Presentation deals with pharmacokinetics of Inhalational agents , starting from pre-anaesthesia era ,developments of inhalational agents , structural significance.

2. Presented By –Dr.Pankaj Kumar ,PG.1st Yr.
Dept. Of Anaesthesiology
Moderator-Dr. Ajit Gupta
(Professor & HOD)
Dept. of Anaesthesiology

3. Pre-ANAESTHETIC ERA

4. •John Hunter(Anatomist,1750)
“Surgery as a humiliating spectacle
of the futility of science and the
surgeon as a savage armed with a
knife.”

5. •Fanny Brawne(English Author,1811)
“When the dreadful steel was plunged
into the breast ,cutting through
veins,arteries ,flesh , nerves I needed
no injunction not to restrain my cries. I
began a scream that lasted
unintermittingly during the
whole time of the incision and ……

7.  1540-Ethyl Ether was first created in a laboratory by a
german scientist “Valerius Cordes”.
 1773- Joseph Priestly discovered N2O.
 1798-Sir Humphary Day experimented with N2O
reported “loss of Pain and Euphoria”.

8. •Sir William Thomas GreenMorton
 “The Public Demonstration of Ether Anaesthesia” on
Oct. 16 , 1846 at Bullfineh Amphitheatre of the
Massachusetts General Hospital.

9. Chloroform-(1847)
David Waldie
Administered to queen
Victoria for childbirth.

10. HALOTHANE -1951
ENFLURANE
ISOFLURANE
SEVOFLURANE…….SO ON

11. INHALATIONAL AGENTS

13. DEVELOPMENTAL HISTORY
NO , Diethyl Ether , Chloroform
discovered and used in 1840s.
Till 1950 , all inhalational agents
were inflammable and toxic to
liver.
Break-Through with the recognition of
replace of H-Atom with the F-atom
decreases flammability led to advent of
Fluroxene.
80yr
1951

14. HALOTHANE- used in 1956
Increases arrythmogenic effects
of epinephrine
Ether derivative - Methoxyflurane .
Not increase arrythmogenic effects of
Epinephrine.
Analgesia at low concentration.
Withdrawn due to its increased blood and
lipid solubility .
Hepato-toxic .
Inc. metabolism increases fluoride
Nephrotoxic
Led

15. Enflurane – 1973
No Arrythmogenic ,No Hepatotoxic
Metabolite-Fluoride, Increases
seizure
Structural isomer Isoflurane -1981
Fewer Side Effects
Resistant to Metabolism.
Totally Fluorinated Desflurane
&Sevoflurane-1994.

16. Pharmacology of Inhalational Agents
• Drug dose
• Tissue concentration
• Time Elapsed
PHARMACO-
KINETICS
• Drug action on organ
system.PHARMACO-
LOGY

17. PHARMACOKINETICS
• From Alveoli into
Pulmonary
capillary
Absorption
(Uptake)
• Throughout Body
Distribu-
tion
(Biotransfor
mation)

18. • Principally Via lungs
Excretion
(Elimination)
• Lowering of drugs in
one compartment by
delivery into another
compartment
Redistribution

19. Alveolar Partial Pressure Of Anaesthesia(PA)
P(Brain ) = P(Alveolar)
Partial pressure of Inhalational Agents delivered by Arterial Blood(Pa)
EQUILIBRATES
Effects of Inhalational agents depends on therapeutic tissue conc. of CNS(PBrain)
EQUILIBRATES

21. Determinant of Partial Pressue Gradient
From
Anaesthetic
Machine to
Alveoli
Anaesthetic
Breathing
System
Alveolar
Ventilation
Functional
Residual
Capacity
Inspired
Partial
Pressure

22. From
Alveoli To
Arterial
Blood
Alveolar to
Venous
Partial
pressure
Difference
Cardiac
Output
Blood -Gas
Partition
Coefficient

23. From
Arterial
Blood to
Brain
Arterial to
Venous
Partial
Pressure
Difference
Cerebral
Blood Flow
Brain Blood
Partition
coefficient

24. Factor Affecting Inspiratiory Conc.(Fi)
Fresh Gas Flow
Rate
Depends on
Vaporizer &
Flowmeter
settings
Higher the rate
of FGF , closer
the inspired gas
conc.(Fi=FGC)
Breathing
Circuit Volume
Corresponds
(Apparatus Dead
Space)
Smaller the
volume
Fi=FGC

25. Circuit
Absorption
Rubber
Tubing
Absorb
Effect of
Rebreathing
It is due to
residual gases
in the circuit.

26. Alveolar Ventilation
Increase in Alveolar Ventilation promotes
increased input of anaesthetic agents
increasing rate of PA Towards PI
It decreases Pco2 due to
hyperventilation.
Decreased Cerebral blood flow
and consequently decreased
delivery of anaesthetic to Brain
But
Results

