local anaesthetics local anaesthetics anton kohút anton kohút
TRANSCRIPT
Local anaestheticsLocal anaesthetics
Anton KohútAnton Kohút
Local annaesthetics (LA) are Local annaesthetics (LA) are drugs emploed to produce drugs emploed to produce transient and reversible loss of transient and reversible loss of sensation in circumscribed sensation in circumscribed region of the bodyregion of the body
History of local anaesthesiaHistory of local anaesthesia
iin 1884, n 1884, cocainecocaine was first was first used as a local used as a local anaesthetic to immobilize anaesthetic to immobilize a patient's eye for eye a patient's eye for eye surgery bysurgery by Carl KollerCarl Koller
Carl Ludwig SchleichCarl Ludwig Schleich is is the pioneer of the pioneer of infiltrationinfiltration anaesthesia anaesthesia in 1892in 1892
(1857 - 1944)
(1859-1922)
Mechanismm and action of LAMechanismm and action of LA
these drugs bind selectively to the these drugs bind selectively to the
intracellular surface of sodium channels intracellular surface of sodium channels and block entry of sodium into the and block entry of sodium into the cellcell block the depolarisation block the depolarisation
LA LA bind more readily to bind more readily to NaNa++ channels in channels in inactivated stateinactivated state - - onset of neuronal onset of neuronal blockade is faster in neurons that are blockade is faster in neurons that are rapidly firingrapidly firing ((statestate--dependent blockadedependent blockade))
EEffect of pHffect of pH
LALA are weak are weak bases bases ((hydrochloride salt hydrochloride salt == water- water-solublesoluble))
only the only the ununionisedionised molecule diffuses molecule diffuses readily readily across cell membranesacross cell membranes
aacidosiscidosis (in (in inflammationinflammation)) partly partly reduces the reduces the action of action of LALA - - most of the most of the LALA is ionised is ionised && therefore unable to cross the cell membrane therefore unable to cross the cell membrane
Mechanismm and action of LA – Mechanismm and action of LA – cont.cont.
Actions on various nerve fibersActions on various nerve fibers LA block conduction LA block conduction in small diameter nerv fibers more in small diameter nerv fibers more
readily when in large fibersreadily when in large fibers
Fibers CFibers C (under 1 (under 1 m, unmyelinated postgaglionic m, unmyelinated postgaglionic and somatic)-and somatic)-autonomic paralysisautonomic paralysis, loss of the , loss of the sensation of itch and tickle pain sensation of itch and tickle pain
Fibers BFibers B (1-3 (1-3 m, myelinated preganglionic ) m, myelinated preganglionic ) autonomic paralysis.autonomic paralysis.
Fibers AFibers A (1-20 (1-20 m, myelinated, somatic, motor and m, myelinated, somatic, motor and some somatic)- sceletal muscle relaxation, loss of some somatic)- sceletal muscle relaxation, loss of thermal and tactil sansation, thermal and tactil sansation, proprioceptive lossproprioceptive loss, loss , loss of sharp pain.of sharp pain.
Mechanismm and action of LA – Mechanismm and action of LA – cont.cont.
Metabolism of LAMetabolism of LA estersesters are primarily inactivated are primarily inactivated in plasmain plasma
by hydrolysis (pseudocholinesterase)by hydrolysis (pseudocholinesterase) - they generally have a relatively short half-- they generally have a relatively short half-
life in the bodylife in the body - in spinal fluid (absence of esterase activity) - in spinal fluid (absence of esterase activity)
duration of anaesthesia is extendedduration of anaesthesia is extended
amidesamides are metabolized are metabolized by liverby liver microsomes microsomes
- metabolites are excreted by urine- metabolites are excreted by urine - liver disease - liver disease cumulation of drugs cumulation of drugs
higher risk of toxicityhigher risk of toxicity
PharmacokineticsPharmacokinetics
LA should act locallyLA should act locally
the duration of action of all agents is prolonged by the duration of action of all agents is prolonged by the addition ofthe addition of adrenalineadrenaline when used forwhen used for infiltration anaesthesia infiltration anaesthesia && peripheral nerve peripheral nerve blocksblocks
aadrenalinedrenaline also increases the duration ofalso increases the duration of extradural anaesthesia extradural anaesthesia when added to when added to procaine, mepivacaine procaine, mepivacaine && li liddocaineocaine but does not but does not alter markedly the duration of action of extradural alter markedly the duration of action of extradural prilocaine, bupivacaineprilocaine, bupivacaine or or etidocaineetidocaine
Vasoconstrictors in local Vasoconstrictors in local anaesthesiaanaesthesia
- to slow absorption- to slow absorption
- to prolong the local action- to prolong the local action
- to decrease toxicity- to decrease toxicity
PharmacokineticsPharmacokinetics(p(practical ractical ppoint oint ))
aadrenaline 1:1000 contains 1 g of drenaline 1:1000 contains 1 g of adrenaline per 1000adrenaline per 1000 ml solution i.e. ml solution i.e. 1mg/ml1mg/ml
tto prepare a 1 in 200o prepare a 1 in 200 000 solution the 000 solution the
1:1000 must be diluted 200 times1:1000 must be diluted 200 times
tthis is achieved by taking 0.1ml (= his is achieved by taking 0.1ml (= 0.1mg) 0.1mg) & & adding 19.9 ml of adding 19.9 ml of LALA solution solution
PharmacokineticsPharmacokinetics((adrenalineadrenaline
contraindicationscontraindications)) adrenalineadrenaline nevernever be used for infiltration be used for infiltration around around
