cology lab assignmnt

General anesthesia is a state characterized by unconsciousness, analgesia, amnesia, skeletal

muscle relaxation, and loss of
reflexes. Drugs used as general anesthetics are CNS depressants with actions that can be
induced and terminated more rapidly
than those of conventional sedative-hypnotics.
Stages of anasthesia:
Depth of central depression associated with increasing dose or time of exposure is traditionally
described as
stages of anesthesia.
Stage 1: Analgesia
In stage 1, the patient has decreased awareness of pain, sometimes
with amnesia. Consciousness may be impaired but is not lost.
Stage 2: Disinhibition
In stage 2, the patient appears to be delirious and excited. Amnesia
occurs, reflexes are enhanced, and respiration is typically irregular;
retching and incontinence may occur.
Stage 3: Surgical Anesthesia
In stage 3, the patient is unconscious and has no pain reflexes;
respiration is very regular, and blood pressure is maintained.
D. Stage 4: Medullary Depression
In stage 4, the patient develops severe respiratory and cardiovascular depression that requires
mechanical and pharmacologic
support.
MECHANISMS OF ACTION
The mechanisms of action of general anesthetics are varied. As
CNS depressants, these drugs usually increase the threshold for
firing of CNS neurons. The potency of inhaled anesthetics is
roughly proportional to their lipid solubility. Mechanisms of
action include effects on ion channels by interactions of anesthetic
drugs with membrane lipids or proteins with subsequent effects
on central neurotransmitter mechanisms. Inhaled anesthetics,
barbiturates, benzodiazepines, etomidate, and propofol facilitate
γ-aminobutyric acid (GABA)-mediated inhibition at GABAA
receptors. These receptors are sensitive to clinically relevant concentrations of the anesthetic
agents and exhibit the appropriate
stereospecific effects in the case of enantiomeric drugs. Ketamine
does not produce its effects via facilitation of GABAA receptor
functions, but possibly via its antagonism of the action of the
excitatory neurotransmitter glutamic acid on the N-methyl-daspartate (NMDA) receptor. Most
inhaled anesthetics also inhibit
nicotinic acetylcholine (ACh) receptor isoforms at moderate to
high concentrations. The strychnine-sensitive glycine receptor is
another ligand-gated ion channel that may function as a target
for certain inhaled anesthetics. CNS neurons in different regions
of the brain have different sensitivities to general anesthetics;
inhibition of neurons involved in pain pathways occurs before
inhibition of neurons in the midbrain reticular formation.
Classification of General anesthetics: paste a pic
1.Inhaled:
The agents currently used in inhalation anesthesia are nitrous oxide
(a gas) and several easily vaporized liquid halogenated hydrocarbons,including halothane,
desflurane, enflurane, isoflurane, sevoflurane, and methoxyflurane. They are administered as
gases; their
partial pressure, or “tension,” in the inhaled air or in blood or other
tissue is a measure of their concentration. Because the standard
pressure of the total inhaled mixture is atmospheric pressure (760
mm Hg at sea level), the partial pressure may also be expressed as a
percentage. Thus, 50% nitrous oxide in the inhaled air would have
a partial pressure of 380 mm Hg.
INTRAVENOUS ANESTHETICS
A. Propofol
Propofol produces anesthesia as rapidly as the intravenous barbiturates, and recovery is more
rapid. Propofol has antiemetic
actions, and recovery is not delayed after prolonged infusion.
The drug is very commonly used as a component of balanced
anesthesia and as an anesthetic in outpatient surgery. Propofol
is also effective in producing prolonged sedation in patients in
critical care settings. Propofol may cause marked hypotension
during induction of anesthesia, primarily through decreased
peripheral resistance. Total body clearance of propofol is greater
than hepatic blood flow, suggesting that its elimination includes
other mechanisms in addition to metabolism by liver enzymes.
Fospropofol, a water-soluble prodrug form, is broken down in the
body by alkaline phosphatase to form propofol. However, onset
and recovery are both slower than propofol. Although fospropofol
appears to cause less pain at injection sites than the standard form
of the drug, many patients experience paresthesias.
B. Barbiturates
Thiopental and methohexital have high lipid solubility, which
promotes rapid entry into the brain and results in surgical anesthesia in one circulation time (<1
min). These drugs are used for
induction of anesthesia and for short surgical procedures. The
anesthetic effects of thiopental are terminated by redistribution
from the brain to other highly perfused tissues but
hepatic metabolism is required for elimination from the body.
Barbiturates are respiratory and circulatory depressants; because
they depress cerebral blood flow, they can also decrease intracranial pressure..
Benzodiazepines
Midazolam is widely used adjunctively with inhaled anesthetics
and intravenous opioids. The onset of its CNS effects is slower
than that of thiopental, and it has a longer duration of action.
Cases of severe postoperative respiratory depression have occurred.
The benzodiazepine receptor antagonist, flumazenil, accelerates
recovery from midazolam and other benzodiazepines.
