Local Anesthetics

Question 1

MoA of Local Anesthetics

Answer 1

Act directly on nerve cells to block their ability to transmit impulses –> by blocking action potential propagation of nociceptive neurons (sodium channels) –> eliminate sensations of pain.

*The molecular targets –> voltage-gated sodium channels –> reduce the influx of sodium ions.
*Local anesthetics have to get intracellularly to exert their action – at the intracellular site of the receptor.

Question 2

The 2 categories of local Anesthetics

Answer 2

1) Amides (longer duration of action)
2) Esters (shorter duration of action)

*end in -caine

Question 3

PK of short-acting Local Anesthetics

Answer 3

• Short-acting local anesthetics –> readily absorbed into the blood from the injection site after administration.
• Limited duration –> unless blood flow to the area is reduced (in case of a vasoconstrictor)

Question 4

PK of long-acting Local Anesthetics

Answer 4

less dependent on the co-administration of vasoconstrictors, unlike short-acting agents

Question 5

Clinical uses of local Anesthetics

Answer 5

Minor surgical procedures often in combination with vasoconstrictors (e.g. epinephrine)

Question 6

What agent is used to increase the onset of action of local anesthetics –> to enhance intracelluar access

Answer 6

Sodium biocarbonate

Question 7

MoA of cocaine

Answer 7

cocaine –> has intrinsic sympathomimetic actions –> Reduces influx of NE
reuptake at nerve terminal. (no need for vasoconstrictor)

Question 8

Adverse effects of local Anesthetics

Answer 8

1) CNS effects
- light-headedness
-sedation
-restlessness
-Nystagmus
-Tonic-clonic convulsions
* sever convulsions –> Coma with respiratory and cardiovascular depression

2) Cardiovascular effects
- Vaodilation (Excpet for Cocaine)
- Heart block is susceptible patients

Question 9

Drugs used as Local Anesthetics

Answer 9

1) Bupivacaine (Amide)
2) Lidocaine (Amide)
3) Cocaine (Ester)
4) Procaine (Ester)
5) Benzocaine (Ester)

end -caine

Question 10

PK of Ester Local Anesthetics

Answer 10

(Cocaine, Benzocaine, Procaine)
–> short-half life
–> matabolised by plasma Cholinesterases

Question 11

PK of Amide local Anesthetics

Answer 11

(Bupivacaine, Liodcaine)
–> Longer half-life
–> Undergo Hepatic metabolism by CYP450 isoenzymes
* Lidocaine – < 2h.
* Bupivacaine – 3-4 h.

Question 12

Administration of Lidocaine and Bupivacaine

Answer 12

1. Analgesia via topical use.
2. Analgesia via injection –> for epidural,
   perineural and subarachnoid.

Question 13

Administration of Cocaine, Procaine and Benzocaine

Answer 13

1. Analgesia.
2. Topical use only for cocaine and benzocaine.

Question 14

Adverse Effects of Cocaine abuse

Answer 14

Cardiovascualr toxicity: (vasoconstriction)
1) Hypertension
2) Cerebral Heamorrahge
3) Arrythmia
4) MI

Question 15

Adverse effects of Bupivacaine

Answer 15

1) Arrythmias
2) Vasodilation
3) Hypotention

Question 16

Why does the treament of Infection increase the effectivness of local anesthetics?

Answer 16

Infection and inflammation lower tissue pH, reducing the diffusion of the agent into the nerve, thus reducing its effectivness

Question 17

How does liver Dysfunction result in toxicity when administrating an Amide local Anesthetic?

Answer 17

Liver Dysfunction–> increases the emlination half-life of amide local Anethetics–> risk of toxicity

Question 18

PK of Cocaine

Answer 18

causes Euphoria and Enhanced mental Alertness