Anaesthetics Flashcards
1
Q
What are the two branches of spinal nerve?
A
Motor and sensory
2
Q
What root do ventral nerves pass through?
A
Ventral Root
3
Q
What root do sensory neurons pass through?
A
Dorsal Root
4
Q
Summarise the function, diameter and myelination of Type a alpha neurons
A
Function: Proprioception, motor
Diameter (microM): 12-20
Myelination: Heavy
5
Q
Summarise the function, diameter and myelination of Type a beta neurons
A
Function: Touch, pressure
Diameter (microM): 5-12
Myelination: Heavy
6
Q
Summarise the function, diameter and myelination of Type a gamma neurons
A
Function: muscle spindles
Diameter (microM): 3-6
Myelination: Heavy
7
Q
Summarise the function, diameter and myelination of Type a delta neurons
A
Function: pain, temperature
Diameter (microM): 2-5
Myelination: Heavy
8
Q
Summarise the function, diameter and myelination of Type b neurons
A
Function: preganglionic ANS
Diameter (microM): <3
Myelination: Light
9
Q
Summarise the function, diameter and myelination of Type c sensory neurons
A
Function: pain
Diameter (microM): 0.3-1.2
Myelination: None
10
Q
Summarise the function, diameter and myelination of Type c sympathetic neurons
A
Function: postganglionic
Diameter (microM): 0.2-1.3
Myelination: none
11
Q
Why do dorsal root ganglion neurons differ from general neurone structure?
A
Their cell bodies in the dorsal root ganglia have a single axon that splits (bifurcates) with one branch going to the periphery and the other into the spinal cord
12
Q
What are nociceptors?
A
Pain-sensing neurons
13
Q
What does the peripheral axon terminal of nociceptors look like?
A
Nerve terminals have bare endings that possesses receptors to noxious stimuli
14
Q
What are 2 mediators for nociceptors?
A
- H+
- ATP
(Are released by damaged tissue)
15
Q
Outline the basis for how local anaesthetics work (3 steps)
A
Local anaesthetics act by blocking sodium channels
Therefore
Local anaesthetics block action potentials
Therefore
Local anaesthetics block nociception
16
Q
What is the structure of a sodium alpha subunit?
A
- Has 24 membrane spanning domains
- Clustered into groups of 4
- Tetrameric channel
- Voltage sensor in the 4th transmembrane domain
17
Q
What are the three states in which a channel can exist in?
A
- Resting
- Open
- Inactivated
18
Q
What is the basic structure of local anaesthetics?
A
- Have an aromatic group
- Amine group
- Either: ester or amide group linking the two
19
Q
How can you identify if a drug has an amide linkage?
A
The prefix (part in front of the ‘caine’) will contain an ‘I’
20
Q
Where are amide linked local anaesthetics broken down?
A
Liver
21
Q
Where are ester linked local anaesthetics broken down?
A
Plasma esterases
22
Q
Do ester drugs or amide drugs have a longer duration of action?
A
Amide act longer than ester linked
23
Q
Which group on local anaesthetics can become protonated?
A
Amine group
24
Q
What does protonated mean for local anaesthetics?
A
- The amine group can become positive
- The charged and uncharged forms are in equilibrium
25
What is protonation dependent upon?
- The concentration of protons
- pH
26
What form of a local anaesthetic is lipid soluble?
The unproponated form- therefore able to cross cell membranes
27
What does the lipid soluble nature of unproponated local anaesthetics mean for a cell?
The equilibrium between charged and uncharged forms exist on both sides of the membrane as the charged form is unable to cross the membrane
28
What does a lower pH mean for the action of local anaesthetics on sodium channels?
Block sodium channels less well
29
What chemical was used to observe the nature of pH's action on sodium channels via local anaesthetics?
QX314 (tertiary amine (four groups on its nitrogen) and so has a permanent positive charge)
30
What were the results on the sodium channels when QX314 was applied to the outside of cells?
It does not block socium channels
31
What were the results on the sodium channels when QX314 was injected to the inside of cells?
Able to block sodium channels
32
What do the experiments using QX314 tell us about local anaesthetic action?
- They block sodium channels from the inside
- It is the charged form that acts on the channel
- The uncharged form is necessary to allow local anaesthetics to pass through the membrane
- Once inside the cell, local anaesthetic becomes protonated again and it is the charged form that blockes the channel
33
What state does the sodium channel need to be in for a stonger blockage?
- Open
or
- Inactivated
34
What is use dependence?
