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Local Anesthetics
Local Anesthetic
A local anesthetic is an agent that interrupts pain impulses in a specific region of the body without a loss of patient consciousness. Normally, the process is completely reversible.
History
The first local anesthetic introduced into medical practice Cocaine, was isolated from coca leaves by Albert Niemann in Germany in the 1860s.
The very first clinical use of Cocaine was in 1884 by Sigmund Freud who used it to wean a patient from morphine addiction.
Freud and his colleague Karl Kollar first noticed its anesthetic effect and introduced it to clinical ophthalmology as a topical ocular anesthetic.
Cocaine was used - 30 years Einhorn (1905) synthesized procaine Lidocaine-1943-Lofgren
Susceptibility of nerve fibers to local anesthetic blockade
In general, small nerve fibers are more susceptible than large fibers; however, – the type of fiber– degree of myelination– fiber length and – frequency- dependence are also important in
determining susceptibility
Order of sensory function block
1. pain
2. cold
3. warmth
4. touch
5. deep pressure
6. motor
Recovery in reverse order
Chemistry
The LAs consists of three parts.
1.A hydrophilic amino group.
2.An intermediate chain (ester or amide).
3.A lipophilic aromatic group.
• LAs are weak bases
• In the body, they exist either as the uncharged base or as a cation.
CLASSIFICATION
Based on there chemistry and duration of action LAs are classified as follows
1. AMIDE TYPE LONG ACTING
Bupivacaine, levo- Bupivacaine, Etidocaine, Ropivacaine INTERMEDIATE ACTING Lidocaine, Mepivacaine2. ESTER TYPE LONG ACTING
Tetracaine (Amithocaine) INTERMEDIATE ACTING Cocaine SHORT ACTING Procaine, Chloroprocaine, Benzocaine.
MECHANISAM OF ACTION
PHARMACOKINETICS
Esters: These include cocaine, procaine, tetracaine, and chloroprocaine. Short duration
They are hydrolyzed in plasma by pseudo-cholinesterase. One of the by-products of metabolism is PABA - the common cause of allergic reactions seen with these agents and also antagonize the action of sulfonamides.
Rarely used for infiltration or nerve block, but are still used topically on mucus membranes
Amides:
These include lidocaine, mepivacaine, prilocaine, bupivacaine, and
etidocaine.
Produce more intense and longer lasting anesthesia
Bind to α1 acid glycoprotein in plasma
They are metabolized in the liver to inactive agents. True allergic
reactions are rare (especially with lidocaine)
PHARMACOKINETICS
Factors affecting local anesthetic action
Effect of pH
Charged (cationic) form binds to receptor site uncharged form
penetrates membrane ,efficacy of drug can be changed by
altering extracellular or intracellular pH
Effect of lipophilicity
Lipid solubility appears to be the primary determinant of
intrinsic anesthetic potency.
Chemical compounds which are highly lipophilic tend to
penetrate the nerve membrane more easily, such that less
molecules are required for conduction blockade resulting in
enhanced potency.
Factors affecting local anesthetic action Cont…
Effect of protein binding increased binding increases duration of action
Effect of vasodilator activity greater vasodilator activity = decreased potency and
decreased duration of action
Factors affecting local anesthetic action Cont…
Types of Local Anesthesia
Infiltration Anesthesia:
Local infiltration occurs when the nerve endings in the skin and
subcutaneous tissues are blocked by direct contact with a local
anesthetic, which is injected into the tissue.
Local infiltration is used primarily for surgical procedures
involving a small area of tissue (for example, suturing a cut).
Surface Anesthesia:
This type of anesthesia is accomplished by the application of a local
anesthetic to skin or mucous membranes.
Surface anesthesia is used to relieve itching, burning, and surface pain.
This technique is often used during examination procedures involving
the respiratory tract.
The topical block easily anesthetizes the surface of the cornea and the
oral mucosa.
Types of Local Anesthesia Cont…
Conduction block anaesthesia:
Two types
1. Field block:- LA is injected subcutaneously in the surrounding area of
the nerves. So that all other nerves coming to a particular field are
blocked.
e.g. scalp and anterior abdominal walls
2. Nerve block:- LA injected around the anatomically localized nerve
trunk. The block is usually described by adding the nerve name.
e.g. radial nerve block, ulnar nerve block.
