Drugs in General Anaesthesia

By Dr Gitanjali Jayatilaka
 Objectives
• To be able to define general anaesthesia
• Triad of general anaesthesia
• Pharmacology of commonly used inhalational
general anaesthetic agents
• Pharmacology of commonly used intravenous
anaesthetic agents
• Post-operative considerations as an intern
 Definition of General Anaesthesia
• an – without
• aesthetos – perception
= anaesthesia

• a pharmacologically induced state of

controlled, reversible unconsciousness
 Triad of GA
• Analgesia

• Hypnosis

• Muscle paralysis

Inhalational and i.v anaesthetic agents cause

hypnosis
Conduct of anaesthesia
3 parts
1 - induction
2 - Maintenance
3 – Emergence/ Recovery
Inhalational anaesthetic agents
 Pharmacodynamics of all the
halogenated vapours
• Prolong activity of GABA on GABAA
Increased Cl conductance
Hyperpolarization of membrane potential

• Enhance activity of 2 pore domain potassium

channels
increased potassium
Hyperpolarization of membrane potential
GABAA Receptor
 Inhalational anaesthetic agents -
Isoflurane
• Physical properties:
Colourless liquid, pungent odor, Irritant to
airways

• Pharmacokinetics:
Quick recovery
0.17% metabolized in liver
 Inhalational anaesthetic agents -
Isoflurane
• Pharmacodynamics:

CVS: reduced systemic vascular resistance

causing hypotension and reflex tachycardia

RS: ventilatory depression

Malignant hyperthermia
 Inhalational anaesthetic agents -
Sevoflurane
• Physical properties:
Pleasant smell

• Pharmacokinetics:
Quick induction of anaesthesia and non- irritant
to airways
5% metabolized in liver
 Inhalational anaesthetic agents -
Sevoflurane
• Pharmacodynamics:
CVS: reduced systemic vascular resistance
causing hypotension but less tachycardia than
isoflurane

RS: ventilatory depression

Malignant hyperthermia
 Inhalational Anaesthetic agents
Halothane
• Physical properties:
Colourless liquid, pleasant smell

• Pharmacokinetics:
Relatively slow induction and recovery as more
soluble in blood
20% metabolized in the liver
 Inhalational anaesthetic agents –
halothane cont.
• Pharmacodynamics:
CVS: reduced cardiac output, bradycardia,
arrhythmias
RS: ventilatory depression, bronchodilation
Liver: hepatic dysfunction
CNS: cerebral vasodilation
Malignant hyperthermia
 Other newer agents
• Desflurane – very quick onset and offset - not
available in Sri Lanka as yet

• Xenon
 Inhalational anaesthetic agents –
nitrous oxide
• Anaesthetic gas at room temperature and
pressure.
• Contained in cylinders
• Good analgesic but weak anaesthetic
• Used as analgesic for pain relief in labour
• Physical properties:
Sweet smell, non- irritant, colourless gas
• Pharmacodynamics – inhibition of NMDA
receptors
 Inhalational anaesthetic agents –
nitrous oxide
• Pharmacodynamics:
RS: hypoxia at recovery
CVS: myocardial depressant
CNS: increased intracranial pressure
Causes increase in pressure in non-compliant air
spaces – middle ear
Prolonged exposure causes agranulocytosis and
bone marrow aplasia
Post-operative nausea and vomiting
Intravenous (iv) General Anesthetic
Agents
 i.v General anaesthetic agents –
Thiopentone Sodium
• Barbiturate

• Physical properties and presentation

Yellow powder, dissolved in distilled water

• Mechanism of action:
Acts on GABA receptor to prevent dissociation of GABA from
receptor

• Pharmacokinetics:
Brain uptake in 30s (rapid onset) from brain tissue to fat (rapid
recovery)
Metabolized in liver and to a lesser extent kidney
 i.v General anaesthetic agents –
Thiopentone Sodium
• Uses:
Induction of anaesthesia
Status epilepticus refractory to treatment
Raised ICP

