Anaesthetics - Principles of Pharmacology Flashcards

1
Q

Anaesthesia:

  • Largest Single Hospital Specialty
  • 78 Consultants in NHSG
  • 125+ including trainees

There are multiple sub specialities which may include what?

A

Paediatrics

Cardiac

Maternity

Trauma

Crit care

Pre-hospital Care

Chronic Pain

Acute Pain

Vascular

Neuro

Hepato-Biliary

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2
Q

what does anaethesia literally mean?

A

without feeling/perception

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3
Q

what is general anaesthesia?

A
  • produces insensibility in the whole body, usually causing unconsciousness
  • Centrally acting drugs – hypnotics/analgesics
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4
Q

what is regional anaesthesia?

A
  • producing insensibility in an area or region of the body
  • Local anaesthetics applied to nerves supplying relevant area

Essence is that the anaesthetic agent is applied to the nerve anywhere from the spinal cord to the periphery and anaesthesia produced in a distal site served by that nerve, therefore effect is remote from the injection

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5
Q

what is local anaesthesia?

A
  • producing insensibility in only the relevant part of the body
  • Local anaesthetics applied directly to the tissues

Local anaesthetic is injected directly into the tissues to be anaesthetised. Unlike regional anaesthesia, anaesthesia is produced at the site of injection

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6
Q

what were the problems in ancient surgery? and what were their solutions?

A
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7
Q

in the early years how was anaesthesia given?

A
  • General anaesthesia delivered as a monotherapy - Single agent e.g. chloroform, ether
  • Toxic effects - cardiac depression, respiratory depression

To achieve the depths of anaesthesia needed to provide surgical operating conditions, e.g. muscle relaxation the patient had to be given very high concentrations of that agent. The muscle relaxation needed for abdominal surgery for instance was essentially a side effect of very deep anaesthesia. This made other, toxic, side effects such as cardiac dysrhythmia very common and frequently fatal

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8
Q

what is shown here?

A

Schimmelbusch Mask

very simple method for administering ether - Metal frame over which Gauze is placed

Ether or chloroform was dripped on and the mask with soaked gauze held over patients face and inhaled air – no added oxygen – was drawn through the gauze picking up the anaesthetic agent as it went

The anaesthetist would stand and slowly drip the agent onto the mask with only very crude control over the amount being inhaled by the patient

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9
Q

what durgs and techniques are now used in the modern era?

A

Huge progress in areas of equipment, monitoring and techniques available. Great advances in safety. Modern anaesthesia v safe

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10
Q

this is a modern anaesthetic machine

what are its functions?

A
  • Regulation of fresh gases and mixing to deliver precise concentrations of gaseous agents
  • Addition of precise concentrations of inhaled anaesthetic gases
  • CO2 removal to allow recirculation of inhaled gases
  • Mechanical ventilation, now microprocessor controlled contained within machine
  • Most monitoring now normally integrated into anaesthetic machine
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11
Q

how safe is anaesthesia now a days?

A

very safe

  • Overall operative mortality approx 1:25 (4%)
  • Anaesthetic mortality 1:400,000 (0.00024%)
  • ASA system: Mortality concentrated in ASA groups 3-5
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12
Q

what is the triad of anaesthesia?

A
  • Hypnosis – unconsciousness. Necessary component of any general anaesthetic
  • Analgesia – 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 is usually still required to suppress reflex autonomic responses to painful stimulus
  • Relaxation – refers to skeletal muscle relaxation necessary to provide immobility for certain procedures, allow access to body cavities and to permit artificial ventilation amongst other things

Each drug, or type of drug may do more than one job

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13
Q

Balanced anaesthesia:

  • Different drugs to do _______ jobs
  • _______ doses separately & therefore more accurately to requirements
  • Avoid ___________
  • Enormous ________

This is the concept introduced on the previous slide of using different drugs to do different ____. Big advantage of balanced anaesthesia is that it allows a great degree of control over the individual components of the _____

A

different

Titrate

over-dosage

flexibility

jobs

triad

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14
Q

what is the problems that may be faced with balanced anaesthesia

A
  • Polypharmacy - Inc chance of drug reactions/allergies
  • Muscle relaxation - requirement for artificial ventilation, means of airway control
  • Separation of relaxation & hypnosis - awareness:

The possibility of having patients awake yet paralysed and unable to communicate (Termed awareness) also now exists as it is possible to have a patient paralysed with muscle relaxant yet insufficiently anaesthetised. This is due to the separation of hypnosis from muscle relaxation making the latter possible without the former

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15
Q

whta are the 2 main groups of genereal anaesthetics?

A

IV

inhalation

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16
Q

General anaesthetic agents, inhaled and intravenous, provide _____________ as well as a small degree of ______ _______. They may to differing extents also provide some analgesia. But for all except Ketamine, analgesia is negligible

They are all potent drugs and the main thing which separates a general anaesthetic drug from a sedative drug really is potency

A

unconsciousness

muscle relaxation

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17
Q

how do genereal anaesthetic agents work?

