General anaesthesia

By Desta H. (B.Pharm, Msc)

Surgery Before Anesthesia
Triad of anaesthesia
 Triads

Anaesthetic agents to produce unconsciousness

(Loss of pain sensation ) ‘Amnesia-hypnosis’ -
the patient doesn’t know what’s going on
 Analgesics (Loss of sensory and autonomic
reflexes)
• Suppression reflex autonomic responses to surgical
stimuli/no movement in response to stimuli
 Neuromuscular blocking agents for muscle
relaxation
• immobility and of insensibility!
Anesthetic Suppression of Physiological Response to Surgery
 Mechanism of action of general anesthetic!
GA changes the nerve cells so that normal communication
among many of them is closed off for a time.
• alter the chemistry of the synapses, the gaps between
the nerve cells.
o sensations of all kinds are temporarily blocked from
reaching the brain.
o the person under anesthesia cannot move parts of the
body. The muscles are completely relaxed, making
surgery easier.
o At any point along nerve system, the pain message can
be blocked. Ultimately, what all anesthetics do is block
the signal for pain.
 Rate of Entry into the Brain: Influence of Blood
and Lipid Solubility
LOW solubility in blood= fast induction and recovery
HIGH solubility in blood= slower induction and recovery.
 What is Balanced Anesthesia?
“Balanced Anaesthesia” - A combination of agents, to
limit the dose and toxicity of each drug

No single drug is capable of achieving all of the desired goals

of anesthesia.

SIDE EFFECTS TOXICITY

GA may not always be the best choice; depending on a

patient’s clinical presentation!
 Stages of anaesthetics

Induction – putting asleep

• Time elapsed between onset of administration of
anesthetic and development of effective surgical
anesthesia.
Maintenance – keeping the patient asleep
• Time during which the patient is surgically
anesthetized.
Recovery/Reversal – waking up the patient
• The time from discontinuation of anesthetic drug
until consciousness is regained.
 SIGNS AND STAGES OF GENERAL ANESTHESIA

I. Stage of analgesia
- Analgesia
- Unaltered consciousness
- Normal pupils

II. Stage of excitement

- Disturbed consciousness (incoordinate movements,
incoherent talk)
- Irregular respiration
- Retching and vomiting
- Incontinence (sometimes)
- Increased blood pressure
- Mydriasis
III. Stage of surgical anesthesia
- Loss of consciousness
- Regular respiration
- Progressive decrease of skeletal muscle tone
- Progressive loss of somatic and autonomic reflexes
- Progressive decrease in blood pressure
- Miosis

IV. Stage of medullary depression

- Loss of consciousness
- No spontaneous respiration
- Cardiovascular collapse
- Mydriasis
 What are General Anesthetics?
• GA - drugs that bring about a reversible loss of pain
sensation, loss of consciousness, skeletal muscle
relaxation, analgesia, amnesia and inhibitions of
undesirable autonomic reflexes.
• administered by an anesthesiologist in order to induce
or maintain general anesthesia to facilitate surgery.
 Inhalation - the patient breathes a gas or vapor into the
lungs  anesthetic can enter the bloodstream
 injection with a hypodermic needle, usually into a vein.
• commonly the two forms are combined, although its is
possible to deliver anesthesia solely by inhalation or
injection.
 Inhalation anesthetics
halogenated hydrocarbon( Contain Fluorine and/or bromide ,
small molecules) end with suffix “flurane “
Methoxyflurane
 Halothane
 Enflurane
 Isoflurane
 Desflurane
 Sevoflurane
 Nitrous oxide
 Structure

