local anesthetics

Question 1

properties of ideal local anasthetic

Answer 1

1. short onset, long duration of action
2. minimal absorption and distribution
3. act predictably and reversibly
4. posses large margin of safety

Question 2

aromatic ring

Answer 2

• lipophilic portion
• determes potency and duration of action
• high affinity for protein remain bound to nerve membrane longer —> longer duration of action

Question 3

intermediate linkage

Answer 3

• determine classification
• ester or amide

Question 4

ester linkage

Answer 4

• metabolized by plasma esterases
• short half-life (rapid hydrolysis)
• allx rxns (derivatives of PABA)
• cocaine, procaine, benzocaine, tetracaine

Question 5

amide linkage

Answer 5

• metabolized by hepatic amidases
• decreases in hepatic function (ie: cirrhosis) or hepatic BF (ie CHF) reduce metabolism –> potential toxicity
• 2 or more “i’s” in name
• lidocaine, mepivicaine, bupivicaine, prilocaine, ropivicaine, dibucaine

Question 6

terminal amine

Answer 6

• hydrophilic portion
• determines onset of action
• depends on pka and tissue pH
• the higher the pKa the higher the concentration of the ionized drug = slower onset (less able to diffuse across membrane)
• acidic environment (ie: abscess, inflammation) favors ionized form –> slower onset (usually have to use generalized anesthesia)
• alkalinization of local anesthetic favors the neutral(diffusable) form –> faster onset
• mix with sodium bicarb

Question 7

mech of action

Answer 7

• unionized form crosses lipid membrane
• once inside, the ionized form is the active form
• binds the intracellular portion of the inactive Na channel –> slows repolarization and prevents further propagation of APs

Question 8

onset of blockade depends on…

Answer 8

1. size of nerve fiber (smaller diameter is penetrated more quickly)
2. degree of myelination (myelinated nerve blocked more quickly- only needs to only be blocked at nodes)
3. firing frequency (the more often a nerve fires the more opportunity there is to bind the inactive sodium channel)
4. fibers blocked from outside-in –> proximal to distal progression

Question 9

order of blockade

Answer 9

sympa tone > temp > pain > light touch > motor

*hypotension is often 1st sign that blockade is working

*pain blocked before pressure

Question 10

vasoconstrictors (pharacokinetics)

Answer 10

• epi often added to decrease absorption, increase neuronal uptake, prolong duration of action, limit toxic side effects, allows for higher dosage

Question 11

systemic toxicity

Answer 11

• **CNS toxcity: **excitiation initially (talkativeness, muscle twitches, sensory disturbances) then depression (hypotension, bradycardia, seizure, coma, respiratory arrest)
• cardiovascular toxicity: at higher concentrations LAs block active/open Na channels –> reduced cardiac excitiability, contractility, conductivity, cardiac arrest

Question 12

local toxicity

Answer 12

• transient neurologic symptoms: linked to use of lidocaine for spinal anesthesia
• neuronal injury (very rare)

Question 13

topical anesthetic

Answer 13

• direct application to eye, mouth, nose, trachea, GU tract
• rapidly absorved from mucus membrane

Question 14

infiltration

Answer 14

• injection direcly into tissue
• used as pre-emptive analgesia before surgical incision

Question 15

regional

Answer 15

• injection around specific nerves/plexuses

Question 16

spinal vs epidural

Answer 16

• spinal: under dura, less anestheti, faster onset
• epidural: above dura, bigger dose, slow controlled onset