Channels that are more active (and thus either open or becoming inactivated) are blocked more strongly than resting channels
35
At what point in transmission do local anaesthetics act?
When an action potential reaches the spinal cord and synapses with other neurons to signal up to the brain
36
How might topical anaesthesia be applied?
Cream, drops, spray on the skin or mucosal tissue such as the nose, throat or eye
37
How is infiltration anaesthesia applied?
Injected into the tissue around the area that needs to be numbed and ususally only effects the more distal parts of the nerve (terminal branches)
38
Why can't you inject infiltration anaesthesia or nerve block into the bloodstream?
They can have serious systemic effects
39
How can you increase the duration of infiltration anaesthesia and nerve block?
Add a vasoconstrictor such as adrenaline
40
How is nerve block applied?
Is injected around the spinal nerve trunk so everything distal will be numbed
41
How is the nerve block injected?
Through the use of imaging techniques such as ultrasound
42
How is intravenous regional anaesthesia applied?
- A pressure cuff is used to cut off the blood supply to a limb
- It is then injected intravenously
- Wait 20 mins (allow the anaesthesia to develop and reduce concentration of local anaesthetic in blood vessels)
- Deflate the cuff
- Begin surgery
43
How is spinal anaesthesia applied?
- Inject into subarachnoid space above the spinal cord
- pain is lost from all regions supplied by nerves that emerge from the spinal cord below the level of injection
44
Where can the spinal anaesthesia be injected?
Bottom part of the spinal column as this is where the subarachnoid space is large anough to avoid damage to the spinal cord when placing the needle
45
Why is spinal anaesthesia not good for childbirth?
Produces motor block
46
How is epidural anaesthesia applied?
- Injected into the epidural space just below the vertebral column
- Performed via a catheter, which can be left in place to facilitate further doses being administered
47
Why is more epidural anaesthesia needed compared to spinal anaesthesia?
Because the epidural space is larger in volume than the subarachnoid space so onset it slower
48
What is intravenous lidocaine used for?
Post-operative pain management strategy in people who do not have cardiovascular problems or epilepsy
49
What is differential blockade?
When sympathetic nervous system function is lost first, followed by pain sensation with touch and motor function only being lost at higher doses
50
What are the three factors affecting the sensitivity of a nerve fibre to block by local anaesthetic?
1. Degree of myelination
2. Fibre diameter
3. Position within the nerve
51
How does the degree of myelination affect the sensitivity of a nerve fibre to local anaesthetic?
- Myelinated neurones transmit action potentials via saltatory conduction and have their sodium channels concentrated at the nodes of ranvier
- Saltatory conduction only takes the blockage of a few nodes to completely prevent action potential transmission
- Therefore, the higher the degree of myelination, the more sensitive to local anaesthetic
52
How does the fibre diameter affect the sensitivity of a nerve fibre to local anaesthetic?
Thin fibres are more sensitive to local anaesthesia than thicker ones- surface area to volume ratio
53
How does the position within the nerve affect the sensitivity of a nerve fibre to local anaesthetic?
Fibres that are closer to the surface of the nerve will be affected more strongly than those towards the centre
54
What happens to brain activity at low, medium and high doses of local anaesthetics?
Low: neuronal activity is depressed
Medium: activity of inhibitory neurons is suppressed more than excitatory ones so convulsions can occur
High: profound depression of the CNS leading to a coma and death
55
What are two effects of local anaesthetics on the heart?
- Reduce the heart rate (arrhythmias)
- Vasodilators
56
How do ester linked drugs sometimes cause allergic reactions?
- Can be metabolised to para-aminobenzoic acid to produce allergies
- Allergies to the preservatives used in formulating the drug for injection
57
What does anaesthesia mean?
- Literally 'without sensation'
- The reversible loss of awareness of pain
58
What are three categories of anaesthetics?
Local
Regional
General
59
Where is the first place to use general anaesthetics?
Mesopotamia (4000 years ago)
60
Who first cultivated the opium poppy?
Sumerians and Babylonians
61
Who is said to have discovered inhaled general anaesthetics?
Humphrey Davy (nitrous oxide in 1800)
62
What was the first inhaled general anaesthetic?
Diethyl ether discovered by Ramon Llull (1275) but noted by Paracelsus (1525)
63
What three general anaesthetic where used in the 1800s?
Nitrous oxide, ether and chloroform
64
What is a serious issue with ether?
Is highly flammable
65
What is a serious issue with chloroform?
Can cause cardiac dysrhythmias
66
Who synthesised Halothane?
