Ch 17 Pharmacology Of Local Anaesthetic Drugs

CHAPTER 17

PHARMACOLOGY OF LOCAL ANAESTHETIC DRUGS

Outline: History of local anaesthesia Pharmacology of local anaesthetic drugs Toxicity and treatment of toxic reactions Individual drugs Autoclaving drugs Vasoconstrictors

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HISTORY OF LOCAL ANAESTHESIA Cocaine was the first local anaesthetic drug in use. It occurs naturally in South America. Cocaine, however, fell in popularity because of its toxicity and the danger of addiction. Procaine (Novocaine) was the next agent used fairly widely. This was followed by cinchocaine and lignocaine. PHARMACOLOGY OF LOCAL ANAESTHETIC DRUGS Several local anaesthetic drugs are available. It is important to become thoroughly familiar with the commonly used ones. Lignocaine (Xylocaine, Lidocaine) is now one of the most popular local anaesthetic agents. Bupivacaine (Marcaine) is used when more prolonged anaesthesia is required. Levobupivacaine (Chirocaine) and ropivacaine (Naropin) are recently introduced drugs with similar properties to bupivacaine but less toxic. Amethocaine is also useful and available in many countries. Local anaesthetics are used mostly in the form of hydrochlorides. The alkaline tissues tend to release the bases which then combine with the nerve tissues. In infected tissues the acid of the pus makes these drugs less active. Local anaesthetics retard or stop the propagation of impulses along the nerves. TOXICITY OF LOCAL ANAESTHETIC SOLUTIONS Causes of toxic reactions • The use of the drug in a dose greater than the safe maximum for that drug. • The accidental injection of the correct dose into a blood vessel. This will result in a very high blood concentration. • The use of the correct dose in a patient who is especially sensitive to the drug. Factors affecting the toxicity of local anaesthetic agents • Quantity of solution used • Concentration of solution used • Presence or absence of adrenaline • Vascularity of the site of injection, e.g. absorption of the drug from the nose, pharynx and respiratory tract is very rapid • Hypersensitivity to the drug (this is rare) • Age, physical status and weight of the patient

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•

The presence of liver or renal disease

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Symptoms, signs and emergency treatment of toxic reactions (See also Chapter 25) Central nervous system (CNS) • Stimulation – tinnitus, circumoral numbness, nystagmus, restlessness, tremor, convulsions followed by • Depression – depressed conscious level, coma Treatment − Give oxygen − Give sufficient diazepam or midazolam to control the convulsion. Thiopentone may also be used in a small dose (e.g. 50 mg). − If associated apnoea, give artificial ventilation with 100% oxygen following intubation with a dose of suxamethonium chloride. Cardiovascular system (CVS) • Pulse – bradycardia, arrhythmias, cardiac arrest • Blood Pressure –hypotension, cardiovascular collapse Treatment: − Give IV fluids. − Give vasopressors and atropine, if necessary. − Give oxygen by mask. − Watch for and be ready to treat cardiac arrest. Respiratory system • Respiratory depression, apnoea. Treatment − Clear airway − Give oxygen by mask − Assist or control ventilation Other side effects Allergic phenomena (rare) These may take the form of bronchospasm, urticaria, hypotension, etc. Reaction to vasoconstrictor drugs Pallor, tachycardia, palpitation, hypertension. INDIVIDUAL LOCAL ANAESTHETIC DRUGS COCAINE produces surface anaesthesia and intense vasoconstriction. Its use is now restricted to ENT surgery. It is rapidly absorbed through mucous membranes. It should never be injected. Cocaine should not be used on a patient having a general anaesthetic, unless

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ECG monitoring is available.

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Systemic effects CNS Stimulation. Euphoria (a sense of well being) which may lead to addiction. CVS Sudden cardiac standstill has occurred; cardiovascular collapse. Muscle Curare-like effect. Safe maximum dose (adults): 1.5 mg/kg by direct application to nasal mucosa. LIGNOCAINE (Lidocaine, Xylocaine) Lignocaine has a faster onset and longer duration than procaine. Lignocaine has low toxicity and is also used as an anti-arrhythmic. Onset of action: 2-5 mins Duration of action: Plain lignocaine: 45 minutes to 1 hour Lignocaine with adrenaline: 1 to 1.5 hours Concentrations of lignocaine commonly used: • Topical: larynx, pharynx 2 – 4% or 10%. • Infiltration: 0.25 – 0.5% with adrenaline 1/200,000. • Nerve block: 1 – 2% with adrenaline 1/200,000. • Spinals: 5% lignocaine for hyperbaric spinals. Safe maximum dose: Plain lignocaine: Lignocaine with adrenaline:

