Prof. S.V.

Tembhurne
Department of Pharmacology
S.N.I.O.P, Pusad. India
Categories of Anesthetics
General anesthetics
Central nervous system (CNS) depressants used to
produce loss of pain sensation and consciousness
Local anesthetics
Used to cause loss of pain sensation and feeling in a
designated area of the body
Does not produce the systemic effects associated
with severe CNS depression

Important difference between general
and local anesthetic are as fallows
Local anesthetics General anesthetics
Site of action CNS Peripheral nerve
Area of body involved Whole body Restricted area
Consciousness Lost Unaltered
Care of vital function Essential

Usually not need
Physiological trespass High Low
Poor health patient Risky Safer
Use in non cooperative
patient

Possible Not possible
Major surgery Preferred Cannot be use
Minor surgery Not preferred preferred

Agents Involved in Balanced
Anesthesia
Preoperative medications
Sedativehypnotics
Antiemetics
Antihistamines
Narcotics

Local Anesthetics
Local Anesthetics ( L As )
Followed general anesthesia by 40 years
Koller used cocaine for the eye in 1884
Halsted used cocaine as nerve block
First synthetic local-- procaine in 1905
Lidocaine synthesized in 1943

Local Anesthetics (LAs)

Local anesthetic can be produced by
cooling.
Clinically used LAs have no/minimal local irritant
action and block sensory nerve endings, nerve
trunks, neuromuscular junction, ganglionic synapse
and receptor (non selective) i.e. structures which
function through increased sodium permeability.
They also reduced release of acetylcholine from
motor nerve endings. Injected around a mixed
nerve they cause anesthesia of skin and paralysis
of voluntary muscle supplied b that nerve.
Classification
Injectable:
1) Low potency, short duration:-Procaine, Chloroprocaine
2) Intermediate potency and duration: - Lignocaine, prilocaine
3) High potency, long duration: - Tetracaine (Amethocaine),
Bupivacaine.Ropivacaine Dibucaine (Cinchocaine)
Surface anesthetics
A) Soluble:
Cocaine
Lignocaine
Tetracaine
Benoxinate
B) Insoluble:
Benzocaine
Butylaminobenzoate (Butamben)
Oxethazaine.
Occasionally use local anesthetics in other
countries:-
Mepivacaine, Etidocaine, cyclomethycaine, Dyclonine,
Proparacaine.
Anesthetics which having local irritancy and
other prominent systemic activity:-
Propranolol, Chlorpromazine, H1 antihistamine, Quinine.
Estered linked local anesthetics: Cocaine,
procaine, Chloroprocaine, Tetracaine, and Benzocaine.
Amide linked Local anesthetics: Lignocaine,
Bupivacaine, Dibucaine, Prilocaine, and Ropivacaine.

Mechanism of action is by reversibly blocking
sodium channels to prevent depolarization
Anesthetic enters on axioplasmic side and
attaches to receptor in middle of channel

Linear molecules that
have a lipophilic and
hydrophilic end
(ionizable)
low pH-- more in
ionized state and
unable to cross
membrane
adding sodium bicarb--
more in non-ionized
state
Two groups: esters and amides
esters metabolized by plasma cholinesterase
amides metabolized by Liver microsomes by
dealkylation and hydrolysis.


Features of Amide LAs
(compared to ester LAs)

Produced more intense and longer lasting anesthesia
Bind to 1 acid glycoprotein in plasma.
Not hydrolyzed by plasma esterase.
Rarely cause hypersensitivity reaction; no cross
sensitivity with ester LAs.
Because of their short duration, less intense analgesia
and higher risk of hypersensitivity, the ester linked LAs
are rarely used for infiltration or nerve block, but are still
used on mucous membrane.
Structure
Pharmacokinetic of Local
Anesthetics:

Soluble surface anesthetics are rapidly
absorbed from mucous membranes and
abraded areas; but absorption from intact
skin is poor. Procaine is negligible bound to
plasma protein, but amide LAs are bound to
plasma protein.
After oral ingestion both procaine and
Lignocaine have high first pass metabolism
in the liver. Thus they are not effective orally
for antiarrhythmic purpose.
Toxicity Profile
Local Anesthetic Action/Toxicity
Central nervous system
initially-- lightheadedness, circumoral numbness,
dizziness, tinnitus, visual change
later-- drowsiness, disorientation, slurred speech,
loss of consciousness, convulsions
finally-- respiratory depression.
Cocaine having more potent action on CNS.
Blood vessels:
Fall in blood pressure due to sympathetic
blockage, relaxation of arteriolar smooth muscle.
Toxic doses of Las produce cardiovascular
collapse.
Cardiovascular
myocardial depression and vasodilation-- hypotension
and circulatory collapse
They have quinidine like antiarrhythmic action.
Procaine cannot used as a antiarrhythmic agent
because of short duration of action and propensity to
cause CNS effect, but its amide derivative
procainamide is a classical anti-arrhythmic action.
At high dose they induce arrhythmias.
Bupivacaine is more cardiotoxic
Lignocaine is used as an antiarrhythmic

Allergic reactions-- rare (less than 1%)
preservatives or metabolites of esters
rash, bronchospasm


Prevention and Treatment of
Toxicity
Primarily from intravascular injection or
excessive dose -- anticipation
aspirate often with slow injection
ask about CNS toxicity
have monitoring available
prepare with resuscitative equipment, CNS-
depressant drugs, cardiovascular drugs

Treatment of Toxicity
Individual compounds
Cocaine-(Obtained from Erythroxylem coca)
South American Indians used to induce
euphoria, reduce hunger, and increase work
tolerance in sixth century
Many uses in head and neck-- strong
vasoconstrictor, no need for epinephrine
Mechanism is similar-- blocks sodium channel,
also prevents uptake of epinephrine and
norepinephrine
May lead to increased levels of circulating
catecholamine-- tachycardia, peripheral
vasoconstriction
Safe limits (200-400 mg)-- use with epinephrine
clinically


Procaine
It is the first synthetic local anesthetics
introduced in 1905.
It is not surface anesthetics.
PABA is released on hydrolysis of
procaine which can antagonized the
antibacterial action of sulfonamide given to
treat the infection.
Procaine penicillin injected i.m. acts for 24
hours.
Lignocaine
Introduced in 1948
Lignocaine hydrochloride is used both topically and by
injection.
It block the conduction within 3 min. where as procaine
may take15 min.
Cross sensitivity with ester LAs is not seen.
Central effect of Lignocaine are drowsiness, mental
clouding, altered taste and tinnitus.
Overdose may cause muscle twitching, convulsion,
cardiac arrhythmias, fall in BP,coma and respiratory
arrest
It is rapidly metabolized in liver by dealkylation to form
monoethylglycinexylidide and glycine xylidide.
Lignocaine is a popular antiarrhythmic
Prilocaine

It is similar to Lignocaine but does not
cause vasodilation at the site of infiltration
and has lower CNS toxicity due to larger
volume of distribution.
It is readily metabolized in liver and
kidneys. The principal metabolite excreted
in the urine is o-toluidine. This is believed
to cause methaemoglobinaemia.
Eutectic Lignocaine/Prilocaine
It can anesthetize the intact skin after
surface application.

Tetracaine (Amethocaine)
A PABA ester, more potent and more toxic
due to slow metabolism.
It is used for surface anesthesia and spinal
anesthesia.

Bupivacaine
It is a potent and long acting (180-360 min.)
amide linked LA: used chiefly for infiltration and
regional nerve block, epidural and spinal
anesthesia.
It has high lipid solubility; distributed in tissue ore
than in blood after spinal and epidural injection.
It is more prone to prolong QT interval and also
cause cardiac depression.
Should not used for intravenous regional
analgesia.

