general anaesthucs Flashcards
what is the role and history of general anaesthetics
Role
●Render patients insensitive to surgical procedures/pain
●Stabilize patients for surgical procedures
●Revolutionized medicine and essentially ushered in modern surgery/medicine
History
●Prior to GA, surgeons used drugs (opiates/alcohol) to immobilize patients but surgery was quick/brutal with hig
what do MAs contain
Cocktail of drugs in addition to GAs used before (premedication), during (perioperative) and after surgery (post operative) to achieve balanced anaesthesia and to aid safer and faster patient recovery
•Premedications (anxiolytics): Diazepines
➢H2 receptor blockers (Ranitidine): prevent gastric acid secretion
➢Autonomic stabilizers (block bronchial and salivary secretion): Atropine
➢Muscle relaxants (Suxamethonium)
➢Analgesics: opioids (Fentanyl)
•Postoperative to prevent PONV
➢Antiemetics (Granisetron; Domperidone)
➢Neostigmine to reverse neuromuscular blockade
what do MAs contain
Cocktail of drugs in addition to GAs used before (premedication), during (perioperative) and after surgery (post operative) to achieve balanced anaesthesia and to aid safer and faster patient recovery
•Premedications (anxiolytics): Diazepines
➢H2 receptor blockers (Ranitidine): prevent gastric acid secretion
➢Autonomic stabilizers (block bronchial and salivary secretion): Atropine
➢Muscle relaxants (Suxamethonium)
➢Analgesics: opioids (Fentanyl)
•Postoperative to prevent PONV
➢Antiemetics (Granisetron; Domperidone)
➢Neostigmine to reverse neuromuscular blockade
what are MAs and where do they act
What are they?
●Most are small, lipid soluble molecules
●Diverse structure: single atoms (xenon) to complex hydrocarbons (thiopental)
●Administered systemically (iv or inhalation)
Where do they act?
●Act on CNS and decrease electrical activity in the brain and spinal cord
●Depress cardiovascular, respiratory and other systems
➢Cocktails of drugs in addition to GA is given to patients to reduce the risk of cardiovascular and respiratory arrest
what are MAs and where do they act
What are they?
●Most are small, lipid soluble molecules
●Diverse structure: single atoms (xenon) to complex hydrocarbons (thiopental)
●Administered systemically (iv or inhalation)
Where do they act?
●Act on CNS and decrease electrical activity in the brain and spinal cord
●Depress cardiovascular, respiratory and other systems
➢Cocktails of drugs in addition to GA is given to patients to reduce the risk of cardiovascular and respiratory arrest
what are the two theories if the mechanism of general anaesthetics
Physiochemical theory: GA doesn’t bind to the receptor, instead dissolves in the lipid membrane of neurons changes the structure of the lipid bilayer affects the mechanism of action of receptors
➢Structural theory: GA interacts with ion channels and receptors to modify central synaptic transmission √
what is the meyer overton rule
potency
Potency of a GA correlates with lipid solubility; NOT the chemical structure of the molecule: Meyer Overton Rule MAC: Minimum Alveolar Concentration of an anaesthetic agent required to prevent movement during surgical procedure in 50% of patients measure of potency
➢Lower MAC = higher GA potency inverse relationship
●Oil:gas partition coefficient: measures the solubility level of the anaesthetic agent in lipids
➢high oil:gas partition coefficient = high solubility
what is the meyer overton rule
potency
Potency of a GA correlates with lipid solubility; NOT the chemical structure of the molecule: Meyer Overton Rule MAC: Minimum Alveolar Concentration of an anaesthetic agent required to prevent movement during surgical procedure in 50% of patients measure of potency
➢Lower MAC = higher GA potency inverse relationship
●Oil:gas partition coefficient: measures the solubility level of the anaesthetic agent in lipids
➢high oil:gas partition coefficient = high solubility
how does the meyer overton rule relate to anaesthetics
Originally it was assumed that non-specific actions of anaesthetic agents were the cause of anaesthesia, i.e.
➢Anaesthetic agents dissolve in cell membrane
➢This perturbs cell membrane structure
➢This affects functions of membrane proteins such as receptors and ion channels
●Non - specific theory: i.e. were “general anaesthetics drugs without receptors”?
➢Not all GA are lipid soluble!
➢Not all lipid soluble molecules are GA!
➢Stereoisomers of GA has different anaesthetic properties despite same lipid solubility!
structural theory \
- what are the two ways that GAs interact with ligand gated ion channels
General anaesthetics either:
➢Increase activity of inhibitory ligand gated ion channels (GABAA receptors)
➢Decrease activity at excitatory ligand gated ion channels (5-HT3 receptors)
how does GA act on GABAA receptors
Almost all GA (except Ketamine, Xenon and Nitrous oxide) potentiate the action of GABA by binding onto the GABAA receptor subtype
➢Ketamine binds to GluA2 subunit of AMPA receptors and NMDA receptors decrease GABAergc inhibitory neurotransmission mostly used as an induction agent
➢Xenon binds to NMDA receptors
➢Nitrous oxide binds to mu and kappa subunits of opioid receptors
how do GA act on k+ channels
GA act on two pore domain K+ channels (TREK)
●Family of “background” K+ channels that modulate neuronal excitability
●Activated TREK channels = K+ ions leave the cell hyperpolarization of the membrane (more negative inside the cell) reduced neuronal activity
●GA opens TREK channels hyperpolarize the neuron neuronal activity is reduced
●Channels comprising of TREK1, TREK2, TASK1 (TWIK-related acid sensitive K+ channels), TASK3, TRESK can be directly activated by volatile or gaseous anaesthetics reducing membrane excitability
● Not affected by intravenous anaesthetics
what are the classes og GA
Anaesthetic agents comprise of 2 main groups:
➢Inhalation anaesthetics
Very diverse group of compounds containing gases such as Nitrous oxide or volatile anaesthetics such as Isoflurane or Desflurane
➢Intravenous anaesthetics
Diverse group of compounds including Propofol, Thiopental (induction agent), Ketamine and Etomidate (postoperative antiemetic agent)
