BP.14 Anaesthetics Flashcards
What are anesthetics?
2) How is this different from analgesics
3) What do local anaesthetics do?
4) General anaesthetics do the same, and one other thing which is ….
are drugs which are used to prevent pain for a limited period of time for surgical or other procedures
2) analgesics are used more to control pain
3) Local anaesthetics prevent localised pain or nociception and also prevent tactile sensation
4) also induce loss of consciousness
What are the 2 broad classes of general anaesthetics:
inhalation anasethetics and intravenous anaesthetics
Which class of drug do they fall into:
Enflurane
Isoflurane
general anaesthetics- inhalation anaesthetics
Which class of drug do they fall into:
Halothane
Nitrous oxide
general anaesthetics- inhalation anaesthetics
Which class of drug do they fall into:
Thiopental
Etomidate
general anaesthetics-
Intravenous anaesthetics
Which class of drug do they fall into: Propofol
general anaesthetics-
Intravenous anaesthetics
WHat are the 2 theories of the mechanism of action of general anaesthetics?
lipid theory (Meyer Overton Theory ) and ion channel theory
What is the lipid theory of general anesthetics?
2) Why did it come about?
3) credited or discredited?
1) agents interacted with lipid bilayer of plasma membrane, causing membrane expansion and consequent inability of membrane to facilitate changes in protein configuration and signalling:
2) strong rela. betweeen anaesthetics potency and lipid solubility
3) discredited
What is the ion channel theory?
Anaesthetics target a number of ligand gated ion channels, including, GABAA, Glycine NMDA,
Depth of anaesthesia determined by concentration in the ___A__ and___B__-
brain
spinal cord
What is the measure of
1) blood solubility?
2) lipid solubility?
1) Blood/gas partition coefficient ,
2) Oil:gas partition coefficient (also tells you potency of the drug)
If the blood/gas partition coefficient is high what will it mean?
slow induction , recovery
as the Lower the solubility in the blood, faster the induction and recovery-less drug needs to be transferred via the lungs to produce equilibrium
If the oil/gas partition coefficient is low what will it mean?
Gives an indication of potency since brain high lipophilicity
The lower the oil:gas pc, the less potent the GA → don’t need a lot into the blood to produce an anaesthetic effect.
How are inhaled anaesthetics usually eliminated?
2) what organ doesn’t get to meabolise it as much?
lungs
2) liver
What side effects are common to inhaled anaesthetics? (5)
- Malignant hyperthermia
- hypotension
- Depressed respiration
- Depressed glomerular filtration and urine output
- Hepatic toxicity
How is the distribution of an inhaled anaesthetic effects? (pharmacokinetics)
e.g. brain vs body fat
Brain good blood flow: high levels
Body fat has poor blood flow so anaesthetic doesn’t accumulate in body fat: (within reason, and in fact obesity is a problem in anaesthesia)
what effects excretion of an inhaled anaesthetic?
pharmacokinetics
ventilation rate
: but anaesthetics cause respiratory depression, and so require controlled ventilation
What is malignant hyperthermia?
2) what can cause it?
1) hypermetabolism, muscle rigidity, muscle injury and increased sympathetic nervous system activity, hyperthermia
2) side effect of inhaled anaesthetics
Intravenous anaesthetics,
1) describe time of onset of action?
2) name 4
1) Short onset of action (20 seconds)
2) THIOPENTAL SODIUM
ETOMIDATE
KETAMINE
PROPOFOL
1) WHat does thiopental and etomidate bind to ?
2) Which is better why?
Thiopental & Etomidate both act on GABAA receptor (on alpha1/beta3 subunit interface)
2) Etomidate
-Wider therapeutic window between anaesthesia and respiratory depression
TI (therapeutic index) LD50/ED50=26
(Thiopental TI =2.5)
-More rapidly metabolised
What receptors does propofol bind to?
GABAa, Glycinereceptro
What on GABA a does propfol bind to ?
beta3 /beta3 or alpha1/beta3 subunit interface
1) Describe metabolism of profol (speed)
2) What organ eliminates it?
