Local Anesthetics

Question 1

Properties of Ideal local anesthetics

Answer 1

1) Short onset, long duration of action
2) Minimal absorption/distribution
3) Act predictably and reversibly without causing tissue damage
4) Large safety margin

Question 2

Aromatic Ring determines ______

Answer 2

lipophilicity, potency

Question 3

Aromatic Ring duration of action is influenced by

Answer 3

protein binding (high affinity for protein binding increase duration of action). Also decreases availability of free drug in blood to reduce potential for toxicity

Question 4

Intermediate linkage determines____

Answer 4

class of drug (amino ester or amino amide). this determines route of metabolism, toxic potential, potential for allergic reaction

Question 5

Esters are metabolized by _____ and have longer or shorter half lives compared to amino amides.

How are they excreted?

Answer 5

1) plasma esterases (plasma cholinesterase)
2) shorter half life

Water soluble metabolites excreted in urine

Question 6

What part of esters causes allergic reactions in some people?

Answer 6

esters are derivatives of PABA

Question 7

Amides are metabolized in ____. What would decrease metabolism/increase toxicity?

How are metabolites cleared?

Answer 7

1) liver
2) decreased hepatic function (cirrhosis) or hepatic blood flow (congestive heart failure)
3) renal clearance

Question 8

cocaine, procaine, benzocaine and tetracaine are all ____

Answer 8

esters (contain only ONE “i”)

Question 9

lidocaine, mepivicaine, bupivicaine, prilocaine, ropivicaine, dibucaine are all ___

Answer 9

amides (all contain at least TWO “i’s”)

Question 10

Terminal amine (hydrophilic portion) correlates with ____ and is determined by ____ and ____.

Answer 10

1) onset of action
2) pKa of local anesthetic
3) pH of local environment

Question 11

Which form of the terminal amine is able to diffuse through cell membrane and which form of the terminal amine is actually active once in the cell?

Answer 11

1) diffuse through membrane = unionized form

2) active in cell = ionized form

Question 12

The higher the pKa of the local anesthetic the (higher or lower?) the concentration of unionized (diffusable) drug at physiologic pH, the (faster or slower?) the onset

Answer 12

1) LOWER

2) SLOWER

Question 13

Acidic pH of local environment (ex: abscess) favors which form of drug? Is onset faster or prolonged?

Answer 13

Shifts equation to the LEFT, ionized form favored, less able to cross membrane, slower onset of block

Question 14

Basic pH of local environment (ex: c-section) favors which form of drug? Is onset faster or prolonged?

Answer 14

Shifts equation to the RIGHT, unionized form favored, more able to cross membrane, faster onset.

Question 15

Mechanism of action of local anesthetics

Answer 15

ionized form of drug (the active form) blocks the intracellular portion of the inactivated voltage gated sodium channel to slow recovery and prevent propagation of action

Question 16

Onset of block depends on what 3 things?

Answer 16

1) size of nerve fiber (small diameter–>penetrates faster)
2) degree of myelination (myelinated nerve only needs to be blocked at nodes of ranvier so blocked more quickly)
3) firing frequency (faster firing–>more inactive channels available)

Question 17

How are nerve fascicles blocked?

Answer 17

From outside in (proximal to distal progression) ie elbows to fingers

Question 18

Order of neuron types blocked first to last

Answer 18

B>C>A delta>A gamma>A beta>A alpha

Question 19

Order of systems blockaded from first to last

Answer 19

sympathetic tone, temperature, pain, light touch, motor

Question 20

Absorption is determined by what 3 factors?

Answer 20

1) site of injection (highly vascular–>fast absorption)
2) presence of vasoconstrictors (epinephrine for ex) will decrease absorption–>inc neuronal uptake–>prolong duration of action–>limit toxic side effects (works best with short acting drugs)
3) local anesthetic agent (highly tissue bound–> more slowly absorbed)

Question 21

Distribution of a drug determined by what 2 factors?

Answer 21

1) tissue perfusion (highly perfused organs get initial uptake, like brain/lung/liver/heart)
2) tissue/blood partition coefficient (strong plasma protein binding retains anesthetic in blood while high lipid solubility facilities tissue uptake)

Question 22

What are the 3 types of systemic toxicity experienced with anesthetic drugs?

Answer 22

1) CNS toxicity
2) Cardiovascular toxicity
3) methemoglobinemia

Question 23

What are the signs of early CNS toxicity?

Answer 23

CNS excitation (excitatory neurons function unopposed) causing decreased inhibition (talkativeness), sensory disturbances (perioral numbness, metallic taste in mouth), restlessness, tremor, tinnitus

Question 24

What are signs of late CNS toxicity and how do you tx?

Answer 24

CNS depression ((lethargy, hypotension, bradycardia, decreased respiratory rate, seizures). Tx by protecting airway, stoping seizure activity with benzodiazepines

Question 25

What are signs of cardiovascular toxicity and how do you tx?

Answer 25

reduction in cardiac conductivity, excitability, contractility (Na/K+block), indirect vasodilation and bradycardia, arrhythmias, hypotension, QRS widening (early sign). Tx with ACLS, Intralipid

Question 26

What is the tx for Methemoglobinemia?

Answer 26

methylene blue

Question 27

What are 2 types of local toxicity experienced with anesthetics?

Answer 27

1) transient neurologic symptoms (often worse than surgical pain; linked to Lidocaine; doesn’t include sensory loss, motor weakness or loss of bladder/bowel); lidocaine fallen out of favor as spinal anesthetic
2) neuronal injury (most feared complication, mechanism poorly understood)

Question 28

True allergy to local anesthetics is rare (apart from PABA). What is actually happening w/patients who claim they are allergic to local anesthetics?

Answer 28

Psychogenically mediated vagal response (syncope, bradycardia, hypotension) or direct effects from epinephrine additive (tachycardia, palpitations)