Principles and Pharmacology of Anaesthetics Flashcards
What does general anaesthetic produce?
Insensibility in the whole body, usually causing unconsciousness
Centrally acting drugs
What does regional anaesthetic produce?
Insensibility in an area or region of the body
What does local anaesthetic produce?
Insensibility in the relevant part of the body only
What is the difference between regional and local anaesthetic?
Local anaesthetic is injected directly into the nerve endings of the tissues which need to be numbed
Regional anaesthetic may be injected at an area remote from that which needs to be numbed e.g. injecting the brachial plexus in the neck area to numb the arm
What drugs are used in modern anaesthetics?
Inhalation anaesthetics Intravenous anaesthetics Muscle relaxants Local anaesthetics Analgesics
What techniques and equipments are used in modern anaesthetics?
Tracheal intubation Ventilation Fluid therapy Regional anaesthesia Monitoring
Where is progress still being made in modern anaesthetics?
Progress in the area of dug development has stopped
Refinements only being made in drugs already available and in methods of delivery
Analgesics are the only medications with identifiable prospect of significant or radical progress
Main areas of progress now are in the use of improved equipment and techniques
What is the triad of anaesthesia?
Analgesia
Hypnosis
Relaxation
How does anaesthesia relate to the triad?
Any anaesthetic can be split into separate components
An individual anaesthetic may consist of varying contributions from all three but it does not require all three
What does hypnosis refer to?
Unconsciousness
Necessary component of any general anaesthetic
What does analgesia refer to?
Pain relief
Can also be the removal of perception of an unpleasant stimulus
Even if patient is unconscious analgesia is often still required to suppress reflex autonomic responses to painful stimulus
What does relaxation refer to?
The muscle relaxation necessary to provide immobility for certain procedures, allow access to body cavities and to permit artificial ventilation
What is balanced anaesthesia?
Different drugs do different jobs
Titrate doses separately and therefore more accurately to requirements
Avoid over-dosage
Enormous flexibility
What is the big advantage of balanced anaesthesia?
It allows a great deal 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, while tailoring the technique to each patient and procedure
Also helps keep the dose of individual drugs down
In what areas does balanced anaesthesia allow flexibility?
Awake - yes/no Analgesia - none, opiate, local Muscle relaxation - yes/no Airway management - none, mask, LMA, ETT Combinations
What can the large number of drugs and techniques available be used for? What does this allow?
To individually tailor anaesthetic to the individual patient, operation and duration
Allows particular patient problems to be circumvented or dealt with and particular demands of the surgery to be overcome
What are the potential problems with balanced anaesthesia?
Polypharmacy
Muscle relaxation
Separation of relaxation and hypnosis
How does muscle relaxation pose a problem?
Patients must have airways managed and ventilation controlled - anaesthetic also paralyses the diaphragm muscle
How does polypharmacy pose a problem?
Drug-drug interactions
Allergies
Adverse drug reactions
How does the separation of relaxation and hypnosis pose a problem?
Means it is possible to have patients awake but paralysed and unable to communicate, and insufficiently anaesthetised
What do general anaesthetic agents provide?
Unconsciousness
Small degree of muscle relaxation
General anaesthetic agents may provide some analgesia, but this is negligible for all but what?
Ketamine
How do all general anaesthetic agents work?
By suppressing neuronal activity in a dose-dependent fashion
Largely done by opening chloride channels which hyperpolarise the neurones or suppress excitatory synapse activity
Why is cerebral function lost “from the top down”, with relative sparing of the more primitive functions e.g. reflexes?
The most complex processes which rely on the greatest and most complex neuronal activity are the most susceptible to inhibition by general anaesthetic so cerebral function is lost “from the top down”
How do IV agents work?
Extremely rapidly, causing unconsciousness basically as soon as they reach the brain
Why do IV agents cross membranes quickly?
They are fat soluble
Give an example of an IV agent
Thiopentone
Propofol
Why will IV agents given as a one-off bolus does cause only temporary unconsciousness?
They leave the circulation very quickly so disappear rapidly from the brain
What is the rapid fall in blood concentration of an IV agent due to?
Mainly due to the drug leaving the circulation and moving to other parts of the body, metabolism of the drug contributes very little to the termination of action of an IV anaesthetic given as a bolus
What are inhalational anaesthetic agents?
All halogenated hydrocarbons
Where are inhalational agents taken up and excreted?
Taken up and almost exclusively excreted via the lungs
What happens at induction using an inhalational anaesthetic?