3) describe recovery?
4) What is it used to treat?
1) rapid
2) Extrahepatic, elimination via plasma (esterases) and lungs
3) rapid
4) day case surgery
What is ketamine?
2) does it causes more or less hypotension than etomidate/propofol?
3) Why is it rarely used?
4) does it have an analgesic effect
NMDA receptor antagonist
2) less
3) Hallucinations, psychosis
4) Does have some good analgesic effect
How do local anaesthetics work?
block electrical signalling in neurones (remeber transfer between neurons is chemical and electrical) by blocking Na+ voltage gated channels
Describe an action potential:
2) What is crucial and propagation of action potentials and electrical signalling?
Na+ influx, then peaks then K+ out.
2) Voltage gated Na+ channels
How many subunits make up voltage gated ion channels?
alpha, beta 1 and beta2.
Describe the alpha subunit of voltage gated ion channels:
2) How is the Beta 2 subunit linked to alpha-subunit?
3) What is the function of the beta units?
The -subunit is a single polypeptide. It contains extracellular domains, 4 transmembrane domains each comprising 6 alpha-helical regions
2) covalently
3) anchor alpha-subunit to lipid membrane
Local anaesthetics are thought to interact with the __A___ subunit and physically ‘___B___ the ___C___. Local anaesthetics binds in the ___D___
The local anaesthetic binding area is located in the ___E___ of the channel
A) alpha (of the Na ion channel) B) plug’ the C) transmembrane pore D) ionised (hydrophilic) form E) inner end
Ideal local anaesthetics if ionised..
if unionised.. interact with nn how?
2) Most anaesthetics are weak/strong acid/bases
- Unionised form gains access through nerve sheath and axon membrane
- Ionised form binds in channel
2) weak bases
Describe general structure of local anaesthetic
of aromatic group (left), ester or amide group (shaded) and amine group (right).
The basic amine side chain/group ensures the molecule is what at physiological pH?
ionised
the aromatic domain of local anaesthetics do what?
ensure lipid solubility
what about the structure of local anaesthetics limits the duration of action?
Duration of action is limited by the hydrolysis of the ester/amide bond and by the lipid solubility of the agent.
Why are local anaesthetics lipid soluble bases?
2) Does this enter the axon , what happens to it?
3) What effect does it have on the axon
1) Have amine group (basic), aromatic group (lipid soluble)
2) enters axon (pH lower inside), becomes reionised (as would be injected into patient within hydrocloride salt in acid solution)
3) re-ionized portion enters the Na+ channels and blocks them, preventing depolarization
How are they metabolised: esters
describe T1/2
Metabolised in plasma by esterases (except cocaine) Shorter T1/2
How are they metabolised: amides
describe T1/2
3) Who do you have to be careful prescribing to ?
Metabolised in liver by CYP3A4,1A2 -longer T1/2
3) individuals with liver failure
How do we restrict site of aciton and prolomg duraiton of a local anaesthetic?
2) How do we accelerate the speed of onset of the anaesthetic
1) inject with adrenaline
2) Use slightly alkaline solution, this will assist in absorption of the anaesthetic into the nerve tissue
Put this in order from most to least sensitive to local anaesthetic effects:
large myelinated axons
small myelinated axons
non-myelinated axons
2) describe axons of nosiceptive fibres and motor axons
small myelinated axons* > non-myelinated axons > large myelinated axons
2) Nosciceptive (pain) fibres are small diameter and particularly sensitive
Motor axons have a large diameter and are less sensitive
the depth of block increases with…
2) what is this known as?
3) why do they occur?
action potential frequency
2) use dependent block
3) the anaesthetic gains access to, and has higher affinity for the channels more readily when it is open and/or inactive
why do side effects occur with local anaesthetics?
they escape into the systemic circulation
what side effects are induced in CNS by local anaesthetics?
confusion and agitation
What sides effects of local anaesthetics cna impact the cardiovascular system?
2) WHy?
reduced CO?, hypotension
2)
Inhibition of sympathetic activity
Inhibition of sodium conductance in cardiac tissue
