P10: Local Anaesthetics Flashcards
What is the synthetic substitute of cocaine
Procaine
What are the major local anaesthetics in use
Lidocaine
Prilocaine
Articaine
Mepivacaine
What is the Infiltration method of local anaesthetic
Injection into tissues to reach nerve branches and terminals for minor surgery
What is the nerve block method of local anaesthetic
Injection close to the nerve trunk causes loss of peripheral sensation, used for surgery or dentistry - lidocaine, prilocaine
What is the surface method of local anaesthetic
Applied as a spray (lidocaine) or powder (benzocaine) to mucus membrnae of the nose, mouth and cornea
What is the spinal method of local anaesthetic
Injected into the subarachnoid space to act on spinal roots and cord - lidocaine
What is the epidural method of local anaesthetic
injected into the epidural space to block spinal roots.
What kind of molecule is lidocaine and describe its features
Amide, slow onset, medium duration of action, widely used
What kind of molecule is prilocaine and describe its features
Amide, rapid onset, low toxicity but can cause methaemoglobinaemia
Effects of cocaine on NA and DA
Blocks the uptake of these amines
What kind of molecule is bupivacaine and describe its features
Amide, slow onset, long duration of action, used for epidural anaesthesia
What kind of nerve fibres as more easily blocked
smaller myelinated fibres like Adelta fibres
Do local anaesthetics bind more strongly to active or inactive channels
Inactive
What is the order of nerve type blockade by increasing concs of LA
Autonomic Pain Temperature Touch Proprioception Skeletal muscle tone
Why are myelinated fibres easier to block than unmyelinated
Myelinated (autonomic etc) express clustered Na+ channels at nodes of ranvier
Unmyelinated (C fibres etc) expressed Na+ channels along length and yh
After voltage gated Na+ channels open what is used to close them
Slow acting inactivation gate that is refractory for 1-5ms
What side of an Na+ channel do LAs work on
Intracellular
As an LA must enter a neuron to work, what increases LA potency
Increased lipophilicty
Increased non-ionised fraction
What is a use dependent block
This means that the more a nerve is stimulated, the faster the onset of the anaesthesia will be
Where do all biological reaction take place
Aqueous solution
What indicates whether a drug is protonated or not
If environmental pHpKa the drug will dissociate and release a proton
Roughly what is the pKa of most LAs
Most LAs are weak bases with pKa - 8.9
Are LAs often ionised at physiological pH
Mainly but not completely ionised as the physiological pH is below the pKa.
What are the 2 main pathways that LAs can block Na+ channels with
Use Dependent - Hydrophilic
Use Independent - Hydrophobic
Why do LAs need to have a weakly basic pKa
It is the ionised form of the drug that binds to the channel interior but only non-ionised forms of the drug can cross the membrane
What happens to an LA is the pKa is too low
Drug will stay deionised inside and outside the cell - no blocking
What happens to an LA is the pKa is too high
Drug will be ionised - no entry into the axon
Due to a combo of pKa and lipophilicity what is a low potency LA
Procaine
Due to a combo of pKa and lipophilicity what is an intermediate potency LA
Mepivacaine
Prilocaine
Chloroprocaine
Lidocaine
Due to a combo of pKa and lipophilicity what is a high potency LA
Tetracaine
Bupivacaine
Etidocaine
Levobupivacaine
What effect does vasodilation have on LAs
Enhanced blood flow at site of action leads to more rapid clearance of administered LA
How do LAs cause vasodilation
blockade of sympathetic vasoconstrictive a1 stimulation
Why is a low dose of adrenaline given with LAs
To cause vasoconstriction (activation of a1 receptors) preventing loss of anaesthetic
Why shouldnt LAs be injected intravenously
Risk of systemic effects
What are the 2 classes of LAs based on their structures
Amides or Esters
Describe ester LAs metabolism, duration of action and toxic potential
- Rapidly hydrolysed, short t1/2
- Hydrolysed by plasma pseudocholinesterase
- Almost no potential for accumulation
- Toxicity is either by direct IV injection or repeated exposure
Describe amide LAs metabolism, duration of action and toxic potential
- More stable of hydrolysis
- Primarily hepatic metabolism
- Can accumulate on repeated dosage
- Dose related toxicity, may be delayed by minutes to hours
What is the easiest way to remember LAs are esters or amides
Amides have an ‘i’ before the ‘caine’ suffix
What are the benefits and risks of amide LAs compared to esters
Amides have longer t1/2
Greater risk of toxicity
What are early signs of CNS toxicity by LAs
Tinnitus
Dizziness
Light-headedness
What are the symptoms of cardiovascular toxicity by LAs
- Hypotension
- Negative inotropism (reduced cardiac contractile force)
- Vasodilation by direct actions on smooth muscle and blockade of SNS (except cocaine)
- Bradycardia leading to asystole through block of cardaic Na+ channels (not always bad - lidocaine is anti-dysrhythmic cus of this)
What usually occurs first CNS or CVS toxicity
CNS
What is the key response method to acute toxicity
Maintain oxygenation and normal CO2
What factors can increase risk of seizure and/or cardiovascular collapse with acute toxicity
- Cold temperature (slows metabolism)
- Metabolic or respiratory acidosis
- Hypoxia
- Pregnancy
