Pharmacology of Pain: Local anaesthetics Flashcards
what do local anaesthetics do?
They produce a transient and reversible loss of sensation (analgesia) in a circumscribed region of the body without loss of consciousness.
is the process of anaesthesia by local anaesthetics reversible or not?
it is reversible
what are the three major classification groups for local anaesthetics?
- Esthers (has two subgroups; all drug names ending in ‘Caine’)
- Amides (all drug names ending in ‘Caine’)
- Quinolone (only drug is centbucridine)
what is the general structure of local anaesthetics?
- aromatic ring - the lipophilic portion
- intermediate (ester or amide) linkage
- terminal amine - the hydrophilic portion
what way does the Na+/K+ pump work on Na+ and K+?
3Na+ out, 2K+ in - creating an overall positive exterior and relatively negative interior at resting potential
how do local anaesthetics work?
- the lipophilic and hydrophilic ends of the drug molecule dissociate
- lipophilic end diffuses across the membrane into the cell (neurone)
- the lipophilic molecule binds to a hydrophilic molecule on the inside of the cell to reform the drug.
- when an action potential occurs, the Na+ channels are opened and the drug molecule binds to the channels blocking Na+ transport into the cell
- this prevents threshold potential from being met as there is no depolarisation therefore no action potential.
which type of fibres have the most sensitivity to local anaesthetics?
C-fibers
what is the vasoactivity of ester local anaesthetics?
-causes vasodilation
what tissue has the highest level of local anaesthetics?
skeletal muscle
what influences the blood level of local anaesthetics?
- Rate at which the drug is absorbed into the cardiovascular system.
- Rate of distribution from the vascular compartment to the tissues.
- Elimination of the drug through metabolic or excretory pathways.
do local anaesthetics cross the blood brain barrier?
yes
how do local anaesthetics enter the blood stream of a developing fetus?
via the placenta
what is the effect of a higher lipid solubility on the drug potency?
-increases the potency hence a lower drug conc can be used hence reducing potential for toxicity
what type of pH increases drug action?
acidic conditions
how are esters cleared?
hydrolysis via cholinesterase
how are amides cleared?
metabolism via hepatic enzymes in the liver
where is prilocaine metabolised?
in the liver and lung
why does articaine have a shorter half-life than other amide anaesthetics?
becasue part of its metabolism occurs in the blood by plasma cholinesterase
where are local anaesthetics excreted
via kidneys
what is the pharmacological action of local anaesthetics on CNS
depression
effect of high levels of local anaesthetics
tonic-clonic convulsions ( epilepsy/ seizures)
at what level do local anaesthetics have anti-convulsant properties?
at a blood level much below that at which the same drug causes seizures
which is more resistant to the effects of local anaesthetics, cardiovascular system (CVS) or CNS?
CVS
what is the effect of increased local anaesthetic blood levels on myocardial depolarisation?
decreases myocardial depolarisation without affecting resting potential
what effect do local anaesthetics have on myocardial excitation, conduction rate and force of contraction?
decreased excitation
decreased conducatance rate
decreased force of contraction
what is lidocaine used therapeutically for?
pre- ventricular contractions and ventricular tachycardia
how do local anaesthetics cause hypotension?
from direct relaxant action on vascular smooth muscle
effect of local anaesthetics on lung?
- relax bronchial smooth muscle
- longer acting anaesthetics may cause more damage to skeletal muscle (lung toxicity)
what the 6 placement sites of local anaesthetics?
- surface/ topical anesthesia
- local infiltration
- peripheral nerve block
- bier block (IV regional anesthesia)
- epidural anesthesia
- spinal anesthesia( subarachnoid)
how does surface anaesthesia work?
on intact skin, apply topically e.g. cream
slowly absorbed
how do we prolong the action of surface anaesthesia?
add a vasoconstrictor e.g. adrenaline
what is the pro of using a surface anaesthesia?
can use larger dose
avoids first pass
how does local infiltration work?
- localised injection of an aqueous solution of local anesthetic sometimes with vasoconstrictor
- can be injected close to nerve subcutaneously
how does peripheral nerve block work?
- injection of an aqueous solution around a nerve trunk
- anaesthesia distal to the site of injection
what is IV regional anaesthesia?
- injection of a dilute solution of local anaesthetic into the limb after application of a tourniquet
- used in fractures and minor surgical procedures
how does epidural anaesthesia work?
- njection of slow infusion via a cannula of an aqueosu solution adjacent to the spinal column, but outside the dura matar into the epidural space
- reuslts in anaesthesia above and below site of injections
- used in obstetrics and surgical procedures
how does spinal anaesthesia work?
- injection of an aqueos solution into thoracic-lumbar subarachnoid space, usually between L3 and L4
- used in combination with opioids
what determines whether or not the spinal anaesthesia will spread within the subarachnoid space?
- the density of the solution
- the posture of the person during the first 10-15 min while the solution flows up or or down the space
what is the major difference between spinal anaesthesia and epidural anaesthesia?
- spinal anaesthesia punctures the epidural space on both sides whilst the spidural anesthesia only punctures one side
how does capsaican work
works mainly by reducing substance P, a pain transmitter
it binds to TRPV1 receptors which are involved in the transmission and modulation of pain
