General Anesthetic Agents

GENERAL ANESTHESIA

References

• Essentials of Medical Pharmacology by KD Tripathi

• Essentials of Pharmacotherapeutics by FSK Barar

• Www.google.com and various appropriate sites.

Contents

• General anesthesia

• Mechanism of Action

• Stages of Anesthesia

• Pharmacokinetics

• Classification

• Nitrous oxide

• Ether

• Ketamine

• Properties of anesthetics

• Complication of anesthesia

• Interactions

• Preanesthetic medication

• Conscious sedation and euthanasia

• References
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 General Anesthetic Agents

General Anesthesia

• Anesthesia (An-without, eisthesis-sensation)

• It is medically induced coma and Anesthesia attempt to eliminate pain impulse from
reaching the brain

• It is neither therapeutic nor diagnostic procedure.

• General anesthesia produces reversible loss of all sensations and consciousness.

• Administered by anesthetist or anesthesiologist to induce and maintain anesthesia to

facilitate surgery or unpleasant procedure.

• Anesthesia depress CNS and causes muscle relaxation and immobility.

• Objectives: To sustain physiological homeostasis during procedure

• Minimizing deleterious effects, improving post operative outcomes.

Features of anesthesia

➢ Loss of all sensations(unconsciousness), especially pain

➢ Sleep and amnesia (loss of memory)

➢ Immobility and muscle relaxation (motor reflexes)

➢ Abolition of somatic and autonomic reflexes

• In modern practice of balanced anesthesia these are produced by combination of

inhaled and i.v. drugs, each drug has specific purpose and drug being selected by
anesthetics or assistant nurse anesthetics.

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 General Anesthetic Agents

• A variety of medications may be administered, with the overall aim of ensuring sleep,
amnesia, analgesia, relaxation of skeletal muscles, and loss of control of reflexes of the
autonomic nervous system

Mechanism of action

• Mechanism not precisely known but the physicochemical property of drug produces
anesthesia

• Minima alveolar concentration of drug produces immobility and different agents act
through different molecular mechanism

• Common areas of the central nervous system whose functions are interrupted or
changed during general anesthesia include the cerebral cortex, thalamus, reticular
activating system, and spinal cord.

• Agents have GABA and the glutamate-activated ion channels ,NMDA receptor families
and ligand gated ion channels as potential pharmacologic targets, but others such as
voltage-gated ion channels, glycine and 5-hydroxytriptamine (5-HT) receptors, are
also involved

• Calcium channel opens by interacting (inhibition) GABA receptor Cl channel complex

and this results in blocking responsiveness to painful stimuli and immobility

Stages of Anesthesia

1. Stage of Analgesia –Also called “Stage 1”, or “induction”anesthesia, is the period

between the initial administration of the induction agents and loss of consciousness.
Patient remains conscious can hear and see and feels dream like state. Amnesia is
developed by end, reflexes and respiration remains normal. Minor operations can be
carried out.

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 General Anesthetic Agents

2. Stage of Delirium- Also called “stage 2” or “excitement stage”, period following loss
of consciousness and marked by excited and delirious activity to beginning of
respiration. During this stage, respirations and heart rate may become irregular.
Excitement is seen-shouting, struggle and holding breath, muscle tone increased, jaws
are tightly closed, and breathing is jerky, vomiting, involuntary micturition or
defecation. Heart rate and BP rise and pupils dilate

3. Stage of surgical Anesthesia- Also called stage 3 extends from regular respiration
to abolition of all reflexes. It is divided into following planes. Major surgeries are
possible in this stage.

Plane 1- Roving eye ball, plane end when eyes become fixed

Plane 2-Loss of corneal and laryngeal reflexes

Plane 3- Pupils dilated and light reflex lost

Plane 4- Intercostals paralysis, shallow respiration.

• As anesthesia passes into deeper planes-muscle tone decreases, BP falls, HR

increases with weak pulse, respiration decreases

4. Medullary Paralysis-Stage 4 anesthesia, also known as "overdose“ is cessation of

breathing to failure of circulation and death.
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 General Anesthetic Agents

• It is the stage where too much medication has been given relative to the amount of
surgical stimulation and the patient has severe brain stem or medullary depression.

• Pupils widely dilated, muscle is flabby, pulse is thready, and this results in a cessation
of respiration and potential cardiovascular collapse. This stage is lethal without
cardiovascular and respiratory support.

• Maintenance

• The duration of action of intravenous induction agents is in general 5 to 10 minutes,

after which time spontaneous recovery of consciousness will occur.

• In order to prolong anesthesia for the required duration (usually the duration of
surgery), anesthesia must be maintained.