CW Suckling of ICI in Widnes
67
What anaesthetic is on the WHO list of essential medicines?
Halothane
68
Where is halothane metabolised and what problems does this cause?
- 20% in the liver
- Therefore can cause liver damage
- Metabolite is trifluroacetic acid which causes hepatitis
69
Who established the 4 stage framework for anaesthesia?
Arthur Guedel
70
What is Stage 1 of anaesthesia?
The patient is conscious but drowsy. They have a reduced response to pain
71
What is Stage 2 of anaesthesia?
- The patient may become delirious and hypersensitive to stimulatoin.
- They may have an increased gag reflex making intubation difficult
- Concerns in this phase include choking, breath holding, movement and vomiting
- It is important to limit the amount of time the patient is in this stage
72
What is Stage 3 of anaesthesia?
- This is the desired state for surgery
- There are 4 sub-stages or 'planes' within stage 3
- As you move through the planes, there is a progressive shallowing of breathing and loss of muscle tone and reflexes
- Plane 3 is said to be the ideal state for surgery, because there is relaxation of the abdominal and thoracic muscles
- Plane 4 results in apnea due to diaphragm paralysis
73
What is Stage 4 of anaesthesia?
In this stage there is medullary paralysis, cessation of respiration and loss of vasomotor control. Without rapid intervention, the patient will die
74
What is balanced anaesthesia?
General anaesthesia normally makes use of a range of drugs that each contribute to making the patient's and the surgeon's time in the operating theatre as trouble free as possible
75
What is Midazolam (benzodiazepine) used for?
Pre-operative sedative/anxiolytic
76
What is Propofol (IV general anaesthetic) used for?
Induction of anaesthesia
77
What is isoflurane/nitrous oxide mixture (inhaled general anaesthetics) used for?
Maintenance of anaesthesia
78
What is suzamethonium (short acting neuromuscular blocking agent) used for?
Relax tracheal muscles to facilitate intubation
79
What is Atracurium (neuromuscular blocking agent) used for?
Relax abdominal muslces to facilitate surgical access
80
What is Fentanyl used for?
Post-operative analgesia
81
What is Neostigmine (ACh esterase inhibitor) used for?
Reverse atracurium block
82
What is glycopyrrolate (muscarinic antagonist) used for?
To reduce bronchial tract secretions; prevent muscarinic effects of AChE block
83
What did Overton and Meyer report?
That the potency of a general anaesthetic is directly proportional to its lipophilicity
84
What does fluidization suggest?
That the membrane becomes less 'stiff' as an anaesthetic accumulates in it
85
What does volume expansion suggest?
The thickness of the membrane alters as anaesthetic accumulates
86
What are two lipid theories of anaesthetics?
- Fluidization
- Volume expansion
87
What are 4 problems with lipid theories?
- The potency of alkyl alochols increases up to around 13 carbons in length, but this is the cut-off point. This suggests binding to a pocket of a defined size within the protein
- Stereoisomers of anaesthetics have identical effects on membranes, but can differ in their anaesthetic potency
- Temperature changes fluidize membrane but do not produce effects similar to general anaesthetics
- Not all lipophilic molecules are general anaesthetics
88
What is the current theory of how general anaesthetics work?
Protein theories
89
What do protein theories suggest?
That anaesthetics alter the way the protein moves between different conformational states
90
How do protein theories explain the lipophilic nature of general anaesthetics?
- The binding sites on target proteins are located in their membrane regions
- Thus, the drug would have to dissolve in the bilayer to be ableto access its target site
- The Mayer-Overton correlatioon can be explained by the fact that anaesthetics have to cross the blood-brain barrier in order to exert their actions, and this depends on lipophilicity
91
According to protein theories what are the target proteins for general anaesthetics?
- Potentiating GABAA receptors and strychnine-sensitive glycine receptors
- Extrasynaptic GABAA receptors may be particularly important targets of general anaesthetics
- Potentiating two-pore-domain potassium channels
- Inhibiting NMDA type or ionotropic glutamate receptors
92
Two pore-domain potassium channels are apart of what family?
Family of channels including 'leak channels'
93
What is the structure of the two pore-domain potassium channels?
- 2 pore forming domains and 4 transmembrane domains
- They assemble as dimers with the two pores forming domains from each subunit. This forms the lining of the channel
- As potassium moves out of the cell it causes depolarisation and inhibition
94
What are 4 advantages of inhalational anaesthetics?
