Local anesthetics and spasmolytics

Question 1

define local anesthetic

Answer 1

any agent that can reversibly block electrical activity of excitable tissues

• decreases neuronal conduction
• blocks impulse conduction in heart

Question 2

For what are painkillers used?

Answer 2

temporary analgesia without the loss of consciousness

Question 3

Provide a brief commentary on the pertinent historical facts regarding local analgesics

Answer 3

cocaine - 1884 - used as local anesthetic in eye
1905 - procaine aka novocaine (antiquated)
1943 - lidocaine aka xylocaine

Question 4

comment on the effect of structure on function of the local anesthetics

Answer 4

all have an aromatic (lipophilic) end and an amino (hydrophilic) end

• the aromatic end gets the molecule into the neuronal membrane
• the amino end becomes ionized inside the membrane

Question 5

Describe the mechanism of action of local anesthetics. What effects does the mechanism have?

Answer 5

the non-ionized from get through the membrane. inside, the hydrophilic side is ionized and binds to a specific site on Na+ channels of excitable membranes. This blocks the Na+ channel.

As a result, you have:

• decreased neuronal induction
• decreased repolarization rate
• increased refractory period

Ultimately, effect is greater when Na+ channels are open. Neurons that fire more rapidly can be affected more often.

Question 6

In regard to local anesthetics, which nerves are affected?

Answer 6

Smaller neurons (pain) are generally more susceptible than larger neurons (motor)
myelinated neurons are more susceptible
the faster the firing rate, the more susceptible is the neuron.

Question 7

Rank susceptibility to local anesthetics. Neurons that translate:

1. warmth
2. touch / pressure
3. pain
4. motor
5. cold

Answer 7

pain > cold > warm > touch / pressure > motor

Question 8

What is the major distinction between local anesthetics

Answer 8

duration of action. all act by same mech.

Question 9

Does the ester linkage have a long or short duration of action?

Answer 9

Short. Ester is metabolized in plasma. Half-life is a matter of minutes. Cholinesterase exerts its effects here.

Question 10

Does the amide linkage have a long or short duration of action?

Answer 10

The amide linkage has a longer duration of action in comparison to the ester linkage. It is metabolized in the liver by CYT P450. Half-life is hours long.

Question 11

Are local anesthetics weak acids or bases?

In what environment are they ionized?

Answer 11

Weak bases

• more acidic environment
• In infected tissue (more acidic) molecules don’t readily enter the cell = local anesthetic activity is decreased.

Question 12

what are the routes of administration of local anesthetics?

Answer 12

topical - skin, mucosa, eye
injection - infiltration, direct nerve block, spinal (subarachnoid space), epidural ( just outside dura mater… child birth)

Question 13

Can local anesthetics be systemically absorbed?

Answer 13

Yes, regardless of administration

Question 14

Which specific local anethetics are more likely to cause allergic reactions?

Answer 14

The esters

Question 15

Name and describe the ester local anesthetics discussed in class.

Answer 15

cocaine - opthalmic, nasal surgery, inhibits NE reuptake in CNS

benzocaine - low solubility, absorbed slowly, long duration of action, used topically

procaine - short half-life, not used topically, doesn’t readily pass mucous membranes

Question 16

Whats the trick to realize when a drug is an amino amide?

Answer 16

it has two letter i’s

Question 17

what doeth procainamide?

Answer 17

used IV for cardiac arrhythmia

-causes lupus-like syndrome in slow acetylators (same as the antihypertensive, hydralazine)

Question 18

what does lidocaine do?

Answer 18

causes CNS side effects, tremors, slurred speech, drowsiness, used IV for arrhythmias

Question 19

What are the CNS and cardiovascular side effects caused by the esters?

Answer 19

CNS: disorientation, dorwsiness, slurred speech, tinnitus, blurred vision

Cardio: alter heart rhythm, tachycardia, arrhythmia

Question 20

What is special about cocaine?

Answer 20

CNS effects. strong vasoconstrictor.

Question 21

What are unique about Tetrodotoxin and saxitoxin?

Answer 21

both are very potent toxins.
TTX: irreversible Na+ channel blocker - Pufferfishes
Saxitoxin: “red tide” aka shell fish causes muscle weakness, resp. paralysis and deaf (as in dead)

Question 22

spasmolytic agents have something known as spasticity. what is spasticity?

Answer 22

muscle hypertonia, excessive contraction of skeletal muscle

-can result from neuronal damage: injury, stroke, MS, ALS, cerebral palsy

Question 23

How does one treat spasticity?

Answer 23

either alter the innervating neurons or act directly on muscle

Question 24

name the 4 neuronal class drugs used to treat spasticity

Answer 24

1. baclofen
2. botulinum toxin
3. diazepam
4. tizanidine

Question 25

how does baclofen work?

Answer 25

GABA agonist - increase activity of inhibitory neurons

Question 26

how do diazepam and other benzodiazepines work?

Answer 26

increase GABA - minor tranqs and muscle relaxers

Question 27

how does tizanidine work?

Answer 27

alpha 2 agonist - inhibit motor neurons

clonidine and alpha-methyl DOPA also function this way

Question 28

How does botulinum toxin work?

Answer 28

inhibits Ach release

Question 29

what antispastic drug acts directly on the muscle? and how?

Answer 29

dantrolene - acts directly on muscle cells - inhibits stimulus induced release of Ca2+ = decreased availability of Ca2+ for muscle

SE: muscle weakness, hepatitis