Pharm of Local Anesthetics Flashcards
In general, how do LAs work?
Block the generation and propagation of APs along nerve fibers
Blockade of voltage-gated Na channels (stabilize the inactivated state of Na channels)
Are LAs selective drugs?
No!!
They act on all excitable tissues (including heart, brain, smooth and skeletal muscle)
Interact with a whole range of membrane associated proteins
Most LAs are weak acids or weak bases?
Weak bases
2 classes of clinically used LAs
Aminoesters
Aminoamides
Typical structure of LAs
Aromatic head (lipophilic)
Amine tail
Connected by alkyl chain (ester or amide linkage)
They’re amphoteric!
Does lidocaine have a chiral center?
No
Does bupivacaine have a chiral center?
Yes
Both isomers are similar in terms of efficacy
The R isomer is more toxic
Is it the base or cation form that is responsible for the blocking action?
Cation
But it is the base that penetrates through lipid membranes
What types of fibers are more resistant to LA blockade?
The thick, fast conducting fibers (motor)
How many consecutive nodes need to be blocked to fully block impulse conduction along a myelinated fiber?
3
Differential block definition
Allows preferential blockade of sympathetic and pain fibers while minimizing impairment of motor function
Benzocaine (amide or ester, use, risk of what)
Aminoester
Used for topical anesthesia only
Risk of methemoglobin formation (can cause cyanosis)
Lidocaine (amide or ester, speed, use)
Aminoamide
Fast onset and intermediate duration of action
Used IV as an anti-arrhythmic and in acute and chronic pain
Bupivacaine (duration of action, good for, a problem)
Lipophilic and potent
Long duration of action
Racemate with high cardiotoxicity (R isomer)
Good sensory/motor block separation
Ropivacaine (isomer, benefits over bupivacaine)
S isomer
Structurally similar but less potent
Lower cardiotoxicity but similar CNS toxicity
Even more motor sparing than bupivacaine
Potency correlates to what property?
Lipid solubility
More soluble = more potent
Onset of action is related to what property?
pKa
Lower pKa = faster onset
Duration of action increases with what 2 properties
Lipid solubility
Protein binding
LAs are mainly excreted through…
Urine
Why do you add vasoconstrictors when giving LAs?
Delay absorption
Prolong LA effect
Reduce systemic toxicity
Where should you NEVER inject an LA with a vasoconstrictor?
Peripheral body parts
Ex: fingers, toes, penis, ears, nose
Can cause tissue necrosis and gangrene
Neurotoxicity from LAs
Concentration dependent neuronal injury
From all of the LAs
Most severe and devastating manifestations
Paraplegia or diffuse injury to cauda equina roots
3 phases of systemic CNS toxicity
Inhibition (sedation/dizziness, numbness, tinnitus)
Excitation (tonic-clonic seizures)
Generalized depression (coma, cardiorespiratory arrest, death)
Which LA is the worst for the heart?
Bupivacaine
In part due to its lipophilicy and potency, can accumulate in the heart
