Local anesthetics

Question 1

Mechanism of action of all local anesthetics

Answer 1

Inhibit voltage gated Na channels.

Block active channels by being passed through them from the intracellular side.

They are all weak bases.

First, they diffuse into the cell in their DEPROTONATED, uncharged form.

Then they bind and inhibit the channel in their PROTONATED, Charged form.

Sodium bicarb co-admin can enhance their effect and speed of onset by increasing the deprotonated form.

Question 2

What are the drugs that block Na channels extracellularly?

Answer 2

Tetrototoxin and Saxitotoxin

Question 3

Order of sensation loss with local anesthetics

Answer 3

Pain

Temp

Touch

Deep pressure

Motor function

Question 4

What are the Ester linked LAs

Answer 4

Cocaine
Procaine
Tetracaine
Cinchocaine
Benzocaine

Degraded by plasma and tissue esterases, especially pseudocholinesterase.

half life: 2 minutes for procaine, ~1 hour for cocaine

Question 5

What are the Amide linked LAs

Answer 5

Lidocaine
PriloCaine
Bupivicaine
Afticaine

Metabolized by liver, often have active metabolites.

Half life
1.5 hours for lidocaine
~4 hours for bupivicane

Question 6

What is the duration of local anesthetics

Answer 6

Local duration is strongly affected by the amount of local blood flow, increased by vasoconstricto, usually epinephrine given i.m.

Question 7

What are the common stuctural components of all the LAs

Answer 7

A lipophilic portion containing an aromatic ring

an Intermediate chain, linked by either an ester or an amide linkage

A small hydrophilic portion

Question 8

What are the types of local anesthesia

6

Answer 8

1. Surface anesthesia
   - nose, mouth, eye. Not effective for skin
2. Infiltration anesthesia
   - Direct injection into tissue. Used for small areas of skin, dermis
3. Intravenous regional anesthesia.
   - A limb has a pressure cuff placed on and LA injected distally. Cuff must remain on for at least 20 minutes after injection of there is high risk for systemic toxicity.
   - For large limb surgeries
4. Nerve block anesthesia, regional anesthesia
   - Injected close to a major nerve trunk
   - dentisty, alveolar nerve, arms, brachial plexus
5. Spinal anesthesia
   - into the subarachnoid space of the spinal cord.
   - acts on spinal roots AND cord at the level and bleow
   - formulated along with glucose and delivered cold to make the solution hyperbaric/sink and control the level affected.
6. Epidural
   - Injected into epidural space
   - Only acts on the roots

Question 9

What LA is used for Spinal anesthesia?

Epidural anesthesia?

Answer 9

Lidocaine

Lidocaine or bupivicaine

Bupivicaine has the longest duration of action

Question 10

What are the adverse effects of local anesthetics

Answer 10

The systemic effects:

CNS:
• Tongue & mouth numbness
• Tinnitus
• Vertigo (dizziness) 
• Tremor 
• Muscle twitching on the face and limbs
• Confusion 

Depression (predominates at low plasma cc.)
• Loss of consciousness, coma
• Respiratory depression
• Cardiovascular collapse,

Excitation (predominates at higher plasma cc.) 
• Anxiety
• Restlessness, agitation
• Vomiting
• Tonic-clonic convulsion
• Death

Cardiovascular system (direct & indirect):
• Negative chronotropic: bradycardia,
ventricular fibrillation, cardiac arrest
• Negative dromotropic: AV block
• Negative inotropic
• Vasodilatation, RR ↓
• Collapse

•Exception: Cocaine - tachycardia, RR , vasoconstriction

Question 11

What other receptors do the LA’s interact with at high doses

Answer 11

the nAChRs.

At high doses local anesthetics cause a non-specific block of nicotinic receptors as well (paralysis)

Facilitate the actions of the NMJ blocking agents.