2. 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.
3. 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
4. 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
5. Order of sensory function
block
1. pain
2. cold
3. warmth
4. touch
5. deep pressure
6. motor
Recovery in reverse order
6. 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.
7.
8. 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, Mepivacaine
2. ESTER TYPE
LONG ACTING
Tetracaine (Amithocaine)
INTERMEDIATE ACTING
Cocaine
SHORT ACTING
Procaine, Chloroprocaine, Benzocaine.
11. 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
12. PHARMACOKINETICS
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)
13. 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
14. Factors affecting
local anesthetic action
Cont…
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.
15. 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
16. 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).
17. Types of Local Anesthesia
Cont…
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.
18. 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.
19.
20.
21. Types of Local Anesthesia
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.
Cont…
22.
23.
24. Types of Local Anesthesia
Cont…
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.
25.
26. Types of Local Anesthesia
Cont…
Intravenous regional anesthesia:
Also referred as Bier’s block
Used for upper limb and orthopedic procedures.
27.
28. 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
29. 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.
30. TOXICITIES OF LOCAL ANESTHETICS
Cont…
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.
31. 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.
32. CNS toxicity
cont..
Excitement:
Tremors, shivering, and convulsions characterize the CNS
excitement.
Depression:
Respiratory depression and, if enough drug is absorbed,
respiratory arrest.
34. TOXICITIES OF LOCAL ANESTHETICS
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.
35. 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
36. 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
37. 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
39. 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
41. Phases of Anesthesia
Induction: putting the patient to sleep
Maintenance: keeping the patient asleep
Emergence: waking the patient up
42. 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.
43. 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.
44. 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.
45. STAGE 4 (Impending Death/Overdose):
Onset of apnea, dilated and nonreactive pupils, and
hypotension to complete circulatory failure.
46. 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.
47. Mechanisms of Action
Enhanced GABA effect on GABAA Receptors
1.
–
–
–
- Etomidate
- Propofol
Block nicotinic receptor subtypes (analgesia)
1.
–
Moderate to high conc’s of inhaled anesthetics
Activate K channels (hyperpolarize )
1.
–
Nitrous oxide, ketamine, xenon
Inhibit NMDA (glutamate) receptors
1.
–
1.
Inhaled anesthetics
Barbiturates
Benzodiazepines
Nitrous oxide, ketamine, xenon, high dose barbiturates
Enhance glycine effect on glycine R’s (immobility)
48. Regional Effects
Immobilization in response to surgical incision
(spinal cord)
Sedation, loss of consciousness (↓thalamic firing)
Amnesia (↓hippocampal neurotransmission)
50. Parenteral Anesthetics
(Intravenous)
Most commonly used drugs to induce
anesthesia
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–
–
–
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Barbiturates (Thiopental* & Methohexital)
Benzodiazepines (Midazolam)
Opioids (Morphine & Fentanyl)
Propofol*
Etomidate
* Most commonly used for
induction
51. Barbiturates & Benzodiazepines MOA:
GABA
Barbiturate
BZDS
1) Both bind to GABAA
receptors, at different sites
• Both cause increase Clinflux 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
53. 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
54. 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 t (3-10 mins).
55. Ketamine
Nonbarbiturate, rapid acting general
anesthetic
Dissociated from the environment,
immobile, and unresponsive to pain
Profound analgesic
56. Ketamine
Selectively blocks the associative pathways
producing sensory blockade
Preserved pharyngeal-laryngeal reflexes
Normal or slightly enhanced skeletal
muscle tone
Cardiovascular and respiratory stimulation
57. 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
59. 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)
60. 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 room
Blood: Gas P. Coeff
– Haltothane
– Desflurane
– Sevoflurane
2.30
0.42
0.69
Halothane & methoxyflurane undergo hepatic metabolism
& can cause liver toxicity.
61. 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).
63. 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
64. 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
Editor's Notes
Common digital nerve block
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Have a student read this slide out loud to the rest of the class
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Have a student read this slide out loud to the rest of the class
