Anaesthetics - Principle of Pharmacology Flashcards
What is the function of anaesthetic?
It is used during procedures and surgical operations to numb sensation in certain areas of the body or induce sleep
What are the four anaesthetic subtypes?
General anaesthesia
Regional anaesthesia
Local anaesthesia
Sedation
What is general anaesthesia?
It is a state of controlled unconsciousness, during which insensibility is produced in the whole body
Which two drug types are used in general anaesthesia?
Hypnotics
Analgesics
What is regional anaesthesia?
It produces insensibility in an area or region of the body
How is regional anaesthesia administered? What does this mean?
We inject anaesthetic near nerves supplying the relevant area
The effect is therefore remote to the injection
What are the two most common types of regional anaesthetic?
Spinal
Epidural
What is the difference between regional anaesthesia and regional analgesia?
Regional anaesthesia results in little or no sensation from the blocked area - warmth, proprioception, light, touch, vibration and pain
Regional analgesia will only remove pain sensation from that area, with other sensations being retained to varying extents
What is local anaesthesia?
It produces insensibility in a small part of the body where the operation is taking place
How is local anaesthesia administered?
We inject anaesthetic directly into the required tissues
What is sedation?
It involves using small amounts of anaesthetic drugs to produce a ‘sleep-like’ state
What is the difference between sedation and general anaesthesia?
Unlike general anaesthesia, sedation will result in some awareness of the procedure
What are the components of anaesthesia triad?
Analgesia
Relaxation
Hypnosis
What is the function of analgesic agents in anaesthesia?
They are used to provide pain relief, whilst also suppressing reflex autonomic responses to painful stimulus
What two drug classes are used in anaesthetic to cause analgesia?
Opiates
Local anaesthetic agents
What is the function of muscle relaxants in anaesthetic?
They are used to relax skeletal muscle enough that patients become immobile
What drug class is used in anaesthetic to cause relaxation?
Muscle relaxants
However, local and general anaesthetics also provide a degree of relaxation
What is the function of hypnotic agents in anaesthetic?
They allow a state of unconsciousness
What drug class is used in anaesthetic to cause hypnosis?
General anaesthetic agents
However, opiates also provide a degree of relaxation
Do individual anaesthetics require all three components of the triad?
No
What is the mechanism of general anaesthetic agents?
They work by suppressing neuronal activity
This is achieved through the opening of chloride ion channels, which hyperpolarises neurones and suppresses their excitatory synaptic activity
This means that they are less likely to reach their threshold potential and are therefore unable to send signals to other neurons
Which functions are inhibited with general anaesthesia first? Why?
Complex processes
This is because these processes are dependent on the greatest amount of neuronal activity
Which functions are relatively spared with general anaesthesia? Why?
Simpler, primitive functions
This is because these processes are dependent on a small amount of neuronal activity
What term is used to describe the order in which general anaesthesia affects cerebral function? Why is this advantageous?
Cerebral function is “lost from top down”
This allows unconsciousness to be achieved while automatic and autonomic functions are persevered, such as respiration and blood pressure homeostasis
Once general anaesthesia has been administered, why is it essential that we monitor patients?
We manage the impacts of anaesthetic agents on vital functions – such as airway maintenance, breathing and cardiovascular function (ABC)
In terms of the anaesthetic triad, what components does general anaesthetic provide?
Hypnosis
A small degree of muscle relaxation
What are the two mechanisms in which general anaesthesia can be administered?
Intravenous
Inhalation
List two intravenous general anaesthetic agents
Thiopentone
Propofol
What is the mechanism of intravenous general anaesthetic agents?
They undergo allosteric binding, which means that they bind to GABA receptors agonistically to open chloride ion channels
How do intravenous general anaesthetic agents produce a rapid onset of unconsciousness?
This is due to their highly lipid soluble nature allowing them to cross the blood brain barrier readily and access neural tissues
How do intravenous general anaesthetic agents produce a rapid recovery?
