PH3113 - Pain and Analgesia 7 Flashcards
How do non-depolarising neuromuscular junction blockers work?
Competitively bind to the alpha subunit of the nicotinic acetylcholine receptor on the post-junctional membrane
- inhibiting the action of acetylcholine
Polar drugs
- unable to cross lipid membranes
- small VoD
Rocuronium
Atracurium
What is the general structure of local anaesthetics?
Lipophilic aromatic ring
Intermediate ester or amide chain
Terminal amine
Why are local anaesthetics formulated as the hydrochloride salt?
Makes them water soluble
What are the physicochemical characteristics of local anaesthetics?
Potency
- correlated to lipid solubility
Duration of action
- closely associated with protein binding
Onset of action
- closely related to pKa
What is the pH of local anaesthetics?
Weak bases
- high pKa
- greater fraction ionised
- unable to penetrate lipid membrane
- low onset of action
- low pKa
- increased fraction unionised
- able to cross lipid membrane
- faster onset of action
What is the mechanism of local anaesthetics?
Interrupt neural condition by inhibiting the influx of sodium ions
Physically block the trans-membrane pore
Two main blocking pathways
- hydrophobic
- via the membrane
- hydrophilic
- via the mouth of the channel
Which nerve fibres are more suited to local anaesthetic?
Local anaesthetics block conduction in small diameter nerve fibres more readily than in large fibres
Pain sensation is blocked more readily than other sensory modalties (touch etc), motor axons are also relatively resistant
What is the toxicity for epidurals and peripheral nerve blocks?
Epidurals
- 1:10,000
Peripheral nerve blocks
- 1:1000
How do surface/topical anaesthetics work?
Lipid-soluble drugs are used that are absorbed from mucous membranes
- lidocaine
Risk of systemic toxicity only when concentrations and large areas are involved
- sensitisation/irritation can occur
Give examples of surface/topical anaesthesia
Lidocaine
- patches
- neuralgia
- ear
- nose
- oropharyngeal use
- EMLA
- teething gel
Amethocaine
- eye drops
- haemorrhoidal preparations
Dibucaine
- haemorrhoid ointment
Tetracaine
- opthalmic preparations
Benzocaine
- dry powder to dress painful skin ulcers
- throat lozenges/spray
- used in condoms to delay ejaculation
Give examples of cellular innate immunity
Neutrophils
Monocytes
Macrophages
Natural Killer Cells
Mast Cells
Give an example of humoral innate immunity
Complement
Give examples of cellular adaptative immunity
B cells
T cells
Give an example of humoral adaptive immunity
Antibodies
Where are T cells generated?
Bone marrow