• Usually this is achieved by allowing the patient to breathe a carefully controlled

mixture of oxygen, nitrous oxide, and a volatile anesthetic agent or by having a
carefully controlled infusion of medication, usually propofol, through an intravenous
catheter

• The inhalation agents are transferred to the patient's brain via the lungs and the
bloodstream, and the patient remains unconscious.

Pharmacokinetics

• Inhalational anesthetics are gases or vapors that diffuse rapidly cross pulmonary
alveoli, depth of anesthesia depend on potency of agent.

• Alveoli Blood Brain

• Large amount of agents are highly blood soluble

• They are practically not metabolized only halothane is metabolized in lungs

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 General Anesthetic Agents

• When anesthetic administration is discontinued then channel of absorption becomes

channel of elimination

• They are eliminated through lungs

Classification of drugs

1. Inhalational

a) Gas- Nitrous oxide

b) Volatile liquids-Ether, halothane, Enflurane, isoflurane, Desflurane, Sevoflurane

2. Intravenous

a) Inducing agents-Thiopentone sod, Methohexitone sod, Propofol, Etomidate

b) Slower acting

➢ Benzodiazepine-Diazepam, Lorazepam, Midazolam

➢ Dissociative-Ketamine

➢ Opioid Analgesics-Fentanyl

Nitrous Oxide

• Nitrous oxide, commonly known as laughing gas, nitrous, nitro, or NOS is a chemical
compound with the formulN2O.

• It is an oxide of nitrogen. At room temperature, it is a colorless, non-flammable gas,

with a slightly sweet odor and taste.

• Onset of action is quick and smooth recovery is rapid. Often used as adjuvant to other
anesthetics. Nontoxic to liver, kidney and brain

• It is used in surgery and dentistry for its anesthetic and analgesic effects.

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 General Anesthetic Agents

• It is known as "laughing gas" due to the euphoric effects of inhaling it, a property that
has led to its recreational use as a dissociative anesthetic

• Inhalation of nitrous oxide is frequently used to relieve pain associated with

childbirth, trauma, oral surgery and acute coronary syndrome (includes heart
attacks). Its use during labor has been shown to be a safe and effective aid for women
wanting to give birth without an epidural. Its use for acute coronary syndrome is of
unknown benefit

Halothane

• It is the only inhalational anesthetic containing bromine. It is colorless and pleasant-

smelling, but unstable in light. It is packaged in dark-colored bottles and contains
0.01% thymol as a stabilizing agent.

• About 20% of inhaled halothane is metabolized by the liver and these products are
excreted in the urine.

• Halothane activates GABAA and glycine receptors. It also acts as an NMDA receptor
antagonist, inhibits nACh and voltage-gated sodium channels, and activates 5-
HT3 and twin-pore K+ channels

• Side effect: Liver injury, hepatitis it is liable to cause cardiac arrhythmias, occasionally
fatal, it is a potent trigger for malignant hyperthermia. it relaxes uterine smooth
muscle and this may increase blood loss during delivery or termination of pregnancy

• halothane anaesthesia has been shown to trigger a skeleta muscle hypermetabolic

state leading to high oxygen demand and the clinical syndrome known
as malignant hyperthermia (MH). The syndrome includes non specific features such
as hypercapnia, muscle rigidity, tachycardia, tachypnoea, cyanosis, arrhythmias and
unstable blood pressure

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 General Anesthetic Agents

• Anaesthesia with halothane may be followed by abnormalities of liverfunction or more

rarely liver damage

Ether (Diethyl ether)

• Diethyl ether, also known as ethyl ether, sulfuric ether, simply ether, or ethoxyethane,
is an organic compound in the ether class with the formula (C2H5)2O.

• It is a colorless, highly volatile flammable liquid.

• It is commonly used as a solvent and was once used as a general anesthetic produces
good analgesia and muscle relaxation by reducing Ach output from motor nerve
ending

• Highly soluble in blood, induction is prolonged and unpleasant with struggling and
breath holding, salivation

• Recovery is slow, post anesthetic nausea and vomiting

• BP and respiration is well maintained but not used now as it is unpleasant and
inflammable properties

• It has narcotic properties and has been known to cause temporary psychological
addiction

Thiopentone sodium

 These are agents which on iv inj produce loss of consciousness and used because of
rapidity of onset. Anesthesia is maintained by an inhalational agents.

 Supplemented by muscle ralaxants and analgesics

 Thiopentone is injected (3-5 mg/kg) as 2.5 % solution produces unconsciousness in

20 sec, enters brain rapidly. Brain gets large amount of drug.

