Common Features

used primarily for maintenance of anesthesia

after IV administration
Very steep dose-response curves and very
narrow therapeutic indice
Nitric oxide and volatile halogenate
hydrocarbons

Decrease cerebrovascular resistance

INHALATIONAL ANESTHETICS
Potency
Uptake and Distribution
defined quantitatively as the minimum alveolar The principal objective of inhalation anesthesia
concentration (MAC)
is a constant and optimal brain partial pressure
(Pbr) of inhaled anesthetic
MAC is the median effective dose (ED50) of the
anesthetic, expressed as the percentage of gas The partial pressure of an anesthetic gas at the
in a mixture
origin of the respiratory pathway is
required to achieve that effect
the driving force moving the anesthetic into the
alveolar space and, hence, into the blood
Potent anesthetic: LOW MAC
Less Potent: High MAC
Steady state
partial pressure n each compartment is
MAC values: compare pharmacologic effects of
equivalent to that in the inspired
different anesthetics
mixture

Increase brain perfusion

They cause bronchodilation but also decrease

both spontaneous ventilation and hypoxic
pulmonary vasoconstriction

Lipid solubility
o More lipid solube the lower
concentration needed to provde
anesthesia thus HIGHER POTENCY

Factors affecting STEADY STATE

1. Alveolar Wash-in
- replacement of normal lung gases with
inspired anesthetic mixture
- directly proportional to FRC
Inversely proportional to ventilator rate
2.

Anemia, Hypercalcemia, Hyponaterima: Decreases

MAC
Hypernatremia: Increases MAC
Brain, Heart, Liver, Kidney and Endocrine glands

Anesthetic uptake
- removal to peripheral tissue other than
brain
- uptake: product of gas solubility in blood,
cardiac output and gradient between
alveolar and blood anesthetic partial
pressure

Solubility n blood
Determined by physical property of
anesthetics
Low (Nitric Oxide)
quickly saturate blod thus faster
effect
few additional molecules to
anesthetic are required to raise
arerial anesthetic partial pssure
High (Halothane)
Dissolves more completely
Slower effect

Mechanism of Action
General Anesthesia
Increased sensitivy of GABA receptors

Increased CL influx and hyperpolarization of neurons

NO and Ketamine:
Inhibits NMDA receptors
Decrease Glutamine activators

Rapidly achieve steady state

Skeletal Muscle
Poorly perfused
Prolongs timerequired to achievesteady
state
Fats

Poorly perfused but alrge capacity to store

Prolongs required to achieve steady state

Cardiac Output
Affects removal of anesthetic to
peripheral tissues
High CO
Removes anesthetic from alveoli
faster due to increased ood flow
through lungs
Takes longer for gas to reach
equilibrium
SLOWER INDUCTION
Low CO
Speeds rateof rise of alveolar
concentration
FASTER INDUCTION
Alveolar to venous partial pressure gradient
Driving force of anesthetic delivey
Greater difference in anesthetic
concentration between alveolar and
venous blood-> Increase uptake->
Decreased Induction

NITROUS OXIDE

Only INORGANIC ANESTHETIC GAS

Colorless and odorless
Nonirritating potent analgesic but weak general anesthetic
Cant produce surgical anesthesia but is commonly combined with other more potent agent
Poorly soluble in blood-> allowing it to move rapidly in and out of the body
DIFFUSION HYPOXIA: complication due to retardation of O2 uptake during recovey
DONT depress respiration and DONT prduce muscle relaxation

Complications:
Megaloblastic anemia
Peripheral neuropathy
Pernicious anemia
Teratogenic effect
Pneumothorax
METHOXYFLURANE

MOST POTENT OF LL
LOWEST MAC
Sweet, fruity odor
HIGH SOLUBILITY

ENUFLURANE

HALOTHANE

ISOFLURANE

DESFLURANE

SEVOFLURANE

Vasopressin-resistant High-Output renal failure

Non-purgent and non-flammabe

Depresses myocardial contractility and sensitizes myocardium to epinephrine
TONIC-CLONIC SEIZURES
Rapid induction
Quick recovery
POTENT ANESTHETIC BUT WEAK ANALGESIC
POTENT BRONCHODILATOR
Used in obstetrics when uterine relaxation indicated

