General Anesthetics, Pharmacology, Pharmaceutical Science, Pharmacokinetics, Pharmacy

1. General Anaesthetics
Dr Kushagra Sharma
PharmD, RPh.

2. Definition:
These are drugs which produce
reversible loss of all sensation
and consciousness.

3. Features:
•Loss of all Sensation (Pain).
•Sleep (Unconsciousness).
•Immobility and muscle relaxation.
•Abolition of somatic and autonomic reflexes.
*First IV aneasthetic “THIOPENTONE” was introduce in 1935.

4. Stages of Anaesthesia:
STAGE I - (State of analgesia)
STAGE II - (State of excitement and delirium)
STAGE III - (State of Surgical Anaesthesia)
STAGE IV - (Stage of Medullary Paralysis)

5. STAGE I - (State of analgesia)
• Consciousness and sense of touch are present.
• Sense of hearing is enhanced.
STAGE II- (State of excitement and delirium)
• Patient shows violent behaviour but definitely in amnesic.
• Irregular rise in BP and RR occurs.
• To avoid all these symptoms a short acting barbiturate,
thiopental sodium, is given I.V. before anaesthetic
administration.

6. STAGE III - (State of surgical anaesthesia)
• Regular Respiration and relaxation of skeletal muscles.
• Ideal Stage of Surgery.
Plane 1. – Roving movement of eyeballs occurs, Respiration and
skeletal muscle tone are normal.
Plane 2. – Most surgical procedure are performed in this plane,
progressive loss of corneal, light and laryngeal reflexes, Respiration
is slow but regular.
Plane 3. – Muscle relaxation occurs, Eye ball movement is absent,
Pupil is dilated, light / corneal and laryngeal reflexes are absent.
Plane 4. – Complete muscle relaxation occurs, Pupil are fully
dilated, complete loss of light / corneal and laryngeal reflexes.

7. STAGE IV - (Stage of Medullary Paralysis)
•This stage occurs due to overdosing.
•Severe Depression of Respiration occurs.
•This stage is fatal and death may occurs.
•Ventilation support is must to prevent death

8. PHARMACOKINETIC PRINCIPLES OF
ANAESTHESIA
•INDUCTION
•MAINTENANCE
•RECOVERY

9. INDUCTION-
• Time to develop effect after administration.
*I.V. agents like Propofol takes 30 to 40 sec. to unconscious (adults).
*Non Pungent agents like sevoflurane are inhaled (children).
MAINTAINANCE-
• After administration vitals, signs and response to stimuli are monitored
continuously to balance the amount of drug inhaled or I.V..
RECOVERY-
• Anaesthetic mixture is withdrawn and patient is monitored for return to
consciousness.

10. Classifications of General Anaesthesia:
INHALATION ANAESTHETICS
Halothane, Isoflurane, Desflurane, Sevoflurane, Nitrous oxide, Methoxyflurane,
Enflurane
INTRAVENOUS ANAESTHETICS
• Barbiturates: Thiopental, Methohexital
• Non Barbiturates: Propofol, Etomidate
• Slow Inducer: Benzodiazepines, Diazepam, Lorazepam and Midazolam
• Dissociative Anaesthetics: Ketamine

11. Mechanism of Action (MOA):
General Anaesthetics

Increases (GABA-a) sensitivity

Increases Chlorine Influx

Hypo-polarization in Neurons

Hence, CNS activities are diminished
*Except Nitrous oxide & Ketamine
(GABAa) – Alpha
aminobutyric acid

12. For Nitrous oxide & Ketamine
• Nitrous oxide & Ketamine do not act on (GABAa) receptors.
It Inhibits NMDA receptors

NMDA receptor is a glutamate receptor

Glutamate is the body’s main
excitatory neurotransmitter
(NMDA) : N-methyl-D-
aspartate Receptor

13. Inhaled Anaesthetics

14. Halothane:
• Its rapid induction and quick recovery made it an anaesthetic of choice.
• It is replaced due to its adverse effect & availability of other anaesthetics with
fewer complications.
Therapeutic Uses:
• Potent anaesthetic but relatively weak analgesic.
• Usually administrated with nitrous oxide, opioids or local anaesthetics.
• It is potent bronchodilators.
• It can be use in obstetrics or as skeletal relaxers.
• It is non toxic in children but toxic in adults.
*Sevoflurane is now agent of choice.

15. Pharmacokinetics:
• It is oxidatively metabolised in body to tissue-toxic hydrocarbons and bromide
ions this may responsible for toxic reactions in adult (especially females).
• Possibly signs are fever, nausea, vomiting & hepatitis.
• However, incidence is low (1 in 10,000) but half of affected patients may die due
to hepatitis necrosis.
Adverse Effect:
• Cardio Effect – Malignant Hyperthermia
• Bradycardia
• Arrhythmias
• Hypotension

16. Isoflurane
• Non toxic to liver & Kidney.
• Used only when cost is the factor.
• High blood solubility.
Adverse effect:
• Hypotension
• Respiratory Refluxes
Desflurane
• Very rapid onset and recovery due to low solubility in blood.
• Popular in OPDs.
• Expensive & toxicity is rare.
Adverse effect:
• Respiratory refluxes.

17. Sevoflurane
• Rapid onset and recovery, due to low solubility in blood.
• Nephrotoxic in nature.
Nitrous oxide
• Potent analgesic but weak general anaesthetic.
• Used as 30% to 50% with oxygen.
• Poorly soluble in blood.
• Most safest anaesthetic if oxygen supply is proper.
Adverse effect:
• Hypoxia

18. Intravenous Anaesthetics

19. • Rapid induction within the time it takes to travel from the site of
administration to the brain.
• Can be maintained by inhalation.
• They act as sedation on low dose.
Propofol
• I.V. sedative & Hypnotics used for induction & maintainance of anaesthesia.
• It is widely use.
Barbiturates (Thiopental)
• Ultra-short acting & high lipid solublity.
• After administration quickly enters in CNS and depressed the functioning in
less than 1 minute.
Adverse effects:
Hypotension, Chest wall spasm, laryngospasm, coughing, bronchospasm.

20. Benzodiazepines
• It is used in conjunction.
• Commonly used is Midazolam
• Erythromycin may prolong their action.
• Respiratory depressant.
Opioids
• Choice of opioids based on duration needed.
• Commonly used is fentanyl.
Adverse effect:
Hypotension, Respiratory depressant, Muscle rigidity, Post anaesthetic nausea &
vomiting.

21. Characteristics of some Anaesthetics
SNo. Characteristics Halothane Isoflurane Desflurane Sevoflurane
1. Arrhythmias Increase - - -
2. Sensitivity to
Dopamine +
Norepinephrine +
Epinephrine
Increase - - -
3. Cardiac Output Decrease Decrease Decrease Decrease
4.
Blood Pressure
Dose
Dependent
Decrease
Dose
Dependent
Decrease
Dose
Dependent
Decrease
Dose
Dependent
Decrease
5. Respiratory
Refluxes
Low
Inhibited
Initial
Stimulation
Initial
Stimulation
Inhibited
6. HepaticToxicity Some Risk Low Risk Low Risk Low Risk
7. RenalToxicity Low Risk Low Risk Low Risk Some Risk

22. ThankYou…