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 General Anesthetic Agents

 Poor analgesic, no painful procedure carried out unless opiod or N2O given, patient
may shout, struggle and show changes in BP and resp.

 Weak muscle relaxant, , BP fall after injection due to vasodilatation but recovers
rapidly

 It can be used for short operations that are not painful.

 Adverse effect: laryngospasm, shivering , pain during recovery

• Thiopental rapidly and easily crosses the blood brain barrier as it is a lipophilic
molecule.

• Once redistributed, the free fraction in the blood is metabolized in the liver. Sodium
thiopental is mainly metabolized to pentobarbital, 5-ethyl-5-(1'-methyl-3'-
hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-c

• arboxypropyl)-2-thiobarbituric acid.

Side effect: thiopental causes cardiovascular and respiratory depression resulting

in hypotension, apneamand airway obstruction. For these reasons, only suitably
trained medical personnel should give thiopental in an environment suitably
equipped to deal with these effects. Side effects include headache, agitated
emergence, prolonged somnolence, and nausea

Contraindications: used with caution in cases of liver disease, Addison's

disease, myxedema, severe heart disease, severe hypotension, a severe breathing
disorder, or a family history of porphyria

• Co-administration of pentoxifylline and thiopental causes death by acute pulmonary

edema in rats.

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 General Anesthetic Agents

Uses

1. Anesthesia

2. Medically induced coma-Barbiturate comas are used to protect the brain during
major neurosurgery, and as a last line of treatment in certain cases of status
epilepticus that have not responded to other treatments.

3. Status epilepticus

4. Euthanasia

5. Lethal injection-Along with pancuronium bromide and potassium chlorie,

6. As truth serum A "truth serum" is a colloquial name for any of a range of psychoactive
medications used to obtain information from subjects who are unable or unwilling to
provide it otherwise.

7. In psychiatries to treat phobias

• The usual dose range for induction of anesthesia using thiopental is from 3 to
7 mg/kg;

Ketamine

• Ketamine is a drug used in human and veterinary medicine, mainly for starting and
maintaining general anesthesia

• Other uses include sedation in intensive care, as a pain killer (particularly in

emergency medicine and patients with potentially compromised respiration and/or
allergies to opiate and barbiturate analgesics), and treatment of bronchospasm.

• It is called dissociaated aesthetic as it produces profound analgesia, immobility,

amnesia with light sleep and feeling of dissociation from own body and surrounding

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 General Anesthetic Agents

• Site of action is cortex and subcortical area

• Respiration not depressed, airway reflexes are maintained, muscle tone increases,
limb movement occur, eyes open.

• It is used for operation on the head and neck. Combined with diazepam used in
angiography, cardiac catheterization and trauma surgery

• Dose 1-3 mg/kg i.v , 5 mg/kg im recovery in 10 min

Properties of ideal anesthetic

• For a patient

• It should be pleasant, non-irritating, should not cause nausea or vomiting, induction

and recovery should be fast with no effects.

• For the surgeon

• It should provide adequate analgesia, immobility and muscle relaxation

• It should be noninflammable and non explosive so that cauterization (burning of a

part of body) can be used

• For the anesthetist

• Administration should be easy, controllable and versatile.

• Margin of safety should be wide, no fall of BP

• Important organ should not be affected

• It should be potent, low dose require, and oxygenation should not affect

• Cheap, stable and easily stored, should not react with storing bottle or rubber tube.

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 General Anesthetic Agents

Complications of general anesthesia

• During anesthesia

• Respirator depression and hypercarbia (elevated Co2)

• Salivation, respiratory secretions

• Cardiac arrhythmias, asystole

• Fall in BP

• Aspiration of gastric contents: acid pneumonitis

• Laryngospasm/asphyxia

• Dreadful perception, recall of events

• Delirium, convulsions and excitatory effects are generally seen with i.v. anesthesia

• Fire and explosion, rare now as non explosives are used.

• After Anesthesia

• Nausea and vomiting

• Sedation-impaired psychomotor function

• Pneumonia

• Organ toxicities, liver, kidney

• Delirium

• Cognitive defects

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 General Anesthetic Agents

Interactions

• Antihypertensive + General anesthetics==BP fall

• Neuroleptics, Opioids, Clonidine, and MAO inhibitors potentiate anesthesia

• If patent is taking corticosteroid, and is to be anesthetized, give 100 mg

hydrocortisone i.p. or adrenal insufficiency and cardiovascular collapse.