Types of Local Anesthesia Cont…
Types of Local Anesthesia Cont…
Epidural Anesthesia
This type of anesthesia is
accomplished by injecting a local
anesthetic into the epidural space.
Widely used to provide analgesia
or anesthesia in surgical and
obstetric practice.
Spinal block Anesthesia:
In spinal anesthesia, the local anesthetic is injected into the subarachnoid space of the spinal cord
Also referred as subarachnoid or intrathecal block anesthesia or spinal anesthesia.
Site- subarachnoid space between L2-L3 or L3-L4
Used to anesthetise lower abdomen, hind limbs.
Types of Local Anesthesia Cont…
Intravenous regional anesthesia:
Also referred as Bier’s block
Used for upper limb and orthopedic procedures.
Types of Local Anesthesia Cont…
PROLANGATION OF ACTION BY VASOCONSTRICTORS
Vasoconstrictors decrease the rate of vascular absorption which allows
more anesthetic to reach the nerve membrane and improves the depth of
anesthesia.
There is variable response between LA and the location of injection as to
whether vasoconstrictors increase duration of action. 1:200,000
epinephrine appears to be the best vasoconstrictor.
Felypressin a synthetic vasopressin – to avoid cardiac complications which
may occur with adrenalin
TOXICITIES OF LOCAL ANESTHETICS
Essentially all systemic toxic reactions associated with local
anesthetics are the result of over-dosage leading to high blood
levels of the agent given.
Therefore, to avoid a systemic toxic reaction to a local anesthetic,
the smallest amount of the most dilute solution that effectively
blocks pain should be administered.
Hypersensitivity
Some patients are hypersensitive (allergic) to some local
anesthetics.
Such allergies are very rare
There are two basic types of local anesthetics (the amide type
and the ester type).
A patient who is allergic to one type may or may not be allergic
to the other type.
TOXICITIES OF LOCAL ANESTHETICS Cont…
Central Nervous System Toxicities
Stimulation followed by depression
Local anesthetics, if absorbed systematically in excessive
amounts, can cause central nervous system (CNS) excitement
or, if absorbed in even higher amounts, can cause CNS
depression.
TOXICITIES OF LOCAL ANESTHETICS Cont…
CNS toxicity cont..
Excitement:
Tremors, shivering, and convulsions characterize the CNS
excitement.
Depression:
Respiratory depression and, if enough drug is absorbed,
respiratory arrest.
Signs of toxicity are:
Tongue numbness, lightheadedness, tinnitus, visual disturbances,
muscular twitching, convulsions, unconsciousness, coma,
respiratory arrest, then cardiovascular collapse.
CNS toxicity cont..
Cardiovascular Toxicities:
Depression of the cardiovascular system.
Peripheral vascular action arteriolar dilation (except cocaine
which is vasoconstrictive)
Hypotension and a certain type of abnormal heartbeat
(atrioventricular block) characterize such depression.
These may ultimately result in both cardiac and respiratory
arrest.
TOXICITIES OF LOCAL ANESTHETICS Cont…
Prevention of toxicity Enquire about history of allergy
Cautiously in liver and myocardial damage
Select proper site –nerve block
Use minimal ED, well diluted preferably with the vasoconstrictor
Wait after injection
Observe the face for any twitching, excitement and tachycardia if any
Observe post operatively for allergic reactions
Lignocaine Most commonly employed
Stable, can be stored at room temperature for long time
Can be autoclaved repeatedly
Has quick onset of action and a high degree of penetration
Also an excellent surface anesthetic
Toxicities are similar to other LA
Recommended for topical use, nerve blocks, infiltration and epidural
injection and for dental analgesia
Can be used in subjects allergic to procaine and other ester type LA
Other uses
Procaine: Forms poorly absorable salt with
benzylpenicilin called procaine penicilin Its amide derivative procainamide is
used as class 1A group of antiarrhythmic
lidocaine: I.V. for management of ventricular
arrhythmias
General Anesthesia
General Anesthesia
Definition:General Anesthesia is the loss of response to & perception of all external stimuli.
