Principles of pharmacology

Question 1

What are the main types of anaesthesia?

Answer 1

General

Regional

Local

Question 2

What is general anaesthesia?

Answer 2

General anaesthesia produced insensibility in the whole body, usually causing unconsciousness

This is achieved using centrally acting drugs (GA agents)

Question 3

What is the difference between local and regional anaesthetics

Answer 3

Regional anaesthetics:

• produces insensibility in an area or region of the body
• achieved by Local anaesthetics applied to nerves supplying relevant area

Local anaesthetics:

• producing insensibility in only the relevant part of the body
• achieved by applying local anaethetic directly to tissues

Question 4

On this lovely photo of an anaesthetic machine - identify what the labelled bits are

Answer 4

Question 5

What is the triad of anaesthesia?

Answer 5

Analgesia - (pain relief)

Hypnosis - (sleepy sleepy time)

Muscle relaxation - (of skeletal muscle)

Question 6

Drugs used in anaesthetics often have effects on multiple parts of the triad of anaesthesia.

What drugs produce hypnosis?

Answer 6

General anaesthetic agents

Opiates do a wee bit too

Question 7

What drugs can produce analgesia?

Answer 7

Opiates

Local anaesthetics

Certain General anaesthetic agents (special K) do a wee bit too

Question 8

What drugs produce muscle relaxaton?

Answer 8

Muscle relaxants

A wee bit - GA & LA

Question 9

What is balanced anaesthesia?

Answer 9

Using a mixture of different anaesthetic agents to do different jobs on the triad of anaesthesia

This way the mixture and so the effects produced can be tailored to the patient and procedure.

It avoids over dosage and gives enormous flexibility

Question 10

What problems are associated with balanced anaesthesia?

Answer 10

Polypharmacy:

• The use of lots of drugs in combo means theres higher risk of allergy or adverse reaction

Seperation of relaxation & hypnosis:

• ‘Awareness’ happens when a patient in surgery is conscious but paralysed

Muscle relaxtion:

• requirements for artificial ventilation

Question 11

How can General anaesthetic agents be administered?

Answer 11

IV

Inhaled

Question 12

What are the effects of general anaesthetic agents on the triad?

Answer 12

All produce Hypnosis

They provide a little bit of relaxation

For all exept Ket - analgesia is negligible

Question 13

How do general anaesthetic agents work?

What is the difference between how IV and inhaled agents work?

Answer 13

Interfere with neuronal ion channels - causing them to be hyper-polarised

Inhaled agents - dissolve in membranes and have a direct physical effect

IV agents - allosteric binding to GABA receptors - which opens chloride channels

Question 14

When GA is administered - in what order are cerebral functions lost?

Answer 14

Cerebral function lost from top down

The most complex cerebral functions are the first to go,

More primitive functions are lost later,

Primitive reflexes are relatively spared

Question 15

How quickly do IV General anaesthetic agents work?

Answer 15

Very quickly

IV agents, e.g. thiopentone or propofol all work extremely rapidly and cause unconsciousness basically as soon as they reach the brain.

They are highly fat soluble drugs and cross basement membranes (incl. the Blood-brain barrier) heavy fast - thus allowing them to act on neural tissues quickly

Question 16

How quickly do IV GA agents leave the circulation?

Answer 16

These are removed very quickly from the circulation but not because they are metabolised quickly…

The rapid fall of [GA agent] in blood is mainly because of it leaving the circulation and moving into other parts of the body

Question 17

Whats this?

Answer 17

Target Controlled Infusion (TCI) pump system

Allows very accurate infusion to achieve specific blood or brain concentrations of agents using complex pharmacokinetic algorithms

Question 18

What types of molecule are Inhaled agents?

How are they excreted?

Answer 18

Inhalational anaesthetic agents are all halogenated hydrocarbons and are taken up and almost exclusively excreted via the lungs

Question 19

With inhaled anaesthetic agents - what is the significance of the MAC value?

Answer 19

MAC (minimum alveolar conc.) 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

As a general - what types of GA agents are used for:

• Induction?
• Maintenance?

Answer 20

Induction = IV*

Maintenance = Inhaled

However, there is an increasing use of IV agents for maintenance - such as IV propofol, opiates (remifentanil)

*Inhaled for children

Question 21

How does General anasethesia affect the Cardiovascular system?

Answer 21

Central effects:

• Depression of cardiovascular centre
  
  • ​this reduces sympathetic outflow which:
    
    • has negative inotropic/chronotropic effect on the heart
    • reduces vasoconstrictor tone –> vasodilation

Direct effects on myocardium and vascular smooth muscle:

• negatively inotropic (reduced strength of heart contraction)
• vasodilation (reduced PVR)
• venodilation (decreased venous return & CO)

All of this contributes to decreased MAP (MAP = CO x SVR)

Question 22

WHat are the effects of general anaesthesia on the respiratory system?

Answer 22

All anaesthetic agents are respiratory depressants:

• reduced hypoxic and hypercarbic drive
• decreased tidal volume and increased rate

Paralyse cilia

Decrease FRC:

• lower lung volumes
• V/Q mismatch

Question 23

What are the indications for usage of muscle relaxants?

Answer 23

Ventilation & intubation

When immobility is essential

Body cavity surgery (for access)

Question 24

What are the problems with muscle relaxant drugs?

Answer 24

Awareness - if not enough hypnosis

Incomplete reversal of effects post op

Apnoea - dependence on airway & ventilatory support

Question 25

Why is intraoperative analgesia needed? (ie if the person is asleep why do they need analgesia)

Answer 25

Prevention of arousal

Opiates contribute to hypnotic effect of GA

Suppression of reflex response to painful stimuli:

• tachycardia, hypertension etc

Question 26

Opiates are an important part of almost every general anaesthetic. They are strong analgesics but also contribute (supplement) to hypnosis

What opiates are used in general anaesthesia?

What are their benefits?

Answer 26

Fentanyl:

• short acting & potent
• only really used for intra-operative analgesia

Morphine, oxycodone:

• used for intro-operative analgesia which we want to continue into the post-operative period

Remifentanil:

• V short acting, V potent
• Has to be given IV

Question 27

How do local anaesthetic drugs work?

Answer 27

Local anaesthetic drugs, lignocaine, bupivacaine and ropivacaine produce analgesia with no hypnosis

Work by blocking Na+ channels and preventing axonal action potential from propagating

Question 28

What are the effects of local/regional anaesthetics on the cardiovascular and respiratory systems?

Answer 28

Affects CVS physiology - proportional to size of anaesthetised area

Respiratory function relatively spared