• Insulin need of diabetic is increased during anesthesia

Preanesthetic Medication

• It refers to use of drugs before inducing anesthesia to make it more pleasant and safe

• It is used to relive anxiety and apprehension preoperatively and to facilitate smooth

conduction

• Amnesia for pre and postoperative events

• Supplementation of analgesic action so tat less anesthetic is needed

• Decrease secretions and vagal stimulation

• Antiemetic effect after recovery

• Decrease acidity and volume of gastric juice

• Sedative antianxiety drugs-diazepam (5-10 mg oral) lorazepam (2 mg/kg im) for

smooth induction

• Promethazine- antiistaminic with sedation andiemetic and anticholinergic

properties

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 General Anesthetic Agents

• Opioids- Morphine (10 mg) or Pethidine (50-100 mg0 i.m. is sued to allay anxiety
and apprehension of the operation, smoothen induction, reduce dose of anesthetic
required

• Disadvantage is that they depress respiration, may cause fall in BP, precipitate asthma
and tend to delay recovery.

• Anticholinergic- atropine or hyoscine (0.6 mg im, /iv) have been used to reduce
salivary and bronchial secretions. Glycopyrrolate is also used

• They also prevent bradycardia and hypotension

• Hyoscine produces amnesia and antiemetic effect but tends to delay recovery

• Neuroleptics- Chlorpromazien (25 mg), haloperidol (2-4 mg), im are infrequently

used for allaying anxiety, smooth induction and antiemetic effect.

• H2 blockers- patient on prolonged operation has risk of gastric regurgitation and

aspiration. Ranitidine (150 mg), famotidine are given at night or morning raises pH
of gastric juice and reduces gastric volume and regurgitation. Routinely used

• Antiemetics- Metoclopramide (10-20 mg)Domperidone, Ondansetron (4-8 mg iv) is

used to reducedd post operative vomiting. Reflux and aspiration chances are also
reduced as it enhances gastric emptying. Metoclopramide and H2 blockers are
combined

Euthanasia

• Refers to the practice of intentionally ending a life in order to relieve pain and
suffering

• Euthanasia may be classified according to whether a person gives informed consent

into three types: voluntary, non-voluntary and involuntary

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 General Anesthetic Agents

• Euthanasia conducted with the consent of the patient is termed voluntary euthanasia.

• Euthanasia conducted where the consent of the patient is unavailable is termed non-
voluntary euthanasia. Examples include child euthanasia, which is illegal worldwide

• Euthanasia conducted against the will of the patient is termed involuntary

euthanasia.

• Dysthanasia is a term generally used when a person is seen to be kept alive artificially
in a condition where, otherwise, they cannot survive; implantable cardiovascular
defibrillator artificial ventilation, ventricular assist devices, and extracorporeal
membrane oxygenation

Conscious Sedation

• Procedural sedation and analgesia, previously referred to as conscious sedation, is

defined as "a technique of administering sedatives or dissociative agents with or
without analgesics to induce a state that allows the patient to tolerate unpleasant
procedures while maintaining cardio respiratory function.“

• Medical uses

• This technique is often used in the emergency department for the performance of
painful or uncomfortable procedures. Common purposes include:

• setting fractures

• draining abscesses

• reducing dislocations

• performing endoscopy

• for cardioversion

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 General Anesthetic Agents

• during various dental procedures

• during transesophageal echocardiogram

• and certain imaging or minor procedures where the patient is unable (or unwilling)
to keep still—especially children

• Agents used

• Sedatives/dissociative agents-Propofol, Ketamine, Etomidate, Midazolam

• Analgesics-Fentanyl, Morphine, Ketamine

• Techniques

• For most agents the person should have had nothing to eat for at least 6 hours. Clear
fluids can be allowed up to two hours before the procedure. An exception to this may
be with Ketamine in children where fasting may be unnecessary.

• Complications

• Complications depend on the sedative agent that is used. Many commonly used
agents can cause respiratory depression, hypoxia and hemodynamic effects. For some
agents antagonists are available that can be used to reverse the effects.

• Safety

• Procedural sedation can be safely performed in an emergency department if

structured sedation protocols are followed.

• Electrocardiography, pulse oximetry, capnography and blood pressure monitoring

are essential, as is the use of supplementary oxygen.

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 General Anesthetic Agents

Probable questions

• Write a note on stages of anesthesia. Add a note on pre and post-anesthetic

medications. 15

• Describe nitrous oxide as general anesthetics (05)

• Define and classify general anaesthetics with suitable examples. Discuss mode of
action of general anaesthetics.

• Discuss various stages of anesthesia.

• Write a note on GABA Receptors.

• Explain the properties of an Ideal Anaesthetic 03

• Note on Pharmacology of halothane 05

• Classify General Anesthetics.03

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