Cocaine

Procaine (ester)

Lidocaine (amide)- intense and longer acting 

Axon 

Must bind to Na Channels inside of the cell 

jump from one node of ranvier to another

Takes 2-3 Nodes for LA to take effect 

Vasoconstriction at low doses

Vasodilation at clinically relevant doses 

The lower the systemic absorption, the higher the safety profile

Dose is direct linear relationships of absorption-not drug concentration or speed of injection 

Highly lipid soluble have prolonged effects because they are stuck in fat 

Metbolized by rapid hydrolysis by psuedocholinesterases

Have PABA metbolites that can cause allergic reaction

Have one i in the name 

Can cause methemoglobinemia

No Baby-Orajel 

Metabolized by CYP450 enzymes in the liver

Have two I in the name 

Prilocaine > lidocaine > Mepivicaine > Ropivicaine > Bupivicaine (rate of metabolism) 

Caused by prilocaine, lidocaine, and benzocaine 

Fe3+ which cannot carry O2

Treatment is methylene blue 1-2mg/kg over 5m in 

Minimum concentration of LA necessary to produce conduction blockade

Cm of motor fibers is 2x that of sensory fibers that why you have differential blockade 

LA are weak bases

Unionized form cross the lipid membrane and then becomes ionized

Ionized form binds to the intracellular sodium channel at the H gate during inactivated-closed state prevent Na+ from going through the channel and causing an action potential 

Directly related to Lipid solubility= more lipid soluble the more potent 

Closely related to protein binding= more lipid soluble the more protein bound and the longer duration of action 

Hydrogen, ion balance

Fiber size, type, and myleination

Vasodilation/Vasoconstrictor properties

Frequency of stimulation of the nerve

pH

Electrolyte concentrations (hypokalemia and hypercalcemia antagonized blockade) 

S enantiomer

Ropivacaine and Levobupivacaine are pure S enantiomers

Most LA are racemic 

Direct relationship to onset of LA

If the pKa of a LA is closer to physiologic pH then it will have a more rapid onset

This is because the ionized portion and unionized portion are in a closer ratio

Lidocaine, mepivacaine, prilocaine, and etidocaine have a pka ~7.6-7.8

Ropivacaine and bupivicaine have a pKa~8.1-8.6 so they have a longer onset 

Chloroprocaine

Has a high pKa and rapid onset

Think it might be due to the high clinical dose we use 

Poorly water soluble

Acidic prepartions

Can alkalinze the solution to make a faster onset- makes more LA available in unionzed form

May cause precipitation 

Weak bases

Aromatic ring- essentential in making the LA lipophilic

Tertiary amine group

Amide or ester connenction 

LA incorporated into liposome

Prolongs duration and decreases toxicity

Slow release formulation

Exparel- liposomal bupivacaine 

Vasoconstrictor

Prolongs LA block by decreasing systemic absorption

5mcg/ml or 1:200,000

Should never be injected into end arteries (ears, nose, penis, fingers) 

Opioids and clonidine 

Work synergistically

Longer, more intense blockade

Clonidine can improve duration of analgesia by 2 hrs

Beware of Ion trapping- fetal pH is usually lower than moms, unionized form crosses placenta but then gets stuck there

Hormonal changes dilate epidural veins so dose should be reduced by 30% reguardless of trimester 

Have reduced plasmaesterase- keep in mind with esters- prolonged block 

3 mg/kg max dose

Highly lipid soluble and potent with longer duration of action

0.25% bupivacaine dose should be equally to how many kg pt is 

Ex. 10 kg pt, 10 ml is max 

4 mg/ kg 

Lidocaine with epi is 7 mg/ kg 

Usually caused by PABA metabolite of esters

Allergy to ester does not mean allergy to amide

Sometimes it's the preservatives (methylparaban) 

Systemic Toxicity 

(LAST)

Most commonly from accidential IV injection during epidural or PNB 

Aspirate before you injection

Usually see signs immediately up to 20 mins

neurotoxic signs before cardiac signs 

Numbness

Tinnitus

Muscle Twitching

Systemic Hypotension

Myocardial depression

Seziures

Unconsciousness 

Apnea

Coma 

Moderate to Severe pain in lower back, buttocks, and posterior thighs

Occurs within 6-36  hr after single shot spinal

Recovery usually within 1-7 days 

Usaully from intrathecal lidocaine- NO LIDOCAINE spinals 

Diffuse injury across the lumbosacral plexus

Have sensory anesthesia, bowel and bladder dysfunction, and paraplegia

Usually lidocaine- no lidocaine spinals 

Lower extremity paresis with variable sensory deficit thats diagnosed as neural blockade resolves

Possibly from thrombosis or spasm of the anterior spinal artery

Precipitous hypotension, cardiac dysrhythmias, AV heart block

Resuscitation resistant- need fat emulsion (Intralipid)

LA does not have enough time to dissociate during diastole 

May be precipitated by beta blockers, dig, calcium channel blockers 

20 % lipid emulsion

1.5 mL/kg over 3 mins

IV infusion of 15 mL/kg/hr 

Topical

Local Infiltration

Aerolized for Fiberoptic Intubation

Peripheral Nerve Blocks

IV regional (Bier Block)

Spinal

Epidural 

Diffuse from the outer surface toward the center

Therfore fibers that are more proximal becomes anesthetized first then distal

Extremity isolated from rest of the systemic circulation by tourniquet

Duration determined by how long tourniquet is inflated 

NO BUPIVACAINE 

Subcutaneous infiltration of large volumes of solution with diluted lidocaine

Provides local anesthesia, bloodless aspirates, and postop analgesia

Slow release of Lidocaine into the circulation that peaks in 12-24 hours

High risk of mortality 

Usually genetic

Will have a dibucaine # < 20

This means that if you give them Succinylcholine they will have apean and paraylsis lasting 2 hours or longer 

70 is normal

40-70 will have a mimimally prolonged effect

<20 will have apnea and paralysis for 2 hours or longer 

Liver Disease

Renal Disease

Malnutrition

Pregnancy 

Malignancy

Burns

Cardiopulmonary Bypass 

(pseudocholinesterase are synthesized in the liver) 

Can cause methemoglobinemia

NO FDA warning on labels

Look for signs of hypoxia

Do not give to children under 2 years