Local anaesthetics Local anaesthetics Anton Kohút Anton Kohút

Local annaesthetics (LA) are drugs emploed to produce transient and reversible loss of sensation in circumscribed region of the body Local annaesthetics (LA) are drugs emploed to produce transient and reversible loss of sensation in circumscribed region of the body

History of local anaesthesia in 1884, cocaine was first used as a local anaesthetic to immobilize a patient's eye for eye surgery by Carl Koller in 1884, cocaine was first used as a local anaesthetic to immobilize a patient's eye for eye surgery by Carl Koller Carl Ludwig Schleich is the pioneer of infiltration anaesthesia in 1892 Carl Ludwig Schleich is the pioneer of infiltration anaesthesia in 1892 ( ) ( )

Mechanismm and action of LA these drugs bind selectively to the intracellular surface of sodium channels and block entry of sodium into the cell  block the depolarisation these drugs bind selectively to the intracellular surface of sodium channels and block entry of sodium into the cell  block the depolarisation LA bind more readily to Na + channels in inactivated state - onset of neuronal blockade is faster in neurons that are rapidly firing (state-dependent blockade) LA bind more readily to Na + channels in inactivated state - onset of neuronal blockade is faster in neurons that are rapidly firing (state-dependent blockade)

E ffect of pH LA are weak bases (hydrochloride salt = water- soluble) LA are weak bases (hydrochloride salt = water- soluble) only the un ionised molecule diffuses readily across cell membranes only the un ionised molecule diffuses readily across cell membranes acidosis (in inflammation) partly reduces the action of LA - most of the LA is ionised & therefore unable to cross the cell membrane acidosis (in inflammation) partly reduces the action of LA - most of the LA is ionised & therefore unable to cross the cell membrane

Mechanismm and action of LA – cont. Actions on various nerve fibers LA block conduction in small diameter nerv fibers more readily when in large fibers LA block conduction in small diameter nerv fibers more readily when in large fibers Fibers C (under 1  m, unmyelinated postgaglionic and somatic)-autonomic paralysis, loss of the sensation of itch and tickle pain Fibers C (under 1  m, unmyelinated postgaglionic and somatic)-autonomic paralysis, loss of the sensation of itch and tickle pain Fibers B (1-3  m, myelinated preganglionic ) autonomic paralysis. Fibers B (1-3  m, myelinated preganglionic ) autonomic paralysis. Fibers A (1-20  m, myelinated, somatic, motor and some somatic)- sceletal muscle relaxation, loss of thermal and tactil sansation, proprioceptive loss, loss of sharp pain. Fibers A (1-20  m, myelinated, somatic, motor and some somatic)- sceletal muscle relaxation, loss of thermal and tactil sansation, proprioceptive loss, loss of sharp pain.

Mechanismm and action of LA – cont. Metabolism of LA esters are primarily inactivated in plasma by hydrolysis (pseudocholinesterase) esters are primarily inactivated in plasma by hydrolysis (pseudocholinesterase) - they generally have a relatively short half-life in the body - they generally have a relatively short half-life in the body - in spinal fluid (absence of esterase activity) duration of anaesthesia is extended - in spinal fluid (absence of esterase activity) duration of anaesthesia is extended amides are metabolized by liver microsomes amides are metabolized by liver microsomes - metabolites are excreted by urine - metabolites are excreted by urine - liver disease  cumulation of drugs  higher risk of toxicity - liver disease  cumulation of drugs  higher risk of toxicity

Pharmacokinetics LA should act locally LA should act locally the duration of action of all agents is prolonged by the addition of adrenaline when used for infiltration anaesthesia & peripheral nerve blocks the duration of action of all agents is prolonged by the addition of adrenaline when used for infiltration anaesthesia & peripheral nerve blocks adrenaline also increases the duration of extradural anaesthesia when added to procaine, mepivacaine & lidocaine but does not alter markedly the duration of action of extradural prilocaine, bupivacaine or etidocaine adrenaline also increases the duration of extradural anaesthesia when added to procaine, mepivacaine & lidocaine but does not alter markedly the duration of action of extradural prilocaine, bupivacaine or etidocaine

Vasoconstrictors in local anaesthesia - to slow absorption - to slow absorption - to prolong the local action - to prolong the local action - to decrease toxicity - to decrease toxicity

