Pharmacology - Local Anesthetics - Vandana Sharma

Question 1

In dealing with anesthetics, potency correlates to:

Answer 1

Lipid solubility

Question 2

The onset of action of an anesthetic depends on what factors?

Answer 2

pKa
Lipid solubility
The more lipid soluble, the faster the onset of the drug

Question 3

The duration of action of an anesthetic depends on:

Answer 3

Protein binding

binding to alpha-1-acid glycoprotein

Question 4

What is the MOA of local anesthetics?

Answer 4

LA bind reversibly to the intracellular portion of the Na channel and inactivate the channel. The threshold for excitation therefore increases, impulse conduction slows, etc.

Question 5

Short-acting ester local anesthetics are inherently safer w/r/t systemic toxicity due to their clearance by:

Answer 5

pseudocholinesterase

Question 6

What is a potential complication of continuous spinal catheters infusing lidocaine in order to permit repetitive dosing to facilitate adequate anesthesia?

Answer 6

Cauda equina syndrome - severe back pain with motor and sensory deficit, loss of bowel and ladder control

An example of local neural toxicity from LA

Question 7

What is TNS?

Answer 7

Transient Neurological Syndrome
transient pain or dysthesia linked to the use of lidocaine for spinal anesthesia, can be severe

Can occur with lidocaine, procaine, mepivicaine

Question 8

Why are many people allergic to anesthetics containing esters?

Answer 8

para-aminobenzoic acid (PABA) metabolites are known allergens (methylparaben is the preservative that metabolizes to PABA)

Question 9

What is the order of nerve depolarization?

Answer 9

1. Resting membrane potential
2. Stimulus –> threshold –> voltage-gated Na channels open
3. Voltage-gated K channels open –> depolarization
4. At peak, voltage-gated Na channels close
5. Repolarization phase –> K channels close

Question 10

What is preemptive analgesia?

Answer 10

The nerve block is performed prior to the incision.

Question 11

LAs all have a similar structure: the aromatic ring, the intermediate linkage, and the terminal amine. What is the function of the aromatic ring?

Answer 11

Aromatic ring = lipophilic portion = greater lipid solubility (correlates to high potency)

Question 12

LAs all have a similar structure: the aromatic ring, the intermediate linkage, and the terminal amine. What is the function of the intermediate linkage?

Answer 12

The intermediate linkage determines the biodegradation and elimination of the drug

Question 13

LAs all have a similar structure: the aromatic ring, the intermediate linkage, and the terminal amine. What is the function of the terminal amine?

Answer 13

The terminal amine tail is able to accept a proton and can go from tertiary to quarternary with a positive charge (weak base)

Question 14

pKa = pH - log ([H]/[HA])

Answer 14

HH equation
when base and acid concentration are equal, log 1=0
and pKa = pH

Question 15

What is pKa?

Answer 15

The pH at which 50% of the molecule exists in ionized form and 50% in non-ionized form

Question 16

What is the effect is there is a big difference between the pH of the blood and the pKa of the anesthetic agent?

Answer 16

Creates more ionized and less lipid soluble (and less potent) drug

Question 17

T/F: Smaller nerves and myelinated nerves get blocked earlier than larger and unmyelinated nerves.

Answer 17

True

Question 18

Can transient neurologic syndrome occur after administration of Bupivicaine or Clorprocaine?

Answer 18

No

More common in lidocaine (and others)

Question 19

What is the cardiac toxicity associated with local anesthetic use?

Answer 19

Much higher doses than CNS toxicity;
Na channel blockade –> depression of myocardial contractility and reduced refractory period
**All local anesthetics except cocaine and ropivicaine are vasodilators which can lead to cardiac arrest

Question 20

What anesthetic has the highest cardiac toxicity potential?

Answer 20

Bupivicaine

Question 21

Why is ropivicaine generally a better choice for an anesthetic than bupivicaine?

Answer 21

Ropivicaine has a larger therapeutic index, less cardiovascular effects and more CNS tolerance than bupivicaine. It’s also slightly less potent