GENERAL

ANESTHETICS
ASSOC.PROF. CHANDRAJEET KUMAR YADAV
DEPRT.OF PHARMACOLOGY
 Introducti
on
Drugs used to induce loss of pain sensation, loss of consciousness,
skeletal muscle relaxation, analgesia, amnesia and inhibitions of
undesirable autonomic reflexes.
 Types of Anesthesia
• General anesthesia

• Local anesthesia
 STAGES OF
ANESTHESIA
• Stage I (analgesia)
-Loss of pain sensation.
-The patient is conscious and conversational.

• Stage II (Excitement)
-Increased respiratory rate.
-Increased, irregular blood pressure.
-Patient may experience delirium & violent
behavior.
-Eye dilated & reactive.
 STAGES OF
ANESTHESIA
• Stage III (Surgical anesthesia)
- Regular respiration & relaxation of Sk.
muscles.
- Eye reflexes decrease until the pupil is fixed.

• Stage IV (coma and death)

- Medullary paralysis.
- Severe depression of vasomotor
- Depression of respiratory centers.
- Death may occur.
 STAGES OF
ANESTHESIA
The III stage is divided into 4 planes.
The order of depression in the CNS is:
1. Cortical centers
2. Basal ganglia
3. Spinal cord
4. Medulla
 STAGES OF
ANESTHESIA
CHARACTER S OF AN IDEAL ANESTHETIC DRUG

1. Smooth and rapid induction.

2. Rapid recovery.
3. Wide safety margin.
4. Minimal side effects.
 Ideal General Anesthesia

Analgesia Need for muscle

Loss of pain ‘Loss of sensory and relaxation
sensation autonomic reflexes’
unconsciousness
‘Amnesia-hypnosis’
 BALANCED ANAESTHESIA
Is the use of more than one drug in combination to fulfil the patient needs.

Beneficial effects

Adverse effects
HOW WE CAN OBTAIN BALANCED ANESTHESIA

Balanced anesthesia is achieved by a combination of

I.V and inhaled anesthesia and Pre-anaesthetic medications
 PRE-ANESTHETIC MEDICATION

 Calm the patient, relieve pain

 Protect against undesirable effects of the subsequently
administered anesthetics or the surgical procedure.
 Facilitate smooth induction of anaesthesia
 Lowered the dose of anaesthetic required
 PRE - ANAESTHETIC MEDICATION

 Opiates: induce analgesia e.g. morphine

 Anticholinergics: prevent secretion of fluids into the respiratory tract e.g.
hyoscine
 Sedatives & anxiolytics: relieve anxiety. e.g. diazepam
 Antihistaminics: allergic reactions. e.g. diphenhydramine
 Antiemetics : post surgical N&V. e.g. metoclopramide, prochlorperazine
 H2-receptor blockers: reduce gastric acidity e.g. ranitidine
 Thiopental: smooth induction
 ADJUNCTS TO GENERAL
ANAESTHETICS
 Pre-anesthetic medication.
 Neuromuscular blocking agents
 e.g. succinylcholine, vecuronium, atracurium
 Facilitate intubation
 Suppress muscle tone.
 General Anesthesia

Inhalational Intravenous

Volatile Slower acting Inducing agents

Gas liquids
Dissociative Opioid
Benzodiazepines
anesthesia analgesia

Ether Thiopental
Halothane Methohexital
Diazepam
Enflurane Propofol
Nitrous oxide Fentanyl Lorazepam
Isoflurane Ketamine Etomidate
Zenon Midazolam
Desflurane Droperidol
Sevoflurane
Methoxyflurane
 MECHANISM OF ACTION OF GENERAL
ANAESTHETICS

Disruption of the function of ionic channels

Disruption of lipids associated with ionic channels

Receptors
• Inhibitory : GABA A, glycine
• Excitatory : nAch, NMDA
 MECHANISM OF ACTION OF GENERAL
ANAESTHETICS

Enhance the action of GABA A and

glycine on receptors leading to
greater entrance of chloride ion
hyperpolarization thus decrease
neuronal excitability.
 Inhalation anesthetics
Are halogenated hydrocarbons
End with suffix “flurane”
 Methoxyflurane
 Halothane
 Enflurane
 Isoflurane
 Desflurane
 Sevoflurane
 Nitrous oxide
 Pharmacokinetics of Inhalation anesthetics

 Rate of induction
 Depth of anesthesia and recovery.
 Inhalation anesthetics
Induction
Time elapsed between onset of administration of anesthetic and
development of effective surgical anesthesia.