Pharmacokinetics (practical point ) adrenaline 1:1000 contains 1 g of adrenaline per 1000 ml solution i.e. 1mg/ml adrenaline 1:1000 contains 1 g of adrenaline per 1000 ml solution i.e. 1mg/ml to prepare a 1 in solution the 1:1000 must be diluted 200 times to prepare a 1 in solution the 1:1000 must be diluted 200 times this is achieved by taking 0.1ml (= 0.1mg) & adding 19.9 ml of LA solution this is achieved by taking 0.1ml (= 0.1mg) & adding 19.9 ml of LA solution

Pharmacokinetics (adrenaline contraindications ) adrenaline never be used for infiltration around end-arteries i.e. penis, ring block of fingers or other areas with a terminal vascular supply (ischaemia, necrosis) adrenaline never be used for infiltration around end-arteries i.e. penis, ring block of fingers or other areas with a terminal vascular supply (ischaemia, necrosis) in patients with diabetes & CV diseases: in patients with diabetes & CV diseases:hypertension severe atherosclerosis hearth failure after IM

Methods of aplication of LA Methods of aplication of LA

Mode of application of LA topical (surface) infiltration plexus block epidural (extradural) spinal (subarachnoid)

Methods of aplication of LA 1. Surface anaesthesia  - the LA solution is applied directly to the mucosal surface: nose and mouth, bronchial tree, oesophagus or genitourinary tract  - LA can be absorbed into the circulation following topical aplication to mucous (mainly tracheobronchial tree)  risk of toxicity  - relatively high doses are often used  tetracaine (2%), lidocaine (2-10%), cocaine (1-4%) 2. Infiltration anaesthesia  - LA are injected directly into the tissues to reach fine nerve branches and sensory nerve terminals  - most frequently used LA  lidocaine (0.5-1%), procaine (0.5- 1%), bupivacaine ( %)

Methods of aplication of LA – cont. 3. Nerve-block anaesthesia - LA are injected close to the appropriate nerve trunks - widely used methods  much less anesthetics are needed :-procaine (0.5-1%), lidocaine (1-2%), mepivacaine (1-3%), bupivacaine ( %) are used 4. Spinal and epidural anaesthesia spinal (subdural) anaesthesia - LA is injected into the lumbar subarachnoid space, which contains cerebrospinal fluid, spinal (subdural) anaesthesia - LA is injected into the lumbar subarachnoid space, which contains cerebrospinal fluid, epidural anaesthesia - LA is injected just outside the dura into a narrow space between the dura and the bony spinal canal epidural anaesthesia - LA is injected just outside the dura into a narrow space between the dura and the bony spinal canal - advantage  relatively small doses of LA are needed - advantage  relatively small doses of LA are needed -unwanted effects in spinal anaesthesia are:  vasodilatation,  bradykardia,  marked fall in arterial pressure -unwanted effects in spinal anaesthesia are:  vasodilatation,  bradykardia,  marked fall in arterial pressure

Side effects of LA CNS - all LA cause stimulation of CNS: - restlessness and tremor  tremor can progress to convulsion - further increasing the dose  CNS depression main threat for life comes from respiratory depression - cocaine has different effect on CNS  doses lower than convulsive produce marked euphoria Treatment: Treatment: restoration of normal ventilation and circulation restoration of normal ventilation and circulation diazepam in prevention and treatment of seizures diazepam in prevention and treatment of seizures

Side effects of LA – cont. Cardiovascular system - myocardial depression and vasodilatation - vasodilatation  partly direct effect on vascular smooth muscle and partly inhibition of sympathetic nevous system (centrally) - this combined effect  marked fall in blood pressure - cocaine  inhibition of adrenaline re-uptake  tachycardia, vasoconstriction and increase of arterial pressure Effects of vasoconstrictors local ischemia, anxiety, tachycardia, hypertension Contraindications of vasoconstrictors hypertension, atherosclerosis, thyreotoxicosis, congestive heart failure hypertension, atherosclerosis, thyreotoxicosis, congestive heart failure Allergy - esters. There is not cross-reactivity with the amides. Allergy - esters. There is not cross-reactivity with the amides.

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