Patient is given a relatively high concentration of the agent to breathe
The gas moves down the concentration gradient into the patient’s blood and finally brain to achieve a high enough partial pressure to produce unconsciousness
What is minimal alveolar concentration?
Concept of the concentration of the drug required in the alveoli which is required to produce anaesthesia with any particular agent
What does a low minimal alveolar concentration value mean?
The agent is more potent - i.e. a more potent agent takes less concentration to produce the same effect as a less potent agent
Low number = high potency
When is inhalational induction advantageous?
Very slow but this can be advantageous where desirable e.g. in a potential obstructing airway
What is the main role of inhalational agents?
Extension or continuation of anaesthesia
How long will a patient breathing an inhalational agent remain unconscious for?
For the duration of the procedure and for as long as the anaesthetic is administered
What happens when a patient breathing an inhalational agents needs to be woken up?
Agent switched off
Patient breathes gas mixture with no agent in it
Reversal of concentration produces fall in alveolar concentration followed by the blood and brain concentrations
Consciousness returns
What is the most common sequence of general anaesthesia?
Intravenous induction followed by inhalational maintenance
All general anaesthetic agents have the same effect on the cardiovascular system - what is this? What is the exception?
Universally depressant
Ketamine is the exception
What are the central effects of GA due to?
Depressant effects of the agent on the CNS and, more specifically, on the cardiovascular centres and nuclei in the brainstem
What effect do GA agents have on sympathetic nerve activity, chronotropic and inotropic effects of the heart, and venous and arterial vasodilatation?
Reduce sympathetic nerve activity and negative chronotropic and inotropic effects of the heart, and venous and arterial vasodilatation
What do direct effects of GA agents arise from?
What do these compound?
Direct effects of the anaesthetic agents on the vascular smooth muscle and myocardium
Compound the effects of the reduced sympathetic activity
What are the central effects of anaesthetic?
Depress cardiovascular centres
Reduce sympathetic outflow
Negative inotropic/chronotropic effect on the heart
Reduce vasoconstrictor tone resulting in vasodilation
What are the direct effects of anaesthetic?
Negatively inotropic
Vasodilation resulting in decreased peripheral resistance
Venodilation resulting in decreased venous return and decreased cardiac output
What worsens the fall in cardiac output caused by anaesthetic?
Negative inotropic effects of a general anaesthetic agent
What anaesthetic agent does not cause respiratory depression?
Ketamine
What is respiratory depression caused by anaesthetic characterised by? How does this contrast with opiate respiratory depression?
Characterised by reduced tidal volumes and a high respiratory rate
Contrasts with opiate respiratory depression which largely preserves tidal volume and is characterised by a low respiratory rate
What is respiratory depression produced by?
By reducing hypoxic and hypercarbic drive via the depression of the brainstem respiratory centres
What is the effect of GA on lung volumes?
Lung volumes are often greatly reduced, which interferes with ventilation-perfusion matching in the lungs
Why is oxygen often needed for several days post-operatively?
The reduction in lung volumes produced by GA often persists for several days post-op so oxygen is still needed
How do muscle relaxants work?
Paralyse skeletal muscle - do this indiscriminately so respiratory and airway muscles also affected
What must be provided if muscle relaxation is provided by systemic muscle relaxant drugs?
Unconsciousness
What are the indications for use of muscle relaxants?
Ventilation and intubation necessary
When immobility is essential e.g. neurosurgery
Body cavity surgery - to allow access
What are the problems with muscle relaxants?
Awareness possible
Incomplete reversal
Apnoea
Why is awareness possible with muscle relaxants?
Due to the separation of unconsciousness from hypnosis which muscle relaxants permit
What might incomplete reversal of the muscle relaxant lead to in the post-op period?
Airway obstruction
Respiratory insufficiency
How do non-depolarising neuromuscular blockers work?
Competitively block nicotinic acetylcholine receptors at the NMJ, preventing opening of Na+ channels
Competitive antagonists to ACh
Prevent ACh from binding to the receptors and opening their sodium channels
How is reversal of non-depolarising NMBs possible?
ACh can be given to overcome the block, anticholinesterases stop the removal of ACh from the synapse by blocking the enzyme cholinesterase which destroys ACh
How do depolarising neuromuscular blockers work?
Depolarise (hyper-stimulate) the motor end plate, putting it into a state which renders the post-junctional membrane refractory to further stimulus
What is the depolarising NMB which is used currently?
Suxamethonium
What are the features of Suxamethonium?
Very rapid onset < 1 min
Short duration of action < 5 min
What are some possible side effects of Suxamethonium?