General anaesthetics are the drugs which causes reversible loss of all the sensations and consciousness
Components of General Anesthesia:
1. Unconsciousness (Hypnosis)2. Analgesia (Areflexia)3. Muscle relaxation
Phases of AnesthesiaInduction: putting the patient to sleep
Maintenance: keeping the patient asleep
Emergence: waking the patient up
STAGES OF GENERAL ANESTHESIA
STAGE 1 (Analgesia): From induction of anesthesia to loss of conciousness (loss of eyelid reflex). Pain is progressively abolished in this stage.
STAGE 2 (Delirium/Excitement): From loss of consiousness to beginning of regular respiration.Characterized by uninhibited excitation. Pupils are dilated and eyes divergent. Agitation, delirium, irregular respiration, and breatholding are commonly seen. Potentially dangerous responses can occur during this stage including vomiting, laryngospasm, HTN, tachycardia, and uncontrolled movement.
STAGE 3 (Surgical Anesthesia):
Regular respiration to caessation of spontaneous breathing
Central gaze, constricted pupils, and regular respirations. Target depth of anesthesia is sufficient when painful stimulation does not elicit somatic reflexes or deleterious autonomic reflexes.
Plane 1 From the return of regular respirations to the cessation of REM.
Plane 2 The Surgical Plane From the cessation of REM to the onset of
paresis of the intercostal muscles.
Plane 3 From the onset to the complete paralysis of the intercostal muscles.
Plane 4 From the paralysis of the intercostal of
this plane the patient will be apneic.
STAGE 4 (Impending Death/Overdose):
Onset of apnea, dilated and nonreactive pupils, and hypotension to complete circulatory failure.
Classic Stages of Anesthesia* Stage 1: Analgesia
– decreased awareness of pain, amnesia Stage 2: Disinhibition
– delirium & excitation, enhanced reflexes, retching, incontinence, irregular respiration
Stage 3: Surgical Anesthesia
– unconscious, no pain reflexes, regular respiration, BP is maintained
Stage 4: Medullary Depression
– respiratory & CV depression requiring ventilation & pharmacologic support.
* Seen mainly with Ether. Not all stages are observed with modern GAs.
Mechanisms of Action1. Enhanced GABA effect on GABAA Receptors
– Inhaled anesthetics - Etomidate– Barbiturates - Propofol– Benzodiazepines
2. Block nicotinic receptor subtypes (analgesia) – Moderate to high conc’s of inhaled anesthetics
3. Activate K channels (hyperpolarize )– Nitrous oxide, ketamine, xenon
4. Inhibit NMDA (glutamate) receptors – Nitrous oxide, ketamine, xenon, high dose barbiturates
5. Enhance glycine effect on glycine R’s (immobility)
Immobilization in response to surgical incision
(spinal cord)
Sedation, loss of consciousness (thalamic firing)
Amnesia (hippocampal neurotransmission)
Regional Effects
CLASSIFICATION
INTRAVENOUS
INDUCING AGENTSThiopentone sodium
MethohexitalPropofol
Etomidate
SLOWER ACTINGDiazepamLorazepamMidazolam
DISSOCIATIVE ANAESTHESIAKetamine
OPIOID ANALGESIAFentanyl
INHALATIONAL
GASNitrous oxide
LIQUIDEther
HalothaneEnfluraneDesfluraneSevoflurane
Parenteral Anesthetics (Intravenous)
Most commonly used drugs to induce anesthesia– Barbiturates (Thiopental* & Methohexital)– Benzodiazepines (Midazolam)– Opioids (Morphine & Fentanyl)– Propofol*– Etomidate
* Most commonly used for induction
Barbiturates & Benzodiazepines MOA:Barbiturate
BZDS
GABA
1) Both bind to GABAA
receptors, at different sites• Both cause increase Cl- influx in presence of GABA• BNZ binding can be blocked by flumazenil.
2) Barbs at high doses - are also GABA mimetic, block Na channels NMDA/glutamate Rs
CN
S E
ffec
ts
Increasing dose
Coma Barbiturates
Benzodiazepines
Hypnosis
Sedation, disinhibition, anxiolysis
Possible selective anticonvulsant & muscle-relaxing activity
Dose Response Relationships
Anesthesia
Medullary depression
Barbiturates
Thiopental & methohexital are highly lipid soluble & can produce unconsciousness & surgical anesthesia in <1 min.
