local anesthetics Flashcards
3 important features of local anesthetics
- Aromatic group
- Linker region (either amide or ester)
Mnemonic: all amides have an “i” before the “caine” - Amino group (can accept a proton)
duration of medication
long lipophilic regions = long lasting drugs
Molecular target of local anesthetics
voltage gated NA+ channel 4 domains (each cross membrane 6 times) Local Anesthetic is too big to enter the channel from outside
henderson hasselbach
log(protenated/unprotenated) = pka - pH
Why does the local anesthetic work better in high pH environement?
in High pH enviroment, drug is unprotenated and LIPOPHILIC, so it is able to get into the cell
What is the less common mechanism of local anesthetic action?
drug diffuses from within the lipid bilayer to channel pore.
if you have a set amount of lidocaine on a wound and then poke the wound more often does the lidocaine perform better ?
Yes! more stimulation = greater effect
how does sensitivity depend on nerve fiber?
Most sensitive are the thinnest:
Generally unmylinated C fibers and Sympathetics ( alpha receptors)
What effect do most local anesthetics have on blood vessels? Why ? how do you reduce the effect?
Vasodialators. Inhibit/block alpha 1 sympathetic receptors. reduce the effect by adding in Epinephrine as a vasoconstrictor
Adverse effects of esters (metabolism)
metabolized by pseudocholinesterase which is super common throughout the body, so there is a low chance of systemic effects.
Metabolism byproduct = local hypersensitivity rxns
Adverse effects of Amides (metabolized)
metabolized in Liver and kidneys so will have systemic effects
Who should not get Amides?
hepatic or renal disease patients
CNS effects?
drowsyness->twitching-> siezures
Cardiac effects?
Arrythmias
Cocaine Properties
Approved only for surface anesthesia
IT IS A VASOCONSTRICTOR
Procaine (Novocaine)
low potency, slow onset, short duration
DOES NOT WORK TOPICALLY
Tetracaine
slow onset, longer and more potent effects
benzovaine
only good for topical anesthesia because of NO ionizable group
Lidocaine
most common. Rapid onset. High extraction by liver on first pass. can be used to treat cardiac arrythmias
Prilocaine (+ adverse)
Weak vasodialator so no epi needed
Large volume of distribution
Rapid elimination
ADVERSE = methemoglobinemia = turns HB from Fe2 to Fe3 ( treat w/ methyline blue)
Bupivicaine
Blocks sensory > motor neurons; useful in labor
More cardiotoxic than equieffective anesthetic doses of
lidocaine; due mainly to the S(+)-enantiomer
Ropivicaine
from Bupivicane without the S+ enantiomer so no cardiac side effects
