Flashcards in 08 29 2014 Local Anesthetics Deck (41):
drug that reversibly blocks impulse conduction -- blocks voltage gated sodium channels
what are characteristics of a perfect local anesthetic?
-low systemic toxicity
-action to span duration of surgery
(lidocaine is close to perfect right now)
Structure Activity Relationship
-aromatic ring (lipophilic group)
- aminde: - NH-CO-CH2-N
-ionizable group (usually a 3 degree amine)
pH/pKA for local anesthetic
log (BH+)/(B)= pka-pH
-more acidic the pH = increase in BH+
-more basic pH = more B
Neural form required to diffuse to side of activation, but charged form is required for activity.
NOTE: infection decreases pH (more acidic)
-can't inject local anesthetic into an inflamed area.
Path of Anesthetic to receptor sites
LA + H+ = LAH+
1. extracellular -- slightly basic
-LA travels through bilayer-- and contacts sodium channel and blocks it.
2. Intracellular -- slightly more acidic
- once LA enters the cell, there is a shift in charge = LAH+
- trapped here
Mechanism of Action of Local anesthestics
Modulated Receptor Hypothesis: LA binding changes conformational state of the channel.
Affinity for activated and inactivated states vs. resting state.
* fibers that fire at a faster rate are more susceptible to the effects of local anesthetics
1. neutral form enters membrane, binding site is on the cytoplasmic face of channel.
2. Charged LA required for binding to channel site.
Frequency dependent block
repeated depolarizatioins produce more effective anesthetic binding--- after rate are more susceptible to effects of local anesthetics
Important properties of local anesthestics
1. highly lipophilic
- helps LA diffuse and stay in fatty membrane
- helps with potency and duration
- slower onset of action
2. High pkA = slows onset of action -- more ionized at same pH vs. another anestethic.
3. High Protein Binding = duration (not metabolized/excreted quickly)
--just short of the Dura
- enter subarachnoid space
-epidural space in caudal canal
2. Infiltrate (local -- numb a specific area on surface)
3. Regional Anesthesias and Analgesia
A. - Peripheral blocks
-plexus anesthesis -- single injection or continuous infusion.
- Individual nerve block (ex femoral)
- IV regional (Bier Block)-- Turnicate and hurts A LOT!!!
B. -Neuraxial Blocks
-spinal (low volume), epidural/caudal (high volume)
Incremental increase in the concentration of LA administered during a Neuraxial Block can cause a loss of what nerves and in which order:
1. Autonomic Pain -- C-fibers
Effect of a Peripheral block (what goes first? and what follows).
motor block occurs before proximal sensory loss (which occurs before distal sensory loss).
Last thing ppl lose is sensation in fingers
Why do they use vasoconstrictors with local anesthetic?
-decreases absorption irrespective of the site of injection
-increases tissue binding for duration of action of long acting drugs
(increase time that locals are at site of action)
BEWARE OF HITTING A VESSEL WITH epinephrine/ Phenylephrine.
- use a low does to test if epinephrine is injected intravascularly -- in 2 min the heart starts beating like crazy!
Elimination of Esters?
Metabolite produced: PABA and derivatives
-PABA is allergenic
-Enzyme deficiency may lead to potentiation of action
Elimination of Amides
Liver CYP450, water soluble metabolites -- urinary excretion.
-low blood flow to liver (portal hypertension, CHF) decrease delivery of LA's to liver-- decreasing amide LA metabolism and increasing halftime and serum concentration.
1. Systemic toxicity
2. Local (neural tissue) toxicity
3. Allergic reactions
4. Methemoglobin formation
How does systemic toxicity occurs when using LAs?
LA acting on other excitatory tissue vs. target nerves.
Range of effects is proportional to LA concentration.
Manifest first as CNS toxicity and then cardiotoxicity
Presentation of CNS toxicity from LAs?
tinnitus, perioral numbness, blurred vision, metallic taste, change in mental status, convulsions.
Presentationm of Cardiotoxicity from LAs?
And drugs that are cardiotoxic?
Depression of excitability and conduction (prolonged QRS)
Arteriolar dilation (Ca channel effect)
Systemic acidosis --> increases sensitivity to LA toxicity (remember pH/pka formula)
Pregnancy increases sensitivity to toxic effects
DRUGS that are cardiotoxic:
Bupivacaine ( amide) is very cardiotoxic (R+)
Ropivacaine less toxic (L+)
How can you try to rescue system from cardiotoxicity form an LA?
IV Lipid Emulsion
VERY LIPOPHILIC -- takes LA away with it.
What happens during local (neural tissue) toxicity from using LAs?
1. Neural injury:
High concentrations for extended period of time can lead to nervous tissue destruction -- membrane damage, cytoskeleton disruption
Motor and sensory loss are seen (Ex. caudal equine syndrome)
Paralysis and paresis may result
2. Transient Neurologic Symptoms (TNS)
associated with spinally administered Lidocaine and certain surgical positions (lithotomy).
associated with pain or sensory abnormalities in the lower back, buttock, or lower extremities. The symptoms of burning pain and dysethesthia in the L5 and S1 dermatomes usually start after the effects of spinal anesthesia have concluded and may last up to hours to four days
NOT ASSOCIATED WITH MOTOR OR SENSORY LOSS
A self-limited neuropathic pain syndrome
Why does Methemoglobinemia occur?
-Drugs that can cause it?
- Plus-oximeter reading?
-Prilocaine metabolites: O-toluidine act as an oxidizing agent to convert Hb 2+ --> Hb 3+
Benzocain can do this too
Causes chocolate colored blood.
Plus oximeter = 85% saturation
Treatment: methylene blue (reducing agent)
Allergic reactions with Esters
PABA --> Hapten Formation --> True IG3 Mediated Allergy
Allergic reactions with Amides
Allergic reactions are rare.
preservative that can cause allergic reactions regardless of LA type
Cocaine (quick facts)
primarily topical, MetHb potential
potent ester --> spinal anesthesia
toxic at relatively low doses (except for short acting ester rule)
TNS implication (rarely used)
short duration LA
-used to have a bad rep
quick onset, moderate duration and toxicity, TNS explication
*DONT USE ON SPINE!*
-longer duration than lidocaine
-lowest pKa of injectable La's
-Acts as a vasoconstrictor
-Associated with methemoglobinemia
-component of EMLA
long duration La with devastating potential for cardiac toxicity
Sensory block > motor block
liposomally encapsulated for delivery up to 72hrs/dose.
Use mostly for spinals because you only need to inject a few ccs.
-long duration with properties similar to bupivacaine but with less cardiotoxicity