• Pharmacodynamics:
CVS: hypotension and reflex tachycardia
RS: apnea, ventilatory depression, laryngeal spasm
Liver: enzyme induction
Acute intermittent porphyria (stimulates mitochondrial
enzyme)
Intra-arterial injection causes arteritis leading to occlusion of
distal circulation
Allergic reactions
 i.v General anaesthetic agents – Propofol
• Isopropyl phenol

• Physical properties and presentation:

Milky liquid

• Mechanism of action: As for TPS

• Phamacokinetics:
Quick induction - < 30s and awakening
Hepatic and extra hepatic metabolism

• Uses:
Induction of anaesthesia
TIVA
 i.v General anaesthetic agents –
Propofol

• Pharmacodynamics:
CVS: hypotension, bradycardia, asystole
RS: ventilatory depression, apnea, suppresses
laryngeal reflexes, bronchodilation
Allergic reaction
Causes spontaneous excitatory movements
Pain on injection
Antiemetic
Propofol infusion syndrome
i.v General anaesthetic agents – Etomidate
• Carboxylated imidazole

• Physical properties and presentation:

Milky liquid

• Mechanism of action: As for TPS

• Pharmacokinetics
Induction – 1 min
Metabolism – plasma and liver

• Uses:
Induction of anaesthesia – especially in cardiovascularly
unstable patients
 i.v General anaesthetic agents –
Etomidate
• Pharmacodynamics:
CVS: cardio stable
RS: ventilatory depression
Involuntary myoclonic movements
Pain on injection
Post -operative nausea and vomiting
Porphyria
Adrenocortical suppression
 i.v General anaesthetic agents – Ketamine
• Phencyclidine derivative
• Produces dissociative anaesthesia

• Physical properties and presentation:

Colourless liquid

• Mechanism of action:
Non- competitive antagonist at NMDA receptors

• Pharmacokinetics:
Can be administered i.v or i.m
Rapid redistribution and hepatic metabolism

• Uses:
Induction of anaesthesia i.v -30-60s, i.m – 2-4minutes,
TIVA
Analgesic agent
Acute severe asthma refractory to treatment
 i.v General anaesthetic agents –
Ketamine
• Maintain pharyngeal and laryngeal reflexes and
spontaneous ventilation.
• Pharmacodynamics:
CVS: tachycardia and hypertension
RS: apnea if rapidly administered, bronchodilation,
increased secretions
CNS: increases cerebral blood flow and intracranial
pressure, myoclonic and seizure activity occur on
EEG
Post operative nausea and vomiting
Emergence delirium
 i.v General anaesthetic agents –
Midazolam
• Benzodiazepine
• Physical properties and presentation:
Colourless liquid
• Mechanism of action:
Facilitates action of GABA
• Pharmacokinetics:
Redistributed from brain to inactive tissue sites,
hepatic metabolism
 i.v General anaesthetic agents –
Midazolam
• Uses:
Induction of anaesthesia
Sedation in the ICU
Premedication

• Pharmacodynamics:

CVS: hypotension
RS: ventilatory depression, apnea
CNS: anterograde amnesia
Considerations after GA
 Considerations after GA
• Examination/monitoring

• Read the notes - surgical and anaesthetic

• Ask yourself what patient requires?

• Awake? Responds to commands? Opens mouth and able to

show tongue? Lift head? Not pale? Not cyanosed? RR
>10<20, HR 60-90 BP within previous recorded range then
should be ok.

• PONV?

• Pain?

• Oral intake? What drugs to continue? comorbidities

Have we accomplished objectives?
• Can you define general anaesthesia?
• What is the Triad of general anaesthesia?
• Do you know and understand the
Pharmacology of commonly used inhalational
and intravenous general anaesthetic agents?
• Are you aware of the Post-operative
considerations of a patient who has
undergone GA?
Questions?
Questions?