Download An ideal local anaesthetic

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Local anaesthetics:
Local anaesthetics: refers to chemical that are applied or administered locally to cause
reversible blockade of axonal conduction with consequent loss of sensations from the
concerned area without affecting consciousness.
Or refers to the state of local analgesia produced by local anaesthetics.it is of different types
depending upon the mode of use of local anaesthetics.
Topical or (surface anaesthesia ) : refers to the state of local anaesthesia accomplished by
applying local anaesthetic directly to mucus membranes or exposed nerve endings so as to
block primarily peripheral exposed nerve terminals . the agents used for this purpose are
called topical anaesthetics. Also include dental analgesics (inserted into carious teeth) or the
agents used on the skin to relieve pruritis. Cutaneous inflammatory conditions or for minor
surgical procedures where relief from pain is required.
Infiltration anaesthesia : Refers to anaesthetizing an area or tissue by making one or more
injections (usually subcutaneous and occasionally into organs or joints spaces) of a local
anaesthetics without taking into consideration the course of the nerve supply.
Spinal anaesthesia : refers to depositing local anaesthetics into the CSF (i.e. subarachnoid
space) so as to block many nerve roots quickly as they emerge from spinal cord. It is also
known as :
Regional anaesthesia : is a general term referring to local anaesthesia that pertains to a larger
area or region of the body.it includes paravertebral , epidural , spinal , nerve plexus blocking or
retrograde intravenous regional anaesthesia.
Retrograde regional anaesthesia : erfers to anaesthetization of extremities by injecting local
anaesthetic into superficial veins(radial or metatarsal) after tying a tourniquet to confine the
drug into the region for action ; the drug diffusing from blood to peripheral nerve sites.
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Refrigeration anaesthesia : refers to anaesthetization of surface , mainly skin , by spraying a
high volatile agent (as alkyl halides) that causes sueface cooling and freezing following
evaporating of agent with consequent tissue heat loss. Such agents are called refrigerant
anaesthetics. Spraying of liquefied carbon dioxide to the skin surface also produces same
action.
Differences between local & general anesthesia :
Parameter
Local anesthetic
General anaesthetic
Site of action
Peripheral nervous system Central nervous system (
(peripheral nerve)
brain)
Mode of action
Block axonal conduction
Alter synaptic transmission)
Consciousness
unaffected
lost
Analgesia
Localized analgesia
generalized
administration
Local deposition away from Systemic
systemic circulation
Systemic availability
:
inhalant
or
parenteral
Undesirable responsible for Requisite for action
toxicity
Toxic
potential
and Low
toxicity
(CNS
stimulation High , CNS depression.
(convulsion , seizures)
An ideal local anaesthetic
An ideal local anaesthetic should qualify four principal qualities : it should be selective and
effective for action and safe and stable for use :
Selective : it should selectively block the function of sensory nerves (reversible paralysis) to
produce local analgesic.
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Effective : it should be effective whether applied topically or upon injection. Onset of action
should be rapid . duration of action should be adequate , neither too short nor too prolonged
to extend recovery period.high potency is desirable so that smaller amounts can be used.
Safe : it implies requirements as i) it should not damage the tissue at therapeutic
concentrations as irritancy be negligible ii) it should be slowly absorbed from the site of
application into the systemic circulation so that its action is prolonged and systemic toxicity is
minimized iii) once absorbed into circulation it should be rapidly detoxified iv) it should
produce low systemic toxicity v) anaesthesia should not be preceded by sensory nerve
stimulation (unlike aconite or phenol) nor followed by hyperaesthesia.
There is none that qualifies all the criteria . however , commonly employed local anaesthetics.
As lidocaine and procaine fulfill most of the criteria at recommended concentrations.
Other agents differ from these mainly with respect to relative potency, duration of action and
toxicity.