- It is relatively easy to maintain certain levels of anaesthesia
- There will be rapid equilibrium between inhaled gas and the patients tissues
- Most general anaesthetics undergo only limited metabolism in the patients body, and they will leave by the same same route as they entered
- This can give rapid emergence anaesthesia
95
What are the disadvantages of inhalational anaesthetics?
- Longer induction and marked stage 2
- Equipment factors and psychological distress (mask over face)
- Require complex, bulky, expensive equipment
- Metabolism, toxicity (patient and staff) and environmental damage (200x the greenhouse effect of CO2)
96
How is inhaled anaesthetic potency expressed?
As its minimum alveolar concentration (MAC)- This is the minimum concentration of the anaesthetic at 1atm pressure that is needed to prevent movement of 50% of subjects in response to incision
97
What does the blood-gas parition coefficient determine?
The induction and recovery speed
98
What is the blood-gas partition coefficient?
A measure of how well the drug dissolves into the blood compared with gas
99
Which is better: a drug with high blood-gas partition coefficient, or low?
Low- will give a more rapid induction and recovery
100
What is the oil-gas partition coefficient?
This is a measurement of anaesthetics lipid solubility and is the idea that high lipid solubility confers to high potency
101
How can the oil-gas partition coefficient imact general anaesthetic pharmacokinetics?
- If the anaesthetic is highly sosluble in fat, lots of anaesthetic will parition into fatty tissue
- Because fat has a poor blood supply, the anaesthetic will take a long time to leave the tissue
- Our patient will have a slowly resolving 'hangover' as the anaesthetic gradually leaks back into their blood and leaves the body via the lungs
- This will be worse the fatter the patient and the more fat-soluble the drug
102
What are the two most common anaesthetics in the UK?
- Nitrous oxide
- Isoflurane
103
Which drug is no longer listed with the BNF?
Halothane
104
What are the 4 haloethers?
- Halothane
- Isoflurane
- Sevoflurane
- Desflurane
105
What are the three main targets for the haloethers?
- Potential GABBA receptors leading to increased inhibitory transmission
- Inihbit NMDA receptors leading to decreases in exitatory transmission
- Potential two-pore domain potassium channels leading to increased neuronal inhibition
106
Outline Isoflurane
- Low toxicity- is not significantly metabolised
- Is cheap- 2x the cost of halothane
- Powerful coronary vasodilatory properties which may worsed ischaemia in parts of the heart that are supplied by the blood vessels with atherosclerosis (coronary steel)
- Neurodegeneration concerns in neonatal animal models
- Hypotension though negative inotropic means (decrease force of contraction) and can also decrease peripheral vascular resistance
- Widely used
107
Outline Sevoflurane
- Has very rapid induction and recovery due to its low blood: gas coefficient
- Neurodegeneration is likely to be caused but less than isoflurane
- Expensive- 5X the cost of halothane
- Low toxicity, there is some metabolism but it is not significant
108
Outline Desflurane
- Toxicity, it can produce significant irritation of the respiratory tract which can lead to coughing. Also high levels of sympathetic activity
- Expensive, similar cost to sevoflurane
- Optically active as has a chiral carbon but is used as a racaemic mixture
- Low blood gas partition coefficient- less soluble than sevoflurane (suitable for obese patients). But has rather low potency
- Evironmental impact is severe with 3700X the greenhouse gas potential of carbon dioxide
109
How does nitrous oxide act?
- Not fully understood
- Moderately potent blocker of NMDA receptors
- Some potentiating actions of GABAA receptors
- Has low potency
110
Why can you not use nitrous oxide as an anaesthetic alone?
- Such low potency
- Even a 80% mixture with O2 does not produce a loss of consiousness
111
What is the usual composition that nitrous oxide is used at?
- 50/50 with oxygen
- Known as Entonox
112
What happens when a patient stops receiving nitrous oxide?
The anaesthetic can transfer very rapidly from the blood to the lungs, reducing the partial pressure of oxygen in the lungs
113
Why can nitrous oxide be a problem for scuba divers?
- Scuba divers can have tiny bibbles of nitrogen in their blood which does not normally cause a problem
- Nitrous oxide can transfer from the liquid phase of the blood into these bubbles and expand them to cause a gas emboli
114
What class of drug is nitrous oxide?
Class C as of November 2023
115
What vitamin is nitrous oxide implemented in?
B12
116
What is the greenhouse gas potential of nitrous oxide?
300x the effect of CO2
117
What is Xenon?
A noble gas
118
Why has Xenon got low levels of toxicity?
Has low reactivity and is not metabolised in the body and has low greenhouse gas potential
119
How does Xenon act in the body?
