A.16

Question 1

Local anesthetics:

Answer 1

1. Ester local anesthetics: Benzocaine, Procaine, Cocaine, 2-Chloroprocaine, Tetracaine
2. Amide local anesthetics: Bupivacaine, levobupivacaine, Lidocaine, Mepivacaine, Ropivacaine, Etidocaine, Articaine, Prilocaine

Question 2

Elimination of Ester analogs

Answer 2

Plasma pseudocholinesterase, Atypical plasma cholinesterase, non-specific esterases (cocaine slow metabolism-liver)

Question 3

Elimination of Amide analogs

Answer 3

P450 isoenzymes (Lidocaine metabolism is intermediate, bupivacaine is slow), elimination by kidney is accelerated by acidificaition of tertiary amine compounds

Question 4

Factors affecting T1/2 of local anesthetics

Answer 4

Severe liver disease
competition with other drugs for the same enzyme (e.g. pseudocholinesterase is metabolizing succincylcholine and mivacurium as well)
↓hepatic blood flow (heart failure)

Question 5

Cocaine

Answer 5

MOA: Na+ ch. blocker and inhibits NE reuptake in the autonomic nervous system;
Effect: prevents propagation of nerve AP. It blocks the VG-Na+ channel from inside of the cell membrane; IND: Procedures requiring high surface activity+vasoconstriction, drug abuse;
SEs: vasoconstrictor by itself, psychostimulant (↑cortical activity; ↑mental performance, ↑social activity, do NOT feel tiredness, hunger, thirst), Stronger and faster thinking&easier social contact.
Abuse: severe HTN+cerebral hemorrhage, arrhythmias, MI;
Extra: Ester, metabolized by Pseudocholinesterase; DOA: 1-2h; ROA: topical / parentral

Question 6

Lidocaine

Answer 6

MOA: Na+ ch. blocker; Effect: ↓Na+-influx→ ↑depol. threshold→ no membrane depol→ block formation of AP→ block regeneration +conduction of nerve impulses;
IND: Local surgical procedures (e.g. dental, obstetrics), Post-operative analgesia, Ventricular arrhythmia, Post-AMI tachycardia, digitalis intoxication;
Contra-IND: severe hypotension, HF;
SEs: CNS effects (dizziness, seizures, nystagmus, twitching, coma), Neurotoxicity (sensory/motor deficits), cardiovascular system (bradycardia, ↓HR, vasodilation→ hypotension);
Extra: Amides, hepatic metabolism by CYP450; DOA: 1-2h, with Epinephrine 2-4h;
ROA: topical useor injection

Question 7

Articaine

Answer 7

MOA: Na+ ch. blocker;
Effect: ↓Na+-influx→ ↑depol. threshold→ no membrane depol→ block formation of AP→ block regeneration +conduction of nerve impulses;
IND: local anesthesia in dental procedures;
Extra: Amides, fastest onset of action among all local anesthetics;
DOA: longer than lidocaine

Question 8

(levo)bupivacaine

Answer 8

MOA: Na+-ch. blocker;
Effect: ↓Na+-influx→ ↑depol. threshold→ no membrane depol→ block formation of AP→ block regeneration +conduction of nerve impulses;
IND: Local surgical procedures;
Extra: Amides, slow onset of action;
DOA: 3-6h; ROA: spinal (epidural) anesthesia

Question 9

Benzocaine

Answer 9

MOA: Na+-ch. blocker;
Effect: Reversibly stabilizes the neuronal membrane→ ↓its permeability to Na+ ions→ depolarization of neuronal membrane inhibited→ blocking the initiation+conduction of nerve impulses;
IND: Tempoary pain relief of toothache, cold sores, sore throat;
Extra: Ester, Highly hydrophobic (penetrates into neuronal membranes), water insoluble (only used for surface anesthesia);
ROA: Topical anesthesia of mouth and throat