General indications of local anaesthetics :
Emergencies :
Minor operation :
Obstetrical practice :
Field conditions :
Patient conditions :
Major operation :
Classification of local anaesthetics :
1- On the basis of chemical features :
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a)- amino-group containing agents :( common category)
i)-Esters : contain esteric linkage : most are benzoic acid esters as cocaine , procaine ,
chloroprocaine , tetracaine , benzocaine, hexylcaine , butamben , proxymetacaine ,
benozinate
ii)-Amides : contain amide linkage : longer acting than esters Lidocaine , prilocaine ,
bupivacaine , mepivacaine , rupivacaine , etidocaine , dibucaine
iii)- Ketone : contain keto group in the intermediate chain / dyclonine
B)-Non-amino agents (non-classical local anaesthetic agents)
i) alcohols : ethanol , phenol , isopropyl alcohol , eugenol , creosote , chlorobutol , benzyl
alcohol , menthol.
ii)-alkyl halides : ethyl chloride and methyl chloride.
2- on the basis of duration of action .
i)-ultra-short duration of action : duration of action brief,less than or equal to 15 minute:
benoxinate , proparacaine
ii)-short acting : duration of action upon an hour : procaine , chloroprocaine , cocaine
iii)-intermediate acting : duration of action upon 1to4 hours. As lidocaine (lignocaine or
xylocaine ) mepivacaine , prilocaine
iv)-long acting : duration of action about 4-10 hours or may be longer // bupivacaine ,
ropivacaine , tetracaine , etidocaine , hexylcaine & cinchocaine.
Factors affecting local anesthetic action:
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1-type of nerve fiber : small (thinner) nerve fibers as thinner sensory and postganglionic
sympathetic fibers (C-type) and preganglionic sympathetic fibers (B-type) are most sensitive to
conduction blockade by local anaesthetics.
Large (thicker) sensory fibers (A-delta type) are moderate sensitive . A-beta & A-gamma fibers
(more thiker) subserving muscle tone and proprioception , are less sensitive while somatic
motor fibers (A-alpha , thikest) are least sensitive to local anaesthetic action .myelination does
not appear to affect nerve sensitivity to the blockade.
Nerve membrane is more permeable to local anaesthetic molecules during depolarization
state than during resting state . this renders sensory fibers in general and the pain fibersin
particular more susceptible to blockade as they tend to generate long-duration action
potential and at higher frequency while motor fibers generates short duration action potential
and at lower frequency.
2-Ph & PKa : commonly used local anaesthetics are weak organic bases with pka in the range
8-9 . tissue ph (about 7.4) favours their ionization (protonation) such that more than 60% of
the drug molecules exist in protonation form.unprotonated form is responsible for diffusion
through lipid matrix.
Protonated form is presumed to enter the membrane through ion channel (during
depolarization state) and to bind specifically to binding sites.
Tissue ph is definitely an important factor that would affect diffusion of the base across the
membrane ; thus local anaesthetics with varying pka values are expected to diffuse the
membranes at varying rate.
Inability of local anaesthetics to block conduction from purulent site is related to the abnormal
environment at purulent sites.such sites are relatively acidic and contain higher potassium
levels as well as rich in anions (e.g proteins , organic phosphates and nucleotides) due to high
cell destruction . acidic ph decreases hydrolysis of acid salt (i.e hydrochloride) thus reducing
release of active organic base. Acidic ph would favour ionization and hence reduce diffusion of
the active base.hydrogen ions are known to block sodium ion channels directly by occupying
its anionic sites.
3-potentiators :
Vasoconstrictor : adrenaline or any other vasoconstrictor reduces rate of absorption of local
anaesthetic from the site od deposition . reduced rate of systemic availability tends to reduce
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systemic toxicity. Duration of action is accordingly prolonged in presence of a vasoconstrictor .
the effect is pronounced with local anaesthetics having pronounced vasodilator action as
procaine and lidocaine . prilocaine has little vasoconstrictor action so can be used without
adrenaline . cocaine is vasoconstrictor so adrenaline is not required.
On the other hand use of adrenaline is contraindicated with cocaine as later tends to
potentiate its sympathomimetic effects by preventing uptake of catecholamines at nerve
terminals.
Hyaluronidase : the enzyme hydrolyses ground substance (i.e hyaluronic acid) so increases
area of diffusion and hence area of effect of local anaesthetics. increased diffusion tends to
reduce duration of effect and increase chances of toxicity as the drug would reach systemic
circulation faster.
