Title 28. PHARMACOLOGY OF LOCAL ANAESTHETICS.pdf ✅

PHARMD GURU Page 1 Local anaesthetics (LAs) are drugs which, when applied topically or injected locally, block nerve conduction and cause reversible loss of all sensation in the part supplied by the nerve. The order of blockade of nerve function proceeds in the following manner – pain, temperature, touch, pressure and finally skeletal muscle power. CHEMISTRY (FIG. 5.6): LAs are weak bases. They consist of three parts: (i) Hydrophilic amino group; (ii) Lipophilic aromatic group; and (iii) Intermediate ester or amide linkage. CLASSIFICATION OF LOCAL ANAESTHETICS: 1. ACCORDING TO CLINICAL USE a) Surface anaesthetics: Cocaine, lignocaine, tetracaine, benzocaine, oxethazaine, proparacaine, butylaminobenzoate. b) Injectable anaesthetics I. Short acting with low potency: Procaine, chloroprocaine. II. Intermediate acting with intermediate potency: Lignocaine, mepivacaine, prilocaine, articaine. III. Long acting with high potency: Tetracaine, bupivacaine, dibucaine, ropivacaine. PHARMACOLOGY OF LOCAL ANAESTHETICS
PHARMD GURU Page 2 2. ACCORDING TO STRUCTURE a) Esters: Cocaine, procaine, chloroprocaine, benzocaine, tetracaine. b) Amides: Lignocaine, mepivacaine, bupivacaine, prilocaine, articaine, ropivacaine. MECHANISM OF ACTION:
PHARMD GURU Page 3  Blockade is frequency dependent.  Action of LA is pH dependent and the penetrability of LA is increased at alkaline pH (i.e. when the unionized form is more). Penetrability is very poor at acidic pH of tissues. In infected tissues, there is a low pH, which causes ionization of the drug. This reduces penetration of LA through the cell membrane, thus decreases the effectiveness of LAs. Therefore, LAs are less effective in inflamed and infected areas.  Diameter of nerve fibres: LAs block small fibres first followed by larger fibres.  Myelinated fibres are blocked earlier than nonmyelinated nerves of the same diameter.  Sensory fibres are blocked earlier than motor fibres because of their high firing rate and longer duration of action potential.  Fibres in the centre are blocked later than the ones located in the circumference of the nerve bundle. FACTORS AFFECTING LOCAL ANAESTHETIC ACTION: COMBINATION OF VASOCONSTRICTOR WITH LOCAL ANAESTHETIC: ADDITION OF A VASOCONSTRICTOR (E.G. ADRENALINE) TO THE LA HAS THE FOLLOWING ADVANTAGES: 1. Slow absorption from the local site which results in prolonged duration of action of LAs.
PHARMD GURU Page 4 2. Decreased bleeding in the surgical field. 3. Slow absorption of LA reduces its systemic toxicity. DISADVANTAGES AND CONTRAINDICATIONS OF COMBINING VASOCONSTRICTOR WITH LA: 1. Intense vasospasm and ischaemia in tissues with end arteries may cause gangrene of the part (e.g. fingers, toes, penis, ear lobule and tip of the nose). Hence, use of vasoconstrictors is contraindicated in these sites. 2. Absorption of adrenaline can cause systemic toxicity – tachycardia, palpitation, rise of BP and precipitation of angina or cardiac arrhythmias. Hence, combined preparation (LA with adrenaline) should be avoided in patients with hypertension, congestive cardiac failure (CCF), arrhythmias, ischaemic heart disease and uncontrolled hyperthyroidism. 3. May delay wound healing by reducing the blood flow to the affected area. PHARMACOLOGICAL ACTIONS: 1. NERVOUS SYSTEM: (a) Peripheral nerves: Autonomic fibres are blocked earlier than somatic fibres. Sensation of pain disappears first followed by temperature, touch, pressure and motor functions. (b)CNS: Most of the LAs cross the blood–brain barrier (BBB) – initially they cause CNS stimulation and then depression in higher doses. They cause excitement, tremor, twitching, restlessness and convulsions. Large doses can cause respiratory depression, coma and death. 2. CARDIOVASCULAR SYSTEM: (a) Heart: LAs, by blocking Na+ channels, decrease abnormal pacemaker activity, contractility, conductivity, excitability, heart rate, cardiac output and increase effective refractory period. (i) At higher concentrations, i.v. administration of LAs may precipitate cardiac arrhythmias. (ii) Bupivacaine is more cardiotoxic than other LAs – may cause cardiovascular collapse and death. (iii) Lignocaine decreases automaticity and is useful in ventricular arrhythmias.