lipophilic aromatic group

intermediate chain (ester or amide)

hydrophilic group (amine)

amide tends to be more stable than esters in the body

as HCl salts w/ pH < 7 b/c it is more soluble and stable than free base

at physiologic or lower pH levels, the ionized cationic form predominates (80-90%) in the body fluid and is water soluble. 

at higher pH levels, the non-ionized (lipid soluble) form predominates. this form can penetrate the neuronal membranes to reach internal surface of sodium channels

acidic medium increases ionization thus decreasing effectiveness

Blocks Na channels in nerves and excitable cells. thus decreases Na influx and conduction of action potentials.

Local Anesthetics bind to the open activated and open inactivated states of the Na channels, thus prolonging inactivation.

The cationic form of the drug has a higher affinity for the R on the intracellular site of the Na receptor. Thus after passing through the neuronal membrane in the NI state, it will gain a H+ and become ionized

increase in threshold for excitation

decrease in impulse conduction

decrease in rate of rise of AP

decrease in AP amplitude

complete block of conduction at high concentrations

1. Small fibers more susceptible to LA than Large fibers

2. Recovery is in reverse order

3. Order of sensitivity: pain, temperature, touch, motor

4. smaller unmyelinated fibers more susceptible to LA

5. However if two fibers are the same diameter, the myelinated one is more susceptible

6. for myelinated fibers, 3 successive nodes of Ranvier must be blocked to inhibit conduction

1. active fibers more sensitive to LA

2. High Freq fibers more sensitive to LA

3. Type C and Adelta blocked >> Aalpha

1. all LA in high concentrations can elicit CNS stimulation followed by Respiratory depression & death

-probably due to blockade of central activity

2. Cocaine causes intense CNS stimulation & euphoria by inhibiting NE & DA reuptake. Lidocaine may initially cause drowsiness & sedation

1. can decrease electrical excitability, conduction rate, and contraction.

- may b useful in arrhythmias (lidocaine) by membrane stabilizing

- Bupivicaine is cardiotoxic.

2. Arteriolar dilation and hypotension

-Except Cocaine

1. NMJ - weak NM block

2. Autonomic ganglia - block

3. Smooth muscle - relax

1. Epinephrine - decrease absorption thus prolongs duration of action by causing vasoconstriction

2. Increase absorption by adding sodium bicarb thus increasing NI form

3. Application to mucosal surfaces may result in rapid absorption

1. Ester LA are RAPIDLY hydrolyzed by plasma cholinesterases

2. Amide LA are SLOWLY hydrolyzed by liver microsomal enzymes

-thus liver impairment can cause Amide LA toxicity

1. Restlessness, anxiety, light headedness, tremor

2. Higher doses may lead to convulsions, coma, CV & Resp depression

3. Treatment --> Diazepam (Valium) or support w/ O2 and mechanical ventilation

1. Ester LA

2. only LA w/ Sympathomimetic effects (vasoconstriction & tachycardia)

3. applied topically to decrease bleeding after ENT surgery

4. Schedule II controlled substance w/ abuse potential

1. Ester LA

2. short duration (15-30mins)

3. Metabolized to PABA - may cause allergic rxn

1. Ester LA

2. potent LA w/ LONG duration (2-3 hrs)

3. Spinal or Epidural anesthesia

1. Ester LA

2. OTC, topical for sunburn, pruritis 

3. Spray for cough

1. Amide LA

2. Intermediate duration of action (30-60 min) for short duration procedures (infiltration blocks, epidural, spinal)

3. Effective anti arrhythmic

4. EMLA - mix of lidocaine & prilocaine that's available topically for venipuncture, IV cannulation, and dental procedures (particularly children)

1. Amide LA

2. Intermediate duration (30 - 60min)

3. May cause methemoglobinemia

- treat w/ IV methylene Blue

Bupivicaine

Ropivacaine

1. Amide LA

2. potent LA w/ Long duration (2 - 3 hrs)

3. Bup used for obstetrics but may cause cardiac depression & ventricular arrhythmia

4. Rop is newer and may cause less cardiac toxicity

1. bradycardia

2. bupivacaine - cardiotoxic

3. cocaine - cns stimulant, vasoconstriction, hypertension, arrhytmias

provide loss of sensation w/o loss of consciousness for:

1. minor surgery

2. obstetrics

3. diagnostic procedures

1. surface anesthesia

2. infiltration anesthesia

3. nerve block

4. spinal

5. epidural

6. control cardiac arrhythmias - Lidocaine

1. reversibly block nerve conduction when applied locally

2. act on every type of nerve fiber and are used to anesthetize a particular region or part of the body

3. Cocaine was the first LA to be discovered

4. Procaine synthesized in 1905 and became the "prototype" LA for many years

5. Lidocaine synthesized in 1943 and became a widely used LA