Rx: induction of anesthesia & short procedures
Actions are terminated by redistribution
With single bolus - emergence from GA occurs in ~ 10 mins
Hepatic metabolism is required for elimination
Opioids (Fentanyl & Remifentanil*) GAs do not produce effective analgesia (except for ketamine).
Given before surgery to minimize hemodynamic changes produced by painful stimuli. This reduces GA requirements.
High doses can cause chest wall rigidity & post-op respiratory depression
Therapeutic doses will inhibit respiration (CO2)
Used for post-op analgesia, supplement anesthetic in balanced anesthesia.
Remifentanil is an ester opioid metabolized by plasma esterases. It is very potent but w/ a short t1/2 (3-10 mins).
Ketamine
Nonbarbiturate, rapid acting general anesthetic
Dissociated from the environment, immobile, and unresponsive to pain
Profound analgesic
Ketamine
Selectively blocks the associative pathways producing sensory blockade
Preserved pharyngeal-laryngeal reflexesNormal or slightly enhanced skeletal
muscle toneCardiovascular and respiratory stimulation
Ketamine (1.5mg/kg)
A “dissociative anesthetic” that produces a cataleptic state that includes intense analgesia, amnesia, eyes open, involuntary limb movement, unresponsive to commands or pain.
Increases heart rate & blood pressure (opposite of other GAs)
Can be used in shock states (hypotensive) or patients at risk for bronchospasm.
Used in children & young adults for short procedures
Side Effects: nystagmus, pupillary dilation, salivation, hallucinations & vivid dreams
Inhaled Anesthetics
Inhaled Anesthetics
Partial pressure or “tension” in inspired air is a measure of their concentration
The speed of induction of anesthesia depends on:
– Inspired gas partial pressure (GA concentration)
– Ventilation rate
– GA solubility (less soluble GAs equilibrate more quickly with blood & into tissues such as the brain)
Elimination Anesthesia is most commonly terminated by redistribution
of drug from brain to the blood & out through the lungs.
The rate of recovery from anesthesia for GAs with low blood: gas PCs is faster than for highly soluble Gas.
Time is $$ in the O.R. & recovery roomBlood: Gas P. Coeff– Haltothane 2.30– Desflurane 0.42– Sevoflurane 0.69
Halothane & methoxyflurane undergo hepatic metabolism & can cause liver toxicity.
Toxicity Malignant Hyperthermia
– Esp. when halogenated GA used with succinylcholine– Rx: dantrolene (immediately)
Halothane:– Halothane undergoes >40% hepatic metabolism– Rare cases of postoperative hepatitis occur– Halothane can sensitize the heart to Epi (arrhythmias)
Methoxyflurane– F release during metabolism (>70%) may cause renal insufficiency after prolonged
exposure.
Nitrous oxide– Megaloblastic anemia may occur after prolonged exposure due to decreases in methionine
synthase activity(Vit B12 deficiency).
PREANAESTHETIC MEDICATION Opioids: Morphine-10 mg
Pethidine 50-100mg i.m.
Sedatve antianxiety : Diazepam 5-10mg orallyLorazepam 2mg i.m.
Anticholinergics : Atropine 0.6mg i.m./ i.v Glycopyrolate 0.1-0.3mg i.m
Neuroleptics: Chlorpramazine 25mg
H2 blockers : Ranitidine 150mg Famotidine 40mg
Antiemetics : Metoclopramide 10-20mg i.m
Dantrolene Interfers with the release of calcium from the sarcoplasmic
reticulum through the SR calcium channel complex.
Used to prevent or reverse malignant hyperthermia (which is otherwise fatal in ~50% of cases w/o dantrolene).
Given by i.v. push at the onset of symptoms (e.g. an unexpected rise in CO2 levels)
Supportive measures & 100% O2 are also used to treat malignant hyperthermia
Nausea & Vomiting
General anesthetics effect the chemoreceptor trigger zone & brainstem vomiting center (cause nausea & vomiting)
Rx: - Ondansetron (5-HT3 antagonist) to prevent
- Avoidance of N2O
- Propofol for induction- Keterolac vs. opioid for analgesia- Droperidol, metaclopromide & dexamethasone