Maintenance
Time during which the patient is surgically anesthetized.

Recovery
The time from discontinuation of anesthetic drug until consciousness is
regained.
 Pharmacokinetics of Inhalation anesthetics

Factors controlling induction & recovery

 The anesthetic concentration in the inspired air: (Direct).
 Blood solubility: Blood: gas partition coefficient (Inverse relation).
 Rate and depth of ventilation (Direct).
Drugs Solubility Induction & Recovery
(Blood : gas partition coefficient )

Methoxyflurane 12 Slow
Halothane 2.3 Slow
Enflurane 1.8 Medium
Isoflurane 1.4 Medium
Sevoflurane 0.69 Rapid
Desflurane 0.42 poor & Rapid
Nitrous Oxide 0.47 Rapid
 Minimum alveolar concentration (MAC)

• It is the concentration of inhalation anesthetic that produce

immobility in 50 % patients in response to surgical incision.

• Potency of anesthetic agents.

• Oil: gas partition coefficient (Direct with potency).

• The lower the MAC value the more potent the drug.

• Decreased by CNS depressants, old people.

• Increased by CNS stimulants.

Drugs MAC POTENCY
Methoxyflurane 0.16
Halothane 0.75
Isoflurane 1.4
Enflurane 1.7
Sevoflurane 2
Desflurane 6-7
Nitrous oxide >100
 POTENCY & INDUCTION & VELOCITY

Drugs
Methoxyflurane: The most potent, low MAC value, slow induction& recovery
Halothane: Potent, slow induction & recovery (pleasant odor)
Enflurane: less potent, medium induction & recovery (pungent odor)
Isoflurane: less potent, medium induction & recovery
Sevoflurane : less potent, rapid induction & recovery (better smell)
Desflurane: Rapid induction & rapid recovery (pungent odor)
Nitrous oxide: The least potent, high MAC value, rapid induction & recovery
 Pharmacological actions of inhalation anesthetics
CNS
-  metabolic rate.
-  ICP (due to cerebral vasodilatation) # in head injuries.
- Dose -dependent EEG changes (Enflurane).

CVS
- Hypotension
- Bradycardia Except (Isoflurane & Desflurane ).
- Myocardial depression (Halothane – Enflurane).
-Sensitize heart to catecholamines (Halothane)
 Pharmacological actions of inhalation anesthetics
Respiratory
- All respiratory depressants
-Airway irritation (Desflurane-Enflurane)

Liver
-Decrease hepatic flow
- Hepatotoxicity (Only halothane)

Uterus & Skeletal Muscles

-Uterine relaxation
- Nitrous oxide has minimal relaxant effect (labor).
- All are skeletal muscle relaxants.
 Halothane
• Potent anesthetic, slow induction and recovery
• Weak analgesic, weak skeletal muscle relaxant.
• Metabolized to toxic metabolites (trifluroethanol) hepatotoxic.
• CVS depression
• Hypotension, bradycardia (vagomimetic action)
•  Myocardial contractility,  Cardiac output
Adverse Effects
1. Hepatotoxicity (repeated use).
2. Malignant hyperthermia.
3. Cardiac arrhythmias.
4. Sensitizes heart to action of catechalamines  arrhythmias.
 Enflurane
• Less potent than halothane.
• Better muscle relaxation, Better analgesic properties.
• is metabolized to fluoride (8%), excreted in the kidney
• More rapid induction and recovery than halothane.
Disadvantages
• Pungent (Less induction -Not for pediatrics).
• CNS stimulation (Epilepsy-like seizure- abnormal EEG).
Contraindication
• patients with seizure disorders.
• Not for renal failures.
 Isoflurane (Forane)
 Potent anesthetic, rapid induction & recovery
 Stable compound (2%).
 Low biotransformation (Less fluoride).
 No nephrotoxicity - No hepatotoxicity.
 Good analgesic action.
 No sensitization of the heart.
 No cardiac arrythmias.

