Pharmacology Third Year

2. Drugs that cause reversible block of nerve conduction
producing transient localized anesthesia without
significantly affecting consciousness.

3. According to their chemical structure:
 Esters:
Cocanie, Procaine, Benzocaine & Tetracaine
 Amides:
Lidocanie (xylocaine, ligocaine), Prilocaiine,
Mepivacaine & Dibucaine.

4. According to their solubility & therapeutic
application:
- Soluble Local anesthetics suitable for
injection: Procaine HCl, Lidocaine HCl
- Soluble Local anesthetics used only topically
on the eye: Cocaine HCl
- Local anesthetics of low solubility used as
powders & ointments: Benzocaine

5. According to their potency
 LA with weak potency & short duration(30-60
min)
Examples: Procaine
Chloroprocaine
 LA with moderate potency and intermediate
duration (1 - 3 hrs)
Examples: Lidocaine (xylocaine)
Prilocaine.
 LA with high potency and long duration(3 – 6 hrs)
Examples: Tetracaine
Bupivacaine

6. Mechanism of action:
local anesthesia blocks voltage dependent sodium
channels from inside the nerve fiber. → prevention
of sodium permeability into the nerves →
membrane stabilization → ↓ impulse generation and
propagation
At alkaline tissue pH= 7.4 They are Unionized
molecules → pass easily through membrane lipid
of nerve fiber → reach cytoplasm ( ionized +
unionized)→ the ionized form bind to Na+
channels blocking Na+ influx prevent initiation
of AP

7. Mechanism of action:

8. Action
Local anesthetic action
 Small fibers before large
 Demylinated before mylinated fiber
 Sympathetic & pain → temperature →
touch& pressure → motor fibers
 Recovery → reverse direction.
Addition of adrenaline→ vasoconstriction→
↓absorption of LA →↓spread →↑duration&
↓toxicity

9. Metabolism :
Esters are fastly metabolized by plasma
and tissues esterases. Thus , they have short
duration. They are metabolized to PABA
(cause allergy in some individuals).
Amides are metabolized slowly by liver
microsomal enzymes. Thus , they have
longer duration

10. Methods of administration and uses
 Surface anesthesia: Direct application of the drug on
accessible surface as skin or mucous membrane
LA with short or intermediate duration are used for this
purpose.
Dosage forms:
Powder , Solutions (spray) , Creams or Ointments.
Benoxinate ( ester LA) used in ophthalmology for corneal
anesthesia because :
 No mydriasis.
 No corneal injury.
Benzocaine used in form of powder or cream on skin
wounds or ulcer, because it is insoluble produces less
systemic toxicity

11. Methods of administration and uses (cont.)
 Infiltration anesthesia: They are injected directly
into the tissue by S.C injection e.g wound
suturing & cysts removal , Circumcisions .
 Nerve block anesthesia:
The anesthetic in injected close to the
appropriate nerve trunks or peripheral nerve at a
site proximal to where anesthesia is desired. e.g.
dental anesthesia

12. Methods of administration and uses (cont.)
 Sympathetic block: It is injected around
sympathetic ganglion.
 Para vertebral block: injected around spinal roots
as they emerge from the paravertebral foramina.
 Caudal anesthesia: injected in sacral canal.

13. Methods of administration and uses (cont.)
 Spinal anesthesia: LA injected in the subarachnoid
space in
the lumbar region.
 Epidural anesthesia Anesthetics injected in epidural
space
Uses
 abdominal, pelvic and lower limbs surgery in
patients unsuitable for general anesthesia.
 Epidural anesthesia is frequently used for painless
childbirth.
Some local anesthetic used for Treatment of cardiac
dysrhythmia e.g. Lidocaine

14. Side effects
The side effects of LA are usually minimum , because they are
applied Locally. They are combined with a vasoconstrictors
such as adrenaline to decrease systemic absorption. But
some side effects may occur due to :High dose is administered
OR They are injected (mistakenly ) into blood vessels
LA Side effects are
 Restlessness, headache &convulsions followed by respiratory
depression
 hypotension and bradycardia
 Hypersensitivity reaction (with ester type)
 Mucosal irritation (cocaine, dibuacine).
Side effects are more with local anesthetic that are potent and
have long duration

15. Influencing Factors
Dosage, high dose cause:
 Fast onset
 Longer duration.
 Increase risk of side effects.
Site of administration : high vascularity cause:
 Short duration.
 High risk of side effects.
Lipid solubility of LA: more lipid soluble more effective.
Infections/ inflammations cause:
- low pH
decrease action : LA are bases thus at low pH they
become more ionized . This will reduce their
penetrations across membranes this reduces
their effects.
- Vasodilation
This Increases absorption to blood and increase risk
of side effects and reduce duration of LA.

16. (LA- Influencing Factors (cont.
Type of solution : Alkalinization of LA solution :
 Less painful.
 Increases non ionization (uncharged)
 Increases diffusion through nerve
 Increases effects.
 Produce fast onset.
Addition of vasoconstrictor ( epinephrine) will:
 Decreases vascular absorption.
 Increases duration.
 Decreases risk of side effects.
 Contraindicated when LA injected around
end arteries ( fingers, toes, ear lobes, nose)
may lead to ischemia and gangrene

17. Other Methods of producing local
anesthesia
Application of cold:
Cooling decreases excitability and conductivity of
nerve
Ischemia to tissues:
by depriving any tissue from its blood supply e.g. by
tourniquet.
Paralysis of sensory nerve endings or fibers with drugs:
Astringents may lead to local anesthesia by
precipitating nerve proteins e.g. ethyl alcohol injected
perineurally in trigeminal neuralgia

18. Thank you