LOCAL ANAESTHETICS Flashcards
Describe the process of generation of neuronal action potential
1) depolarization occurs –> Resting Na+ channels open –> Na+ enters cells
(sharp upward stroke)
2) Na+ channels close (inactivation), K+ channels open –> K+ leaves cell
3) Na+ channels = inactivated –> restored to resting state but K+ channels = still open therefore cell refractory
4) Na+ and K+ channels BOTH = restored to resting state –> so cell will respond normally to further depolarizing stimulus (post refractory phase)
define what is meant by Local Anesthetics
Drugs which reversibly block neuronal conduction when applied locally
what are common features of structure of LA
COMMON FEATURES:
- all have aromatic region
- all have basic amine side chain
- bridging groups = either ESTER (e.g cocaine) or AMIDE (e.g Lidocaine) bond
“Ester smokes cocaine”
exceptions: Benzocaine = weak LA –> no basic side chain
(good surface local anesthetic)
Describe the MoA of LA
a) Hydrophilic Pathway (use dependent) - MOST LA
- only unionized LA –> can pass through lipid memb –> and outer memb of sensory neurone –> to pass into inside of neurone
- LA needs access to inside of neurone to work
- unionised form blocks multi- sensitive NA+ channel
binds to site iside channel and blocks na+ influx - reduce propagation of Na+ channels
more rapidly neurones are firing –> more Na+ channels = in open state –> increase in effect of LA
b) hydrophobic pathway (e.g benzocaine)
- unionized drug drops into (closed) ion channel
- channel don’t need to be open
note: ALL LA = WEAK BASES
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What re the main effects of LAs
They:
- Prevent generation and conduction of APs
- Do NOT influence resting membrane potential
( only affect generation of AP) - May also influence channel gating
Selectively block
a) small diameter fibres (great preference for LA)
b) non myelinated fibres
multi-sensitive sodium channel = in 3 states
what are the 3 states?
- resting
- open state
- inactivate state
- -> goes back to resting state
–> some LA binds preferentially to inactivated state
(prolong refractory period) –> contribute to action of LA effects
LA –> shows PH dependency –> because they are weak bases
PKa 8-9
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What are some routes of administration of LAs ?
- Surface anaesthesia
- Mucosal surface (mouth, bronchial tree)
- Spray
- High concentrations → can cause systemic toxicity - Infiltration anaesthesia
- LA Directly into tissues → sensory nerve terminals
- (subcutaneous application)
- Minor surgery
- Adrenaline co-injected
–> Adrenaline = vasoconstrictor –> so lower dose of LA can be used
–> also reduced risk of systemic toxicity
(not extremities –> as it can cause ischemia of digits) - Intravenous regional anaesthesia
- i.v. distal to pressure cuff
- Limb surgery
- Systemic toxicity of premature cuff release (keep cuff on for at least 20 mins) - Nerve block anaesthesia
- LA injected close to nerve trunks e.g. dental nerves
- Widely used – low doses – slow onset
- Vasoconstrictor co-injection (e.g adrenaline) - Spinal anaesthesia
- injected into Sub-arachnoid space – spinal roots
- (between L4 + L5)
- Abdominal, pelvic, lower limb surgery
- Low doses
- keep aware of any ↓ b.p.; prolonged headache
- can mix w Glucose (↑ specific gravity) –> increase density of solution –> manipulate LA target area (tilt bed to meet target site) - Epidural anaesthesia
- inject into Fatty tissue of epidural space – spinal roots
- similar uses as spinal anaesthesia and painless childbirth
- DSAVTG = Slower onset – higher doses –> more risk for systemic toxicity
- But allows more restricted action w less effect on b.p.
Describe pharmacokinetic properties of
a) Lidocaine
b) Cocaine
Describe pharmacokinetic properties of
BOTH –> good absorption –> can be used as surface anesthetics
a) Lidocaine absorption = good PPB = 70% Metabolism = Hepatic N-dealkylation Plasma T1/2 = 2h
b) Cocaine absorption = good PPB = 90% Metabolism = Liver + Plasma + non-specific Esterases Plasma T1/2 = 1h
NOTE Bupivacaine = more resistant to metabolism
–> DoA = 6 hr
epidural anaesthesia
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What are SE of Lidocaine
CNS (paradoxical)
- stimulation
- restlessness, confusion
- tremor
CVS (Na+ Channel Blockade)
- myocardial depression
- vasodilatation
- ↓ b.p.
What are SE of Cocaine
(Sympathetic action stimulation)
CNS
- euphoria, excitation
CVS
- ↑ C.O.
- vasoconstriction
- ↑ b.p.
Lidocaine:
A: Inhibits reuptake of 5-hydroxytryptamine
B: Blocks voltage-gated K+ channels
C: Is a competitive muscarinic cholinoceptor antagonist
D: Is a weak base
E: Is a general anaesthetic
ANS: D: Is a weak base
Which ONE of the following statements about local anaesthetics is INCORRECT? They:
A: Cause blockade of voltage-sensitive sodium channels
B: Block rapidly firing neurones more readily than more slowly firing neurones
C: Enhance action potential propagation
D: Are largely ionised at physiological pH
E: Have their durations of action increased if injected with adrenaline
ANS: C: Enhance action potential propagation
