Local Anesthetics & Muscle Relaxants

Question 1

Procaine (Novocain)

Answer 1

 First synthetic local anesthetic, procaine is an ester-
type drug
 Well absorbed and rapidly metabolized by butyryl-
cholinesterases
 Short duration of action
 Metabolic product is para-aminobenzoicacid (PABA),
which can cause allergic reactions and inhibit
sulfonamide action
 Used for infiltration anesthesia and diagnostic nerve
blocks
 Lacks topical activity
 Minimal systemic toxicity and no local irritation

Question 2

Tetracaine (Pontocaine)

Answer 2

 Tetracaine is an ester-type drug
 Slow onset of action (10 minutes)
 Long duration of action: about 2-3 hrs
 Approximately 16X more potent and more toxic than procaine
 Severe toxicity with high volume peripheral blocks
 Preferred for ophthalmological use (retrobulbar)
 Spinal anesthesia - Combined with 10% dextrose to
increase the specific gravity; solution is more dense
than CSF (hyperbaric)

Question 3

Benzocaine (Americaine)

Answer 3

 Benzocaine is an ester-type drug
 Very lipophilic; pKa of 3.5, thus always in non-ionized
form at physiological pH (~7.4)
 Readily transported through membrane, minimal
binding to Na+channel
 Used topically only to treat sunburn, minor burns and
pruritus in OTC preparations
 FDA Drug Safety Communication: Risk of
methemoglobinemia

Question 4

Cocaine - MoA

Answer 4

• Ester type drug
• Inhibits Na+channels secondary to its effect on increasing
  DA the CNS and periphery

Question 5

Cocaine - Uses

Answer 5

 Topical anesthesia of mucous membranes typically
around the upper respiratory tract
 Can reduce bleeding (dental)

Question 6

Cocaine - Side Effects

Answer 6

CNS and cardiovascular

 Use with caution in addicts or with other drugs that
increase catecholamines

Question 7

Lidocaine (Xylocaine)

Answer 7

 Lidocaine is the prototype amide drug (amide
kinetics)
 Rapidly absorbed; intermediate duration of action
 Rapid onset of anesthesia
 Greater potency and longer duration of action than
procaine
 Moderate topical activity and minimal local irritation
 Wide range of applications; preferred for infiltration
blocks and epidural anesthesia

• Not preferred for spinal blocks; risk of TNS

Also used as an antiarrhythmic agent

Question 8

Prilocaine (Citanest)

Answer 8

 Prilocaine is an amide-type drug
 Intermediate duration of action
 Highest rate of clearance of the amides
 Methemoglobinemia-due to metabolites
• Excessive methemoglobinin blood (chocolate color)
• Shortness of breath, fatigue, dizziness, dysrhythmias,
seizures, coma, death
• Do not use in patients with methemoglobinemia
• Can be reversed with methylene blue
 Contraindicated in cardiac or respiratory disease
 Largely limited to use in dentistry

Question 9

Bupivacaine (Marcaine)

Answer 9

 Bupivacaine is an amide-type drug
 Long duration of action
 Analgesia for post-operative pain control
 Spinal anesthesia, infiltration blocks and epidural
anesthesia
 Greater cardiotoxicity than other amides (S-
enantiomers)
• Higher degree of lipophilicity
• Diffuses away from cardiac channels slower
 More potent sensory block than motor block
 Preferred as epidural during labor and childbirth

Question 10

Ropivacaine (Naropin)

Answer 10

 Long-acting, amide-type LA
 The S-enantiomer of bupivacaine
 Less lipid soluble and cleared more rapidly than
bupivacaine
• Less likely to produce adverse events
• Less cardiac toxicity than bupivacaine
 Metabolized by CYP3A4-possible interactions with
other drugs
 Used for peripheral and epidural blocks
 Vaso-constricting effects at clinical doses

Question 11

Mepivacaine (Carbocaine)

Answer 11

 Mepivacaine is an amide-type drug; similar to 
    bupivacaine
 Intermediate duration of action
 Preferred for peripheral nerve blocks
 Not used topically
 Not used in labor anesthesia