end-arteriesend-arteries i.e. penis, ring block of fingers or i.e. penis, ring block of fingers or other areas with a terminal vascular supply other areas with a terminal vascular supply (ischaemia, necrosis)(ischaemia, necrosis)
in patients with in patients with diabetesdiabetes && CV diseasesCV diseases::hypertensionhypertension
severe atherosclerosissevere atherosclerosis
hearth failure hearth failure
after IMafter IM
Methods of aplication of Methods of aplication of LALA
Mode of application of LA
topical (surface)
infiltration
plexus block
epidural (extradural) spinal (subarachnoid)
Methods of aplication of LAMethods of aplication of LA1. Surface anaesthesia1. Surface anaesthesia- the LA solution is applied directly to the mucosal - the LA solution is applied directly to the mucosal
surface: nose and mouth, bronchial tree, oesophagus surface: nose and mouth, bronchial tree, oesophagus or genitourinary tractor genitourinary tract
- LA can be absorbed into the circulation following - LA can be absorbed into the circulation following topical aplication to mucous (mainly tracheobronchial topical aplication to mucous (mainly tracheobronchial tree) tree) risk of toxicityrisk of toxicity
- relatively high doses are often used - relatively high doses are often used tetracaine (2%), tetracaine (2%), lidocaine (2-10%), cocaine (1-4%)lidocaine (2-10%), cocaine (1-4%)
2. Infiltration anaesthesia2. Infiltration anaesthesia- LA are injected directly into the tissues to reach fine - LA are injected directly into the tissues to reach fine
nerve branches and sensory nerve terminalsnerve branches and sensory nerve terminals- most frequently used LA - most frequently used LA lidocaine (0.5-1%), lidocaine (0.5-1%),
procaine (0.5-1%), bupivacaine (0.125-0.25%)procaine (0.5-1%), bupivacaine (0.125-0.25%)
Methods of aplication of LA – Methods of aplication of LA – cont.cont.3. 3. Nerve-block anaesthesiaNerve-block anaesthesia- LA are injected close to the appropriate - LA are injected close to the appropriate nerve trunksnerve trunks - -
widely used methods widely used methods much less anesthetics are needed much less anesthetics are needed ::-procaine (0.5-1%), lidocaine (1-2%), mepivacaine (1-3%), -procaine (0.5-1%), lidocaine (1-2%), mepivacaine (1-3%), bupivacaine (0.25-0.75%) are usedbupivacaine (0.25-0.75%) are used
4. Spinal and epidural anaesthesia4. Spinal and epidural anaesthesia spinal (subdural) anaesthesiaspinal (subdural) anaesthesia - LA is injected into the - LA is injected into the
lumbar subarachnoid space, which contains cerebrospinal lumbar subarachnoid space, which contains cerebrospinal fluid, fluid,
epidural anaesthesiaepidural anaesthesia - LA is injected just outside the dura - LA is injected just outside the dura into a narrow space between the dura and the bony spinal into a narrow space between the dura and the bony spinal canalcanal
- advantage- advantage relatively small doses of LA are needed relatively small doses of LA are needed --unwanted effectsunwanted effects in spinal anaesthesia are: in spinal anaesthesia are:
vasodilatation, vasodilatation, bradykardia, bradykardia, marked fall in arterial marked fall in arterial pressurepressure
Side effects of LASide effects of LA
CNSCNS- all LA cause stimulation of CNS: - restlessness - all LA cause stimulation of CNS: - restlessness
and tremor and tremor tremor can progress to convulsion tremor can progress to convulsion- further increasing the dose - further increasing the dose CNS depression CNS depressionmain threat for life comes from respiratory main threat for life comes from respiratory
depressiondepression- cocaine has different effect on CNS - cocaine has different effect on CNS doses doses
lower than convulsive produce marked euphorialower than convulsive produce marked euphoria
Treatment:Treatment: restoration of normal ventilation and circulationrestoration of normal ventilation and circulation diazepamdiazepam in prevention and treatment of in prevention and treatment of
seizuresseizures
Side effects of LA – cont.Side effects of LA – cont.Cardiovascular systemCardiovascular system- myocardial depression and vasodilatation- myocardial depression and vasodilatation- vasodilatation - vasodilatation partly direct effect on vascular smooth partly direct effect on vascular smooth
muscle and partly inhibition of sympathetic nevous muscle and partly inhibition of sympathetic nevous system (centrally)system (centrally)
- this combined effect - this combined effect marked fall in blood pressure marked fall in blood pressure- cocaine - cocaine inhibition of adrenaline re-uptake inhibition of adrenaline re-uptake tachycardia, tachycardia,
vasoconstriction and increase of arterial pressurevasoconstriction and increase of arterial pressure
Effects of vasoconstrictorsEffects of vasoconstrictorslocal ischemia, anxiety, tachycardia, hypertensionlocal ischemia, anxiety, tachycardia, hypertensionContraindications of vasoconstrictorsContraindications of vasoconstrictors hypertension, atherosclerosis, thyreotoxicosis, congestive hypertension, atherosclerosis, thyreotoxicosis, congestive
heart failureheart failure
Allergy Allergy - - esters. There is not cross-esters. There is not cross-reactivity with the amides.reactivity with the amides.
diclofenac, felbinac, ibuprofen, diclofenac, felbinac, ibuprofen, ketoprofen, piroxicam, naproxen, ketoprofen, piroxicam, naproxen,
flurbiprofen and others.flurbiprofen and others.