Ropivacaine
It is a congener of Bupivacaine, equally
long acting but less cardiotoxic.
It block the fiber involved in pain
transmission
Used for postoperative and labour pain, it
can also be employ for nerve block.
Dibucaine (Cinchocaine)
It is a most potent, most toxic and longest
acting LA (180-600 min.).
Used as a surface anesthetics on less
delicate mucous membrane (anal canal)
and occasionally for spinal anesthesia of
long duration.
Benoxinate
It is a good surface anesthetics for the
eye; has little irritancy.
0.4 percent solution rapidly produce
corneal anesthetics
Benzocaine and
Butylaminobenzoate (Butamben)
Both are PABA derivative can antagonise
sulphonamide locally.
It is hydrolysed by esterases in the plasma to 4-
aminobenzoic acid.
It has very low aqueous solubility, these are not
significantly absorbed from mucous membrane
or abraded skin.
Produce long lasting effect without systemic
toxicity.
Is often used in combination with other drugs for
temporary local relief of pain associated with
dental procedures, sore throat, hemorrhoids and
pruritis.


Oxethazaine

Topical anasthetics,unique in ionizing to a
very small extent even at low PH values.
Effective in anaesthetising gastric mucosa
despite acidity of the medium. swallowed
along with antacid it afford symptomatic
relief in gastric, drug induced gastric
irritation,gastroesophageal reflex and
heartburn of pregnancy
Methods of Administering Local Anesthetics
Topical/Surface anesthesia
Infiltration anesthesia (infiltered under the skin in the area of
operation)
Conduction block (injected around nerve trunk)
Field block
Nerve block
Spinal anesthesia (injected in subarachnoid space)
Drug used in spinal anesthesia are: Lignocaine, Tetracaine,
Bupivacaine, Dibucaine
complication of spinal anesthesia:
Respiratory paralysis -Pulmonary complication
Hypotension due to sympathetic blocker.
Headache
Neurological complication
septic meningitis
Nausea and vomiting
Intravenous regional anesthesia -mainly used for
upper limb and orthopedic procedure.
Epidural anesthesia: Lignocaine and Bupivacaine are
most popular epidural Anastasia. It divided into 3
category depending on the site of injection.
Thoracic-used generally for pain relief from thoracic
/upper abdominal surgery.
Lumber: produce anesthesia of lower abdomen,
pelvis and hind limb.
Caudal :given in sacral can produce anesthesia of
pelvic and peripheral region-used mostly for vaginal
delivery,anorectal,and genitourinary operation.
Duration of action of both anesthesia is prolong by
adrenaline. Cardiovascular complication are similar to
spinal anesthesia but neurological and headache are
less.


General
Anesthetics
Goals of General
Anesthetics
Analgesia
Loss of pain perception
Unconsciousness
Loss of awareness of ones surroundings
Amnesia
Inability to recall what took place

History of Anesthesia
Ether synthesized in 1540 by Cordus
Ether used as anesthetic in 1842 by Dr.
Crawford W. Long
Ether publicized as anesthetic in 1846 by
Dr. William Morton
Chloroform used as anesthetic in 1853 by
Dr. John Snow

History of Anesthesia
Endotracheal tube discovered in 1878
Local anesthesia with cocaine in 1885
Thiopental first used in 1934
Curare first used in 1942 - opened the
Age of Anesthesia
Basic Principles of Anesthesia
Anesthesia defined as the abolition of
sensation
Analgesia defined as the abolition of pain
Triad of General Anesthesia
need for unconsciousness
need for analgesia
need for muscle relaxation

Potent CNS depressants
General anesthesia = most severe state of
intentional drug-induced CNS depression
= opioid narcotic + volatile anesthetic
(no pain +unconsciousness)
Depression of all CNS functions
- sedation, sleep, depressed reflexes,
amnesia, unconsciousness

Risk Factors Associated With
General Anesthetics
CNS factors
Cardiovascular factors
Respiratory factors
Renal and hepatic function