ADVERSE EFFECTS:
Increased Sensitivity to Catecholamines
Inhibited respiratory reflexes
Increased risk for Hepatic toxicity
Cardiac Effects
o Atropine-sensitive Bradycardia (Decrease CO)
o Cardiac Arrhytmias
o Concentration dependent hypotension (Tx: Phenylephrine)
o Malignant Hypertension (Tx: Dantrolex)
NOT TOXIC TO LIVER OR KIDNEY
DONT INDUCE CARDIAC ARRHYTHMIAS OR SENSITIZE HEART TO CATECHOLAMINES
Dose-dependent Hypotension
Stimulates Respiratory Reflexes
Corneal Steal Syndrome
o Dilatation of normal coronary arteries and divert blood away from stenotic lesions
o Regional MI during tachycardia or drops of perfusion present
GOOD BRONCHODILATOR
Purgent
Very rapid onset and recovey due to LOW blood solubility
Popular anesthetic for outpatient procedures
Stimulates respiratory reflexes-> not used for inhalational induction
Boils at rom temperature at high altitude
Auses rapid wash in and wash ot
Most commonly used because of its sweet odor
Halogenated with fluorine
Non-pungency and rapid increase in alveolar
Concentration
Excellent choice for pediatric and adult
patients
Low blood solubility
Rapid emergence

Compound A
- Fluoromethy-2,2-difluoro-1-vinyl ether)
- Nephrotoxic end product of soda lime +
Sevoflurane
o Avoid in patients with pre-existing renal dysfunction

Contraindications:
- Severe hypovolemia
- Susceptibility to malignant hyperthermia
- Intracranial hypertension

INTRAVENOUS ANESTHETICS
RAPID ONSET, SHORTER HALF-LIFE
LESSER ENVIRONMENTAL RISK vs INHALATIONAL ANESTHESIA
DESCRIPTION
INDUCTION
RECOVERY
After entering blood: % of drug binds to plasma
Primary role as induction agents
Due to redistribution from site in the CNS
proteins and the rest are free
Maintenance with total
Drug diffuses into other tissues with less bod
intravenous anesthesia
supply
Degree of protein binding
Rapid redistribution
Secondary uptake (Skeletal muscle): plasma
depends on physil characterstic of the
Shorter half lives
concentrion of the drug falls allowing the
drug
Environmental risk of
drug to diffuse out of the CNS
IONIZATION and LIPID SOLUBILITY
inhalational agents
Rapid distribution to vessel rich
High proportion of initial drug bolus is divered to the
tissues
cerebral circulation and then passes along a
concentraton gradientfrom blood into the brain
IV Non-opiods Anesthetics
Widely used to facilitate rapid
Rate of transfer:
induction of anesthesia
ARTERIAL CONCENTRATION of the FREE
High lipid solubility allows for rapid
DRUG
induction
LIPID solubility
Terminationredistribution of
Degree of Ionization
the drug into less perfused and
inactive tissues such as skeletal
muscles
and fats

Characteristics of an Ideal Intravenous

Anesthetic
Agent

EFFECT OF REDUCED CO ON ANESTHETICS

Reduced CO: body compensates by diverting
more CO to the cerebral circulation thus
GREATER PROPORTION of IV Anesthetics enters
the Cerebral circuion
SLOW TITRATION OREDUCED DOSAGE: key to
safe induction patients with Reduced CO

Thiopental and other barbiturates are

not ideal IV anesthetics because they
provide only HYPNOSIS.
The ideal IV anesthetic drug would
provide hypnosis, amnesia, analgesia
and muscle relaxation
without undesirable cardiac and
respiratory depression
Physical Properties
Soluble in water
Stable in solution
Stable to light exposure
Absence of pain on injection
No local irritation
Long shelf life
Pharmacokinetic Properties
Rapid onset of action
Ability to titrate
Predictable duration of effect
Short duration of effect
Short elimination doses half-life
Rapid recovery
Rapid biotransformation
Inactive metabolites
Nontoxic metabolites
Pharmacodynamic Properties
Reliable induction of anesthesia
Anxiolytic at sub-anesthetic doses
Analgesic at sub-anesthetic doses
Amnesic at sub-anesthetic
Minimal cardiovascular effects
High therapeutic index
Small interindividual variation
No allergy