A

All general anaesthetic agents work by suppressing neuronal activity in a dose dependent fashion

  • Interfere with neuronal ion channels
  • Hyperpolarise neurones = Less likely to “fire”
  • Inhalational agents dissolve in membranes: Direct physical effect
  • Intravenous agents – allosteric binding: GABA receptors - open chloride channels

This is largely done by opening chloride channels which hyperpolarise the neurons, suppressing excitatory synaptic activity. The common mechanism then is that neurons become (reversibly!) hyperpolarized and therefore less able or likely to reach their threshold potential and fire, sending signals (as propogated action potentials) to other neurons

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18
Q

in general anaesthesia, what processes are lost first and last?

A
  • Cerebral function “lost from top down”
  • Most complex processes interrupted first
  • LOC early - hearing later
  • More primitive functions lost later
  • Reflexes relatively spared - Primitive - Small number of synapses
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19
Q

Not surprisingly the most complex processes which rely on the greatest and most ________ neuronal activity (i.e. consciousness) 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 ________ (i.e. spinal reflexes) and other automatic functions

A

complex

reflexes

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20
Q

what is required in anaesthetic management?

A
  • ABC – Long drawn out resuscitation
  • Mandates airway management
  • Impairment of respiratory function and control of breathing
  • Cardiovascular impact
  • Care of the unconscious patient
21
Q

intravenous anaesthesia:

  • ______ onset of unconsciousness - 1 arm - brain circulation time
  • Rapid recovery due to disappearance of drug from ________, Redistribution V’s Metabolism

highly fat soluble drugs and cross _________ membranes extremely quickly. They therefore cross the _______ ______ _______ rapidly and get into neural tissues very quickly

A

Rapid

circulation

basement

blood brain barrier

22
Q

intravenous anaesthesia:

This rapid fall in blood concentration is due mainly to what?

A

the drug leaving the circulation and moving to other parts of the body

Muscle picks up the drug more slowly but the effect is large because of the relative high mass of skeletal muscle in the body. Fatty tissue picks up drug even more slowly but given lengthy enough exposure can store large amounts due to the high fat solubility of these drugs.

23
Q

inhalational agents = drug is delivered into the blood via the _______

intravenous agents = injected directly intravenously

The route used is determined by the physical properties of the drugs – intravenous agents cannot be vapourised and therefore cannot be breathed

Inhalation agents cannot be injected and can only be vapourised and inhaled. The intravenous injection of an inhalational agent is often ______

A

alveoli

lethal!

24
Q

whta is a Target Controlled Infusion (TCI) pump system?

A

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

Big problem with Total Intravenous anaesthesia (TIVA) is that we currently can’t measure the drug concentration in real time

Therefore we use computers to calculate what is in essence, a real time guess

The calculations are based on mathematical models which mimic the movement of anaesthetic drug into different tissues as described on the previous slide

25
Q

Inhalational Anaesthetics:

Halogenated ____________

  • Uptake and excretion via _____
  • Partial pressure gradient - lungs > blood > brain
  • cross alveolar BM _____ - arterial partial pressure equates closely to alveolar partial pressure
  • MAC = ______________________ (Measure of potency - Low number = ____ potency)
A

hydrocarbons

lungs

easily

minimum alveolar concentration

high

26
Q

MAC is the concept of the concentration of the drug required in the alveoli which is required to produce __________ with any particular agent.

Therefore a low MAC value means an agent is ______

A

anaesthesia

potent

27
Q

what is the speed of induction of inhalation anaesthetics?

A

slow (compared to IV agents)

28
Q

what is the maintenance of anaesthesia like in inhalation anaesthesia?

A

prolong duration - very flexible

The patient breaths a gas mixture containing the inhalational anaesthetic for the duration of the procedure and will remain unconscious for as long as the anaesthetic is administered

29
Q

how is awakening done form inhaled anaesthetics?

A
  • stop inhalational admin
  • washout - reversal of concentration gradient
30
Q

Inhalational agents undergo very little actual ___________ in the body and are almost completely just ________ back out again completely __________

A

metabolism

breathed

unchanged

31
Q

another strength of inhaled agents is our ability to measure them

how is it done?

A

measure CO2 in expelled gas and know when end of experation is and measure the concentration of anaesthetic in same gas flow

This represents Alveolar gas and gives info regarding alveolar gas concentrations

give apox value of arterial concentration

no direct way of measuring IV anaesthetic conecetraiton

32
Q

what ist he sequence of GA?

A

The most common sequence of general anaesthesia is Intravenous induction followed by inhalational maintenance

More modern agents with more sophisticated infusion techniques (computer controlled infusions) allow use of intravenous maintenance which has claimed advantages of better recovery

33
Q

All general anaesthetic agents IV or inhalational have adverse effects on the cardiovascular system and are almost universally depressant (Ketamine is the exception)

physiology of GA: how does GA affect the CVS centrally?

A

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

depress cardiovascular centre:

  • reduce sympathetic outflow
  • negative inotropic/chronotropic effect on heart
  • reduced vasoconstrictor tone → vasodilation
34
Q

physiology of GA: how does GA affect the CVS directly?

