08 29 2014 Local Anesthetics Flashcards
Esters
Cocaine Tetracaine Benzocaine Procaine Chlorprocaine
Amides
Lidocaine Mepivacaine Priolocaine Bupivacaine Bupivacaine SR Proivacaine EMLA
Local anesthetic
drug that reversibly blocks impulse conduction – blocks voltage gated sodium channels
what are characteristics of a perfect local anesthetic?
- non-irritating
- transient effect
- low systemic toxicity
- quick onset
- action to span duration of surgery
(lidocaine is close to perfect right now)
Structure Activity Relationship
- aromatic ring (lipophilic group)
- Intermediate chaine
- ester: -COO-CH2-CH2-N
- aminde: - NH-CO-CH2-N
- ionizable group (usually a 3 degree amine)
pH/pKA for local anesthetic
-weak bases
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+
- extracellular – slightly basic
- LA travels through bilayer– and contacts sodium channel and blocks it. - 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
- highly lipophilic
- helps LA diffuse and stay in fatty membrane
- helps with potency and duration
- slower onset of action - High pkA = slows onset of action – more ionized at same pH vs. another anestethic.
- High Protein Binding = duration (not metabolized/excreted quickly)
Epidural
Neuraxial Block
–just short of the Dura
Spinal block
Neuraxial block
- enter subarachnoid space
Caudal block
Neuraxial block
-epidural space in caudal canal
Clinical uses
- Topical
- Infiltrate (local – numb a specific area on surface)
- 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:
- Autonomic Pain – C-fibers
- Sensory
- Motor
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?
plasma pseudocholinesterase
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.
Adverse Effects?
- Systemic toxicity
- Local (neural tissue) toxicity
- Allergic reactions
- 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
- propofol
VERY LIPOPHILIC – takes LA away with it.