This is due to their imminent disappearance from circulation
This decrease in blood concentration is due to the redistribution of these drugs from circulation to other body compartments
How does the blood concentration of anaesthetic change after administration? Why?
Initially, the blood concentration is high, however this decreases rapidly
This is because the drug moves into highly perfused tissues
What does the blood concentration of general anaesthesia correlate to?
Brain concentration
How does the muscle concentration of anaesthetic change after administration? Why?
Muscle absorbs anaesthesia more slowly, however the effect is large
This is due to the relative high mass of skeletal muscle in the body
How does the fat concentration of anaesthetic change after administration?
Fat absorbs anaesthesia even more slowly than muscle, due to its lack of perfusion
However, it can store large amounts due to the high lipid solubility of these drugs
What is the function of target controlled infusion (TCI) machines?
These machines automate the dosing of intravenous drugs during surgery
What is the advantage of target controlled infusion (TCI) machines?
They allow accurate infusions of anaesthesia to achieve specific blood/brain concentrations
What is the mechanism of inhalation general anaesthetic agents?
They dissolve in the lipid layer of cell membranes, resulting in a direct effect on transmembrane proteins to suppress neuronal activity
What type of molecules are inhaled general anaesthetics?
Halogenated hydrocarbons
Describe the mechanism in which inhaled general anaesthetic agents enters the body
At induction, a high concentration of the agent is administered
This creates a high partial pressure gradient in the lungs, allowing the drug to move into the patient’s blood and finally the brain.
What is MAC (in terms of inhaled general anaesthesia)?
Minimum alveolar concentration
It refers to the drug concentration required in the alveoli to produce anaesthesia
What does a low MAC value mean?
It refers to a highly potent drug, in which a small concentration is required to produce a state of unconsciousness
How fast are inhaled general anaesthetic agents induced? In which circumstances could this be advantageous?
Slowly
In patients with obstructing airway disease
How long is inhaled anaesthesia administered for?
It is administered for the duration of the procedure, and the patient will remain unconsciousness for as long as the anaesthetic is administered
How do we awaken a patient on inhaled general anaesthesia?
Once the procedure has concluded, the anaesthetic agent is no longer administered, and the patient inhales a gas mixture with no agent in it – referred to as a washout mixture
This reverses the concentration gradient, producing a fall in alveolar concentration followed by blood and brain concentration
How are inhaled general anaesthesia agents metabolised?
They undergo little metabolism in the body and are therefore almost completely exhaled again unchanged
How do we monitor inhaled general anaesthetic agents?
We measure CO2 levels in expired gas, as this allows the end tidal portion of the gas stream to be identified and thus analysed
This represents alveolar gas
Due to the fact that inhalation agents are highly lipid soluble, the alveolar drug gas concentration is equivalent to the arterial drug gas concentration. This is because these drugs can cross the basement membranes readily
What is the main advantage of inhaled general anaesthesia compared to intravenous?
We can reliably monitor inhaled general anaesthesia
How is general anaesthesia administered in practice?
General anaesthesia induction is usually intravenous followed by inhalation maintenance
What are the recent developments in the administration of general anaesthesia?
There have been developments in intravenous maintenance via computer controlled infusion mechanisms
They usually involve the administration of propofol with opiates, such as remifentanil
What central effects does general anaesthesia have on the cardiovascular system?
It produces inhibitory effects on the cardiovascular centres and nuclei of the brainstem, resulting in the following effects…
- A reduced sympathetic nerve activity
- A negative inotropic/chronotropic effect on the heart
- Vasodilation
What direct effects does general anaesthesia have on the cardiovascular system?
It produces direct effects on vascular smooth muscle and the myocardium, which results in further vasodilation and venodilation
Why does general anaesthesia decrease blood pressure?
