A5. Local anasthetic

Question 1

Local anesthesia

Mode of Action

Answer 1

• *Inhibition of voltage-dependent Na+-channels** (higher affinity to the inactivated receptor state) → reduced influx of Na+ ions → membrane depolarization is prevented → conduction of action potential is blocked.
• Elevated extracellular Ca2+ → partially antagonizes the action of local anesthetics (membrane hyperpolarization favours resting receptor state)
• Elevated extracellular K+ → enhanced effect of local anesthetics (membrane depolarization favours the inactivated receptor state – higher affinity)

Question 2

Relationship and importance of ionized and non-ionized states

Answer 2

Both the non-ionized and the ionized forms of the drug play important roles:
- Non-ionized form → crosses axonal membrane
- Ionized form → blocks the inactivated Na+ channel (from within the cell)
*Local tissue infection → more acidic environment

**Potential administration of local anesthetics with NaHCO3 to enhance uptake

Question 3

Local Anesthetics : 3 amides

Answer 3

Lidocain(A5, B16) -Short acting

Articaine(A5) -Short acting

Bupivacaine (A5) -long acting

Question 4

Lidocain(A5, B16)

Answer 4

-Short-acting drugs

• Topical use or injection (perineural, epidural, subarachnoid); rarely used IV- -Hepatic metabolism via CYP450
• Duration of action 1-2 h’, with epinephrine 2-4 h’- Short-duration, local surgical procedures (dental, ophthalmology, throat, urology, obstetrics)
• Post-operative analgesia- Produce autonomic blockade in ischemic conditions

- Side effects:

1. CNS effect : Dizzness, Vomiting, Anxiety, Nystagmus, Depression, Coma, Death

2. Cardiovascular effect : (-)Chronotropic effect, AV block, Cardiac arrest. Vasodilation

Question 5

Articaine(A5)

Answer 5

-Rapid acting Drug

• local surgical procedures (dental, ophthalmology, throat, urology, obstetrics)
• Post-operative analgesia- Produce autonomic blockade in ischemic conditions
• Side effects:

1. CNS effect : Dizzness, Vomiting, Anxiety, Nystagmus, Depression, Coma, Death

2. Cardiovascular effect : (-)Chronotropic effect, AV block, Cardiac arrest. Vasodilation

Question 6

Bupivacaine (A5)

Answer 6

-Long acting drug

- Parenteral (usually not topical or IV)

• Hepatic metabolism via CYP450- Duration of action 3-6 h’- Longer-duration, local surgical procedures

- Side effects:

1. CNS effect : Dizzness, Vomiting, Anxiety, Nystagmus, Depression, Coma, Death

2. Cardiovascular effect : (-)Chronotropic effect, AV block, Cardiac arrest. Vasodilation

Question 7

Local Anesthetics : 3 Esters (1 in the list)

Answer 7

Procaine(not in the list) -Short acting

Tetracaine(not in the list) -Long acting

Cocaine(A5) -Surface acting

Question 8

Procaine(not in the list)

Answer 8

-Short acting drug

- Parenteral (usually not topical or IV)

- Metabolism by plasma cholinesterase (pseudocholinesterase)

• Duration of action 30-60 min’, with epinephrine 60-90 min’- Short-duration, local surgical procedures

- Side effects:

1. CNS effect : Dizzness, Vomiting, Anxiety, Nystagmus, Depression, Coma, Death

2. Cardiovascular effect : (-)Chronotropic effect, AV block, Cardiac arrest. Vasodilation

Question 9

Tetracaine(not in the list)

Answer 9

-Long acting drug

• Duration of action 2-3 h’

- Used primarily for spinal anesthesia

Question 10

Cocaine(A5)

Answer 10

-Surface acting drug

• Intrinsic sympathomimetic effect due to its inhibition of norepinephrine reuptake into nerve terminals

- Topical or parenteral

• Metabolism by plasma cholinesterase (pseudocholinesterase)
• Duration of action 1-2 h’
• Procedures requiring high surface activity and vasoconstriction
• Drug of abuse

-Side effects: Vasoconstrictor by itself, Psychostimulant (cortical acitivity↑, Mental performance↑, social activity↑, Tiredness↓)

*due to the blockade of NE re-uptake

*except for cocaine, all local anesthetics are vasodilators