A

direct effects of anaesthetic agents on vascular smooth muscle and myocardium which compound the effects of the reduced sympathetic activity

  • negatively inotropic
  • vasodilation → decreased peripheral resistance
  • venodilation = decreased venous return, decreased cardiac output
35
Q

physiology of GA: how doe sanaesthesia affect the respiratory system?

A

•All anaesthetic agents are respiratory depressants:

  • Reduce hypoxic and hypercarbic drive
  • Decreased tidal volume & increase rate
  • Paralyse cilia
  • Decrease FRC (functional residual capacity) (may be a prolonged effect):
  • Lower lung volumes
  • VQ mismatch
36
Q

what are muscle relaxants?

A

only effect one limb of the triad of anaesthesia

interfering wIth neuromuscular junction in skeletal muscle, dont effect cardiac or smooth muscle, only the somatic skeletal msucle effected

If muscle relaxation is provided by systemic muscle relaxant drugs then unconsciousness must be provided. Being paralysed and awake is extremely unpleasant.

These drugs do exactly what the name says. They relax (i.e. paralyse) skeletal muscle. They do this indiscriminately and unfortunately respiratory and airway muscles are affected as much as any other

37
Q

what are the indications for muscle relaxants?

A
  • ventilation & Intubation
  • when immobility is essential - microscopic surgery, neurosurgery
  • body cavity surgery (access)
38
Q

what are the problems with msucle relaxants?

A
  • awareness
  • incomplete reversal → airway obstruction, ventilatory insufficiency in immediate post op period
  • apnoea = dependence on airway & ventilatory support
39
Q

what is the most important single component of the triad?

A

analgesia

Most commonly analgesia is used in conjunction with unconsciousness as part of a balanced general anaesthetic technique with or without muscle relaxation. Regional techniques usually provide reasonable muscle relaxation by blocking motor nerves so spinal or epidural analgesia may not require additional muscle relaxation.

40
Q

what can be used to cause analgesia?

A
41
Q

why may you give intraoperative analgaesia?

A
  • Prevention of arousal - pain wakes you up
  • Opiates contribute to hypnotic effect of GA
  • Suppression of reflex responses to painful stimuli
  • e.g. tachycardia , hypertension
42
Q

what are opiates used for and what is their role?

A

main role is anagesia and they supplement hypnosis

43
Q

what are some examples of opiates and their effects?

A

Fentanyl – short acting & potent. Really only used for intra-operative analgesia

Morphine, Oxycodone, more conventional opiates - used for intro-operative analgesia which we want to continue into the post-operative period

Remifentanil - Very highly potent and extremely short acting – has to be given by infusion. High potency allows it to be used as a very potent adjunct to inhalation and intravenous agents allowing them to be used in lower doses and permitting faster recovery. Doesn’t provide any postoperative analgesia – wears off too fast!

44
Q

what does local anaesthetics do?

A

lots of analgaesia and little muscle relaxant as blocks both motor and sensory nerves

no hypnosis

Work by blocking Na+ channels and preventing axonal action potential from propagating. Pharmacologically filthy with effects on every tissue so toxic if delivered wrongly (i.e. intravenously!!)

45
Q

Much progress in ability to deliver analgesia with ________ techniques, either alone or in conjunction with __. Biggest benefit is avoidance of reliance on opioid analgesics.

A

regional

GA

46
Q

Local and Regional Analgesia - what are the effects?

(may need to listen again, slide 38)

A
  • Retain awareness / consciousness
  • Lack of global effects of GA
  • Derangement of CVS physiology - proportional to size of anaesthetised area
  • Relative sparing of respiratory function (Therefore regional techniques may be preferred in a patient with concomitant respiratory problems)
47
Q

Ultrasound Guided Regional Anaesthesia:

US to guide needle placement for regional anaesthesia

Ultrasound allows safer and more effective delivery of the local anaesthetic (LA) drug with less likelihood of the LA going intravenously or direct nerve or vascular injury which can happen with blind, anatomical landmark based, needle positioning

slide shows a needle approaching the brachial plexus in the interscalene groove. Yellow line highlights needle which is coming in from the right

Nerves are the dark bundles three in a row one above another

A

USS with a needle in plane approach to the femoral nerve – again, yellow line highlights needle, approaching from the left this time. Nerve is bright oval with two dark dots just below needle tip. Dark area about needle tip is injected local anaesthetic. Big dark circle to right is the femoral artery. Approach would probably be to inject half of the local anaesthetic here and reposition needle below the nerve to surround it with drug and ensure effectiveness of the block. The Artery is clearly seen and can be avoided. Safety feature is the ability to see the injectate in the tissues therefore we know the injection is not intravascular

48
Q

Summary:

  • Large heterogenous specialty
  • Unconsciousness - ABC, long drawn out resuscitation
  • Developments:
  • Little new pharmacology
  • Technology driven - Monitoring, Infusion technology, Imaging
A