Local Anesthesia

Question 1

Actions of Local Anesthesia

Answer 1

1. Block nerve conduction of sensory impulses from the periphery of the CNS
2. Abolish sensation (Motor in high conc.) in a limited area w/o producing unconsciousness

Question 2

Components of Local Anesthesia

Answer 2

1. Lipophilic group - Aromatic ring
2. Intermediate chain - Ester or Amide
3. Ionizable group - Tertiary amine

Question 3

Duration of action due to intermediate groups

Answer 3

Ester have a shorter duration of action

- more prone to hydrolysis than amide links

Question 4

pK values of Local anesthetics

Answer 4

Weak bases w/ pK values around 8-9 = Faster onset

- larger fraction in body is in cationic form

Question 5

Different form of Local anesthetics

Answer 5

1. Cationic form - Most active at receptor site

2. Uncharged form - Important for penetration of biologic membranes

Question 6

MOA of Local Anesthetics

Answer 6

• Block voltage-gated Na channels
• Binds to receptors near the intracellular end of the channel –> Blocks channel
• Abolish Action potential when enough is applied to nerve fiber

Question 7

Liposolubility, Potency, Duration of action, pKa & Onset of action

Answer 7

Liposolubility correlates w/ Potency & Duration of onset
- Inc liposolubility = Inc Potency, DOA and toxicity

pKa correlated w/ Speed of Onset of action
- Closer pKa to body pH = Faster onset

Question 8

Prolongation of Action by Vasoconstriction

Answer 8

Vasoconstriction –> Dec blood flow –> Dec systemic absorption –> Keep drug @ nerve –> Inc neuronal uptake –> Prolongs action & Dec systemic toxic effects

• Epinephrine

Question 9

Prolongation of Action by vasoconstriction in Spinal Anesthesia

Answer 9

Epi acts on A2-adrenoceptors –> Inhibits Substance-P release –> Dec pain

vasoconstriction may have AEs:
- Delayed wound healing, tissue edema & necrosis

Question 10

Vasoconstriction by Cocaine

Answer 10

Cocaine constricts Blood vessels by potentiating action of NE; preventing it’s own absorption

Question 11

Metabolism of Local Anesthetics

Answer 11

Ester-linked –> Metabolized by tissue & plasma esterase (pseudo-cholinesterase) –> Shorter DOA

Amide-linked –> Metabolized by Liver microsomal Cytochrome P450 –> Longer DOA

Question 12

Classification of Local Anesthetics by Duration of action

Answer 12

Short- acting

• Procaine
• Chloroprocaine

Intermediate- acting

• Lidocaine
• Mepivacaine
• Prilocaine

Long-acting

• Tetracaine
• Bupivacaine
• Etidocaine
• Ropivacaine

Question 13

CNS Toxicity of Local Anesthetics

Answer 13

CNS stimulation followed by CNS depression
Stimulation – Restlessness, tremor –> Clonic convulsions (high blood levels)

Depression – Resp. failure –>Death

Benzo is used as premedication to provide prophylaxis against seizures

Question 14

Why is Benzodiazepine used when large doses of Local anesthetics?

Answer 14

• Local anesthetics can cause clonic seizures; Benzos are given as prophylaxis against seizures.

Question 15

PNS Toxicity of Local Anesthetics

Answer 15

Toxic to nerve tissue @ excessively high concentrations

Question 16

CVS Toxicity of Local Anesthesia

Answer 16

1. Block Na channels –> Dec cardiac pacemaker activity, excitability & conduction
2. Dec strength of Cardiac contraction –> Arteriolar dilation –> Hypotension

BUPIVACAINE is most cardiotoxic local anesthetic
NOT COCAINE

Question 17

Most Cardiotoxic local anesthesia

Answer 17

Bupivacaine

Question 18

CVS effects of Cocaine

Answer 18

• Vasoconstriction
• HTN
• Cardiac arrhythmias

Question 19

Blood Toxicity of Local Anesthetics

Answer 19

Prilocaine (large doses) –> Accumulation of metabolite o-toluidine (oxidizing agent) –> Converts Hemoglobin to Methemoglobin

Question 20

Allergic reactions of Local anesthetics

Answer 20

Ester-linked anesthetics are metabolized to P-aminobenzoic acid derivatives which cause allergic reaction in a small percentage of population

Amine-linked allergies are rare bc they are not metabolized to P-aminobenzoic acid

Question 21

Drug interactions of Local Anesthesia

Answer 21

Procaine (hydrolysis) –> Para-aminobenzoic acid (PABA)

PABA inhibits the action of Sulfonamides

Question 22

How to differentiate between Ester & Amide anesthetics by name?

Answer 22

Esters have 1 “i”

Amides have 2 “i”