Via antagonism ofnthe glycine site on the NMDA receptors
120
What 5 advantages does Intravenous Anaesthesia have over inhalational methods?
- Rapid Induction
- Limited stage 2
- Simple apparatus
- Relatively pleasant induction
- No atmosphere pollution
121
What are 4 disadvantages of intravenous anaesthesia compared to inhalational methods?
- Once its in, its in: the level of anaesthesia can be difficult to control
- Recovery can be slow due to redistribution metabolism
- Anaesthesia has a finite duration (infusion can get around)
- Vein damage can occur
122
How is intravenous anaesthesia usually used?
- For induction in a balanced anaesthetic protocol
- Because there is a small stage 2- once reached stage 3- inhalational can be used to maintain anaesthesia during surgery
- Can be used for the whole procedure in short surgeries
123
What family of anaesthetics is sodium thiopental part of?
Barbiturate plus hypnotic/anaesthetic agents
124
Why is the induction of sodium thiopental good?
It is very lipid soluble and so crosses the blood-brain barrier very quickly which makes induction dependent on blood flow (rapid)
125
What does sodium thiopental's oil: blood partition coefficient look like?
Is high
Means the hangover effect occurs
126
How does sodium thiopental act in the synapse?
- Positive allosteric modulation of GABAA receptors
- Can also directly activate at high doses (dangerous)
- Also might act as inhibitors of AMPA
127
What is propofol's trade name?
Divipram
128
How does propofol act?
- Allosterically potentiates GABAA receptors
- At higher doses may be able to directly activate the receptor
129
How is propofol administered?
Via emulsion ("milk of amnesia")
130
What is propofol's recovery profile?
- Is metabolised very quickly so has rapid recovery
- Has little to no hangover effect
- Lower rates of post-operative nausea
131
What is the most common side effect of propofol and how can this be combatted?
- Pain when it is injected
- Managed using analgesic agents
132
What is a scary side effect for propofol?
Can cause hypotension and decrease respiraoty drive
133
What drug is Etomidate very similar to?
Propofol
134
What are three side effects of Etomidate?
- Post operative nausea and vomiting
- Pain at injection site
- Supress the production of steroids by the adrenal cortex
135
How does ketamine act?
non-competative antagonist at NMDA receptors
136
What are other drugs within the same class as ketamine?
PCP (angel dust) and MK801
137
At low doses what does ketamine do?
- Rapidly acting anti-depressant
- Produce human models of schizophrenia
138
At medium doses, what does ketamine do?
Produces analgesia
139
At moderate doses what does ketamine do?
Produces a 'dissociative state'- partly conscious but will experience a loss of perception, amnesia, sedation and immobility
140
At high doses what does ketamine do?
Loss of consciousness
141
What is a main advantage of ketamine?
Has little effect on respiration and blood pressure (may even increase blood pressure)
Useful in emergency situations where the patient's injury may not be fully known
142
What is ketamine sometimes used as an adjunt medication for?
- Opioids
- it acts synergistically with opioids to potentiate their action
- This allows a lower dose of opioid to be used
143
What are the main side effects of ketamine?
- Can induce bizarre behaviour such as hallucinations
- NMDA antagonism can produce neurodegeneration and bladder damage whe abused
144
What type of anaesthetic causes malignant hyperthermia?
- Haloether inhalational agents
- Depolarizing neuromuscular blocking agent- suxamethonium
145
What is malignant hyperthermia characterised by?
- Muscle rigidity
- Increased body temperature
- Rhabdomyolysis
- Kidney failure
146
What type of mutation do people at high risk of malignant hyperthermia experience?
- Mutation in an L type calcium channel subunit
- Mutation in the ryanodine receptor
147
What action occurs to induce malignant hyperthermia?
Calcium floods out of the sarcoplasmic reticulum triggering systained muscle contraction and generating a large amount of heat
148
What is untreated malignant hyperthermia mortality rate?
80%
149
What is the muscle relaxant for malignant hyperthermia called?
Dantrolene
150
What is the mortality rate for patients who are treated with a muscle relaxant?
5%
151
How does Dantrolene work?
Blocks the ryanodine receptor, preventing the release of calcium from the SR
152
What is neurolept anaesthesia?
Involves the use of an antipsychotic and an opioid
153
What are neurolept anaesthesia most commonly used for?
To sedate large animals
154
What is Large animal Immobilon a mixture of?
Acepromazine and Etorphine
155
What is etorphine?
An opioid 2000X more potent than morphine
156
What is the antidote for etorphine called?
Revivion
