Anaesthetics Flashcards
What are the three main effects of anaesthetic drugs?
Unconsciousness
(action on the reticular dormationa nd ARAS)
Loss of reflex’s
(Affects the sensory input to the reflex arc)
Analgesia
(reduced transmission of conscious sensation)
What are the two main groups of anaesthetics, and how do they differ in administration?
General
(Intravenous eg. propofol)
(Inhilation eg. isofluorane)
Local
(same as general but administered in low doses to affect small localised regions)
How are local anaesthetics grouped?
Split into 2 groups according to structure (normally have a ‘caine ending)
Amino-esters = metabolised in the plasma
Amino-amides = metabolised in the liver
What is the mechanism of local anaesthetics?
Via sodium channel block which dampens down neuronal activity and reduces sensory transmission to the cortex
2 ways:
Directly entering the channel when its open (more channels open the bigger the effect = use dependence)
Accessing channel by crossing the axonal membrane and binding from the inside
Give a clinical example of when local anaesthetics wouldnt work and why.
When the tissue is inflamed.
Local anaesthetics ability to work is pH-dependent - inflammatory soup in damaged tissue tends to be acidic
Local anaesthetics ionise in acidic pH = reduces their ability to cross the neuronal membrane and attach to the sodium channel
How is sensation affected by administration of local anaesthetics?
Local anaesthetics work more easily on smaller or un-myelinated nociceptive sensory fibres (A-delta and C-fibres) and unmyelinated autonomic fibers.
This is because the access to the sodium channels via the membrane is easier than across the larger and highly myelinated proprioceptive fibres
What 3 factors need to be taken into consideraton when selecting a local anaesthetic?
Needs to be:
Agent with low irritant effect and toxicity
Rapid onset of action
Half-life to allow adequate time to do a procedure
Name 3 commonly used local anaesthetics and their uses and half lives
Lidocane (amide) = 1-2 hours
(Local infiltratioin, nerve block, dental and topical)
Bupivacaine (amide) = 1-3 hours
(Local infiltration, peripheral nerve block, epidural, and sympathetic nerve block)
Benzocaine (ester) = <1 minuite
(Throat lozenges)
What are the main side effects of local anaesthetics?
Local irritation and inflammation occuring at the site of administration
Can be exasberated by the use of local vasoconstrictors or trauma to tissue on administration
Rarely there can be systemic side effects on the use of local anaesthetics.
What causes this and what are the systemic side effects?
Caused by overadministration of of the agent, leading to increased plasma levels of the drug
Cardiovasuclar changes
(Caused by local vasodialation or cardiotoxicity through binding in the heart)
CNS chnages
(Light-headedness, sedation, loss of consciousness)
Anaphylaxis
(Rare and only found with ester drugs)
What do general anaesthetics do?
Induce a loss of sensation, altered state of consciousness and a loss of memory for what happens under its influence
Name and explain the 6 steps in the process of anaesthesia
Premedicaion
Benzodiazepine to reduce anxiety and help with memory loss
Induction
Inhalation of IV administration of the anaesthetic
Muscle relaxation and intubation
Uses a neuromuscular blocking agent to relax the muscles during long surgical procedures
Maintenance
Inhilation or IV administration
Analgesia
Administration of agents to reduce pain on recovery from surgery
Reversal
Of both neuromuscular blocking agent and anaesthetic
Results in return of consciousness
What are some benifits of Inhilation anaesthetics?
Very potent and readily mixed with oxygen for administation (25% to prevent hypoxia)
Low blood solubility = rapid induction and recovery with fewer lingering effects
The speed of effect means anaesthetic levels can be quickly adjusted
Nitrous oxide (simple gas) can be used in combination with volitile liquids when administering inhilation anaesthetics.
Give an example of a volitile liquid and explain why NO is used.
Isoflurane
NO is not very potent but can be used in combiation with other inhilarion agents.
It provides some analgesia, so when used in combination it can mean reductions in the required doses of other drugs
What are the 4 factors that depth and speed of recovery from inhilation anaesthetics are linked to?
