LOCAL

ANESTHETICS

Dr. Prabowo Wicaksono Y.P., SpAn

Anesthesiology Department
UNISSULA Medical Faculty
2012

DEFINITION OF LOCAL ANESTHETICS (LA)

A drug which reversibly prevents transmission of the nerve impulse
in the region to which it is applied, causes reversible local analgesic
effect, without affecting consciousness.
STRUCTURAL CLASSIFICATION
Local anesthetics generally have a lipid soluble lipophilic aromatic
group and a charged hydrophilic amide group. The bond between
these two groups determines the class of the drug.
There are 2 classes: Aminoamide and Aminoester

Amides: lignocaine, bupivacaine and prilocaine

Esters: cocaine and amethocaine
Ester linkage is more easily broken than the amide bond so the ester
drug are less stable in solution and cannot be stored for as long as
amides.
Ester metabolism result in production of para-aminobenzoate (PABA)
which is associated with allergic reaction. Amides in contrast very
rarely cause allergic phenomena: amides are now more commonly
used than esters.

MECHANISM OF ACTION
Disruption ion channel function within the neuron cell membrane
preventing the transmission of the neuronal action potential by binding
of the local anesthetics molecules to sodium channels, preventing
influx sodium channel into nerve cell preventing propagation of the
action potential.

pKa of LOCAL ANESTHETICS DRUGS

All local anesthetics are weak bases, meaning that they exist in two
forms: unionized (B) and ionized (BH+).
The pKa of a weak base defines the pH at which both forms exist is equal
amounts. As the pH of the tissue differs from the pKa of the specific drug,
more of the drug exists either in its charged or uncharged form.
At physiological pH (7.4) all LA are more ionized than unionized.
As the drug must enter the cell in order to have its effect, it must pass
through the lipid cell membrane. Unionized drug will do this more readily
than ionized drug. Therefore the drug which is more unionized at
physiological pH will reach its target site more quickly than the drug
which is less so.
Lignocaine (lidocaine) has a pKa of 7.9 and is approximately 25%
unionized at pH 7.4.
Bupivaccaine has a pKa 8.1 and is approximately 15% unionized at ph
7.4.
Therefore Lignocaine has a faster onset of action than bupivacaine.
The closer the pKa of LA to physiological pH (7.4), the more unionized
form it has, the faster the onset.

Why LA often dont work in infected tissue?

The infected tissue tends to be more acidic environment than usual. As
the pH is reduced, the fraction of unionized LA is reduced and
consequently the effect is delayed and reduced. Infected tissue may
also have an increased blood supply hence more anesthetics may be
removed from the area before it can affect the neuron.
PHARMACOKINETICS OF LOCAL ANESTHETICS
ABSORBTION AND DISTRIBUTION
Local anesthetic drugs are administrated to the area around the nerve
to be blocked, some of the drug will be absorbed into the systemic
circulation. How much will depend on the vascularity of the area to
which the drug has been applied, vasodilatory or vasoconstrictive effect
of the drug, tissue and plasma protein binding. The more protein bound
the agent, the longer the duration of action.
METABOLISM AND EXCRETION
Ester and amide anesthetics differ in their metabolism.
Ester are broken down rapidly by plasma esterase to inactive
compounds and consequently have a short half life. Ester metabolism
excretion are renal.
Amides are metabolized hepatically by amides. This is a slow process,
hence their half life are longer and they can accumulate if given in
repeated doses or by infusion

EFFECT ON FOETUS
Ester are metabolized rapidly, so little remains in the maternal
circulation to cross placenta.
Amide are more likely to cross placenta. Of this, placental transfer is
greater in less protein bound agent such as lidocaine.
CLINICAL USES OF LOCAL ANAESTHETICS
Available as injection, sprays, creams and gels. The drugs may also be
combined with other local anesthetics or additives to enhance their
effect e.g. adrenaline, bicarbonate and glucose.
Adrenaline acts as a vasoconstrictor, to minimize the vasodilator effect
of (for example) lignocaine and decreases the rate at which drug is
removed from the site of action by absorption into the systemic
circulation. It also reduces traumatic (surgical) blood loss from the
surgery site.
Bicarbonate increases the pH of the environment when administrated,
more drug will be present in its unionized form and speed the onset.
Glucose is added to bupivacaine in order to increase the baricity of the
solution to greater that of CSF, resulted in more controlled spread of
solution within the intrathecal space.

POSSIBLE HARMFULL EFFECTS OF LOCAL ANAESTHETICS

Local anesthetics may be toxic if sufficient amounts are absorbed into
the systemic circulation. Bupivacaine appears to be most dangerous,
although all can be harmful.
Clinical toxicity appears to be relate to the effects of the drug on the
Central Nervous System (CNS) and cardiovascular system.
CNS effect: tingling of the lips, slurred speech, reduce level of
consciousness, and seizures.
Cardiac effect: arrhythmias and reduced myocardial contractility
Unexpected LA toxicity can occur where the pharmacokinetics of the
drugs are altered by co morbidity such as cardiac or hepatic failure.
Toxicity depends on the amount of free drug in plasma; this relates to 3
factors:
1.Dose given
2.Rate of injection
3.Site of injection (the greater the blood supply to the area injected, the
greater the systemic absorption. Sites of absorption from greatest to
least:
intrapleural > intercostal > pudendal > caudal > epidural >
brachial plexus > infiltration.

