Pharm 30 - Principles of local anaesthesia Flashcards
What are local anaesthetics
Drugs which reversibly block neuronal conduction when applied locally
Action potentials are all or nothing. Motor end plate potentials are …?
Graded
In an action potential, which opens faster (and closes slower); VGSC or VGKC
VGSC
What are the 3 main structural regions of local anaesthetics
- Aromatic region
- Basic amine side-chain
- Above two linked together by ester or amide bond
LAs can be classified according to their bond
Ester = cocaine
Amide - lidocaine
Ester smokes cocaine
Benzocaine is the exception, why
It is a LA with an alkyl side chain
It is a surface anaesthetic (used in lozenges, etc)
Local anaesthetics only work from …. the neurone
Inside
Local anaesthetics are weak bases (pKa 8-9). Only what form passes through connective tissue and axon membrane?
Unionised
Describe the hydrophilic pathway (MAIN m.o.a of LAs)
- Unionised LA enters neurone
- Inside neurone, LA ionised (BH+) –> enters open Na+ channel —-> binds to binding site of Na channel (which sits inside the channel) –> inhibits Na influx
Local anaesthetics exhibit use-dependency, meaning?
More active cell = more Na channels open at any given time = LAs block more channels and have greater effect
Describe the hydrophobic pathway of LAs
- LA enters membrane
- Directly drop into Na channel (if very lipid soluble e.g. benzocaine)
- Ionised in Na channel - Na channel can be open or closed in this pathway
What are the effects of LAs
- Prevent generation and conduction of APs
- DONT influence resting membrane potential
- May also influence channel gating
- Selectively block small diameter fibres and non-myelinated fibres
Infected tissue tends to be more acidic. What does this mean for LA
LA gets more ionised than normal, smaller proportion passing into channel and blocking Na
What are the routes/methods of adminstration
- Surface anaesthesia - mucosal surface, spray. High concentrations may cause systemic toxicity
- Directly into tissues - sensory nerve terminals - minor surgery, adrenaline coinjection (but not to extremities as can cause ischaemia) to vasoconstrict - this means LA duration longer in local area- reduce risk of systemic SE and reduce bleeding
- IV regional anaesthesia - IV distal to pressure cuff, used in limb surgery. Systemic toxicity if premature cuff release
- Nerve block anaesthesia - close to nerve trunks (e.g. dental nerves) - used widely in low doses, has slow onset. Vasoconstrictor connection
- Spinal anaesthesia - subarachnoid space (spinal roots). Used in abdominal, pelvic, lower limb surgery, low doses. Watch for decrease BP, prolonged headache. Mix w glucose to increase specific gravity
- Epidural anaesthesia - fatty tissue of epidural space. Used for painless childbirth, abdominal, pelvic, lower limb surgery. Slow onset, higher doses needed, more restricted action so less effect on BP
Outline the pharmacokinetics of lidocaine
Lidocaine Absorption - Good PPB - 70% Metabolism - Hepatic n-dealkylation Plasma t1/2 - 2hrs
Outline the pharmacokinetics of cocaine
Absorption - good
PPB - 90%
Metabolism - Liever and plasma, non specific esterase’s
Plasma t1/2 - 1hr