Rate of alveolar absorption
(depends on depth of inspiration and the concentration of the concentration of the agent administered)
Speed of equilibration
(balance of anaesthetic concentration in the air, blood and fats, which depends on solubility of the agent)
The relative concentations at equlibrium
Cardiac output
(controls delivery of drug o the brain)
Regarding inhilation anaesthetics, what is the activity of the agent linked to?
The blood:gas partition coefficent
Indicates solubility
The oil:gas partition coefficent
Indicates the relationship between concentration of inhaled ages and that in the fat (brain/lipid membranes)
What is the potency of an inhilation anaesthetic calculated as?
Minimum alveolar concentration (MAC) required to immoilise 50% of patients during noxious stimulation
What is the Meyer-Overton theory based on?
The correlation between lipid solubility of inhaled anaesthetics and minimum alvelolar concentration.
States that anaesthesia occured when a sufficent number of inhilational anaesthetic molecules had accumulated in the lipid cell membrane, regardless of the drug type
What are the main side effects of inhilation anaesthetic agents?
Reduce activity throughout the body, via depression of cardiac output and blood pressure
Cause respiritory depression through an action on teh brainstem respiritory centres
Cause irritation of the respiritory tract, resuting in bronchospasm and laryngospasm
Why are IV anaesthetics not used alone for long term anaesthesia?
IV is used to induce anaesthesia and maintainace is provided by inhilation or a combination of inhilation and IV
This is due to accumulation affects and slow redistribution
What are the 5 most commonly used IV anaesthetics?
Thiopental
Propofol
Etomidate
Ketamine (slower acting)
Midazolam (slower acting)
There is not just one mechanism of action for all the drugs
In general, how do IV anaesthetics work?
Supress consciousness through a reduction of activity within the CNS with agents acting on both the inhibitory and excitatory pathways
Thiopental and Midazolam increase activity at the GABA receptor (inhibitory)
Ketamine blocks glutamatergic NMDA receptors (excitatory)
What are the side effects of general anaesthetics?
Vary according to the concentration, duration and drug used
Decreased cardiac contractitlity
Respiritory depression (in overdose, leading to respiritory failure and death)
Decreased CNS fucntion
Reduced sympathetic activity
Why might opiods be given alongside anaesthetics?
When given at induction, opoids can provide analgesia and reduce the dose of antibiotic required to have a seditive effect
Their effect on the CV and respiritory system can also help counteract the effects of invasive treatments, reducing HR, BP and resp rate increases that are caused by the stress
Name 3 fast acting opiods used in combination with anaesthetics
Fentanyl
Alfentanil
Remifentanil
What are epidural anaesthetics used for?
Use general or local anaesthetics and sedatives to remove sensation
Use analgesics to block pain sensation specifically
Why does epidural anaesthetic have more of a effect on sensory rather than motor functions?
Sensory neurons are significantly more sensitive to the effects of local anaesthetics than motor neurons
Linked to the levels of myelination and the ease of entry of the anaesthetic
Epidurals do have an effect on the motor system but it is drug and concentration dependent
Midazolam = seditive and muscle relaxant effects
What sensation is removed during labour when a epidural is used?
Pain is removed, but pressure sensation is not
Whar are the most commonly used anaesthetics?
Bupivacaine and Lidocaine
Why may other agents be added to an epidural?
To prolong the duration of the block and decrease bleeding and toxicity
Adrenaine is the most commonly added
Opoids (fentanyl and morphine) can be added for muscle relaxing and analgesica properties
What is the Bromage scale?
A scale used to determine the level of epiduaral block.
Asseses and grades the patients ability to move their legs following induction - 4 levels:
1) Complete block
Patient is unable to move the knees or feet
2) Almost complete block
Patient demonstrates an inability to flex the knees but has the ability to flex the feet
3) Partial block
Patient can partially flex the knees and resist gravity and has movemnt of the feet
4) No block
Patient can flex the knees and feet fully
What are the two groups of neuromuscular blockers?
Depolarising
Non-depolarising
Both groups are used to relax muscle by blocking the activity at the neuromuscular junction
What is the mechanism of depolarising neuromuscular blockers?
