Local Anesthetics

Question 1

Local Anesthetics

Overview

Answer 1

Used for relief of pain in specific regions or areas of the body

Often in order to perform a particular procedure

Question 2

Structure & Metabolism

Answer 2

• Divided into amides and esters
• All local anesthetics have an aromatic group at one end (benzyl derivative)
• With one exception (benzocaine), an amine at the other end
• All weak bases
• Strong lipophilic character

Question 3

Amides

Answer 3

• Amides contain two “i’s” as in lidocaine
• Inactivated in the liver by cytochrome p450 system
• Action will be prolonged in pts w/ ↓ liver function

Question 4

Esters

Answer 4

• Esters contain only one “i” as in tetracaine
• Inactivated mainly by the plasma cholinesterease
• More rapidly inactivated than the amides

Question 5

Epinephrine Effects

Answer 5

For some local anesthetics:

• Co-administration of epinephrine ⇒ vasoconstriction
• Prevents local anesthetic from diffusing away from site of injection
• ⊕ of α₂ adrenergic receptors may also have an analgesic effect
• Epinephrine should not be used in an area that lacks collateral blood flow
  
  • Digits, nose, ears, and penis

Question 6

Lipophilic Anesthetics

Answer 6

Anesthetics that are more lipid soluble:

• More potent
• Longer duration of action
• Take longer to achieve the clinical effect
• Extensive protein binding also ↑ duration of action

Question 7

General

Mechanism of Action

Answer 7

• Un-ionized (neutral) form enters nerve
  
  • Onset of action strongly dependent upon local pH
    
    • Alkaline ⇒ fast
    • Acidic ⇒ slow
  • Bicarbonate could be used as an adjuvant to ↑ onset of action
  • Infections which lower the pH can slow the onset of action
• Gains a proton ⇒ ionized (charged) form
• Ionized form of weak base blocks Na⁺ channels by binding to an internal sequence
  
  • High affinity binding to the inactivated state
  • Depends on Na⁺ channel activity ⇒ use-dependent (frequency-dependent)
  • Very important for antiarrhythmic activity of some local anesthetics

Question 8

Fiber Types

Answer 8

• Small, high frequency fibers more susceptible to local anesthetic block than are larger fibers
  
  • Ex. type C fibers that carry nociceptive signals (pain)
• In fibers of equal size, myelinated are more susceptible than unmyelinated fibers
• Nerves of small diameter and very active (high frequency impulses) will be preferentially blocked
  
  • Ex. pain fibers carrying signals from damaged tissue

Question 9

Fiber Location

Answer 9

Effect partially dependent on position of fibers in nerve bundle:

• In the extremities:
  
  • Nerves innervating proximal sites are on outside
  • Nerves innervating distal sites are on the inside
  • Larger motor fibers are on the outside
  • Smaller sensory fibers are on the inside
• Medial site admin (eg “spinal” block) ⇒ block may proceed from proximal to distal
• Direct injection @ site of pain ⇒ knock out signals mediated by nerve endings right there, bringing immediate relief

Question 10

Order of Anesthesia

Answer 10

The loss of sensation occurs in the following order:

Pain

Temperature

Touch

Movement

Question 11

Local Anesthetics

Uses

Answer 11

• Topical (Surface) ⇒ skin and mucosa
• Infiltration (infl) ⇒ direct injection (eg knee)
• Peripheral Nerve Block (PNB) ⇒ injected close to nerve trunks (eg Brachial)
• Spinal ⇒ injection into subarachnoid space near spinal cord
• Epidural ⇒ injection just above dura surrounding spinal cord, near spinal nerve roots
• Systemic ⇒ may be used for postoperative pain and chronic pain

Question 12

Adverse Effects

Answer 12

• Major side effects result from escape of the drugs into the circulation
• Distribution into the circulation occurs w/ most applications (except topical)
• Risk of adverse effects is dose- and age-dependent
• Effects are system specific

Question 13

CNS Effects

Answer 13

• Low doses:
  
  • Tremors
  • Oral numbness
  • Dizziness
  • Confusion
  • Agitation
• High doses:
  
  • Muscle twitching
  • Convulsions
  • CNS depression & respiratory arrest

Question 14

Cardiovascular Effects

Answer 14

• Vasodilation (exception = cocaine)
• Myocardial depression (less often)
  
  • Possibly leading to ↓ CO
• Ventricular arrhythmias and cardiac arrest (Rare)
  