200 mg (i.e. 3 mg/kg) 500 mg (7 mg/kg)

It is important to calculate the volume of local anaesthetic that can safely be used. • 1% solution has 10 mg/ml • 2% solution has 20 mg/ml • 5% solution has 50 mg/ml BUPIVACAINE (Marcaine) is a newer local anaesthetic drug. It is four times as potent as Lignocaine, so a 0.5% solution of bupivacaine is equivalent to 2% lignocaine. Onset of action: 20 mins Duration of effect: 5 to 6 hours or longer Formulations: 0.25% plain 0.5% plain 0.25% with adrenaline 1/200,000 0.5% with adrenaline 1/200,000 0.5% heavy (with glucose) Safe maximum dose: 2 mg/kg for plain bupivicaine 2.5 mg/kg for bupivacaine with adrenaline

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LEVOBUPIVACAINE (Chirocaine) is an isomer of bupivacaine introduced recently. It has similar properties to bupivacaine but is less cardiotoxic. Onset of action: 20 mins Duration of effect as for bupivacaine Formulations 0.2% 0.5% 0.75% (not for use in obstetrics) Safe maximum dose 2mg/kg AMETHOCAINE HYDROCHLORIDE (Pontocaine, Tetracaine) belongs to the cocaine and procaine group of drugs. It is used to produce surface infiltration and caudal and spinal anaesthesia. Amethocaine is potent and relatively toxic. It may deteriorate on autoclaving. Onset of action: 5-10 minutes Duration: 2 hours The maximum dose that could be used for spinals is 15- 20 mg. It is mixed with equal quantities of CSF or 10% Dextrose. LOCAL ANAESTHETICS USED FOR SPINAL in NON-PREGNANT PATIENTS (Doses in the sitting position) Drug Lignocaine Amethocaine Bupivacaine

Concentration (%) 5 1 0.5

Duration (hours) 1.5 1.5 – 2 5–8

Dose Range for fit adult 1 – 2 ml 1 – 2 ml 2 – 3 ml

Fixation time For spinals, using lignocaine: 5 to 20 minutes. Amethocaine takes longer: a minimum of 10 minutes. For Caesarean section under spinal anaesthetic see Chapter 19

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EMLA is a local anaesthetic cream, a 50:50 mixture of lignocaine and prilocaine (25 mg of each per ml). It produces surface anaesthesia. A thick layer of cream is applied to the skin and covered with a plastic dressing. Onset of Action: > 1 hour Indications • IV cannulation in children and nervous adults. • Any superficial but painful skin procedure, e.g. skin grafts. Problems • EMLA produces pallor, oedema and vaso-constriction at site of application. • Absorption of drugs can be excessive, especially in neonates. AUTOCLAVING LOCAL ANAESTHETIC SOLUTIONS The commonly used solutions are very stable and it is possible to autoclave lignocaine, procaine and bupivacaine without any deterioration in potency. Repeated autoclaving of solutions used for spinal anaesthesia, however, can lead to some deterioration (especially with amethocaine) and therefore should be avoided. If the spinal anaesthetic solution changes colour it should be discarded. VASOCONSTRICTORS Local anaesthetic solutions are available with or without added vasoconstrictor drugs (adrenaline). The local anaesthetic drugs (all except cocaine) dilate blood vessels. This results in an increased rate of absorption and a decreased duration of action on the nerves. The vasoconstrictor drugs (e.g. adrenaline) produce vasoconstriction at the site of action of the local anaesthetic solutions. This results in an increased duration of action and a decrease in the absorption of the drug into the circulation. Hence, the side effects of the local anaesthetic drugs are minimised. A bigger total dose of local anaesthetic can be used. The concentration of adrenaline used is 1/200,000 (i.e. 1mg of adrenaline in 200 ml of solution). The total dose of adrenaline used must not exceed 1mg (i.e. 1ml of a 1:1000 solution) for the adult patient. Caution • The use of adrenaline in spinal anaesthetic solutions is not recommended although it is sometimes added to lignocaine where there is not a longer acting drug available. There is a risk of causing permanent neurological damage. • Adrenaline–containing local anaesthetics should not be used on fingers, toes, ears or penis. • The use of adrenaline in surface anaesthetic solutions applied to

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mucous membranes does not prolong the duration of the block.

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