L20- Local Anesthetics

Question 1

describe the intended goals / actions of local anesthetics

Answer 1

• block nerve conduction: sensory impulses (PNS) to CNS
• high doses may abolish sensation and motor control

-no LOC

Question 2

describe the general structure of local anesthetics

Answer 2

• lipophilic group (aromatic ring)
• *Intermediate group- Ester (1 I in names) or Amide (2 Is in names)
• ionizable group (tertiary amine)

Question 3

(esters/amides) are more prone to hydrolysis, therefore they have (2) in terms of drug actions

Answer 3

Esters –> shorter half-life

Question 4

Local Anesthetics are commonly weak (acids/bases) with a pKa of (2). At physiological pH, 7.4, anesthetics will be in (cat/an)-ionic form.

Answer 4

1- weak bases
2- pKa: 8.0-9.0
3- cationic

Question 5

describe the function of the uncharged form and ionized form of local anesthetics

Answer 5

Uncharged: penetration of biological membranes (to diffuse into cells / neurons

Ionic: active form that binds intracellular receptors

Question 6

local anesthetics preparations usually also contain (1) to assist the action of the anesthetic through (2) mechanism having (3) effects on anesthetics

Answer 6

1- epinephrine
2- vasoconstriction (keep drug in local area longer)
3- neuronal uptake is enhanced —- systemic toxic effects are reduced

Question 7

a (1) is not added to local anesthetic preparations in areas with end artery supply, like (2) locations because of fear of losing (2) due to (3) processes

Answer 7

1- vasoconstrictors

2- fingers, toes, ears, nose, retina, penis,

3- delayed wound healing, tissue edema, necrosis

Question 8

(1) is a local anesthetic that constricts blood vessels by potentiating the action of (2), and therefore preventing the absorption of (1) itself

Answer 8

1- cocaine (ester)

2- NE

Question 9

compare ester-linked and amide-linked anesthetics in terms of metabolism

Answer 9

Esters: shorter half-lives

• more prone to hydrolysis
• metabolized by tissue and plasma cholinesterases (pseudocholinesterase)

Amides: longer half-lives
-degraded by liver – microsomal cytochrome P450 system

Question 10

describe the MOA of local anesthetics, simply

Answer 10

• lipophilic form crosses neuronal membrane
• switched to ionic form
• binds to receptors (intracellular) near V-gated Na channels
• blocks V-gated Na channels
• prevents / abolishes APs

Question 11

Local Anesthetics, pharmacology:

• potency correlates to (1)
• speed of onset of action correlates to (2)
• duration of action correlates to (3)
• toxicity correlates to (4)

Answer 11

1, 3, 4- liposolubility

2- pKa (closer to body pH –> faster the onset — more in ionic form)

Question 12

list the common ester local anesthetics

Answer 12

(Note- 1 I in name)

• cocaine
• benzocaine
• procaine, chloroprocaine

-tetracaine

Question 13

list the common amide local anesthetics

Answer 13

(Note- 2 Is in name)

• lidocaine
• prilocaine
• mepivacaine
• bupivacaine
• ropivacaine
• etidocaine

Question 14

list the short-acting local anesthetics

Answer 14

procaine, chloroprocaines (esters)

Question 15

list the intermediate-acting local anesthetics

Answer 15

lidocaine, mepivacaine, prilocaine (amides)

Question 16

list the long-acting local anesthetics

Answer 16

• tetracaine (esters)

- bupivacaine, etidocaine, ropivacaine (amides)

Question 17

list the CNS AEs of local anesthetics

• initial response
• secondary response

Answer 17

1st) CNS stimulation => restlessness, tremor, clonic convulsions (toxic rxn to excess levels)
2nd) respiratory depression –> death

Question 18

CNS AEs of local anesthetics are treated prophylactically with….

Answer 18

benzodiazepine –> to prevent seizures

Question 19

the main PNS AE for local anesthetics is….

Answer 19

toxicity to nerve tissue at high concentrations (destruction)

Question 20

Local anesthetics may cause CVS toxicity due to its (1) action affecting the heart and possibly leading to (2) and or (3).

Answer 20

1- blockade of Na channels

2- [cardiac depression of pacemaker activity, excitability, and conduction] –> arrhythmia

3- [dec contractility] –> arterial dilatation + hypotension

Question 21

______ is the only local anesthetic that may cause vasoconstriction, hypertension, and cardiac arrhythmias

Answer 21

cocaine:

• vasoconstriction / HTN due to NE potentiation
• arrhythmia due to Na channel blockade

Question 22

______ is the most cardiotoxic local anesthetics

Answer 22

bupivacaine

Question 23

list the systemic AEs of local anesthetics as plasma concentrations inc

Answer 23

(from lowest concentration to highest)
drowsiness
paresthesia in mouth/tongue
tinnitus, auditory hallucinations
muscular spasms
seizures
coma
respiratory arrest
cardiac arrest

Question 24

Prilocaine may lead to accumulation of its metabolite (1) which is responsible for causing (2), treated with (3)

Answer 24

(at large doses)
1- o-toluidine
2- converts Hb –> methemoglobin (–> hypoxia)
3- methylene blue

Question 25

Ester type local anesthetics are converted to (1) metabolite which can cause (2) in a small portion of the population.

Answer 25

1- PABA (p-aminobenzoic acid derivatives)

2- allergic reaction

Note- amides very rarely ever cause allergic reactions – no conversion into PABA

Question 26

______ is the main contraindication / drug interaction to avoid with use of ester type local anesthetics (procaine mainly)

Answer 26

Sulfonamides:

• Procaine –> PABA (p-aminobenzoic acid derivatives)
• inhibits actions of Sulfas (used as antibiotic)