General Anaesthetics Flashcards
Define anaesthesia
abolition of sensation
What is the triad of anaeasthia
- need for unconsciousness
- need for analgesia
- need for muscle relaxation (primarily loss of reflexes)
What is the general action of anaesthetics?
action through depressing CNS activity (brain and spinal cord)
Describe inhalation anaesthetics
simple, unreactive compounds
short chain molecules, no one chemical class
Describe the lipid theory for the mechanism of anaesthetic action and the evidence for it
- concentration of agents require to immobilise tadpoles is inversely proportional to its lipid:water partition coefficient, i.e. the more lipid soluble, the less you need to generate an anaesthetic effect
- 0.0mM works for any agent
- anaesthesia expands lipid volume by 0.4% –> incorporated into membrane
- high pressure reverses the anaesthetic effect
Describe the protein thereby for the mechanism of anaesthetic action and the evidence for it
- proteins are the targets, lipid solubility required for access to binding domain
- Meyer correlation can be mimicked by binding to certain enzymes
- ‘cut off’ phenomenon - increasing carbon length, increases lipid solubility but does not always increases anaesthetic potency
- stereoisomers may have identical lipid solubility but may bind differently to proteins and so have different anaesthetic effects.
What are the molecular targets for general anaesthetics?
- K+ channel activation –> decrease membrane excitability
- GABAa receptor –> increase inhibition
- NMDA receptor (glutamate), 5HT, ACh
- inhibitory ligand gated channel e.g. glycine
Describe the conc dependent effects of anaesthetics and the therapeutic window and potential for overdose
As concentration increases the following functions are lost:
- memory
- consciousness
- movement (fully anaesthetised)
- CVRS response –> death
Therapeutic window exists between movement and CVRS responses
- 2-3 times the clinical dose = overdose
Name and describe the 4 stages of anaesthesia
Stage 1 = ANALGESIA
- drowsiness, reflexes intact, still conscious
Stage 2 = DELIRIUM (INDUCTION)
- excitement, delirium, incoherent speech, loss of consciousness, inresponsve to non-painful stimuli, muscle rigidity, spasmodic movements, cardiac arrythmias, vomiting, choking –> dangerous phase
Stage 3 = SURGICAL ANAESTHESIA
- unresponse to painful stimuli (true analgesia), breathing regular, abolition of reflexes, muscle relaxation, synchronised, EEG
Stage 4 = MEDULLARY PARALYSIS
- pupillary dilation, resipiration/circualation caseses, EEG wanes –> death
What two things make a good anaesthetic?
potent and fast acting
- two separate properties of an agent
What determines potency?
How is it measured?
How does it influence dose?
- Lipid solubility (gas:partition coefficient) is the main determinant of anaesthetic potency
- MAC: a measure of anaesthetic potency in awn
Minimal Alveolar Concentration is: the concentration of anaesthetic in the alveoli required to produce immobility in 50% of patients when exposed to a noxious stimulus - affected by patient’s sex, height and weight)
- Alveolar concentration = brain concentration
- MAC is inversely proportional to lipid solubility i.e. the more soluble in oil/lipid, the lower the anaesthetic in the patients inspired air required to produce anaesthesia
Why is it important that an anaesthetic is fast acting?
What are the main factors that influence pharmacokinetics?
- rapid induction phase and recovery are important properties –> control over depth of anaesthesia
- main factors are the properties of the drugs themselves and physiological factors
Describe the compartments that aneasthetic compounds must equilibrate through and how
GAS - blood:gas partition coefficient BLOOD - tissue:blood partition coefficient BRAIN
What influences the transfer of anaesthetics to the alevoli?
- concentration of anaesthetic in the air
- rate and depth of breathing
- an increase in each of these leads to an increased speed of induction
What influences the transfer of anaesthetics to the blood?
- solubility in blood, the more soluble the larger the capacity the blood has so more molecules required to saturate the blood
- a relatively insoluble gas, transfer to brain is faster
- lower blood:gas partition coefficient –> increases speed of induction
- also rate of pulmonary blood flow –> higher CO leads to faster transfer
What influences the transfer of anaesthetics from blood to tissue?
- -> solubility in tissue i.e. tissue:blood partition coefficient for all anaesthetics = 1 in lean tissue (brain, muscle) –> conc in the brain rises fast
- -> solubulity in tissue >1 in adipose tissue, high capacity so decreases speed of induction (obese patients), accumulation if highly lipid soluble, slowed recovery
- -> tissue blood flow, high in lean tissue –> fast transfer, low in adipose tissue
- -> conc in blood vs tissue, as conc in tissue increases, the transfer decreases
Describe the elimination of inhalation anaesthetics
- mainly via the sun, dependent on factors involve in speed on induction in reverse
- metabolism not important for most anaesthetics
- isoflurane = 0.2%, N2O = 0.04%
- exceptions = methoxyflurane, halothane, –> possibility for liver toxicity
Give advantages and disadvantages of the following:
- halothane
- enflurane
- isoflurane
- sevoflurane
- nitrous oxide
Halothane \+ potent, fairly fast - poss. liver toxicity Enflurane \+ less liver damage - poss. seizures Isoflurane \+ rapidly acting, muscle relaxation - bad smell Sevoflurane \+ pleasant odour, rapid recovery - metabolites --> renal damage? Nitrous oxide \+ very rapid, good analgesic - low potency, normally combined with other agents
What is meant by combined anaesthesia?
using combinations of different drugs for optimal clinical effect with lowest risk
Give examples of intravenous anaesthetics and when they are used
Mechanism of action
- commonly used for indiction as short acting and rapid onset
- can be used alone for short procedures
MoA = interactions with specific receptors, enhance GABAa receptor action (thiopental, midazolam, propofol, etomidate) or NMDA receptor antagonist (ketamine)
What is ketamine described as?
What are its effects?
What is its mechanism of action?
Ketamine = a ‘dissociative’ anaesthetic
- lasts 10-20mins
- rapid onset –> sensory loss, analgesia, paralysis, surgical anaesthesia, but no loss of consciousness
What are the 3 types of adjuncts to general anaesthetics?
- premedication
- muscle relaxants
- antiemetics
Give examples of premedication and their uses
- to decrease anxiety and pain, to induce amnesia without loss of conciousness
- benzodiazepines –> sedation, anxiolysis, amnesia (lorazepam, midazolam)
- opioids –> pain relief (morphine, fentanyl, pethidine)
- antimuscarinics –> dry in secretions to facilitate intubation and ventilation (atropine, hyoscine, glucopyronium)
Give examples of muscle relaxants and their uses
- to relax deep abdominal, tracheal and diaphragm muscles without need for deeper anaesthesia
- benzodiazepines –> muscle relaxant
- neuromuscular blockers (tubicurarine, pancuronium —> assisted respiration required
Give an example of an antiemetic and its uses
metoclopramide
anti-emetic to decrease peri-operative nausea in induction phase