Non-competitive/agonist neuromuscular blockers
Also includes anticholinesterases
Depolarising NMB binds to the Ach receptor causing prolonged depolarisation (receptor closes and repolarises even though agonist is still bound) and the site to be blocked = prevents depolarisation and muscle contraction
Initial depolariation causes fasciculation of the muscles prior to relaxation occuring = increases likelihood of post-operative muscle pain
What is the most common neuromuscular blocker used?
Suxamethonium
Only administered IV
Rapid acting = muscle relaxation within 1 min
Rapidly metabolised by plasma cholinesterase (5-10 mins) so requires a constant infusion to maintain the blockade
What group of neuromuscular blockers do anticholinesterases fit into?
Give and example of one
Depolarising neuromuscular blockers
Neostigmine
How do anticholinesterases work when used as neuromuscular blockers?
(Acetylcholinesterase)
Work non-competitivly to increase the levels of Ach in the junctional cleft by blocking acetylcholinesterase breakdown of Ach
Cause muscle paralysis by overloading the system = activating all Ach receptors at maxiumum and leaving no room for additional movement
(similar to neuromuscular blockers)
What are the issuses associated with acetylcholinesterase inhibitors?
They increase activity in the PNS causing bradycardia, increased secretion and increased peristalsis
Give an example of a neurotoxin that works in a similar way to anticholinesterases
Botulinum toxin A ( botox)
Works to reduce muscle activity by blocking pre-synaptic release of Ach
Used clinicnally to treat muscle spazams and tic
Also known for its cosmetic uses
What is the mechanism of non-depolarising neuromuscular blockers?
Known as competitive or antagonist neuromuscular blockers
Compete with Ach to bind to the Ach receptors
Once bound they prevent depolarisation thereby blocking the effect of Ach
Also act pre-synaptically to reduce calcium entry = reduces the release of transmitter from presynaptic vesicles
Do not cross theh blood brain barrier = no effect on teh CNS
Name 2 common non-depolarising neuromuscular blockers
Atracurium
Vecuronium
Other than their direct mechanisms how do depolarising and non-depolarising neuromuscular blockers differ?
Non-depolarising have a slower onset time (2-5 mins) with a duration between 15-90 mins
Non-depolarising are also water soluble and show no accumulation with repeated doses = more suitible for long term use
What can happen is neuromuscular blockers and inhilation anaesthetics are taken together?
Inhilation anaesthetics can increase the effects of neuromuscular blockers
Must talior the cocentrations used by correlating teh effects of multiple drugs
Need a balanced level of anaesthesia, analgesia and muscle relaxation
Which group of neuromuscular blockers is always chemically reversed prior to recovery?
What are the drugs used to do this?
Non-depolarising
Neostigmine (anticholinesterase)
- Specific for a non-depolarising blockade
- Rapid (1 min)
- Effects last for 20-30 mins
Sugammadex (Selective relaxant binding agent)
Anticholinesterases work as a depolarising neuromuscular blocker (acetylcholineseterase inhibitors).
What other function can they have?
Also work to reverse the effects of some non-depolarising neuromuscular blockers eg. atracurium
But they can prolong the action of depolarising neuromuscular drugs eg. suxamethonium
In the event that anticholinesterases must be given, what else can be given to counteract the side effects?
Bradycardia and increased secretions as a result of the muscuranic effects on the PNS are the side effects
Give Glycopyrronium or Atropine prior to, or with a reversing agent
How do selective binding agents work to undo the blockade caused by neuromuscular blockers?
Give an example of one
Sugammadex
Selective relaxant binding agent used for raid reversal of NMB blockade and acts by forming a complex with the drug by encapsulating it to inactivate it
Well tollerated, no effect on the cholinergic nervous system, minimises the risk of residual paralysis and is rapidly cleared form the plasma and excreted within 24 hours
What is the difference between moderate sedation and general anaesthesia?
In moderate sedation patients are conscious but relaxed and verbal contact can be maintained
With general anaesthesia there is no conscious awareness/the patient is without feeling/sensation
Name the scale used to rank sedation levels.
The Ramsay sedation scale
