SWU-Matias H Anzar Memorial College of Medicine

Department of Pharmacology and Toxicology

Case No. 53
Inhalation Anesthetic Agent

Learning Objectives:
1. List the characteristics of the ideal general anesthetic agent.

Intravenous Agent
= The ideal i.v. anesthetic agent has a rapid onset of action and is quickly cleared from the
bloodstream and CNS, facilitating control of the anesthetic state (e.g., allowing titration of effect).
The ideal agent also protects vital tissues, has other desirable pharmacologic effects (e.g., an
antiemetic effect), does not affect the circulatory system or cause other adverse effects, and is
inexpensive.

Inhaled Agent
= Characteristics of the ideal inhaled anesthetic agent include ample potency, low solubility in
blood and tissues, resistance to physical and metabolic degradation, and a protective effect in
and lack of injury to vital tissues. Physical and metabolic degradation can yield compounds that
cause injury. Other ideal characteristics include the lack of a propensity to cause seizures,
respiratory irritation, and circulatory stimulation; little or no effect on the ozone layer; and a low
acquisition cost.

2. Describe the pharmacokinetic parameters of inhalation anesthetics that influence the onset of and
recovery from anesthesia.

PHARMACOKINETICS
Inhaled anesthetics, volatile as well as gaseous, are taken up through gas exchange in the alveoli.
Uptake from the alveoli into the blood and distribution and partitioning into the effect compartments are
important determinants of the kinetics of these agents. An ideal anesthetic should have a rapid onset
(induction), and its effect should be rapidly terminated. To achieve this, the effect site concentration in the
CNS (brain and spinal cord) will need to change rapidly. Several factors determine how quickly the CNS
concentration changes.

UPTAKE & DISTRIBUTION

A. Inspired Concentration and Ventilation

The driving force for uptake of an inhaled anesthetic is the alveolar concentration. Two
parameters that can be controlled by the anesthesiologist determine how quickly the alveolar
concentration changes:

1. Inspired concentration or partial pressure

-Increases in the inspired partial pressure increase the rate of rise in the alveoli and thus accelerate
induction. The increase of partial pressure in the alveoli is usually expressed as a ratio of alveolar
concentration (F A ) over inspired concentration (F I ); the faster F A /F I approaches 1 (1 representing
the equilibrium), the faster anesthesia will occur during an inhaled induction.
2. Alveolar ventilation
- The other parameter that directly controls the rate by which F A /F I approaches 1 is alveolar
ventilation. An increase in ventilation will increase the rate of rise. The magnitude of the effect varies
according to the blood:gas partition coefficient.

B. Factors Controlling Uptake

-The increase of F A /F I , which is an important determinant of the speed of induction, is opposed by the
uptake of anesthetic into the blood, which is determined by pharmacokinetic parameters unique to the
anesthetic agent as well as patient factors.

1. Solubility
One of the most important factors influencing the transfer of an anesthetic from the lungs to the
arterial blood is its solubility characteristics. The blood:gas partition
coefficient is a useful index of solubility and defines the relative affinity of an anesthetic for the blood
compared with that of inspired gas.

2. Cardiac output
Changes in pulmonary blood flow have obvious effects on the uptake of anesthetic gases from the
alveolar space. An increase in pulmonary blood flow (ie, increased cardiac
output) will increase the uptake of anesthetic, thereby decreasing the rate by which F A /F I rises, which
will decrease the rate of induction of anesthesia. An increase in cardiac output and pulmonary blood flow
will increase uptake of anesthetic into the blood, but
the anesthetic taken up will be distributed in all tissues, not just the CNS. Cerebral blood flow is well
regulated and the increased cardiac output will therefore increase delivery of anesthetic to other tissues
and not the brain.

3. Alveolar-venous partial pressure difference

The greater this difference in anesthetic gas tensions, the more time it will take to achieve equilibrium
with brain tissue.

ELIMINATION
A. Ventilation
Two parameters that are useful in controlling the speed of induction of and recovery
from inhaled anesthesia:

1. Concentration of anesthetic in the inspired gas

- cannot be reduced below

2. Alveolar ventilation
-only way to speed recovery

B. Metabolism
-Modern inhaled anesthetics are eliminated mainly by ventilation and are only metabolized to a very
small extent; thus, metabolism of these drugs does not play a significant role in the termination of their
effect.
-Have important implications for their toxicity.
-Hepatic metabolism may also contribute to the elimination of and recovery from some older volatile
anesthetics

(Source: Katzung Basic and Clinical Pharmacology 12th edition page 430)
3. List the advantages and disadvantages of commonly used inhalation
anaesthetic agents

4. List the commonly used intravenously administered

anesthetic agents and adjunct agents used in balanced
anesthesia.
INTRAVENOUS ANESTHETIC AGENTS
Barbiturates
Benzodiazepines
Dexmedetomidine
Etomidate
Ketamine
Propofol
Opioids
BALANCED ANESTHESIA
Induction Agent
fentanyl
lidocaine
propofol
succinylcholine

Maintenance
Agent
Sevoflurane,
Desflurane,
Isoflurane
Fentanyl, Morphine,
Diluadid, Demerol
Rocuronium,
Vecuronium,
Mivacurium
Nitrous oxide
Propofol

5. Discuss the disadvantage of nitrous oxide as an inhalation anesthetic agent.

Disadvantages of nitrous oxide/oxygen inhalation may include:

Lack of potency/ a weak general anesthetic

Dependant largely on psychological reassurance
Patient must be able to breathe through the nose
Poorly soluble in blood and other tissues, allowing it to move rapidly in and
out of the body