TREATMENT OF LA TOXICITY
Treatment for CNS toxicity (seizures) of LA is essentially supportive.
Ensure that the airway is patent and the patient is breathing
spontaneously. Apply supplemental oxygen. Lay the patient flat.
Ensure that the patient has iv access and that intravenous fluid is
running. Check the patients pulse and blood pressure. If the patient
is unconscious, chin lift / jaw thrust maneuver can be applied. Do not
place any devices between patients teeth if they are seizing.
If seizures does not rapidly self resolve, then intravenous midazolam
(0.05 mg-0.1 mg/kg) or diazepam 5-10 mg/kg) may be administered
to control seizure activity.
An alternative approach would be to secure airway following induction of
anesthesia with propofol and administration of propofol infusion.

Intravenous lipid emulsion (intralipid 20%) appears to be effective at

minimizing adverse cardiovascular outcomes. It is believed that the
lipid acts as a bank for local anesthetic the drug has more affinity
for the lipid than for cardiac tissue; as the amount of LA
(bupivacaine) bound up to cardiac tissue is reduced, normal
contractile function results.
Dosage of intralipid for LA toxicity: initial bolus 100 ml (1.5 ml/kg
over 1 minute) followed by 400 ml (0.25 ml/kg) over 20 minutes.
Repeat bolus can be administrated subsequently: 100 ml at 5 minute
intervals repeated 2 times and then 400 ml administrated over 10
minutes
CPR should be continued until the circulation has been reestablished.

LIDOCAINE (XYLOCAINE or LIGNOCAINE)

History
The first amide type LA.
Synthesized under the name xylocaine by Swedish chemist Nils
Lofgren in 1943.
Usage: common LA and antiarrhytmic drug.
Used topically to relieve itching, burning and pain from skin
inflammation.
Injected as dental anesthetic or as local anesthetic for minor surgery.
Rapid onset of action and intermediate duration.
Suitable for infiltration, block and surface (topical) anesthesia.
Lidocaine also has antiarrhytmic drug for treatment of ventricular
arrhythmias.

CONTRAINDICATIONS
Heart block (2nd and third degree)
Severe Sinoatrial block
Serious adverse drug reaction to lidocaine or amide LA
Concurrent treatment with quinidine, procainamide
Prior use of Amiodarone
Hypotension not due to arrhtymia
Bradycardia
Accelerated idioventricular rhythm
Pacemaker
Porphria
ADVERSE EFFECT
Adverse drug reaction (ADRs) are rare when lidocaine is used as local
anaesthetics and is administrated correctly.
Most ADRs associated with lidocaine for anesthesia relate to
administration technique ( resulting in systemic exposure) or
pharmacological effects of anesthesia, and allergic reaction rarely occur.

Systemic exposure to excessive quantities of lidocaine mainly result in

CNS and CV effect.
CNS effects: CNS excitation (nervousness, tingling around the mouth/
circumoral paraesthesia), tinnitus, tremor, dizziness, blurred vision,
seizures) followed by depression, and with increasingly heavier
exposure: drowsiness, loss of consciousness, respiratory depression
and apnea.
CV effect: hypotension, bradycardia, arrhythmias and or cardiac arrest
some of which may be due to hypoxemia secondary to respiratory
depression.
OVERDOSE
Can be result of excessive administration via topical or parenteral
routes, accidental oral ingestion of topical preparation by children,
accidental intravenous injection, or prolonged use of subcutaneous
infiltration anesthesia during cosmetic surgical procedures.
MAXIMAL DOSE
Without adrenaline: 3 mg/kg bodyweight
With adrenaline: 7 mg/kg bodyweight.
Onset : 5-10 minutes
Duration: 1-2 hours (without adrenaline), 2-4 hours (with adrenaline)

Lignocaine Recommended Dosages (70

kg adult)

Procedure
Volume

Concentration
Plain

Infiltration

Adrenaline

0.5%

40

100

1.0%

20

50

2.0%

10

25

PEHACAINE
Only available in Indonesia
INDICATION
Local Anesthetics
CONTRAINDICATION
Local inflammation or sepsis, tirotoksikosis, end arteriole or extremity.
SPECIAL PRECAUTION
Hypertension, Ischemic Heart Disease, Insufficiency Cerebrovascular,
Heart Block
PREPARATION
1 amp 2 ml, each ml 20 mg Lidocaine + 0.0125 mg Adrenaline (12.5
microgram) or 1/80.000.
Adrenaline acts as a vasoconstrictor to minimize the vasodilator effect
of lidocaine and decrease the rate at which the drug removed from the
site of action by absorption into the systemic circulation. It also reduces
traumatic (surgical) blood loss from the site by the same mechanism.

THE END