Session 8 - Anaethetics Flashcards
Give two overall types on anaethetics
Inhalational
Intravenous
Give five types of inhalational anaesthetic
o Nitrous Oxide (N2O)
o Isoflurane
o Desflurane
o Sevoflurane
Give three types of intravenous agents
o Propofol
o Thiopental
o Ketamine
Outline the five main areas affected anatomically during general anaethesia
o Reticular Formation (Reticular Activating System) Depressed (Responsible for transference of pain signals) Hindbrain, midbrain, thalamus o Thalamus Transmits and modified sensory information o Hippocampus depressed Memory o Brainstem depressed Respiratory and some CVS o Spinal cord Dorsal horn – analgesia Motor neuronal activity (MAC)
Name four types of anaesthesia
General Anaesthesia
Regional Anaesthesia
Local Anaesthesia
Dissociative Anaethesia
What is general anaethesia and what does it effect?
Affects the whole body and typically involves use of intravenous and inhalational anaesthetics with adjuvants. They reversibly inhibit sensory, motor and sympathetic nerve transmission (Not parasympathetic?)in the CNS to produce unconsciousness and absence of sensation.
What does regional anaethesia effect?
This involves rendering large, specific regions of the body insensate. The region is determined by transmission block between that part of the body and the spinal cord. Both spinal and epidural anaesthesia can achieve this. The patient remains conscious, but may also be administered adjuvants depending on the procedure.
What is local anaethesia?
Involves a more defined peripheral nerve block with injection of a local anaesthetic. Used for tooth extraction, or for example, procedures on the hand and fingers, foot or big toe, or internally in the urethra when performing cystoscopy.
What is dissociative anaethesia?
Uses agents such as ketamine that inhibit transmission of nerve impulses between higher and lower centres of the brain. Used in children and the elderly for short procedures, as they are less susceptible to its postoperative hallucinogenic effects.
How do anaesthetic agents exert their effect?
effects by affecting postsynaptic transmission of both inhibitory and excitatory Ligand Gated Ion Channels.
What is important about the interaction between inhaled agents and their sites of action?
Weak and easily reversed
Name the two overarching types of ion channel anaesthetics effect
Inhibitory ligand gated ion channel
Excitatory ligand gated ion channel
What are two types of inhibitors ligand gated ion channel that anaesthetics effect?
GABA activated chloride channels
Glycine activated chlorine channels
What do anaesthetics do (naming one in particular) at GABA activated chloride ion channels
o Many inhalational and IV anaesthetics have a primary effect on GABAA
Propofol exerts its main sedative effect on this channel
o Bound anaesthetics increase sensitivity to GABA and increase Cl- currents
o This Hyperpolarises the neurone and decreases its excitability
o There are multiple binding sites, depending on the anaesthetic being used
What do anaesthetics do at Glycine activated Chloride ion channels?
o Bound anaesthetics increase sensitivity to Glycine and increase Cl- currents
o This Hyperpolarises the neurone and decreases its excitability
o Glycine ligand gated ion channels are especially important in signalling inhibitory neurotransmission in the spinal cord and brainstem and act to reduce the response to noxious stimuli
What are the two excitatory ligand gated ion channels effected by anaesthetics?
Neuronal nicotinic Ach receptors
NMDA receptors
Outline Neuronal Nictonic Ach Receptors
o Bound anaesthetics inhibit some subtypes of neuronal Nicotinic Ach receptors
o This reduces excitatory Na+ currents caused by Ach binding
o This is considered to likely contribute to analgesia and amnesia rather than sedation
Give the action of NMDA receptors and the two major anaesthetics that have an effect on them
o NMDA receptors are responsive to glutamate, the major excitatory neurotransmitter in the brain
o Nitrous Oxide (N2O) and Ketamine exert their action here
o Bound anaesthetics reduce Ca2+ currents, which are involved in further modulation of synaptic responses
What is MAC?
Minimum Alveolar Concentration (MAC)
The alveolar concentration (at 1 atmosphere of pressure) at which 50% of subjects fail to move to surgical stimulus (unpremedicated breathing O2/air)
Which is better, low or high MAC?
The lower the MAC value, the more potent the inhaled anaesthetic is, as the MAC closely relates to its lipid solubility (able to get to the necessary high concentrations in the cell membrane easier).
When is surgical depth achieved in terms of MAC?
1.2-1.5
How can MAC be reduced?
When given in comination with other agents, such as nitrous oxide or fentanyl
What three physiological states can have a major impact on anaesthesia?
Reduced Cardiac Output
Ventilation Rate
Shock
What is Blood:Gas co-efficient?
The blood:gas coefficient describes the volume of gas in litres that can dissolve in one litre of blood.
If isoflurane has a B:G coefficient of 1.4, what does that mean?
a litre of blood could dissolve 1.4 litres of Isoflurane
What two things determines distribution of anaesthetic around the body?
Relative blood supply to each organ or tissue
Specific tissue uptake capacity for the anaesthetic
What is the tissue blood co-efficietn
Once the anaesthetic is in the blood, the Tissue:Blood coefficient determines how readily it will move into the tissues.
What does a brain:blood coefficient of 1.6 mean?
For an equivalent volume of brain to blood, the brain will take up 1.6 times as much anaesthetic.
