Pharmacology-Local Anesthetics

Question 1

What similarities do many local anesthetics have with one another?

Answer 1

Lipophilic ring and a hydrophilic secondary or tertiary amine

Question 2

What characteristic of local analgesics separates them into two classes?

Answer 2

The intermediate chain. There are esters and amides.

Question 3

What happens to the effects of a local anesthetic as you increase hydrophobicity?

Answer 3

Potency and duration increase along with side effects. Ordered below are the local anesthetics in order of hydrophobicity.

Question 4

What is the pKa of local anesthetics?

Answer 4

8-9

Question 5

Where do most local anesthetics bind?

Answer 5

The intracellular side of Na+ channel pores.

Question 6

A patient goes to the dentist because they have an infected root canal. Before drilling, none of the local anesthetic is working. Why is it not working?

Answer 6

Infected tissue is more acidic. Acidic tissue = more cationic local anesthetic that cannot cross the cell membrane and get to its site at the Na+ channel

Question 7

What are the different conformations of the Na+ channel? When are the local anesthetics effective?

Answer 7

At the intermediate, open and inactivated conformations reveal the local anesthetic binding sites. Just not at the resting conformation.

Question 8

How do local anesthetics affect the action potential threshold, rate of rise of action potential and resting membrane potential?

Answer 8

Threshold is increased, rate of rise of AP decreases and resting membrane potential is unaffected because it is set by K+ channels.

Question 9

What nerves are most and least susceptible to local anesthetics? Consequently, in what order does sensation loss occur with continued administration of local anesthetics?

Answer 9

C > A-delta > A-gamma > A-beta > A-alpha. Increased size and myelination decrease susceptibility due to critical length (how far an action potential needs to propagate to continue the signal down the axon). Sensation loss proceeds in this manner: Pain -> Temp -> Touch -> Deep pressure -> Motor

Question 10

Why do nerves with greater firing frequency have a higher susceptibility to block by local anesthetic?

Answer 10

The binding site for the local anesthetic is inside the Na+ pore. The more the nerve fires, the more the pore is open and susceptible to block.

Question 11

What factors affect absorption of locally injected anesthetics as they begin to be cleared from the injection site into the systemic circulation?

Answer 11

Dose, vascularity of site, inclusion of vasoconstrictor w/dose (EPI) and chemical properties of the local anesthetic.

Question 12

What molecules are often included in local anesthetics that get injected into nerve roots around the spinal cord and why?

Answer 12

EPI and Clonidine. These agonize alpha-2 which decrease neurotransmitter released at the nerve terminal. They also inhibit release of substance P.

Question 13

Once the local anesthetics are in the blood stream, how are they cleared?

Answer 13

Ester-type local anesthetics are hydrolyzed rapidly by plasma cholinesterase (pseudocholinesterase) and metabolized by PABA (p-aminobenzoic acid). Amide-type local anesthetics are metabolized slow by CYP450 in the liver.

Question 14

What are CNS toxicities you need to be aware of when using local anesthetics?

Answer 14

1) Stimulation 2) Seizures 3) CNS depression 4) Death. Inhibitory GABAergic neurons are inhibited 1st with high doses of local anesthetic, hence the early sign of CNS stimulation in toxicity.

Question 15

What cardiovascular toxicities exist when using local anesthetics?

Answer 15

Decreased myocardial excitability, decreased BP and arrhythmias (at high doses only). This is because local anesthetics directly block myocardium and smooth muscle Na channels. They also have indirect effects on autonomic neurons.

Question 16

What are early and late symptoms that tell you youhave too much local anesthetic in the blood stream? What is different about bupivacaine?

Answer 16

Bupivacaine is more lipophilic and causes cardiovascular depression before convulsions.

Question 17

Why do you inject anesthetic next to the nerve instead of into the nerve?

Answer 17

Prolonged exposure of the nerve to the anesthetic can cause direct neurotoxicity

Question 18

What local anesthetic can cause the condition seen in the patient below? How would this condition progress with continued use of the anesthetic?

Answer 18

Topical benzocaine. This is methemoglobinemia, caused by o-toluidine mediated conversion of hemoglobin to methemoglobin. This patient has chocolate cyanosis, which can lead to anxiety, fatigue, tachycardia, coma and death.

Question 19

What are common side effects seen with the ester-type local anesthetics?

Answer 19

These anesthetics form the PABA metabolite, which is a cause of various hypersensitivity reactions (allergic dermatitis, asthma, anaphylaxis)

Question 20

What are rare side effects seen with the amide-type local anesthetics?

Answer 20

Hypersensitivity reaction to the preservatives in the anesthetic solution.

Question 21

If a patient has hypersensitivity to an amide-type local anesthetic what type would you give them?

Answer 21

Ester-type. There is hypersensitivity within classes but not between classes.

Question 22

Why does the nasal septum commonly necroses in patients who chronically use cocaine?

Answer 22

Chronic vasoconstriction

Question 23

In what situations would you not apply a topic anesthetic?

Answer 23

Sunburns, other burns. Regional areas stripped of epidermal layers absorb the anesthetic and can cause systemic toxicity.

Question 24

What local anesthetic can be used in the eye?

Answer 24

Proparacaine

Question 25

A patient comes to the ED and needs stitches. What local anesthetic injection technique would you use to numb the area?

Answer 25

Infiltration: injection of lots of fluid directly into tissue

Question 26

A patient comes in to have a cyst drained via ultrasound guidance. What local anesthetic injection technique would you use to numb the area?

Answer 26

Field block: injection of lots of fluid around border of the cyst. This numbs the area without contaminating the surgical field.

Question 27

What local anesthetic injection techniques would you use in surgical procedures?

Answer 27

Nerve blocks, epidural blocks and intrathecal injections

Question 28

What toxins can reversibly block Na+ channels?

Answer 28

Tetrodotoxin (puffer fish & fugu sushi) and saxitoxin (red tide ingested by fish)