Disadvantages
Pungent (Not for pediatrics).
 Desflurane
 Pungent odor (irritation - Cough)
 Rapid induction & fast recovery (Low solubility).
 Less potent than halothane.
 Less metabolized (0.05 %).
 Low boiling point (special equipment).
 Sevoflurane

• Better smell
• Less potent than halothane
• Rapid onset and recovery (Low solubility)
• Less metabolized (3- 5% fluoride)
• Little effect on HR
• No airway irritation (preferable for children)
 Nitrous Oxide (N2O)
• Potent analgesic.
• Weak anesthetic (Low potency, combined).
• Rapid induction & Recovery (Low solubility).
• No muscle relaxation, No respiratory depression.
• Not hepatotoxic, minimal CVS adverse effects.

Adverse Effects
1. Diffusion Hypoxia: (respiratory diseases).
2. Nausea and vomiting.
3. Inactivation of B 12  megaloblastic anemia.
4. Bone marrow depression-Leukopenia (chronic use).
5. Abortion - Congenital anomalies
Therapeutic Uses
1. Outpatient anesthesia (Dental procedures).
2. Balanced anesthesia.
3. Neuroleptanalgesia.
4. Delivery

Contraindications
1. Pregnancy.
2. Pernicious anemia.
3. Immunosuppression.
 Rationale for combining halothane/isoflurane and
nitrous oxide:
(a) The concentration (MAC) of halothane/isoflurane required to produce anaesthesia is reduced

when given with N2O because of second gas effect. As the concentration of

halothane/isoflurane required is reduced, the side effects of halothane/isoflurane (hypotension

and respiratory depression) are reduced.

Second gas effect: N2O rapidly diffuses, whereas halothane/isoflurane diffuses poorly into the

blood (alveoli blood brain). When these (halothane/ isoflurane and N 2O) anaesthetics
are administered simultaneously, halothane/ isoflurane also enters the blood rapidly along with
rapidly diffusible gas (N2O). This is known as ‘second gas effect’.
(b) Because of reduction in the dosage, recovery will be faster.

(c) Halothane/isoflurane is a potent anaesthetic and poor analgesic, whereas N2O is a good

analgesic and poor anaesthetic; hence, the combined effect of these two drugs results in potent

anaesthesia and good analgesia.

Diffusion Hypoxia. Nitrous oxide has low blood solubility – when the administration of N2O is

discontinued, it rapidly diffuses from the blood into alveoli and causes marked reduction of

PaO2 in the alveoli resulting in hypoxia which is known as diffusion hypoxia. It can be avoided

by giving 100% O2 for a few minutes immediately after N2O is discontinued.

 Inhalation anesthetics
Characters Anesthetic drugs
For veterinary use only Methoxyflurane
Non irritant - Potent anesthetic, Weak analgesic. Halothane
Can be used in children
Stable compound (2%), Low biotransformation (Less fluoride). Isoflurane
No nephrotoxicity - No hepatotoxicity.
is metabolized to fluoride (8%) Enflurane
Contraindicated in patients with seizure disorders.
Not for renal failures.
Less metabolized (0.05 %), low boiling point (special equipment) Desflurane

Better smell, little effect on HR, No airway irritation (children) Sevoflurane

Potent analgesics, Minimal CVS adverse effects, contraindicated in Nitrous oxide
pregnancy
04/09/2025
 Side effects of inhalation anesthetics
Side effects Anesthetic drugs
Slow induction, nephrotoxicity Methoxyflurane
.)??????( Slow induction and recovery Halothane
Sensitization of heart to catecholamines
Hepatotoxicity, Malignant hyperthermia

Pungent odor, Airway irritation Desflurane

Pungent (less induction -Not for pediatrics). Enflurane

Airway irritation
CNS stimulation (Epilepsy-like seizure- abnormal EEG).

