1. LOCAL ANAESTHESIA

2. Local Anesthetics
Local anesthesia is any technique to induce the absence of sensation in a specific part of the body, generally for the aim of inducing local analgesia, that is, local insensitivity to pain, although other local senses may be affected as well.
Reversible inhibition of sensory nerve impulse conduction
Prevent transmission of information to the CNS
No loss of consciousness
Local anesthetics produce a reversible regional inhibition of sensory nerve impulse conduction, preventing transmission of sensory information to the CNS without a loss of consciousness.

3. Clinical Usefulness Depends on: Inherent Anesthetic potency
Rate of onset
Duration of effect
Which in turn is dependent on:
Physiochemical properties
Inherent vasodilator activity

4. Physiochemical Properties
Lipid Solubility
Protein Binding - duration
pKA – determines onset of anesthesia

5. Pharmacokinetics of Common Local Anesthetics
Molecular weight
pKa
Protein binding
Maximum dose (mg)
Lidocaine
234
7.9
65 %
300
500 w/ Epi
Racemic bupivacaine
288
8.01
95 %
175
225 w/ Epi
Ropivacaine
328.89
8.07
94 %
150
L-bupivacaine
324.9
8.09
> 97 %
Slide 22
As to the pharmacokinetics of common local anesthetics, levobupivacaine has the highest protein binding which is >97%. The importance of this is that the levobupivacaine will remain tightly protein bound to the neuronal membrane thus prolonging the duration of action.

6. Vasodilator Properties
All except cocaine exhibit biphasic effect on vascular smooth muscle
Extreme low concentration provides vasoconstriction
Concentration for regional anesthesia provides vasodilatation

7. NON PHARMACOLOGIC FACTORS INFLUENCING ACTIVITY
Dosage
Addition of vasoconstrictor
Site of injection
Additives
Mixture of LA

8. Dosage Site on Injection
Primary qualities of regional anesthesia (onset, duration, depth) are related to the mass of the drug  volume x concentration
Site on Injection
Due to the particular anatomy of the area of the injection, variation in the rate of absorption & amount of drug used
In Spinal anesthesia, lack of nerve sheath around spinal cord are responsible for the rapid onset

9. Mixture of Local Anesthesia
Additives
CO2
NaHCO3 – increase pH near pKA more ionized  faster entry faster onset
KCl
Dextran
Mixture of Local Anesthesia
 basis is for the mixture of local anesthesia to compensate for the short duration of action and the long latency of others

10. Clinically Useful Local Anesthesia
AMINO-ESTERS
Ester link between aromatic and main portion of the molecule
AMINO-AMIDES
Amide linkages

11. Local Anesthetics ClassificationNH C O
1) Amides
CH3
CH2 N
CH3
Lidocaine, Bupivacaine, Ropivacaine, Levobupivacaine C O
2) Esters
Slide 4
. Furthermore, local anesthetics are classified into amides and esters depending on the linkage between the hydrophilic quarternary amine portion (NH3) and lipophilic unsaturated benzene ring that make up its typical structure.
As a review and for easier recall, remember that all amides have 2 Is such as lidocaine, bupivacaine, ropivacaine and the newest in the market levobupivacaine. While esters have one I like procaine, chloroprocaine, cocaine and tetracaine.
Procaine, Chloroprocaine, Cocaine, Tetracaine

12. Mechanism of Action
Prevent generation and conduction of nerve impulses by decreasing or preventing the large transient increase in permeability of excitable membranes to Na+

13. Indications for local anesthesia
Most frequent use: regional anesthesia.
Analgesic espescially post operative pain.
Lidocaine (Xylocaine) also reduces blood pressure response to direct laryngoscopic tracheal intubation, an effect probably secondary to generalized cardiovascular depression.
Treatment of intractable cough.

14. Local Anesthetics Mechanism of Action
blocks voltage-sensitive Na+ ion channels in neuronal membrane
prevent Na+ influx (Depolarization)
prevent transmission
of nerve impulses
Slide 10
Levobupivacaine shares the same mechanism of action as with other traditional local anesthetics.

15. Low anesthetic potency & short duration of action  procaine & chloroprocaine
Intermediate anesthetic potency & duration of action  lidocaine, mepivacaine & prilocaine
High anesthetic potency and prolonged duration of action  tetracaine, bupivacaine : racemic and levobupivacaine, ropivacaine,
ethidocaine

16. Essential Precautions:
Secure intravenous access before injection of any dose that may cause toxic effects.
Always have adequate resuscitation equipment and drugs available before starting to inject.

17. Advantages of local anaesthesia
Non inflammable.
Excellent muscle relaxant effect.
During local anesthesia the patient remains conscious.
It requires less skilled nursing care as compared to other anesthesia like general anesthesia.
Maintains his own airway.