Myalgia
Anaphylaxis
Malignant hyperthermia
When is unconsciousness not necessary for a procedure?
When analgesia is good enough that the patient cannot feel the unpleasant stimulus of the procedure e.g. regional anaesthesia which can be used alone or as part of a combined technique
How is anaesthesia most commonly used?
In conjunction with unconsciousness as part of a balanced general anaesthetic technique, with or without muscle relaxation
Why might spinal or epidural anaesthesia not require additional muscle relaxation?
Regional techniques usually provide reasonable muscle relaxation by blocking motor nerves so spinal or epidural may not require additional muscle relaxation
How does analgesia contribute to general anaesthesia?
Pain can cause a patient to wake up, analgesic drugs reduce the arousal effects of the pain of the surgery so contribute to general anaesthesia
Opiate analgesics also have a sedative effect which contributes to general anaesthesia
What will good intraoperative analgesia suppress?
Unwanted reflex responses to painful stimuli such as tachycardia, hypertension and gross movements
Why might regional anaesthesia allow lighter levels of general anaesthesia to be used?
By eliminating painful surgical stimuli
How are regional and local anaesthesia provided?
Application of local anaesthetic to nerves
Where is most of the benefit in local and regional anaesthesia?
In post-operative pain relief, blocks can last for many hours post-op or can be continued by using catheters and infusions
What are examples of local anaesthetics?
Lignocaine
Bupivacaine
Prilocaine
How do local anaesthetics work?
By blocking the voltage gated sodium channels on axons and preventing propagation of the nerve signals
Will act indiscriminately on many tissues as all excitable membranes contain sodium channels, so selectivity depends on where it is put
What effect does ionisation have on the speed of local anaesthetic?
Drugs must be un-ionised to cross membranes
Local anaesthetic drugs which are less ionised in the tissues work faster
What tissues are relatively resistant to local anaesthetic?
Inflamed tissues with a lower pH
What is the main factor which limits local anaesthetic use?
Toxicity - produced by high plasma levels
If absorbed from the tissues at a higher rate than it is removed then plasma level will rise
If high doses are injected into areas of high absorption then absorption will be high and likely exceed rates of removal
What does toxicity depend on?
Dose used
Rate of absorption
Patient weight
Drug - bupivacaine > lignocaine > prilocaine
What are the signs and symptoms of local anaesthetic toxicity?
Circumoral and lingual numbness and tingling Light-headedness Tinnitus, visual disturbance Muscular twitching Drowsiness Cardiovascular depression Convulsions Coma Cardiorespiratory arrest
Why are some nerve fibre types easier to block than others?
Due to different physical attributes of different nerve fibre types - thickness and myelination
Motor fibres relatively hard to block while pain fibres are relatively easy
Why might regional anaesthetic techniques be preferred in a patient with concomitant respiratory problems?
Regional anaesthesia physiological effects are mainly cardiovascular with relative sparing of respiratory function
What is the increasing physiological impact of different types of anaesthetic (least to most)?
Local anaesthesia Field blocks Plexus blocks Limb blocks Central nervous block e.g. epidural, spinal
What are the physiological effects of regional blocks due to?
Sympathectomy resulting from blockage of mixed spinal nerves
What does the sympathectomy caused by regional blocks result in?
Veno and vaso-dilatation
What are the respiratory effects of regional blocks caused by?
The motor block produced by local anaesthesia block of mixed spinal nerves
What blocks will interfere with respiratory function more?
Higher and more extensive blocks
What are the effects of regional blocks on the respiratory system?
Decreased FRC
Increased V/Q mismatch
What are the indications for spinal/epidural anaesthesia?
Avoidance of general anaesthesia
Severe respiratory disease - less respiratory physiological impact
Avoid airway problems
Allergies/reactions to GA agents
What are the contraindications for spinal/epidural anaesthesia?
Patient refusal Fixed cardiac output e.g. aortic/mitral stenosis Infection Bleeding diathesis/anticoagulation Technical difficulties Spinal/neurology problems
What are the features of spinal anaesthetic?
Injection is subarachnoid Block to T4, 3-4ml local anaesthetic Rapid onset - 5 min Complete block Usually all modalities Duration 2-3 hours, cannot be extended Hypotension in 30-40%
What are the features of epidural anaesthetic?
Injection is extradural Block to T4, 20+ml local anaesthetic Slow onset, 30-45 min Segmental block Good analgesia with motor and some sensory sparing Duration 3-4 hours, extendable Hypotension in 10-20%