Weak anesthetic (low potency, combined). Nitrous oxide

Diffusion hypoxia, Nausea and vomiting.
Inactivation of B 12  megaloblastic anemia, congenital anomalies
04/09/2025
 General Anesthesia

Intravenous

Slower acting Inducing agents

Dissociative Thiopental
Opioid analgesia Benzodiazepines
anesthesia Methohexital
Propofol
Etomidate
Diazepam Droperidol
Ketamine Fentanyl Lorazepam
Midazolam
 Intravenous anesthetics
 Ultra short acting barbiturates e.g. thiopental, methohexital
 Benzodiazepines (diazepam, lorazepam, midazolam)
 Opioids (fentanyl)
 Ketamine
 Propofol
 Etomidate
 Intravenous anesthetics
 NO need for special equipments.
 Rapid induction & recovery EXCEPT benzodiazepines
 Injected slowly (rapid induction).
 Recovery is due to redistribution from CNS.
 Analgesic activity: Opioids & ketamine
 Amnesic action: benzodiazepines & ketamine.
 Can be used alone in short operation & Outpatients anesthesia.
CHARACTER S OF INTRAVENOUS ANAESTHETIC DRUGS
Drug Induction and recovery

Thiopental Fast onset, slow recovery, hangover

Etomidate Fast onset, fairly fast recovery, less hangover

Propofol Fast onset, rapidly metabolized, very fast recovery

Ketamine Slow onset, Dissociative anesthesia

Produces good analgesia and amnesia.
Fentanyl Slow onset

Midazolam Slower onset than other agents, has amnesic effect

 Ultrashort acting barbiturates
e.g. Thiopental, Methohexital
 Rapid onset of action 1 min (high lipid solubility).
 Ultra short duration of action 15 - 20 min
 Metabolized slowly by the liver (slow recovery)
 Potent anesthetic.
 CNS:  ICP (Used in head injuries).
 CVS collapse & respiratory depression, precipitate porphyria attack,
hypersensitivity reaction.
 Used for induction in major surgery and alone in minor surgery.
Advantages of Thiopentone

1. Rapid induction of anaesthesia and rapid recovery.

2. Does not sensitize the myocardium to circulating catecholamines.

Disadvantages/Adverse Effects of Thiopentone

1. Depresses the respiratory centre.

2. Depresses the vasomotor centre and myocardium.

3. Poor analgesic.

4. Poor muscle relaxant.

5. Causes laryngospasm.

6. Accidental intra-arterial injection causes vasospasm and gangrene of the arm.

7. It can precipitate acute intermittent porphyria by inducing the synthesis of ALA synthase,

hence contraindicated in susceptible individuals (absolute contraindication).

 Propofol
 Hypnotic (Non Barbiturate).
 Rapid onset, short duration of action, Faster recovery than thiopental
 Rapidly metabolized in liver (10 times - Elimination ½ = 30 – 60 min).
 Decreases  ICP
 Has Antiemetic action.

Side Effects
 Hypotension (PVR).
 Excitation (involuntary movements), Pain at site of injection
 Expensive, Clinical infections due to bacterial contamination
 Benzodiazepines
e.g. Midazolam, Diazepam , Lorazepam
 No pain, have anxiolytic and amnesic action
 Slow induction & recovery.
 Cause respiratory depression.
 Used in induction of general anesthesia.
 Alone in minor procedure (endoscopy).
 In balanced anesthesia (Midazolam).
 Etomidate
 Ultrashort acting hypnotic (Non Barbiturates).
 Rapid onset of action, short duration of action.
 Rapidly metabolized in liver (less hangover).
 Minimal CVS and respiratory depressant effects.

Disadvantages/Adverse Effects

1. Has poor analgesic effect.

2. High incidence of pain on injection, postoperative nausea and vomiting.
3. Restlessness and rigidity are common.
4.Involuntary movements during induction (diazepam).

5.Adrenal suppression
 ketamine
 Dissociative anesthesia (Analgesic activity, amnesic action, immobility,

complete separation from the surrounding environment).