D. Ketamine
This drug produces a state of “dissociative anesthesia” in which
the patient remains conscious but has marked catatonia, analgesia,
and amnesia. Ketamine is a chemical congener of the psychotomimetic agent, phencyclidine
(PCP), and inhibits NMDA glutamate
transmission. The drug is a cardiovascular stimulant, and this
action may lead to an increase in intracranial pressure. Emergence
reactions, including disorientation, excitation, and hallucinations,
which occur during recovery from ketamine anesthesia, can be
reduced by the preoperative use of benzodiazepines.
E. Opioids
Morphine and fentanyl are used with other CNS depressants
(nitrous oxide, benzodiazepines) in anesthesia regimens and are
especially valuable in high-risk patients who might not survive a
full general anesthetic. Intravenous opioids may cause chest wall
rigidity, which can impair ventilation. Respiratory depression with
these drugs may be reversed postoperatively with naloxone. Neuroleptanesthesia is a state of
analgesia and amnesia is produced
when fentanyl is used with droperidol and nitrous oxide. Newer
opioids related to fentanyl have been introduced for intravenous
anesthesia. Alfentanil and remifentanil have been used for induction of anesthesia. Recovery
from the actions of remifentanil is
faster than recovery from other opioids used in anesthesia because
of its rapid metabolism by blood and tissue esterases.
F. Etomidate
This imidazole derivative affords rapid induction with minimal
change in cardiac function or respiratory rate and has a short duration of action. The drug is not
analgesic, and its primary
advantage is in anesthesia for patients with limited cardiac or
respiratory reserve. Etomidate may cause pain and myoclonus on
injection and nausea postoperatively. Prolonged administration
may cause adrenal suppression.
G. Dexmedetomidine
This centrally acting α2-adrenergic agonist has analgesic and
hypnotic actions when used intravenously. Its characteristics
include rapid clearance resulting in a short elimination half-life.
Dexmedetomidine is mainly used for short-term sedation in an
ICU setting. When used in general anesthesia, the drug decreases
dosage requirements for both inhaled and intravenous anesthetics.Effects of Inhaled
Anesthetics
1. CNS effects—Inhaled anesthetics decrease brain metabolic
rate. They reduce vascular resistance and thus increase cerebral
blood flow. This may lead to an increase in intracranial pressure.
High concentrations of enflurane may cause spike-and-wave activity and muscle twitching, but
this effect is unique to this drug.
Although nitrous oxide has low anesthetic potency (ie, a high
MAC), it exerts marked analgesic and amnestic actions.2. Cardiovascular effects—Most inhaled
anesthetics decrease
arterial blood pressure moderately. Enflurane and halothane are
myocardial depressants that decrease cardiac output, whereas
isoflurane, desflurane and sevoflurane cause peripheral vasodilation. Nitrous oxide is less likely
to lower blood pressure than are
other inhaled anesthetics. Blood flow to the liver and kidney is
decreased by most inhaled agents. Inhaled anesthetics depress
myocardial function—nitrous oxide least. Halothane, and to a
lesser degree isoflurane, may sensitize the myocardium to the
arrhythmogenic effects of catecholamines.
3. Respiratory effects—Although the rate of respiration may be
increased, all inhaled anesthetics cause a dose-dependent decrease in
tidal volume and minute ventilation, leading to an increase in arterial CO2 tension. Inhaled
anesthetics decrease ventilatory response to
hypoxia even at subanesthetic concentrations (eg, during recovery).
Nitrous oxide has the smallest effect on respiration. Most inhaled
anesthetics are bronchodilators, but desflurane is a pulmonary irritant
and may cause bronchospasm. The pungency of enflurane causes
breath-holding, which limits its use in anesthesia induction.
4. Toxicity—Postoperative hepatitis has occurred (rarely) after
halothane anesthesia in patients experiencing hypovolemic shock
or other severe stress. The mechanism of hepatotoxicity is unclear
but may involve formation of reactive metabolites that cause
direct toxicity or initiate immune-mediated responses. Fluoride
released by metabolism of methoxyflurane (and possibly enflurane
and sevoflurane) may cause renal insufficiency after prolonged
anesthesia. Prolonged exposure to nitrous oxide decreases methionine synthase activity and
may lead to megaloblastic anemia.
Susceptible patients may develop malignant hyperthermia whenanesthetics are used together
with neuromuscular blockers (especially succinylcholine). This rare condition is thought in some
cases to be due to mutations in the gene loci corresponding to the
ryanodine receptor (RyR1). Other chromosomal loci for malignant hyperthermia include mutant
alleles of the gene-encoding
skeletal muscle L-type calcium channels. The uncontrolled release
of calcium by the sarcoplasmic reticulum of skeletal muscle
leads to muscle spasm, hyperthermia, and autonomic lability
(Table 16-2). Dantrolene is indicated for the treatment of this
life-threatening condition, with supportive management.