Pcol Finals - Local Anesthetics

What is the common mechanism of action of the local anesthetics when in their usual dose?

a. Inhibition of ligand-gated Na+ channel

b. Inhibition of voltage-gated Na+ channel

c. Stimulate K+ efflux

d. Stimulate Ca2+ efflux e. Inhibition of Na+/K+ ATPase

b. Inhibition of voltage-gated Na+ channel

Loss of sensation at a specific region of the body

Local Anesthetic

Administered near or directly to the target site

Local Anesthetic

TYPES OF LOCAL ANESTHETICS:

○ Shorter duration of action due to hydrolytic action of plasma esterases

ESTERS

TYPES OF LOCAL ANESTHETICS:

○ Have one “I” in their name

ESTERS

TYPES OF LOCAL ANESTHETICS:

○ E.g., Tetracaine

ESTERS

TYPES OF LOCAL ANESTHETICS:

Carboxylic acid + alcohol – prone to hydrolysis hence shorter duration

ESTERS

TYPES OF LOCAL ANESTHETICS:

○ Longer duration of action (metabolized by hepatic amidases); mainly metabolized in the liver

AMIDES

TYPES OF LOCAL ANESTHETICS:

○ Have two “I” in their name

AMIDES

TYPES OF LOCAL ANESTHETICS:

○ E.g., Lidocaine

AMIDES

MOA:

● Blocks the voltage gated/ voltage-dependent _____ → influx of_____ is reduced/inhibited → depolarization is prevented → block the conduction of action potential

sodium channels (Na+ channels); sodium

○ 1st drug discovered to produce numbness

COCAINE

○ D/A: Abuse potential and CNS/CV toxicity

COCAINE

○ MOA: Prevents the termination of action of catecholamines; inhibits reuptake of cat

COCAINE

Lipophilic ester of benzoic acid

BENZOCAINE

D/A: Methemoglobinemia(systemic route)

BENZOCAINE

○ 1st injectable anesthetic

PROCAINE

○ D/A: Short acting

PROCAINE

○ Allergic reaction

PROCAINE

○ Longer duration of action but limited spinal anesthesia

TETRACAINE

○ 1st amide anesthetic with less toxicity and longer duration of action

LIDOCAINE

■ When given as a spinal anesthetic → most neurotoxic

LIDOCAINE

What drug is co-administered with lidocaine? The reason is it increases the half life and decrease the systemic absorption of lidocaine.

epinephrine

Fiber type A Diameter size, Myelination, Order of block

Largest,Heavy, Last

Fiber type A function: Proprioception, Motor

Fiber type A (Alpha)

Fiber type A function: Pressure, Touch

Fiber type A (Beta)

Fiber type A function: Muscle spindles

Fiber type A (Gamma)

Fiber type A function: Pain & Temperature

Fiber type A (Delta)

Fiber type function: Preganglionic

Fiber type B

Fiber type function: PAIN Postganglionic

Fiber type C

Fiber type C Diameter size, Myelination, Order of block

Smallest, None ,First

Local Anesthetic route of administration

Topical

ROUTE OF ADMINISTRATION

● TOPICAL

○ Vicinity of n____, m_____, r_____

nerve endings, major nerve trunks, region of spinal cord

Local anesthetic TOXICITY:

○ Light-headedness or sedation

○ Restlessness

○ Nystagmus

○ Tonic-clonic seizures → Coma → Respiratory and cardiovascular depression

CNS

Local anesthetic TOXICITY in the CNS

○ Light-headedness or sedation

○ Restlessness

○ Nystagmus

○ Tonic-clonic seizures → Coma → Respiratory and cardiovascular depression

Local anesthetic TOXICITY:

○ Vasoconstrictor (Cocaine) → Severe hypertension with cerebral hemorrhage (drug of abuse)

○ Severe cardiotoxicity (Bupivacaine)

CVS

Local anesthetic TOXICITY in the CVS

○ Vasoconstrictor (Cocaine) → Severe hypertension with cerebral hemorrhage (drug of abuse)

○ Severe cardiotoxicity (Bupivacaine)

What local anesthetic is a vasoconstrictor in the CVS

Cocaine

Effect of cocaine as a vasoconstrictor in the CVS

Severe hypertension with cerebral hemorrhage (drug of abuse)

What local anesthetic causes severe cardiotoxicity

Bupivacaine

What local anesthetic causes Methemoglobinemia

Prilocaine (metabolizes to → o-toluidine)

What does Prilocaine,a local anesthetic, cause

Methemoglobinemia (when metabolized to o-toluidine )

What does Procaine,a local anesthetic, cause

Allergic reaction

What local anesthetic causes allergic reaction

Procaine

What common local aneshetic Has a thiophene ring instead of benzene ring → more lipid soluble

ARTICAINE

What common local aneshetic is Less associated with neurotoxicity

CHLOROPROCAINE

What common local aneshetic is for Topical use on ENT; Controlled substance

COCAINE

What common local aneshetic is a Reference standard; may cause neurotoxicity

LIDOCAINE

What common local aneshetic is Metabolized to ortho- toluidine

PRILOCAINE

Examples of Amide Local Anesthetics

• Articaine

• Bupivacaine

• Levobupivacaine

• Lidocaine

• Mepivacaine

• Prilocaine

• Ropivacaine

Examples of Ester Local Anesthetics

• Benzocaine

• Cocaine

• Procaine

• Tetracaine