The benefits are discernible only when vasoconstrictor is also used along with the
hyaluronidase ; duration and area of effect are nearly doubled . use of hyaluronidase in
veterinary practice is not recommended i)-it is costly ii(-tends to interfere with local
anaesthetic action especially when used alone. Iii)-chances of systemic toxicity by local
anaesthetics are increased iv)-its use has limited applications i.e infiltration or subcutaneous
anaesthesia.
Toxicity and complication of local anaesthetics
Local effects : local damage consists of transient or permanent injury to tissues due to the
irritancy . recommended concentrations are practically non-irritant.
Tetracaine is more irritant , 8-10 fold more than procaine. Nerve damage can be result if high
concentrations are deposited into nerves or very close to the nerve.
Proparacaine causes a transient corneal roughening for 30-60 minutes.
Systemic effects : is determined by balance of rate of absorption to the rate of destruction of
local anaesthetics.the toxicity is primarily due to CNS stimulation presumably due to inhibition
of GABA ergic synaptic function leading to restlessness , muscle tremors , convulsive seizures
Death occurs rarely due to respiratory failure.
Neurostimulation is followed by depression of all CNS functions.
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Cardiovascular , respiratory and skeletal muscle functions may be affected following epidural
and or spinal anaesthesia as a complication of the particular route.
Allergic reactions : allergic dermatitis or topical asthmatic attack has been observed in humans
with exclusively ester type local anaesthetics , some ester metabolite acting as a hapten.the
occurance is , however is rare.
Factors affecting systemic toxicity of local anaesthetics :
1-type of drug : toxicity potential of a drug appears to be related to anaesthetic potential,thus
highly potent drugs are also highly toxic . Cocaine induced CNS stimulation is primarily related
to potentiation of central biogenic amines as cocaine prevents reuptake of released biogenic
amines at presynaptic sites.
Hyaluronidase can potentiate toxicity by increasing area of absorption and hence rate of
diffusion of local anaesthetic into systemic circulation . adrenaline reduced toxicity by reducing
absorption rate.
It may lead to cardiac arrhythmias if used in higher concentrations and is particularly
dangerous to use with cocaine.
2-species : susceptibility to convulsions is related to degree of CNS development , primates are
more sensitive than domestic animals.horses are more sensitive than swine.ruminants
particularly cattle appear to be least sensitive . among birds, parakeets are extremely sensitive
to lethal effects of procaine.
3-route : the toxicity is obviously greater if drug goes inadvertently into vein while it is
intended for local deposition or if tourniquet is loosely applied while attempting retrograde
intravenous regional anaesthesia.MLD of procaine , cocaine and cinchocaine on subcutaneous
use are respectively about 1/10 , 1/8 , ¼ of intravenous amounts.
4-ambient temperature : avoid infiltration of local anaesthetics into the tissues under high
ambient temperature , excessive absorption follows due to cutaneous vasodilation this is
particularly true with thin skinned and very young animals as puppies.
Classical local anaesthetic :
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Organic bases are poorly water soluble except cocaine and tetracaine which show little water
solubility. Hydrochlorides are quite soluble in water. Aqueous solution of hydrochlorides are
acidic except tetracaine and benoxinate salts that are neutral.aqueous solution of dyclonine
Hcl is acidic to neutral.
The esters are a class less stable than amides . the aqueous solutions are sterilized by
autoclaving or by filtration cocaine & tetracaine are less stable to heat so their solutions are
sterilized by controlled heat in the presence of bactericide.
It is recommended to keep aqueous solution of local anaesthetics in air-tight containers and
away from light.
Cocaine : local anaesthetic potency is 3 times that of procaine.
Onset of action is about 5 minutes and duration of action 20-45 minutes (topical) and up to
2hours (spinal). It is vasoconstrictor and mydriatic agent.
The drug was once choice anaesthetic for all uses.
Its now exclusively recommended for topical anaesthesia ; 2-4% solution for ophthalmic
anaesthesia, and 5-10% for other mucosal uses.
Vasoconstrictor potential restricts its prolonged ophthalmic use as it favour ischemia and
coroneal ulceration.
It is advantageous on other mucosal uses as it reduces operative bleeding . high tissue irritancy
disfavours its use as infiltration agent.
Systemic toxicity potential is at least 4 times of procaine . it is a scheduled drug so not freely
available for use , there is high abuse (addiction) potential to its psychomitic action (i.e
euphoria).