Pharm: 27 - Local Anesthetics

Front 1

What is the mechanism of local anesthetics?

Back 1

- Bind reversibly to a site within the pore of voltage-gated Na+ channels (penetrates into nerve in unionized form)
- Blocks Na+ entry when channel is opened
- Reversibly block nerve conduction - block AP initiation and propagation on nociceptive neurons - eliminates pain sensation
- Acts on every type of nerve fiber

Front 2

What are the effects of local anesthetics?

Back 2

Cause sensory loss and motor paralysis of innervated area

Front 3

What are the different methods of local anesthesia?

Back 3

- Topical
- Local infiltration
- Nerve block
- Spinal anesthesia
- Epidural anesthesia

Front 4

How is topical anesthesia administered?

Back 4

- Applied to skin, mucous membranes, or ulcerated surfaces
- Ophthalmic (for cornea and conjunctiva)

Front 5

How is local infiltration anesthesia administered?

Back 5

- Local injection of agent into tissues irrespective of course of cutaneous nerves
- Provides regional anesthesia around sites of injection

Front 6

How is nerve block anesthesia administered?

Back 6

Injected around individual nerves or nerve plexuses that lead to operative site

Front 7

How is spinal or epidural anesthesia administered?

Back 7

Injected into CSF in lumbar space

Front 8

How is epidural anesthesia administered?

Back 8

Injected locally into epidural space in the sacral, thoracic, lumbar, or cervical regions

Front 9

Are local anesthetics strong/weak acids/bases?

Back 9

Weak bases

Front 10

What are the results of inhibition of voltage-gated Na+ channels?

Back 10

- Slows rate of depolarization
- Reduces height of AP
- Reduces rise of AP
AND
- Slows axonal conduction
- Prevents propagation of AP
- Increases threshold potential
BUT
- No change in resting membrane potential

Front 11

When do local anesthetics get into the voltage-gated Na+ channels?

Back 11

- Gain access more easily when channel is open
- Higher affinity for inactive channel than unopened channel (unactivated --> activated --> inactive)
- Resting nerves are less sensitive to block

Front 12

What does the degree of block by local anesthetics depend upon?

Back 12

Frequency of nerve stimulation and resting membrane potential

Front 13

What kind of nerves are less sensitive to local anesthetics?

Back 13

Resting nerves

Front 14

What kind of nerves are more sensitive to local anesthetics?

Back 14

Nerves with positive membrane potential

Front 15

How does the charge of the local anesthetics affect their mechanism?

Back 15

- Charged forms bind to channel
- Uncharged form penetrates into the nerve

Front 16

How does pH affect the efficiency of the local anesthetics?

Back 16

- Efficacy decreased when tissue pH is decreased such as during infection or inflammation
- Better penetration at higher pH (more basic) because unionized

Front 17

What other drugs are local anesthetics administered with to increase efficacy? Why? Examples?

Back 17

- Administered with vasoconstrictors
- Decreases rate of vascular absorption, increasing depth of anesthesia
- Less potential for systemic toxicity
- E.g., epinephrine or phenylephrine

Front 18

Which kind of fibers are blocked first by local anesthetics?

Back 18

- Autonomic fibers
- Small non-myelinated C fibers (mediating pain sensation)
- Small myelinated Aδ fibers (mediating pain and temperature sensation)

Front 19

Which kind of fibers are blocked later by local anesthetics?

Back 19

Larger myelinated Aδ, Aβ, and Aα fibers (mediating postural, touch, pressure, and motor information)

Front 20

How do Nodes of Ranvier factor in to the action of local anesthetics on nerve fibers?

Back 20

- Spacing of nodes of Ranvier increases with size of nerve fiber
- Fixed number of nodes must be blocked to prevent conduction
- Therefore, smaller nerve fibers will be blocked more quickly

Front 21

What is the general order of the block of sensation by local anesthetics?

Back 21

1. Pain
2. Cold
3. Warmth
4. Touch
5. Deep pressure

Front 22

What is the general order of the recovery of sensation by local anesthetics?

Back 22

1. Deep pressure
2. Touch
3. Warmth
4. Cold
5. Pain
(opposite of the order of block)

Front 23

What are the types of local anesthetics?

Back 23

- Ester
- Amide

Front 24

What are the ester local anesthetics?

Back 24

- Cocaine
- Procaine
- Tetracaine
- Benzocaine

Front 25

What are the amide local anesthetics?

Back 25

- Lidocaine
- Bupivacaine
- Ropivacaine

Front 26

Which organs do local anesthetics affect?

Back 26

Interfere with function of all organs in which conduction or impulses occur (CNS, autonomic ganglia, NMJ, and muscle)

Front 27

What are systemic toxic reactions related to for local anesthetics?

Back 27

High concentrations of the local anesthetic in the circulation (therefore, use the smallest amount to effectively block pain sensation)

Front 28

What kind of injection of local anesthetics can cause irreversible damage?

Back 28

Intraneuronal injection (accidental)

Front 29

Which form of the local anesthetic is less toxic?

Back 29

S-enantiomers are usually less toxic than R-enantiomers

Front 30

What kind of CNS toxicity do local anesthetics cause?

Back 30

- If absorbed systemically, may cause CNS stimulation --> restlessness, tremor, may lead to convulsions
- Central stimulation followed by depression
- Death d/t respiratory depression

Front 31

What kind of CV toxicity do local anesthetics cause?

Back 31

- General depression of cardiovascular system
- Usually seen after CNS effects are produced
- Can develop hypotension and arrhythmias leading to cardiac arrest

Front 32

What kind of hypersensitivity reactions do local anesthetics cause? Important?

Back 32

- Rarely --> allergic dermatitis or typical anaphylactic-like reaction
- Must be distinguished from side effects of co-administered vasoconstrictors

Front 33

Which kind of anesthetics are more common to cause hypersensitivity reactions?

Back 33

Ester local anesthetics

Front 34

How are local anesthetics metabolized?

Back 34

- Esters - primarily via plasma esterases
- Amides - metabolized in liver (use with caution in patients w/ severe liver disease)