27. Anaesthetic Breathing System
Volume of External
Breathing Sys.
• Increased volume
increases dead
space.
Solubility of
Anaesthetic to
Rubber or Plastic
• It decreases PA
Gas Flow from
Machine

28. Factors Affecting Alveolar Conc(PA)
 Alveolar membrane poses no barrier to the transfer of
anaesthetic gases in pulmonary circulation.
 PA depends on the uptake of anaesthetic agents by
pulmonary circulation.
Greater the uptake
Slower the rate of rise of PA
Slower the rate of Induction

29. Concentration Effect
 It is another factor affecting Alveolar partial pressure.
 It is the effect of PI on the rise of PA.
 Higher the Inhalational Partial Pressure ,the more
rapid PA approaches PI
 It depends on the conc. of the inhaled agents in the
small lungs due to uptake of all gases in the lung.
 It also depends on the tracheal inflow augmentation to
fill the space created after the uptake of gases.

30. SECOND-GAS EFFECT
 It is the ability of one Gas (Fisrt Gas) when taken in
high volume to increase the uptake of another gas
(Second Gas) administered simultaneously.
 Example – If NO is administered in high volume
along with O2 …..uptake of O2 increases.

32. Solubility of Inhalational Agents
 Solubility of inhalational agents is expressed by
Partition Coefficient.
 It is the distribution of the inhaled agents between two
phases at equilibrium.
 Partition Coefficient is temp. dependent i.e., solubility
of gas in a liquid is decreased with the increase of
temp. of liquid.
 Example- Halothane has a blood gas coeffiecient of 2.4
means halothane conc. in blood 2.4 times as its conc.
In alveolar gas

34. Blood:Gas Partition Coefficients
 Pa and PA approaching PI is inversely related to the
solubility of the anaesthetic agents in blood.
 Higher the blood solubility of the agents, lesser is the
availability of the agents for equilibration between PA
and PA to PI.
 By increasing the PI above the pressure required for
maintenance of anaesthesia may resolve this
discrepancy upto some extent- Overpressure.

36. Factor affecting Blood:Gas partition coefficient
• Decreased solubility of volatile anaesthetics
in anaemic blood results increase in PA and
thus rapid induction.
Hematocrit
• Ingestion of fatty meal alters the composition of
blood resulting 20% increase on the solubility of
volatile anaesthetics in blood
Lipid and
Protein content
• Blood solubility of Halothane ,Enflurane ,Methoxyflurane,
Isoflurane are 18% less in Neonates and Elderly.
• However , remains constant for Sevoflurane in Neonates and
Elderly.
Age

37. Partial pressure remains same but
concentration differs

38. Cardiac Output
Increased
C.O>Rapid
uptake>Decreased
PA and slow
Induction
Cardiac output
more influences
the rate of change
of PA of soluble
gases
Volatile Agents
depressing C.O
exerts +feedback
i.e, Volatile agents
depresses c.o
>Increases
PA>Increases
depth of
anaesthesia

39. ALVEOLAR TO VENOUS PARTIAL PRESSURE
DIFFERENCE
 It reflects tissue uptake of the inhaled anaesthetics.
 Tissue uptake affects uptake at the lungs.
 Vessel rich tissues (Brain ,Heart, Kidney) accounts approx
10% of the body tissues but receives 75% of the cardiac
output.
 Results rapid equilibrium with Pa within 3 time constant.
 So, uptake of volatile anaesthetic decreases greatly after 3
time constant.
 Continued uptake of anaesthetic after the saturation of
vessel rich tissues suggest the entrance of anaesthetic into
skeletal muscle and the fat.
 So Anaesthetic uptake continues maintain PA-VD.

40. RECOVERY FROM ANAESTHESIA
 Depicted by rate of decrease of PBrain= PA
Factors affecting Recovery from
Anaesthesia
Tissue conc. Of
Inhaled
anaesthetic.
Solubility of
agents & duration
Failure to reach
equilibrium by
certain Tissues
continue to draw
agents from blood
even during
recovery.
Anaesthesia
Breathing System
Exhaled Gases
Metabolism of
Anaesthetics

41. DIFFUSION HYPOXIA
Abrupt discontinuation
of N2O.
Decrease in
PN2O(Blood)leads to
diffusion of N2O from
Blood to Alveoli.
Diffusion leads to
decrease PO2 in the
Alveoli due to dilution
and results Hypoxia
Simultaneous decrease
in PCO2 due to dilution
leads to decrease in
ventilation drive
worsening Hypoxia
All these events are
prominent in first 1 to 5
mints after
discontinuation.

42. SAVE TREE SAVE LIFE