Mechanism
Mechanism
The research finding that the anesthetics act on ligand
gated ion channels (but not voltage sensitive ion
channels) are the major target of anesthetics action. The
GABAA receptor gated chloride channel is the most
important of these. Many inhalation anesthetics,
barbiturates, benzodiazepines and propofol potentiate
the action of inhibitory transmitter GABA to open chloride
channels.
Action of glycine (activate chloride channels) in the
spinal cord and medulla is augmented by barbiturates,
propofol and many inhalation anesthetics. This action
may block responsiveness to painful stimuli resulting in
fluorinated anesthetics and barbiturates, in addition,
inhibit neuronal cation channel gated by nicotinic
cholinergic receptor.
Nitrous oxide and ketamine donot affect GABA or glycine
gated chloride channels. Rather they selectively NMDA
type of glutamate receptor. This receptor gated mainly
calcium selective cation channel in the neurones and
their inhibition appears to be the primary mechanism of
anesthetics action of ketamine as well as nitrous oxide.
the volatile anesthetics have little action on this receptor.
Neuronal hyperpolarization caused by general
anesthetics has been ascribed to activation of a specific
type of potassium channels, while inhibition of
transmitter release from presynaptic neurones has been
related to interaction with certain critical synaptic protein.
Local anesthetics which act primarily through blocking
axonal conduction, The general anesthetics appear to
act by depressing synaptic transmission.
Stages of Anesthesia
Stage 1: The analgesia stage
Stage 2: The excitement stage
Stage 3: Surgical anesthesia
Stage 4: Medullary paralysis

Stage 1: The analgesia stage
Start from beginning of anesthetic inhalation and lasts
upto the loss of consciousness. Pain is progressively
abolished during these stage patient remains abolished
during this stage. Patient remains conscious, can hear
and see, and fees a dream like state. Reflexes and
respiration remain normal. Though some minor and even
major operation can be carried out during this stage, it is
rather difficult to maintain-use is limited to short
procedure.

Stage 2: The excitement stage/ Stage
of Delirium:
From loss of consciousness to beginning of regular respiration.
Excitement is seen-patient may shout, struggle and hold his breath;
muscle tone increases, jaw are tightly closed, breathing is jerkey;
vomiting, involuntary micturition or defecation may occur. Heart rate
and BP may rise and pupils dilate due to sympathetic stimulation.
No stimulus should be applied or operative procedure carried out
during this stage.
Stage 3: Surgical anesthesia :
Extends from onset of regular respiration to cessation of
spontaneous breathing. This has been divided into 4
planes which may be distinguished as Phase1: Roving
eyeballs. This plane ends when eyes become fixed.
Plane2: loss of corneal and laryngeal reflexes.
Plane 3: pupil starts dilating and light reflex is lost
Plane 4: intercostals paralysis, shallow abdominal
respiration, dilated pupil.
Stage 4: Medullary paralysis:
Cessation of breathing to failure of circulation and death.
Pupil is widely dilated, muscles are totally flabby, pulse is
thready or imperceptible and BP is very low.
Pharmacokinetics of
inhalation anesthetics:

Inhalation anesthetics are gases or vapors that
diffuse rapidly across pulmonary alveoli and
tissue barriers. the depth of anesthesia depend
on the agent (MAC is an index of potency) and
its partial pressure(PP) in the brain, while the
induction and recovery depend on the rate of
change of PP in the brain.
Transfer of anesthetics between lung and brain
depends on a series of tension gradient which
may be as
Alveoli Blood Brain
Elimination
When anesthetic administration is
discontinued, gradient are reversed and
the channel of absorption (pulmonary
epithelium) becomes the channel of
ellimination.
Most of general anesthetics are eliminated
unchanged. metabolism is significant only
for halothane. Other are practically not
metabolized
Classification

Inhalational Intravenous
Gas:
Nitrous oxide (blue cylinder)
Prototype anesthetic
gas
Cyclopropane (orange
cylinder)
Has a rapid onset of
action and a rapid
recovery
Ethylene (red cylinder)
Less toxic than most of
the other gas
anesthetics

