Anaethetics Flashcards
What is the clinical use of depolarising blocking agents acting at the NMJ
suxamethonium - only drug
used if fast brief neuromuscular block is req.- tracheal intubation before surgery needed
Very short acting 10 mins- hydrolysed by plasma cholinesterases
What is a depolarising block and give examples
Inhibition of transmission at the NMJ
depolarising muscle relaxants (nicotinic agonists) such as nicotine, ACh, suxamethonium (selective for the muscle nAChRs)
Non-competitive- increased agonist exacerbates the effect
Give examples of general anaesthetics
Ketamine
Thiopental
Propofol
Etomidate
Give examples of inhalation anaesthetics
Halothane
Sevoflurane
desflurane
Isoflurane
Nitrous Oxide
How do drugs work on GABAa receptors in anaesthetics
Enhance activity of GABAa
GABAa receptors are ligand-gated Cl- channels consisting of 5 subunits
Anaesthetics bind to hydrophobic pockets in diff. GABAa receptor subunits
How do drugs affect Glutamate receptors in anaesthetics
glutamate is the excitatory NT in CNS
NMDA receptors are site of action for NO, xenon, isoflurane
Mutation in membrane domains reduce alcohol-induced inhibition of receptors - therefore may not work
xenon and isoflurane inhibit NMDA R by competing w glycine for its regulatory site
Ketamine
increases BP and HR and no effect on respiration
can be used in low tech environments
powerful analgesics
Unwanted S/E - hallucinations, delirium
Neuromuscular blocking drugs
Inhibition of transmission at the NMJ can be done by 2 ways:
Competitive inhibition of nicotinic receptors- non-depolarising block
Depolarising block (nicotinic agonists)
Give an example of a non-depolarising block and a brief MOA
Tubocurarine is non-depolarising neuromuscular block- paralysis
inhibition is competitive (overcome by ACh)
What are the pharmacokinetics of inhalation anaesthetics
Anaesthetics first have an equilibrium with alveoli
equilibrium in blood should be rapid- ideal
Inhalation rapidly reaches the required arterial blood conc.
Blood must become saturated for transfer to tissues- slow
Discuss Propofol
rapid onset and rate of distribution
Can be used as continuous infusion but maintaining desired concs are hard!
No hangover-> metabolised quickly and no cumulative effects
propofol and thiopental cause CV and respiratory depression
Discuss thiopental
Shows saturation kinetics: large/repeated doses can cause plateau in blood concs to become elevated as accumulation occurs as the metabolism saturates
What is the role of voltage gated potassium channels in anaesthetics
Two pore domain K channels
Activated by low conc volatile and gaseous anaesthetics to reduce membrane excitability
What is the use of non-depolarising blocking agents
Used as a muscle relaxant during surgery
Pancuronium- long DOA
Vencuronium- intermediate DOA
atracurium- intermediate
Mivacurium- short DOA
What drugs are given when anaesthesia is given
sedative premedication- benzos
IV anaesthetic for rapid induction- propofol
Inhalation anaesthetic-NO and isoflurane
Muscarinic antagonists to reduce bronchial and salivary secretion- atropine
analgesia for pain relief at end of surgery -morphine
what physiological factors determine the induction and recovery of inhalation anaesthesia
Alveolar ventilation rate-greater the minute volume faster the equilibrium
Cardiac output- reduction of alveolar perfusion reduces alveolar abs. of the anaesthetic so speeds up induction. Has to be balanced with the reduced cerebral blood flow
