Local Anesthetics Dr. Pond Flashcards
What do local anesthetics have in common structurally?
-lipophillic group -> aromatic ring)
-hydrophillic domain -> usually a tertiary amine
connected by an alkyl
How does the pH affect local anesthetics?
the protonation of the tertiary amine depends on the pKa of the compound and the local pH
Which form of the local anesthetic is preferred in order to work? Protonated or unprotonated?
There must be a balance between the two
the target is the inner site of the voltage-gated Na+channel -> so it has to cross the membrane first
-unprotonated form to cross the membrane
-protonated form to actually bind to the inner part of the receptor
How are the different local anesthetics categorized?
by the type of intermediate chain (alkyl chain) that connects the lipophilic aromatic ring to the hydrophilic tertiare amine
-Ester intermediate chain
-Amide intermediate chain
What are the Ester local anesthetics?
Cocaine
Tetracaine
Procaine/Chloroprocaine !!!
Benzocaine!!!
What are the Amide local anesthetics?
Mepivacaine
Ropivacaine
Lidocaine !!!
Bupivacaine !!!
Prilocaine !!!
Amides have an “i” before -caine
How might Ester local anesthetics be broken down and what is it is the metabolic product?
plasma esterases
-> product: para-aminobenzoic acid (PABA)
-> CAUTION: with allergies
-> can’t sterilize it repeatedly, bc not as stable
Where are Amide local anesthetics metabolized?
in the liver by CYP enzymes
-can undergo repeated high temperature sterilization without losing potency
Where are local anesthetics usually administered?
by injection into the
-dermis
-the soft tissue
-> in the area of the nerves
What is affected by the absorption and distribution of local anesthetics?
-Duration of action
-Toxicity
the onset is not affected bc we apply it locally and it works pretty quickly
What affects the absorption of local anesthetics?
Vascularization (amount of blood vessels)
-> fe the mouth isvery vascular
What might be given additionally to local anesthetics when applied to a vascular area of the body?
Vasoconstrictor
-alpha-1-agonist (like Epinephrine)
-> Reduce systemic absorption
-> prolongs the duration of action
-> reduces toxicity
What is the MOA of local anesthetics?
it blocks voltage-gated Na+channels
-crosses the membrane and binds the inner part
Which state of the Ca2+ channel is preffered by local anesthetics?
the activated and inactivated state
-when depolarized
-it prefers more rapid-firing neurons
REMINDER route of pain signal
-REMINDER: the nocireceptor receives pain signal and forwards it along the axon -> to the dorsal root ganglion (DRG) -> to the dorsal horn of the spinal cord -> secondary neuron -> to the brain
Where exactly on the neuron do local anesthetics work?
on the axon along the primary afferent neuron
-> blocking voltage-gated Na+ channels (inner part) -> prevents depolarization and the action potential transmission
Which type of axons are primarily sensitive to local anesthetics?
Type C: small sized (diameter)
Type B: somewhat bigger -> some myelination are more sensitive local anestheitcs
Which drugs are usually used for surface anesthesia?
Benzocaine -> mucous membranes (mouth, nose, throat)
Cocaine -> cornea
other surface: skin
What does infiltration anesthesia refer to?
injection of local anesthetic into the affected area without the need to target nerve tracks
-> dentis for example
What does nerve block anesthesia refer to?
injecting the local anesthetic into or adjacent to the peripheral nerves and plexuses
-> larger area of action
-> the entire area distal to the site of injection is affected
-> for patients with chronic pain
Which parts of the body will affected when local anesthetics are injected intrathecally?
-anesthetize a large fraction of the lower body
injection into the CSF (Cerebrospinal fluid) around the spinal cord
minimal plasma level -> so less toxicity
Where in the spinal cord is the CSF located?
between the Dura mater and Pia mater
-> subarachnoid space
How is Epidural anesthesia different from an intrathecal injection?
it is injected above the dura mater into the epidural space
-> more likely to be absorbed into the bloodstream from the epidural space
What is a possible complication of the Epidural injection?
Wet tap
-> when puncturing the dura it can leakage of spinal fluid -> creating a killer headache
What are the adverse effects of local anesthetics?
-cardiovascular: bradycardia, hypotension
-GI: metallic taste, N/V
-CNS: drowsiness, dizziness, nervousness, blurry vision
-> should be minimal since applied locally and low systemic absorption
What are possible (rare) CNS toxicites when applying high concentrations of local anesthetics?
-neural toxicity
-twitching followed by tonic-clonic convulsions
->due to depression of cortical descending inhibitory pathways
What are possible cardiovascular toxicities of local anesthetics?
at high doses:
-slow conduction in atria and ventricles
-reduced excitability of heart muscle
-> can cause cardiac arrest
-may also depress the strength of cardiac contraction -> arteriolar dialtion (body reacts to low BP and creates less resistance for increased blood flow)
exception: cocain -> which is a stimulant