 Acts by blocking NMDA receptor.

 Rapid onset of action, short duration, is given IV, IM (Children).

  BP & cardiac output (central sympathetic activity).

  Increases plasma catecholamine levels,  ICP


Site of action: cortex and subcortical areas.
highly lipid soluble, rapidly enters highly perfused organs like brain, liver and heart; later, it
redistributes to less perfused organs. metabolized in liver; excreted in urine and bile.
Uses
1. For operations on the head, neck and face.
2. For dressing burn wounds.
3. Well suited for children/asthmatics undergoing short procedures.
Adverse Effects and Contraindications
1. Increases BP and heart rate, hence is contraindicated in patients with hypertension and
ischaemic heart disease.
2. Increases intracranial pressure.
3. Causes emergence delirium and hallucinations.
 Opiate drugs
Fentanyl, Alfentanil, Sufentanil, Remifentanil
Rapid onset, Short duration of action, Potent analgesia.

Uses
Neuroleptanalgesia (Fentanyl + Droperidol ).
Neuroleptanesthesia (Fentanyl+Droperidol+ nitrous oxide).

Side Effects
Respiratory depression, bronchospasm (wooden rigidity).
Hypotension, nausea & vomiting
Contraindication
1. Head injuries.
2. Pregnancy.
3. Bronchial asthma.
4. Chronic obstructive lung diseases.
5. Hypovolemic shock (Large dose only).
Neuroleptanalgesia
 A state of analgesia, sedation and muscle relaxation without loss of
consciousness.
 used for diagnostic procedures that require cooperation of the patient.
 Innovar (Fentanyl + Droperidol ).
 Contraindicated in parkinsonism.

Neuroleptanesthesia
A combination of (Fentanyl + Droperidol + nitrous oxide).
 EFFECTS OF INTRAVENOUS DRUGS ON CVS SYSTEM

Drug Systemic BP Heart rate

Propofol ↓ ↓
Thiopental
Etomidate No change or slight ↓ No change

Ketamine ↑ ↑
SIDE EFFECTS OF INTRAVENOUS ANAESTHETIC DRUG
Drug Main side effects
Thiopental CVS collapse and respiratory depression (Laryngospasm, bronchospasm), porphyria

Etomidate Adrenocortical suppression, Excitatory effects during induction

pain at site of injection, Post-operative NV

Propofol CVS and respiratory depression, Excitation (involuntary movements)

Pain at injection site, expensive.

Ketamine Psychotomimetic effects following recovery (vivid dreams, hallucination)

Postoperative nausea, vomiting ， salivation
Risk of hypertension and cerebral hemorrhage

Midazolam Slow induction & recovery

Minimal CVS and respiratory depression
Opioids Respiratory depression, Bronchospasm (wooden rigidity).
Hypotension, Nausea & vomiting, Increase in ICP, Urinary retention.
Fentanyl Prolongation of labor & fetal distress.
CONTRAINDICATION OF INTRAVENOUS ANAESTHETIC DRUGS

Drug Contraindications
Thiopental Porphyria, severe hypotension (hypovolemic & shock patient)
Chronic obstructive lung disease.

Propofol CVS and respiratory depression

Fentanyl Head injuries, Pregnancy, Bronchial asthma,

Chronic obstructive lung diseases.
Hypovolemic shock (Large dose only).
Ketamine CV diseases (hypertension-stroke).
Head injuries.
Midazolam Respiratory patients
 CONSCIOUS SEDATION

 It is a level of CNS depression where a patient does not lose consciousness but is able to
communicate and cooperate during the procedure/treatment.
 It is used in:
1. Uncooperative patients.
2. Anxious patients.
3. Emotionally compromised patients.
 It should be avoided in chronic obstructive pulmonary disease (COPD), pregnancy,
prolonged surgery, psychoses, etc.
 The drugs used are BZDs such as diazepam (oral, i.v.), midazolam (i.v.) and temazepam
(oral); nitrous oxide " oxygen (inhalation); propofol (i.v. infusion) and fentanyl (i.v.).
Thank you