Due to its vasodilatory effects, there is reduced venous return to the heart and therefore decreased cardiac output
The cardiac output is further reduced by the negative inotropic effects of general anaesthesia on the heart
In addition to this, arterial vasodilation leads to a reduced systemic vascular resistance (SVR)
Due to the relationship: MAP = CO X SVR, blood pressure is significantly reduced
What two things maintain normal blood pressure after the administration of general anaesthesia?
We administer intravenous fluids
We administer vasopressor drugs
What effects does general anaesthesia have on the respiratory system?
It produces inhibitory effects on the respiratory centres of the brainstem
This reduces the hypoxic and hypercarbic drive, resulting in reduced tidal volumes and an increased respiratory rate
In addition to this, general anaesthesia decreases functional residual capacity (FCR), which results in reduced lung volumes and VQ mismatch
This effect persists into the postoperative period
Why do patients require oxygen after surgery with general anaesthesia?
The effects of reduced lung volumes and VQ mismatch persists into the postoperative period
What anaesthetic agent results in no adverse effects on the cardiovascular and respiratory system?
Ketamine
What is the mechanism of muscle relaxants?
They interact with the nicotinic acetylcholine receptors at the neuromuscular junction
Do muscle relaxants produce an effect on smooth or cardiac muscle?
No
In terms of the anaesthetic triad, what components do muscle relaxants provide?
Relaxation
What other component of the triad has to be used in combination with relaxation? Why?
Hypnosis
This is because paralysation whilst being conscious can be extremely unpleasant for the patient
What are the three complications associated with muscle relaxants?
Awareness
Incomplete Reversal
Apnoea
Why do muscle relaxants have a risk of awareness complications?
This occurs when muscle relaxants are given in combination with an insufficient dose of the hypnotic agent
What effects occur when muscle relaxants incompletely reverse?
The residual effects of muscle relaxants persist into the postoperative period
This may lead to immediate airway obstruction and respiratory insufficiency
What are opiates?
They are substances with active ingredients that are naturally derived from opium
What are the four opiates used in anaesthetic?
Fentanyl
Remifentanil
Morphine
Oxycodone
What are the two features of fentanyl?
Short-acting
Potent
What are the analgesic purposes of fentanyl?
It is an intra-operative analgesia
What are the two features of remifentanil?
Extremely short-acting
Highly potent
What are the analgesic purposes of remifentanil? Why?
This drug can be added to inhalation and intravenous agents to allow administration of lower doses and faster recovery rates
It is a highly potent drug
What is the feature of morphine and oxycodone?
Long-acting opiate
What are the analgesic purposes of morphine and oxycodone?
It is an intra-operative analgesia, which continues into the post-operative period
In terms of the anaesthetic triad, what components do opiates provide?
Analgesia
A small degree of hypnosis
List three examples of local anaesthetic drugs
Lidocaine
Bupivacaine
Ropivacaine
What is the mechanism of local anaesthetic drugs?
They work by blocking sodium ion channels and thus preventing axonal action potential from propagating
Why do we not administer local anaesthetic drugs intravenously?
Due to the fact that these drugs are not tissue specific, it is important that they are not prescribed intravenously as toxic effects can occur throughout the whole body
How do we administer local anaesthetic?
Local anaesthetic injections are usually guided with ultrasound technology
What is the advantage of ultrasound guided administration of local anaesthetic?
This allows for safer and more effective delivery of these drugs, reducing the likelihood of nerve or vascular injury
In terms of the anaesthetic triad, what components do local anaesthetic drugs provide?
Analgesia
A small degree of muscle relaxation
What are the physiological effects of local anaesthetic?
It produces some physiological effects; however, they are mainly cardiovascular with relative sparing of respiratory function
The cardiovascular effects produced lack global effect and instead become proportional to the size of the anaesthetised area
In which patients are local and regional anaesthetic techniques preferred? Why?
In those with severe respiratory conditions
There are little respiratory effects
What is a side effect of lidocaine?
Mental state change
