Pharmacology 29 - Local Anaesthesia Flashcards
List the effects of local anaesthetics
- Prevent generation and conduction of action potentials
- Do not influence resting membrane potential
- May also influence channel gating
- Selectively block small diameter fibres (A delta and C fibres for pain) and non-myelinated fibres
- Weak bases (pH dependent - pKa 8-9)
- Difficult to anaesthetise infected tissue, as it tends to be acidic
What are local anaesthetics?
- Drugs which reversibly block neuronal conduction when applied locally
- Weak bases
List the routes of administration of local anaesthetics
- Surface anaesthesia
- Infiltration anaesthesia
- Intravenous regional anaesthesia
- Nerve block anaesthesia
- Spinal anaesthesia
- Epidural anaesthesia
Describe surface anaesthesia
- Mucosal surface (mouth, bronchial tree)
- Spray (or powder)
- High concentrations needed can cause systemic toxicity
Describe infiltration analgesia
- Injected directly into tissues (eg. to a wound) affecting sensory nerve terminals
- Used in minor surgery (removing cysts, suturing - due to risk of systemic toxicity)
- Adrenaline co-injection used to reduce risk of systemic toxicity via vasoconstriction (not used extremities due to risk of ischaemic tissue damage)
Describe intravenous regional anaesthesia
- i.v. distal to pressure cuff (only time anaesthetic is injected into the blood stream)
- Limb surgery (diffuses into the tissue)
- Systemic toxicity of premature cuff release (risk of bolus, cuff left on for at least 20 minutes)
Describe nerve block anaesthesia
- Close to nerve trunks e.g. dental nerves (requires accurate injection)
- Widely used method, advantageous as low doses are needed, however there is slow onset
- Vasoconstrictor co-injection
Describe spinal anaesthesia
- Injected into the sub-arachnoid space, diffuses into spinal roots
- Used in abdominal, pelvic, lower limb surgery
- Low doses (limited systemic toxicity)
- Causes a decrease in blood pressure (affect on preganglionic sympathetic neurones)
- Prolonged headache due to CSF leakage and anaesthetic reaching the brain
- Glucose added to the injection to increase specific gravity, allowing more localised action
Describe epidural anaesthesia
- Injection into the fatty tissue of epidural space, diffuses into the spinal roots
- Used in abdominal, pelvis, lower limb surgery and painless childbirth
- Slower onset (as injected into the fatty tissue space), with higher doses needed
- More restricted action with less effect on blood pressure (sympathetic neurones)
Describe pharmacokinetic properties of lidocaine and cocaine
- Lidocaine and cocaine both well absorbed
- Cocaine 90% plasma protein bound, lidocaine 70% plasma protein bound
- Lidocaine metabolised by hepatic N-dealkylation (amide)
- Cocaine metabolisted by liver and plasma, non-specific esterases (esther)
- Lidocaine 2 hour half life
- Cocaine plasma half life 1 hour
List unwanted effects of lidocaine
Common side effects of most local anaesthetics
CNS (paradoxical, once higher concentration depression occurs)
- Stimulation
- Restlessness, confusion (inhibited GABA)
- Tremor
CVS (sodium channel blockade)
- Myocardial depression
- Vasodilation
- Decreased blood pressure
List unwanted effects of cocaine when used as local anaesthetic
CNS
- Euphoria
- Excitation
- Possibly tremor and convulsions
CVS
- Increased cardiac output
- Vasoconstriction
- Increased BP
Via. sympathetic actions
Describe generation of a neuronal action potential
- Depolarisation as resting sodium channels open and sodium enters cells (from resting potential -70mV)
- Sodium channels close (inactivation following depolarisation), potassium channels open and potassium leaves the cell
- Sodium channels restored to resting state, but potassium channels still open, therefore the cell is refractory (harder to respond to stimuli)
- Sodium and potassium channels restored to resting state, therefore the cell will respond normally to further depolarising stimulus
Compare action potentials and NMJ
- Action potentials all or nothing
- NMJ graded, dependent on acetylcholine receptors
Describe structure of local anaesthetics
- Aromatic region
- Basic amine side chain (tertiary)
- Ester or amide bond (gives rise to the two different groups).
List examples of local anaesthetics
- Cocaine (esther)
- Lidocaine (amide)
Which local anaesthetic has no basic amine side-chain?
Benzocaine (weak but useful surface anaesthetic eg. throat lozenge)
Describe MOA of local anaesthetics
- Injected close to connective tissue sheath
- Reaches equilibrium between ionised and unionised form
- Unionised form crosses connective tissue sheath and axonal membrane to enter the neuron
- Equilibrium within the neuron between ionised and cationic form
Hydrophilic pathway
- Cationic form binds inside the voltage sensitive sodium channel (stereochemically inhibits influx of sodium into the cell)
- Reduces action potential propagation
- Ion channels must be open for this to work
Hydrophobic pathway (less important)
- As lipid soluble anaesthetics enter the membrane of the neuron, they dissolve in the membrane
- They can therefore enter the sodium channel when closed in the cation form
Describe use dependency in local anesthetics
- The more the neurone is used the more effectively the drug can block the neurone
- In neurons firing rapidly sodium channels are open more than they are closed so the anaesthetics are therefore more effective