Liquids:
Ether
Halothane
Enflurane
Isoflurane
Sevoflurane
Desflurane
Methoxyflurane
Inducing agent
Thiopentone sodium
Methohexitone sodium
Propofol
Etomidate
Slowly acting drugs
Benzodiazepines
Diazepam
Lorazepam
Midazolam
Dissociative anesthesia
Ketamine
Opioid analgesia
Fentanyl
Inhalational Anesthetic Agents
Inhalational anesthesia refers to the
delivery of gases or vapors from the
respiratory system to produce anesthesia
Pharmacokinetics--uptake, distribution,
and elimination from the body
Pharmacodyamics- MAC value
Nitrous Oxide
Prepared by Priestly in 1776
Anesthetic properties described by Davy in 1799
Characterized by inert nature with minimal
metabolism
Colorless, odorless, tasteless, and does not
burn.
Simple linear compound
Not metabolized
Only anesthetic agent that is inorganic

Major difference is low potency
MAC value is 105%
Weak anesthetic, powerful analgesic
Needs other agents for surgical
anesthesia
Low blood solubility (quick recovery)



Nitrous Oxide Systemic Effects
Minimal effects on heart rate and blood
pressure
May cause myocardial depression in sick
patients
Little effect on respiration
Safe, efficacious agent

Nitrous Oxide Side Effects
Manufacturing impurities toxic
Hypoxic mixtures can be used
Large volumes of gases can be used
Beginning of case: second gas effect
End of case: diffusion hypoxia
Inhibits methionine synthetase (precursor to
DNA synthesis)
Inhibits vitamin B-12 metabolism
Dentists, OR personnel, abusers at risk

Ether
It is highly volatile liquid, produces irritating vapors which
are inflammable and explosive.
Ether is a potent anesthetics, produce good analgesia
and marked muscle relaxation by reducing Ach output
from motor nerve ending
It is highly soluble in blood-induction is prolonged and
unpleasant with struggling, breath holding, salivation and
marked respiratory secreations(atropine must be given
as premedication to prevent the patient from drowsing in
his own secretion.
Post anesthetics nausea, vomiting and retching are
marked.
It does not sensitize the heart to adrenaline and is not
hepatotoxic.
Halothane
Synthesized in 1956 by
Suckling
Halogen substituted ethane
Volatile liquid easily vaporized,
stable, and nonflammable
Most potent inhalational
anesthetic
MAC of 0.75%
Efficacious in depressing
consciousness
Very soluble in blood and
adipose
Prolonged emergence

Halothane Systemic Effects
Inhibits sympathetic response to painful
stimuli
Inhibits sympathetic driven baroreflex
response (hypovolemia)
Sensitizes myocardium to effects of
exogenous catecholamines- ventricular
arrhythmias
Halothane Systemic Effects
Decreases respiratory drive-- central
response to CO
2
and peripheral to O
2
Respirations shallow-- atelectasis
Depresses protective airway reflexes

Depresses myocardium by reducing
intracellular calcium concentration-- lowers
BP and slows conduction
Mild peripheral vasodilation


Halothane Side Effects
Halothane Hepatitis -- 1/10,000 cases
fever, jaundice, hepatic necrosis, death
metabolic breakdown products are hapten-protein conjugates
immunologically mediated assault
exposure dependent.
Malignant Hyperthermia due to intracellular release of
calcium from sarcoplasmic reticulum causing
persistent muscle contraction and heat production--
1/60,000 with succinylcholine to 1/260,000 without
halothane in 60%, succinylcholine in 77%
Classic-- rapid rise in body temperature, muscle
rigidity, tachycardia, rhabdomyolysis, acidosis,
hyperkalemia, DIC


Malignant Hyperthermia (continued)

treatment--early detection, d/c agents,
hyperventilate, bicarb, IV dantrolene (2.5
mg/kg), ice packs/cooling blankets,
lasix/mannitol/fluids. ICU monitoring
Susceptible patients-- preop with IV
dantrolene, keep away inhalational agents
and succinylcholine
Enflurane
Developed in 1963 by
Terrell, released for
use in 1972
Stable, nonflammable
liquid
Pungent odor
MAC 1.68%