8 1 2

7 C C O C 3

6 5 4

MW 1 2 3 4 5 6 7 8
Diethyl ether 74 H H CH3 H H H H H
Fluroxene 126 H H =CH2 H F F F
Methoxyflurane 165 F H H H F Cl H Cl
Desflurane 168 H F H F F F F F
Isoflurane 184 H F H F Cl F F F
Enflurane 184 F F H F F Cl H F
Sevoflurane 200 H H F H CF3 F F F
 Chemical structures of inhaled anesthetics.
• Differ in the rate of induction, depth of anesthesia and
recovery.
 SAR of Inhaled Anesthetics
 halogenations of hydrocarbons and ethers increases
 anesthetic potency and potential for inducing cardiac
arrhythmias in the following order F<Cl<Br.
 Ethers that have asymmetric halogenated carbon tend to be
good anesthetics ( Enflurane).
 Halogenated methyl ethyl ethers (Enflurane and Isoflurane) are
more stable, potent, and have better clinical profile than
halogenated diethyl ethers.
 fluorination decrease flammibity and increase stability of
adjacent halogenated carbons.
 Complete halogenations of alkane and ethers or full
halogenations of end methyl groups decrease potency and
enhances convulsant activity.
e.g, Fluoroethyl (CF3CH2OCH2CF3) is a potent convulsant
 the presence of double bonds tends to increase chemical
reactivity and toxicity.
 Pharmacological actions of inhalation anesthetics
CNS :  metabolic rate,  ICP (due to cerebral vasodilatation) C/I in
head injuries.
- Dose -dependent EEG changes (Enflurane).
CVS : Hypotension , Bradycardia Except (Isoflurane & Desflurane ),
Myocardial depression (Halothane – Enflurane).
-Sensitize heart to catecholamines (Halothane)
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.
 Summary -Inhalation anesthetics
Characters Anesthetic
drugs
For veterinary use only Methoxyflurane
Non airway irritant, Potent anesthetic, Weak analgesic. Can Halothane
be used in children
Stable compound Low biotransformation (Less fluoride Isoflurane
(2%)). No nephrotoxicity - No hepatotoxicity.
metabolized to fluoride (8%), Contraindicated in patients Enflurane
with seizure disorders and renal failures.
Less metabolized (0.05 %), low boiling point (special Desflurane
equipment)
Better smell, little effect on HR, No airway irritation, Can be Sevoflurane
used in children)
Potent analgesics, weak anesthetic, Minimal CVS adverse Nitrous oxide
effects, contraindicated in pregnancy

02/18/2025
 Summary - Side effects of inhalation anesthetics
Side effects Anesthetic
drugs
Slow induction, nephrotoxicity Methoxyflurane
Slow induction and recovery, Sensitization of Halothane
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
 1. 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
 More rapid induction & recovery than halothane
 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
 Less potent than halothane.
 Pungent odor (irritation - Cough)
 Rapid induction & fast recovery (Low solubility).
 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)
• Weak anesthetic (Low potency, combined).
• Rapid induction & Recovery (the lowest blood: gas partition
coefiicient).
• Potent analgesic.
• 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.
Intravenous anestheti cs
 General Anesthesia

Intravenous

Slower acting
Di Inducing agents
Diss az
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tive a
ane ana aze Propofol
lges m
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Ke
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Fe es Droperidol
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Chemical structures of intravenous anesthetics.
 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

 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
Fentanyl retention, 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
 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.
 Thiopental

• Barbiturate
• Dose 3-7 mg/kg
• Effects: hypnosis, atiepileptic,
antanalgesic
• Side effects
– CVS: myocardiac depression, CO
– apnea
• Problems with use
– Extremely painfull and limb threatening
when given intra-arterially
– Hypersensitivity reactions 1: 15 000
• Contraindications
– Porphyria
 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).
  ICP, Has Antiemetic action.
Side Effects
 Hypotension (PVR).
 Excitation (involuntary movements), Pain at site of
injection
 Expensive, Clinical infections due to bacterial
contamination
Propofol
• Phenolic derivative
• Dose1- 2.5 mg/kg
• Effects : hypnosis
• Side effects
– CVS: myocardiac depression, SVR, CO
– Hypotension due to vasodilatation.
– Respiratory depression
– Hypersensitivity 1 : 100 000
• Other effects
– Pain on induction especially small hand veins
– Nausea and vomiting less likely
• Relative contraindications
– Children under 3
 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.
 Involuntary movements during induction (thus combined
with diazepam).
 Postoperative nausea & vomiting.
 Pain at sit of injection.
 Adrenal suppression
 Etomidate
• Ester
• Dose. 0.3 mg/kg
• Effects : hypnosis
• Side effects
– CVS: very little effect on HR, CO, SVR
– Minimal respiratory depression
• Problems with use
– Pain on injection
– Nausea and vomiting
– Adrenocortical suppression
– Hypersensitivity reaction 1: 75 000
• Relative Contraindications
– Porphyria
 ketamine
 Dissociative anesthesia (Analgesic activity, amnesic action,
immobility, complete separation from the surrounding
environment).
 Rapid onset of action, short duration, is given IV, IM (Children).
  BP & cardiac output (central sympathetic activity).
  Increases plasma catecholamine levels,  ICP
 Potent bronchodilator (asthmatics).
 Used in (hypovolemic, shock & elderly) patients.
 Post operative hallucination vivid dreams &
disorientation &illusions
 Risk of hypertension & cerebral hemorrhage,  ICP
 Ketamine

• Phencyclidine derivative
• CV effects -  HR, BP, CO, O2 consumption
• RS - RR, preserved laryngeal reflexes
• CNS – dissociative anaesthesia, analgesia,
amnesia
• Use – analgesic in Emerg. Med
 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
 SUMMARY – IV anaesthetics
• Mechanism of action – via receptors
• Used for anaesthesia and sedation
• Used for induction
• Propofol used for maintenance as well
• Thiopental, propofol, etomidate
• All cause CV and respiratory depression