pharmacology of local anesthetics, defilnition, classification, mechanism of action, therapeutic uses

1. Local anesthetics
Dr. R. Padmavathi

2. Definition: Drugs that cause loss of sensation without loss of consciousness
Local anesthetics reversibly block generation and conduction of nerve
impulses
Act on every type of nerve fiber
Also act on cardiac muscle, skeletal muscle and the brain
Cocaine is the first naturally derived local anesthetic agent discovered in 1860
Because of toxicity produced by cocaine a synthetic derivative procaine was
discovered in 1905

3. Local anesthetics are amphiphilic in nature
They contains hydrophilic group on one side and lipophilic aromatic group on the
other, which are connected by the alkyl chain through an amide or ester linkage

4. Classification
Esters Amides
Procaine
Tetracaine
Benzocaine
Cocaine
Lidocaine (Xylocaine)
Mepivacaine
Bupivacaine
Etidocaine
Ropivacaine

5. MOA
Block voltage gated Na+ channels
↓
↑Threshhold potential of neurons
↓
↓Generation of impulses
↓
↓Conduction of impulses
↓
Loss of sensation

7. Local Actions
They affect all types of neurons; sensory, motor and Autonomic Neurons
The blockade occurs more rapidly in
Small Neurons > Larger Neurons
Myelinated Neurons > Non Myelinated Neurons
Recovery- in reverse order

8. Systemic actions
• CNS
Blockade always occurs as inhibitory first and excitatory next
Causes sequential (dose dependent) stimulation- inhibition
Euphoria → Excitement → Mental Confusion → Restlessness → Tremors → Muscle Twitchings
→ Convulsions → Unconsciousness → Respiratory Depression → Cardiac Arrest → Death
• CVS
 Have depressant action
↓Automaticity
↓ Excitability
↓ Conductivity
↓ Contractility

9. Blood vessels
Arteriolar vasodilation
Occurs by their direct action on blood vessels
Indirectly due to sympathetic blockade
Fall in BP
Cocaine- Inhibits noradrenaline(NA) Reuptake
↑NA at synapse
→vasoconstriction
↑ BP (hypertension)

10. • ADR’S
Hypersensitivity: Common with ester-linked LA
Rashes, angio-edema, dermatitis and rarely anaphylaxis
CNS: Same as pharmacological actions
ringing in ears, metallic taste, numbness around lips
Cocaine - euphoria (unique in its ability to stimulate CNS)
Cauda equina syndrome (Spinal anesthesia)
CVS
Hypotension, cardiac arrythmias, cardiac arrest
Hypertension (cocaine)
Cauda equina syndrome (CES) is a
condition that occurs when the bundle
of nerves below the end of the spinal
cord known as the cauda equina is
damaged. Signs and symptoms include
low back pain, pain that radiates down
the leg, numbness around the anus,
and loss of bowel or bladder control.

11. Lidocaine
CVS depression
Respiratory arrest
Coma
Convulsions
Unconciousness
Musclar twitching, visual disturbance, light headedness, numbness of
tongue
------------------------------
Antiarrhythmic
Anticonvulsant
PLASMA
CONCENTRATION

12. Therapeutic Uses
1. Surface anesthesia:
Topically for analgesia ; ulcers, burns (mouth, nasal, cornea, vagina, throat)
2. Infilteration anesthesia: minor surgeries

13. Therapeutic Uses
3. Nerve block: injected locally to produce regional anesthesia (e.g., dental and
other minor surgical procedures)
4. Spinal anesthesia: injection into CSF to produce anesthesia for major surgery
(e.g., abdomen or childbirth)

14. 5. Intravenous anesthesia: limb surgeries
6. i.v. infusion: for control of cardiac arrhythmias (e.g., lidocaine for ventricular
arrhythmias)
7. Local injection: at end of surgery to produce long-lasting post-surgical analgesia
(reduces need for narcotics)