Question 12

Etidocaine (Duranest)

Answer 12

 Etidocaine is an amide-type drug; long duration of
action
 Inverse differential block - may cause motor block
before or without sensory block

Question 13

Articaine (Septocaine)

Answer 13

 Articaine is an amide-type local anesthetic
 However, it also has an additional ester group which
subjects it to metabolism by plasma esterases
- This decreases half-life and potential for systemic
toxicity
 Widespread use in dental medicine due to its larger
therapeutic window and low potential for systemic
toxicity
 Allows for the injection of more drug later into the
procedure
 Adverse effects: although rare,may include the
development of persistent paresthesias (3 times
more likely with articaine)

Question 14

Dibucaine (Nupercainal)

Answer 14

 Amide-type drug
 Used as spinal anesthetic outside of US; still used as 
    topical in US
 Dibucaine number test - Measure of 
    butyrylcholinesteraseactivity

Question 15

Diazepam (Valium) - MoA

Answer 15

 Acts on the GABAA receptor to facilitate GABA-mediated presynaptic inhibition in the spinal cord
Different alpha subtypes of the receptor mediate different responses
• alpha1 - sedative (Z drugs) and anticonvulsant
effects
• alpha2 - anxiolytic
• 2/3/5 -muscle relaxant
 Diazepam affects all the subtypes

Question 16

Diazepam (Valium) - Uses

Answer 16

 Dose sufficient to act as muscle relaxant produces
heavy sedation
 Useful for local muscle trauma
 Adjunct in chronic spasticity

Question 17

Baclofen (Lioresal) - MoA

Answer 17

 Agonist at GABAB receptors (Gi/o-protein coupled;
metabotropic)
 Stimulation opens K+channels - hyperpolarization
 Presynaptic inhibition of Ca++ influx - decreases
transmitter release
 Inhibits AC and cAMP formation and
decreases release of excitatory
transmitters in brain & spinal cord

Question 18

Baclofen (Lioresal) - Side Effects

Answer 18

drowsiness, weakness, increased seizure activity, respiratory depression may occur w/ intrathecal administration

Question 19

Tizanidine (Zanaflex) - MoA

Answer 19

 a2 receptor agonist
 Produces both pre-and post-synaptic inhibition of
spinal cord synaptic activity to decrease muscle
spasticity
 Inhibits pain transmission in dorsal horn

Question 20

Tizanidine (Zanaflex) - Uses

Answer 20

 Used for chronic and acute muscle spasms

Question 21

Tizanidine (Zanaflex) - Side Effects

Answer 21

 sedation, some hypotension
 dry mouth, weakness, falls in elderly
 hepatotoxicity

Question 22

Dantrolene (Dantrium) - MoA

Answer 22

 Inhibits Ca++release from the sarcoplasmic reticulum
by blocking the ryanodine receptor 1 (RyR1) channel
 Interferes with excitation-contraction coupling of
actin and myosin in the skeletal muscle fiber
 Minimal effects on cardiac or smooth muscle b/c
Ca++release mediated by different receptor, RyR2

Question 23

Dantrolene (Dantrium) - Uses

Answer 23

 Used to treat neuroleptic malignant syndrome,

malignant hyperthermia

Question 24

Dantrolene (Dantrium) - Side Effects

Answer 24

weakness, sedation possible

Question 25

Botulinum Toxin (BoTox)

Answer 25

 Inhibits ACh release from nerve at neuromuscular junction  Small amounts injected locally to control muscle spasms following stroke or neurological injury  Effects persist for weeks to months  Large amounts can be very toxic; spread of toxin to unwanted areas may be problematic

Question 26

Drugs for Acute Local Muscle Spasms

Answer 26

 Brain stem sedatives; Decreases neuronal activity in spinal cord  Used for acute spasms cause by local tissue trauma/muscle strain  Limited effectiveness but may alter perception of pain  Significant sedation Cyclobenzaprine (Flexeril) -prototype • Antimuscarinic activity - sedation and confusion, hallucinations  Carisoprodol (Soma) • Similar to barbiturates; Popular drug of abuse; Caution in recovering addicts