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 re-established.

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 Concentration
Plain Infiltration 0.5% 1.0% 40 20

Volume
Adrenaline 100 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