General and local anaesthetic agents Flashcards
Describe mechanism of local anaesthetics
- Block voltage-gated Na+ channels on neurons and other “excitable” tissue: Block the propagation of action potentials
- LA act on Na+ channel from the inside of the cells: must cross membrane first
- Some selectivity: LA block small diameter fibres (e.g. pain) before larger fibres (e.g. motor), LA can block pain without disrupting motor function
Describe psychochemical properties of LA
- LAs are weak bases: poor water solubility - need to combine with strong acid to be soluble
- pKa is pH where ionized and non-ionized LA are in equilibrium (around pH 9): non-ionized LA crosses membrane -> amount of non-ionized LA determined onset speed; ionized LA binds with Na+ channel
Describe binding with sodium channel for Local anaesthetics
Hydrophilic pathway -> LA crosses membrane fully:
- Non-ionized LA crosses membrane fully
- Ionized LA binds to OPEN channel (i.e. use dependency)
Hydrophobic pathway -> LA only partly crosses membrane
- Non-ionized LA enters membrane
- Ionized LA binds to channel from within membrane
- Channel can be open or closed (i.e. no use dependency)
Describe the use of vasoconstrictors (e.g. Epinephrine) with LA
- Vasoconstrictors reduce blood flow
- Effects: Increases duration of LA, minimizes dosage and keeps LA local - decreases toxicity.
List the types of local anaesthetics
All local anaesthetics are derived from cocaine (end in -caine)
- Fast onset but short duration: Lignocaine, prilocaine
- Slow onset but long duration: Bupivacaine, ropivacaine
Describe the uses of local anaesthetics
- Surface (spray) -> used on: nose, mouth, cornea (not skin) -> drug: lignocaine
- Infiltration (inject tissue) -> used on minor surgeries -> most drugs
- Intravenous regional -> limb surgery -> lignocaine, prilocaine
- Nerve block (inject close to nerve trunks) -> Surgery, dentistry -> Most drugs
- Spinal (inject subarachnoid space) -> Major surgery when General anaesthetics cannot be used -> mainly lignocaine
- Epidural (epidural space) -> As above and for painless childbirth -> Mainly lignocaine and bupivacaine
Explain difference between local anaesthesia and general anaesthesia
Local anaesthesia -> Acts on PNS (since only applied locally); blocks sodium channels for signal propagation.
General anaesthesia:
- Acts on CNS: mechanism isn’t known (under investigation)
- Effects: loss of consciousness, block pain blockage anterograde amnesia (can’t lay down memories), immobility
- Intravenous GA given to induce anaesthesia
- Inhalational GA given to maintain anaesthesia
List the stages of general anaesthesia
- Analgesia
- Excitement
- Surgical anaesthesia
- Medullary Depression (want to avoid this stage)
Name premedications required before general anaesthesia is given
Painkillers, reduce secretions, reduce nausea/vomiting, neuromuscular blockage.
Give examples of intravenous general anaesthesia
intravenous GA for induction.
Thiopental:
- Fast acting (30 seconds) but short lasting (3 min)
- Use for induction
- Narrow therapeutic window
- Adverse effects: “hangover” afterwards, laryngeal spasms, cardiac and respiratory depression
Midazolam:
- Slower acting and recover
- Less risk of cardiac and respiratory depression
- Larger therapeutic window
Propofol:
- Fast acting (30 seconds) and longer lasting
- Used alone in short procedures
- No hang over
- Cardiac and respiratory depression risk (in overdose)
Give examples of inhalation general anaesthesia
Function: for maintenance, for maintaining patient under GA.
- N2O (Nitrous oxide) -> used early but lacks potency
- All end in -ane.
- halothane: metabolites cause liver damage, risk of cardiovascular and respiratory depression
- Isoflurane: causes hypotension, less cardiac depression, widely used
- Desflurane and sevoflurane -> fast induction and recovery
- Nausea and vomiting are side effects of all inhalation GA.
