General anasthetics (flipped lecture) Flashcards
In what way are general anaesthetics grouped?
Grouped by method of administration
What are the types of general anaesthetics? (2)
-Chemical
-Physical
What are the types of chemical general anaesthetics? (2)
-Inhalational
-Intravenous
What is the lipid theory of general anaesthetics?
Anaesthetics cause membrane expansions, by entering lipids of plasma membrane and becoming more fluid like
What does Minimal Alveolar Concentration(MAC) do?
(in patients for general anaesthesia)
Minimal alveolar concentration abolishes response in 50% of patients to surgical incision
What does an anaesthetic drug being more lipid soluble mean in terms of drug concentration?
Less conc of drug is required to make patients unresponsive to incisions
What points go against lipid theory of general anaesthetics? (4)
-Temp effect, doesn’t increase fluidity of membranes and does the opposite
-Finite number of binding sites for general anaesthetics, shows that specific receptors involved
-In homologous compounds, as they get bigger there is a loss of activity
-Some general anesthetics altered the affinity of GABAa receptors
What receptors do many GAs bind to? (2)
GABA and GABAa receptors
What GABAa subunits do volatile GAs and intravenous GAs bind to? (2)
-Volatile GAs bind at interface of a and b subunits of GABAA
-Intravenous GAs bind only on b subunit of GABAA
What do low concentrations of volatile GAs activate?
Low concentrations of volatile GAs activate Two Pore Domain K channels
What receptors do Ketamine and nitrous oxide block?
NMDA receptors
What else can be inhibited by GAs other than ion channels?
Synaptic machinery
What effect do GAs have on synaptic transmission? (3)
(Directly regulate synaptic transmission) - Decreased
-Inwards currents regulated by voltage gated sodium channel gets smaller and smaller
-Amplitude of AP inhibited by GAs (general anesthetics)
What effects do low conc GAs have on neurotransmission in these parts of the CNS? (4)
Reticular formation
Hippocampus
Thalamic sensory relay nuclei parts of the cortex
Some volatile anaesthetics inhibit
Reticular formation - unconscious
Hippocampus - short term amnesia
Thalamic sensory relay nuclei parts of the cortex - analgesia
Some volatile anaesthetics inhibit - spinal reflexes
What effects do GAs in a high conc have on the brain? (4)
Loss of these functions:
-Respiration
-Reflexes
-Motor control
-Autonomic regulation
(In absence of artificial respiration –> DEATH)
How do GAs decrease CNS transmission? (2)
-Increases in GABA changes the balance of excitory neurons
-When increases amount of inhibition increases
What is the first stage of anaesthesia and what happens in it? (2)
First stage - Analgesic
-Reduced responsiveness to pain but still partially conscious and can respond, achieved by nitrous oxide
What is the second stage of anaesthesia and what happens in it? (2)
Second stage - Excitement
-Exaggerated reflexes, dangerous state which is undesirable, reflexes not wanted as patient will give bigger reflex response to stimuli even without being conscious
What is the third stage of anaesthesia and what happens in it? (2)
Third stage - Surgical
-Patient is unconscious, lost response to painful stimuli, has also lost reflexes and will have short term amnesia
What is the fourth stage of anaesthesia and what happens in it? (2)
Fourth stage - Medullary paralysis
-Loss of cardiovascular reflexes and respiratory paralysis – causes death
How do we control anaesthesia? (4)
-Rapid induction, loss of consciousness
-Analgesia (ability to not feel pain)
-Muscle relaxation (common to give neuromuscular blockers as well)
-Rapid recovery
Which stages of anaesthesia do we want to avoid in operations? (2)
Stage 2 - Excitement
Stage 4 - Medullary paralysis
What are the advantages of intravenous anaesthetics? (3)
-Easy to administer
-Rapid induction (20-30 sec)
-Rapid recovery less ‘hangover’ can be useful for day-case surgery
What are disadvantages of intravenous anaesthetics? (4)
-Pain at site of injection
-Short duration of action due to redistribution
-Hangover due to accumulation in body fat
-side effects
(respiratory depression)
(cardiovascular depression (not etomidate))
Why do intravenous anaesthetics have a rapid induction
They are lipid soluble, cross BBB very fast
What does a low therapeutic index mean in anaesthetics?
Low therapeutic index so can move very fast between anaesthetic stages so can be very dangerous
What are inhalation anaesthetics useful for?
Useful for maintaining surgical anaesthesia easy to control conc as rate of ventilation = conc
What does speed of induction and recovery depend on? (2)
-Solubility in blood
-Body fat
How does more fat effect speed of induction? (2)
-Slow perfusion (passage through blood)
-Slow equilibration
(large partition coefficient)
How does low blood solubility effect speed of induction? (2)
-More rapid induction
-Equilibrates more rapidly with concentration in blood
What is rate of equilibration regulated through?
Alveolar ventilation
How does high blood solubility effect speed of induction?
-Increased potency
(Slowed recovery)
How do you change concentration of inhalational GA?
-To speed up rate of delivery to drug to CNS can increase ventilation rate
-Can removed drug by decreasing conc of drug and increasing rate of ventilation
What is depth of anaesthesia determined by?
-Tension of inhalational anaesthetic in brain ~ blood ~ alveolar air
What is Malignant Hypothermia? (3)
-When exposed to general anaesthetics these patients get a big rise in body temp, heart rate and reflexes, ryanodine receptor activated by anaesthetic
-Big increase in calcium levels
-Increased oxygen in muscle and increased Co2 so more heat in the patient
Who is Malignant Hypothermia observed in?
-Malignant hypothermia observed in patients with mutation in ryanodine receptor
How can you stop Malignant Hypothermia?
-This is potentially life-threatening, can stop administration, cool patient and give the Dantolinne which is a ryanodine inhibitor
