory arrest

Question 36

differential blockade in LA

Answer 36

One useful property of LA block of peripheral nerves is differential block. This is due to differential
penetration into different nerve types. Myelinated, thick fibres are relatively spared. Pain fibres are
blocked easily (luckily). Due to the different physical attributes of different nerve fibre types (thickness
and myelination) some are easier for LA to block than others. Luckily for us motor fibres are relatively
to block and pain fibres relatively easy. This means we can provide analgesia without paralysis. Very
useful – e.g. patient with abdominal surgery can get good analgesia from epidural analgesia but still
be able to use abdominal muscles to cough.
• Retain awareness/consciousness
• Lack of global effects of GA
• Derangement of CVS physiology proportional to size of anaesthetised area
• Relative sparing of respiratory function

Question 37

types of regional and llocal anesthesia

Answer 37

• Local anaesthesia
• Field blocks – hernia repair
• Plexus blocks
• Limb blocks e.g. femoral N and sciatic N
Figure 6 Neuraxial Block CVS
• Central neural (neuraxial) block
o Epidural
o Spinal

Question 38

physiology of neuraxial block: resp

Answer 38

• Inspiratory function (relatively) spared
o Unless high block
• Expiratory function relatively impaired
o Cough dependent on abdo muscle function
• Decrease FRC – airway closure c.f. GA
• Increased V/Q mismatch
Respiratory effects are produced by the motor block produced by LA block of mixed spinal nerves.
Higher and more extensive blocks interfere with respiratory function more. Abdo muscles are
primarily expiratory function while inspiratory muscle (intercostals and accessory muscles) are served
by higher nerve roots. Therefore, inspiration will tend to be relatively spared compared with
expiration in spinal and epidural anaesthesia.