Local anesthetics (VK)

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.



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.


Intravenous regional anesthesia:

Also referred as Bier’s block

Used for upper limb and orthopedic procedures.


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.


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.


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

Education

Local anesthetics (VK)