Enflurane Systemic Effects
Potent inotropic and chronotropic depressant
and decreases systemic vascular resistance--
lowers blood pressure and conduction
dramatically
Inhibits sympathetic baroreflex response
Sensitizes myocardium to effects of exogenous
catecholamines arrhythmias.
Respiratory drive is greatly depressed-- central
and peripheral responses
increases dead space
widens A-a gradient
produces hypercarbia in spontaneously breathing
patient



Enflurane Side Effects
Metabolism one-tenth that of halothane-- does
not release quantity of hepatotoxic metabolites
Metabolism releases fluoride ion-- renal toxicity
Epileptiform EEG patterns
Stimulates salivary and respiratory secretion.

Isoflurane
Synthesized in 1965 by
Terrell, introduced into
practice in 1984
Isomer of enflurane
Not carcinogenic
Nonflammable, pungent
Less soluble than
halothane or Enflurane
MAC of 1.30 %
Isoflurane Systemic Effects
Depresses respiratory drive and ventilatory responses--
less than enflurane
Myocardial depressant-- less than enflurane
Inhibits sympathetic baroreflex response-- less than
enflurane
Sensitizes myocardium to catecholamines -- less than
halothane or enflurane.
Produces most significant reduction in systemic vascular
resistance-- coronary steal syndrome, increased ICP
Excellent muscle relaxant-- potentiates effects of
neuromuscular blockers


Isoflurane Side Effects
Little metabolism (0.2%) -- low potential of
organotoxic metabolites
No EEG activity like enflurane
Bronchoirritating, laryngospasm
Sevoflurane and Desflurane
Low solubility in blood-- produces rapid
induction and emergence
Minimal systemic effects-- mild respiratory
and cardiac suppression
Few side effects
Expensive

Desflurane has distinct property in their high
volatility, lower oil: gas partition coefficient and
very low solubility in blood and tissue because of
which induction and recovery are very fast.
Patient can discharge few hours after surgery.
Sevoflurane is polyfluronated anesthetic which
is intermediate between isoflurane and
desflurane,no problem in induction.
Sevoflurane does not cause sympathetic
stimulation and airway irritation even during
rapid induction.
Intravenous Anesthetic
Agents
First attempt at intravenous anesthesia by
Wren in 1656-- opium into his dog
Use in anesthesia in 1934 with thiopental
Many ways to meet requirements-- muscle
relaxants, opoids, nonopoids
Appealing, pleasant experience

Inducing agent:
Thiopental
Barbiturate
Water soluble
Alkaline
Dose-dependent
suppression of
CNS activity--
decreased
cerebral
metabolic rate
(EEG flat)

Thiopental Systemic Effects
Rapid onset of action; ultrashort recovery period
Varied effects on cardiovascular system in
people-- mild direct cardiac depression-- lowers
blood pressure-- compensatory tachycardia
(baroreflex)
Dose-dependent depression of respiration
through medullary and pontine respiratory centers
IV route: Onset 1 min; duration 2030 min
T

: 38 hours; metabolized in the liver, excreted

in the urine


Thiopental Side Effects
Noncompatibility
Tissue necrosis--gangrene
Tissue stores
Post-anesthetic course
Laryngospasm occur generally when respiratory
secretion or other irritant are present it can prevented
by atropine premedication and administration of
succinylcholine immediately after thiopentone.
Succinylcholine and thiopentone react chemically-
should not mixed in same syringe.