  • W/ unintentional high plasma levels of local anesthetics
  • Can occur w/ normal IV doses of bupivacaine

Question 15

Hypersensitivity Reactions

Answer 15

Local dermatitis w/ some topicals

Rare systemic allergic response w/ injected esters

(due to p-aminobenzoic acid metabolite)

Question 16

Drug Interactions

Answer 16

• Local anesthetic blockade ⇒ loss of visceral and skeletal muscle tone
  
  • Potentiate effect of neuromuscular blocking drugs
  • Use w/ caution in myasthenia gravis pts
• Drug that ↓ hepatic blood flow (such inhaled anesthetics) will ↓ the elimination of amide anesthetics

Question 17

Lidocaine

Answer 17

• Potency:
  
  • Intermediate
• Duration:
  
  • Short (0.75-2 hrs)
• Uses:
  
  • All uses including topical
• Adverse effects:
  
  • Cardiac and respiratory arrest, arrhythmias, decreased cardiac contractility, hypotension
  • Seizure, tinnitus, dizziness, paresthesia, tremor, somnolence
  • Skin irritation, constipation
• Comments:
  
  • Used with epinephrine
  • Used for neuropathic pain

Question 18

Prilocaine

Answer 18

• Potency:
  
  • Intermediate
• Duration:
  
  • Short (0.5 -1 hrs)
• Uses:
  
  • Infiltration
  • Topical
  • Combined with lidocaine (EMLA)
• Adverse effects:
  
  • Same as lidocaine, but methemoglobinemia due to o-toluidine
• Comments:
  
  • Does not require coadministration of epinephrine because it has vasoconstrictive properties

Question 19

Mepivicaine

Answer 19

• Potency:
  
  • Intermediate (slightly greater than lidocaine)
• Duration:
  
  • Short (1-2 hrs)
• Uses:
  
  • All uses
• Adverse effects:
  
  • Same as lidocaine
• Comments:
  
  • Less vasodilation than lidocaine, so does not require epinephrine
  • Unsuitable for prolonged epidural infusion because of accumulation in fetus

Question 20

Bupivacaine

Answer 20

• Potency:
  
  • High
• Duration:
  
  • Long (1.5 – 8 hrs)
• Uses:
  
  • All uses
• Adverse effects:
  
  • Same as lidocaine but greater cardiotoxicity especially at high doses
• Comments:
  
  • Epinephrine adds little to duration
  • Lower concentration used in obstetrics are less toxic and provide pain relief w/o motor block
  • Postoperative pain / Pain of surgical incision

Question 21

Ropivacaine

Answer 21

• Potency:
  
  • High
• Duration:
  
  • Long (1.5 -8 hrs)
• Uses:
  
  • All uses
• Adverse effects:
  
  • Less cardiotoxic than bupivicaine
• Comments:
  
  • Alternative to bupivicaine

Question 22

Amide Drugs

Answer 22

Question 23

Cocaine

Answer 23

• Potency:
  
  • Low
• Duration:
  
  • 0.5 – 1 hr
• Uses:
  
  • Topical
• Adverse effects:
  
  • Could accelerate coronary atherosclerosis, tachycardia
  • Seizure, CNS depression or excitation, anxiety
• Comments:
  
  • Still popular due to vasoconstrictive properties
  • Used primarily in the eye and as part of a combination with tetracaine and epinephrine

Question 24

Tetracaine

Answer 24

• Potency:
  
  • Low
• Duration:
  
  • 1.5 – 6 hrs
• Uses:
  
  • Spinal, topical
• Adverse effects:
  
  • Cardiac or respiratory arrest and hypotension
  • CNS depression or excitation
• Comments:
  
  • Slow onset due to high pKa

Question 25

Procaine

Answer 25

• Potency:
  
  • Low
• Duration:
  
  • 0.5 – 1 hrs
• Uses:
  
  • Infl., (dental procedures)
• Adverse effects:
  
  • Same as tetracaine
• Comments:
  
  • A short acting analogue 2-chloroprocaine is used in obstetrics

Question 26

Benzocaine

Answer 26

• Potency:
  
  • Low
• Duration:
  
  • 0.5 -1 hr
• Uses:
  
  • Topical
• Adverse effects:
  
  • Methemoglobinemia
• Comments:
  
  • Used on mucous membranes

Question 27

Ester Drugs

Answer 27