What does a muscle:blood coefficient of 2.9 mean?
So at equilibrium, the muscle tissue compartment takes up proportionately almost double the amount of Isoflurane than the brain
What does a fat:blood coefficient of 45 mean?
The Fat:Blood Coefficient is 45
Fat absorbs nearly 30 times the amount of Isoflurane than the brain
This gives a very large reservoir of anaesthetic that can redistribute during the recovery phase
Do volatile inhaled agents undergo hepatic metabolism?
No
How are volatile inhalational agents expelled?
Elimination is the reverse of distribution and absorption. As the surgery is finished the anaesthetist carries out a controlled withdrawal of anaesthesia, ensuring adequate oxygenation.
As the concentration in the blood drops, the anaesthetic moves out of the cell membranes and back into the venous blood. This travels back to the alveolus to be eliminated unchanged. The rate of recovery is similar to the rate of induction for inhalational agents. The elimination is led by the well-perfused tissues (Brain, kidneys, liver), followed by muscle and then fat.
What is propofol used as in anaesthetics?
An inducer, which rapidly causes a patient to undergo anaethesia
Why do IV agents need careful admin?
Dose related effects not easily reversed when administered
Outline the distribution of propofol overtime
o IV bolus in the arm results in rapid distribution to the well vascularised CNS, with proportionately lower distribution to muscle and fat
o Propofol then rapidly redistributes from the CNS to the other compartments
For a single dose, surgical anaesthesia is maintained for about 5 minutes
Muscle and fat have a much larger capacity for Propofol than the CNS
o Further supplementary doses may be given if the anaesthetist is using Propofol as an adjunct in order to lower the fluranes MAC. It can also be used alone for surgical procedures of short duration of about 20-30 minutes.
What metabolism does propofol undergo?
Unlike the fluranes, Propofol undergoes hepatic and extrahepatic conjugation. These result in a t½ of about 2 hours.
This elimination means Propofol does not contribute to a prolonged post procedural ‘hangover’ during recovery.
What is an adjuvant drug in anaesthetics?
Adjuvant drugs are required to produce an effective and balanced anaesthesia. Individual agents usually have a specific effect on CNS function related to their group. These are normally given as adjuvants with one of the fluranes acting as the principal inhalational anaesthetic producing unconsciousness:
Name five adjuvant drugs in anaesthesia
Benzodiazepines Propofol Nitrous Oxide Opioids Neuromuscular Blocking Agents
What do benzodiazepines do?
E.g. Midiazolam
Exert agonist effect on GABAA receptors
Used to induce anxiolysis (anxiety inhibition) and amnesia
Given about an hour or so before surgery as a pre-med
What does nitrous oxide do?
Reducing main inhalational agent MAC
Does not produce sufficient anaesthetic depth on its own
Allows for significant reduction in the effective MAC of fluranes.
Rapid controlled pulmonary elimination is highly advantageous in minimising recover time
What do opioids do?
For analgesia
Morphine and Fentanyl are two opiates commonly used during surgery
Fentanyl is much more potent (100x) inducing analgesia almost immediately and acting over 30-60 minutes.
What do neuromuscular blocking agents do?
Abolish reflexes that occur with significantly invasive procedures and induce muscle relaxation
Act as either competitive Nicotinic Ach receptor antagonists
Tubocurarine, Pancuronium
Or as Nicotinic Ach receptor depolarising agonists
Succinylcholine
What is included in a pre-surgical review of a patient?
o Age o BMI o Prior medical and surgical history o Current medication o History of drug abuse o Fasting time o Airway assessment
What is peri-surgical monitoring during anaesthetic and adjuvant delivery ?
o Direct control and monitoring of gaseous mixture calculation for % partial pressures of O2, Flurane, N2O, Nitrogen
o Mechanical rate of ventilation
What is monitored during srugery?
Cardiovascular function ECG BP Respiratory function Pulse oximetry Expired CO2 used to assess ventilation state Thermoregulatory function Early detection of malignant hyperthermia
What are the three stages of anaesthesia?
Induction
Maintenance
Recovery
What is induction of anaesthesia?
Propofol is normally administered and the beginning of inhalational agent delivery. Adjuvants will also be administered intravenously.
What is maintenance of anaesthesia?
The anaesthetist keeps the adjuvants in balance to maintain adequate anaesthetic depth.
What is recovery?
The agents are withdrawn and physiological function monitored closely to make sure it can be maintained without support. Antidotes may be given as necessary to facilitate this.
Outline the four different depth levels of anaesthesia?
1) Analgesia
2) Excitement
3) Surgical Anaesthesia
4) Respiratory Paralysis and Death
Why is the excitement phase now uncommon?
As inducement occurs so rapidly with propofol
What occurs in surgical anaesthesia?
o Profound CNS depression
o Skeletal muscles fully relaxed
o Breathing may need to be assisted and cardiac function affected
o Attained with an effective integrated MAC between 1.2 and 1.5
o Four levels describing increasing depth until breathing weak
When does respiratory paralysis and death occur?
o Once above 2.2 MAC (Isoflurane) there is an increasing risk of Stage 4, with severe medullary depression leading to respiratory and cardiac arrest and death
What is the name for the different stages of depth of anaesthesia when it analyses signs?
Guedel’s Signs