Other uses
Occasionally used for rapid control of
convulsion.
I.V infusion of subanasthetic doses can be
used to facilated psychiatric verbal
communication with psychiatric pateint.
Methohexital
Similar to thiopentone,3 times more potent
It has a quicker and briefer(5-8 min) action.
Vascular complication are rare
It is more rapidly metabolized than thiopentone
Etomidate
Structure similar to
ketoconozole
Direct CNS depressant
(thiopental) and GABA
agonist
Redistribution

Etomidate Systemic Effects
Little change in cardiac function in healthy and
cardiac patients
Mild dose-related respiratory depression
Decreased cerebral metabolism.
it suppress the production of steroid from
adrenal and is not suited for continuous i.v. use.
It is poor analgesic

Etomidate Side Effects
Pain on injection (propylene glycol)
Myoclonic activity
Nausea and vomiting (50%)
Cortisol suppression

Propofol
Rapid onset and short duration of action
Myocardial depression and peripheral
vasodilation may occur-- baroreflex not
suppressed
Not water soluble-- painful (50%)
Minimal nausea and vomiting

Slower acting drugs
Benzodiazepine
Produce sedation and amnesia
Potentiate GABA receptors
Slower onset and emergence
BZDs are poor analgesic: an opoids pr nitric oxide is usually added if the
procedure is painful

BZDs decrease muscle tone by central action,
but require neuromuscular blocking drugs for
muscle relaxation of surgical grade.
They donot provoke postoperative nausea or
vomiting.
Involuntary movement are not stimulated.
The anesthetic action of BZDs can be reversed
by flumazenil
Diazepam
Often used as premedication or seizure
activity, rarely for induction
Minimal systemic effects-- respirations
decreased with narcotic usage
Not water soluble-- venous irritation
Metabolized by liver-- not redistributed
Lorazepam
Slower onset of action (10-20
minutes)-- not used for induction
Used as adjunct for anxiolytic
and sedative properties
Amnesia are more profound
Not water soluble-- venous
irritation

Midazolam
More potent than diazepam or
lorazepam
Induction slow, recovery
prolonged
May depress respirations when
used with narcotics
Minimal cardiac effects
Water soluble: non irritating
Dissociative anesthesia:
Ketamine
Pharmacologically related to the hallucinogen phencyclidine
Interrupts cerebral association pathways -- Dissociative
anesthesia
Stimulates central sympathetic pathways
Primary site of action is the cortex and subcortical area; not in
reticular activating system.


Ketamine has been recommended for
operation on the head and neck, in patient
who have bled, in asthamatic(relieves
bronchospasm).
It is good for repeated use; particularly
suitable for burn dressing.
It may dangerous for hypertensive and in
ischemic heart but is good for hypovolemic
patient.
Ketamine Systemic and Side Effects
Characteristic of sympathetic nervous
system stimulation-- increase HR, BP, CO
Maintains laryngeal reflexes and skeletal
muscle tone
Emergence can produce hallucinations
and unpleasant dreams (15%)

Clonidine
It is selective 2 adrenergic agonist used as a
antihypertensive.
Stimulation of central 2 adrenoceptors produces
sedation and analgesia.
Administered before surgery, clonidine reduce
the dose of anesthetic/analgesic drug, resulting
in less overall depression of cardiovascular
function for the same level of anesthesia.

Narcotic agonists (opiods)
Used for years for analgesic action-- civil war for
wounded soldiers
Predominant effects are analgesia, depression
of sensorium and respirations
Mechanism of action is receptor mediated
Minimal cardiac effects-- no myocardial
depression
Bradycardia in large doses
Some peripheral vasodilation and histamine
release -- hypotension
Side effects nausea, chest wall rigidity,
seizures, constipation, urinary retention
Meperidine, morphine, alfentanil, fentanyl,
sufentanil are commonly used
Naloxone is pure antagonist that reverses
analgesia and respiratory depression
nonselectively- acts 30 minutes, effects may
recur when metabolized