18. Less pulmonary complication.s
Aspiration of gastric contents unlikely.
Less nausea and vomiting.
Contracted bowel so helpful in abdominal and pelvic surgery.
Postoperative  analgesia.
There is reduction surgical stress.
Earlier discharge for outpatients.

19. Suitable for patients who recently ingested food or fluids.
Local anesthesia is useful for ambulatory patients having minor
procedures.
Ideal for procedures in which it is desirable to have the patient awake and cooperative.
Less bleeding.
Expenses are less.

20. Disadvantages of local anaesthesia
There are individual variations in response to local anesthetic drugs.
Rapid absorption of the drug into the bloodstream can cause severe, potentially fatal reactions.
Apprehension may be increased by the patient's ability to see and hear. Some patients prefer to be unconscious and unaware.

21. Direct damage of nerve.
Post-dural headache from CSF leak.
Hypotension and bradycardia through blockade of the sympathetic nervous system.
Not suitable for extremes of ages.
Multiple needle bricks may be needed.

22. TOXICITY Local Anesthetic Toxicity Systemic – CNS, CVS
Local – neural & skeletal muscle irritation
Specific – addiction, allergy, methemoglobinemia

23. LOCAL ANESTHETIC TOXICITY
Depend on blood level of local anesthetic delivered to the brain and heart
Appropriate dose and technique rarely causes adverse reaction
Toxic levels – usually due to intravascular injection or excess dose in extravascular administration

24. Systemic Toxicity CNS Toxicity Related to intrinsic anesthetic potency
LOW DOSE – excitatory
Mechanism: selective blockade of inhibitory Pathway in the cerebral cortex  allows facilitatory neurons to function unopposed
LARGE DOSES – CNS depression
Mechanism: inhibition of both facilitatory & inhibitory Pathway
Sign: convulsion ceases, respiratory depression, arrest

25. Subjective CNS Symptoms
light headedness
Dizziness
Visual & Auditory disturbances – difficulty in focusing & tinnitus
disorientation
drowsiness

26. Objective CNS Signs (at low dose)
shivering
Muscular twitching
Tremors – muscles of face and distal parts of the extremities
convulsions – tonic, clonic

27. Factors that Affect CNS Toxicity
Potency
Rate of Injection
Rate at which a particular blood level is attained

28. Effects of Increase pCO2 on CNS Toxicity
pCO2 level is inversely related to convulsive threshold
Enhances cerebral blood flow so more local anesthetic is delivered to the brain
Decrease plasma protein binding of local anesthetics, more local anesthetic available to the brain

29. CVS Toxicity – Cardiac, Vascular
Cardiac Effect
Dose dependent negative inotropic action – depends on potency of LA
Inhibit Na conductance in fast channels
High concentration of lidocaine, procaine & tetracaine can block slow calcium channels
Increase LV EDP, direct pulmonary vasoconstriction effect

30. Cardiotoxicity INDIRECT EFFECTS a) block sympathetic  innervation
b) other CNS-mediated mechanisms
a) Block  Na+ channels conduction delay & QRS prolongation
b) Block K+ & Ca++ channels
Slide 11
The cardiotoxicity of local anesthetics may be brought about indirectly or directly. Indirect effects of local anesthetics are brought about by blocking sympathetic innervation or through other CNS mediated mechanisms. They may also act directly by blocking the sodium channels thereby delaying the conduction of nerve impulses & prolonging the QRS complexes. Likewise, local anesthetics may have a direct effect on cardiac activity by blocking the potassium and calcium channels.

31. CVS Toxicity Peripheral Vascular Effects (BIPHASIC)
LOW DOSE – stimulates myogenic contraction and augments basal tone leading to higher pressure
HIGH DOSE – inhibits myogenic activity vasodilation
COCAINE – initial effect is vsaodilatation followed by vasoconstriction at low and high doses
Mechanism of Action – inhibits re-uptake of NE by tissue binding site, therefore no re-uptake leading to increase free NE, potentiating the effects of adrenergic stimulation.(hypertension and ventricular ectopia)

32. Local Toxicity
The more potent longer acting local anesthetics (e.g. Bupivacaine, ethidocaine): > degree of localized skeletal muscle damage than less potent shorter acting agents like Lidocaine and Prilocaine
Reversible
No clinical signs of local irritation

33. Specific Toxicity Methemoglobinemia – PRILOCAINE Allergy
Mechanism: degraded in the liver to ortotoluidine which causes oxidation of Hb
 requires 600mg Prilocaine to produce clinical level of Methemoglobenemia
Reversed with Methylene blue
Allergy
AMINO ESTERS  derivatives of para-amino-benzoic-acid (allergenic)