mark (L9-?) Flashcards
3 main neurophysiological changes of anaesthetsia
- unconsciousness,
- loss of response to painful stimuli (analgesia)
- loss of reflexes
difference between local and general anaesthetics (and 2 types of general anaesthetics)
Local anaesthetics: act locally to block nerve conduction (lignocaine)
General anaesthetics: act in the brain to cause a loss of consciousness
- Used for operations (induction and maintenance) and experimentally
- 2 major types of general anaesthetics (GA): inhalation (gases) and IV infusion
general anaesthetics specifics
they have a wide
variety of chemical structures
No strict structure-activity relationship
(unlike opioids)
led to the idea that anesthetics have a non-specific action
stage`1 of anaesthesia
Still awake but drowsy
Distorted perception
At end of stage: analgesia
Useful stage for obstetrics (gas and air)
stage`2 of anaesthesia
(EXCITATION)
Loss of consciousness
Inhibition depressed before motor centres: exaggerated reflexes (vomiting)
Stimulation of CNS: uncontrolled movements, vocalisations
Loss of temperature control: flushing of skin
Irregular breathing and cardiac dysrhythmia
(dangerous phase)
stage`3 of anaesthesia
Regular breathing
Cough and vomit reflex depressed
Pupils initially constrict but as get deeper into stage pupils dilate
Large skeletal muscles relax (see later about muscle relaxants)
Drop in blood pressure
Corneal reflex disappears
(As get deeper: breathing becomes shallow, precipitous fall in blood pressure, feeble pulse, pupils widely dilated)
stage`4 of anaesthesia
No ventilation due to depression of medulla oblongata (respiratory centres)
why are the stages of anaesthesia are difficult to measure
Most of the signs of Guedel’s classification depend upon muscular movements (including respiratory muscles), and thus with paralyzed patients’ clinical signs are no longer detectable.
Use of multiple agents obscures signs
Stages of anaesthesia measured in this way are often thought of as obsolete
Can the EEG be used to monitor the depth of anaesthesia?
As anaesthesia deepens the amplitude of the high frequency components of EEG
falls with an increase at the lower frequencies.
However:
- These changes are agent dependent,
- Various pathophysiological events also affect the EEG (e.g. hypotension, hypoxia, hypercapnia).
patient state index
it’s one EEG method of assessing hypnosis and
was developed by comparing large numbers of EEGs during induction,
maintenance and emergence.
Cerebral function monitor (CFM)
Signal is filtered, semi-logarithmically compressed, and rectified. Represents the overall electrocortical background activity of the brain.
Bispectral index (BIS)
it is statistically based, empirically derived complex parameter.
GA mechanisms of action
3 MAJOR THEORIES
- Lipid theory
- Protein theory
- Combination of both (lipid/protein interface)
define the lipid theory
GA agents dissolve in membrane leading to:
- changes in bilayer thickness
- changes in order parameters
- changes in curvature elasticity
These effects may then effect the proteins present in membrane
3 pieces of supportive evidence :
1) Pressure reversal (give the patient anaesthesia, get them to breathe and increase the pressure to push the anaesthetic out of the lipid)
2) No defined chemical structure of GAs
3) Meyer-Overton correlation
Problems with the lipid theory
- Stereoisomers
- New compounds do not fit Meyer-Overton correlation
- Increase carbon chain length (cut off effect)
- Non-immobilisers
- Small increases in temperature produce similar changes in membrane density and fluidity but do not produce anaesthesia.
- Similar correlation with partition of GAs into protein
define the carbon cut off
if you add more carbons to the chain, it will become more lipid soluble but a worse anaesthetic. this is called the the carbon cut off (or chain cut off or carbon effect)
the protein theory
General anaesthetics bind to specific membrane proteins
3 major proteins are implicated:
- GABAA receptor (inhibitory)
- 2 pore K+ channels (control resting potential)
- NMDA receptor (excitatory)
Evidence: Mutate channels in animal models and either reduce or increase anaesthetic potency
Criteria for identifying relevant anaesthetic protein targets
- Reversibly alters target function at clinically relevant concentrations (MAC see later)
- Protein Target expressed in appropriate anatomical location in brain/spinal cord (next slide)
- Stereo selective effects in-vivo parallel actions on the target in vitro
- Target exhibits appropriate sensitivity and insensitivity to model and non-anaesthetic compounds
Properties of an ideal anaesthetic
Rapid action and recovery Minimal irritant properties Miscible with air/oxygen (no risk of explosion) Analgesic Muscle relaxant
No single anaesthetic has these properties so use a combination of agents
Minimum Alveolar Concentration (MAC)
To measure the potency of an anaesthetic we use the minimum alveolar concentration
definition: Alveolar partial pressure of an inhaled anaesthetic,
which prevents movement in response to a standard noxious
stimulus in 50% of patients
Pharmacokinetics of inhaled agents
Greater solubility in the blood the slower it is acting (which is contradicting)
The more the drug can dissolve, the more rapid is the onset (counterintuitive)
Recovery from anaesthesia
Rate of reduction of alveolar partial pressure determines the rate of recovery from the aesthetic.
Elimination of inhaled anaesthetics mainly by ventilation through the lungs.
Factors decreasing the length of recovery
Reduction of the inspired concentration
High alveolar ventilation
Low blood gas solubility
Short duration of anaesthesia (little anaesthetic dissolved in low perfusion tissue)
how and when are intravenous anaesthetics (propofol)
Also used as a maintenance agent as part of an anaesthetic technique called “total intravenous anaesthesia” . It is given in conjunction with an opioid and muscle relaxants.
Can causes apnoea (respiratory depression) and a fall in blood pressure due to effects on myocardial contractility and peripheral resistance
other intravenous anaesthetics
propofol
etomidate (induction of anaesthetisia, rapid recovery with no hangover)
ketamine (Rarely used (hallucinations), Abuse potential and dependence, It is used for paediatric anaesthesia, Useful if repeated administration is required, Novel treatment for depression)
most commonly used inhalation anaesthetics
halothane
isoflurane
sevoflurane
desflurane