Muscle Relaxants
Current use of inhalational and previous
intravenous agents do not fully provide
control of muscle tone
First used in 1942-- many new agents
developed to reduce side effects and
lengthen duration of action
Mechanism of action occurs at the
neuromuscular junction
Muscle Relaxants
Neuromuscular Junction
Non-depolarizing Muscle
Relaxants
Competitively inhibit end plate nicotinic
cholinergic receptor
Intermediate acting (15-60 minutes):
atracurium, vecuronium, mivacurium
Long acting (over 60 minutes):
pancuronium, tubocurarine, metocurine
Difference-- renal function
Non-depolarizing Muscle
Relaxants
Tubocurare-- suppress sympathetics, mast
cell degranulation
Pancuronium-- blocks muscarinics
Reversal by anticholinesterase-- inhibit
acetylcholinesterase
neostigmine, pyridostigmine, edrophonium
side effects muscarinics stimulation
Depolarizing Muscle Relaxants
Depolarize the end-plate nicotinic receptor
Succinylcholine used clinically
short duration due to plasma cholinesterase
side effects-- fasiculations, myocyte rupture,
potassium extravasation, myalgias
sinus bradycardia-- muscarinic receptor
malignant hyperthermia

Techniques
History and physical examination
Induction
Maintenance
Emergence
Drug interaction
Antihypertensive + general anesthetics= BP may
fall markedly.
Neuroleptics, Opoids, Clonidine and Monoamine
oxidase inhibitor= potentiate anesthetics.
Halothane, sensitizes the heart to Adrenaline.
Corticosteroid + general anesthetics can
precipitate adrenal insufficiency and
cardiovascular collapse.
Need of Insulin is increased during general
anesthetics
Agents Involved in Balanced
Anesthesia
Preoperative medications
Sedativehypnotics
Opiods
Antiemetics
Anticholinergics
Antihistamines
Neuroleptics
Narcotics

Why there is need to give
preoperative medication
For relief of anxiety and facilated smooth induction.
Amnesia for pre- and postoperative events.
Supplement analgesic action of anesthetics and
potentiate them so that less anesthetics is needed.
Decrease the secretion and vagal stimulation caused by
anesthetics.
Antiemetics effect extending to the postoperative period.
Decrease acidity and volume of gastric juice so that it is
less damaging if aspired.
Sedative-antianxiety drugs: BZDs have become popular drug for
preanesthetics because they produce tranquility and smoothen
induction, there is loss of recall of preoperative events. They
counteract CNS toxicity of anesthetics. Barbiturate is absolute.
Promethazine: is an antihistaminic with sedative, antiemetic and
Anticholinergics properties. It is particularly use in children.
Anticholinergics: Atropine or hyoscine have been used, primarily
to reduce salivary and bronchial secretions. The main aim of their
use now is to prevent vagal bradycardia and hypotension, and
prophylaxis of laryngospasm which is precipitated by respiratory
secretion. they dilate pupils, abolish the pupilary sign and increase
signs and increase chances of gastric reflex by decreasing tone of
lower esophageal sphincter.
Glycopyrrolate: Is a longer acting quaternary atropine substitute. it is
a potent antisecretory and antibradycardiac drug; acts rapidly and
less likely to produce central effect.
Neuroleptics: chlorpromazine,triflupromazine or haloperidol are
frequently used in premedication. They allay anxiety, smoothen
induction and have antiemetic action. however they potentiate
respiratory depression and hypotension caused by the anesthetics
and delay recovery.
Involuntary movement and muscle dystonias can occur, specially in
children.

Antihistamines: H2 blockers, patient undergoing prolonged
operations, obese patients are at increased risk of gastric
regurgitation and aspiration pneumonia.Ranitidine or Famotidine
given night before and in the morning benefit by raising PH of gastric
juice; may also reduce its volume and thus chances of regurgitation.
prevention of stress ulcer is another advantage.
Antiemetics:metaclopramide preoperatively is effective in reducing
post operative vomiting. By enhancing gastric emptying and tone of
LES, it reduces the chance of reflux and its aspiration.
Extrapyramidal effect and motor restlessness can occur.
Domperidol is nearly as effective and does not produce
Extrapyramidal side effect.
Opiods: Morphine or pethidine ally anxiety and apprehension of the
operation, produce pre- and post operative analgesia, smoothen
induction, reduce the dose of anesthesia required and supplement
poor analgesic(thiopentone, halothane) or weak nitrous oxide
anesthetics.
Use of opiods is now mostly restricted to those having preoperative
pain. When indicated fentanyl is mostly injected just before
induction.


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