Inhaled

Halothane: [Flurothane]

• Overview: Halothane (Fluothane)

○ Halothane (Fluothane), a nonflammable liquid at room
temperature is a halogenated alkane derivative.
○ Halothane (Fluothane) vapor has been described as having a
sweet, non-pungent odor which made it and agent of choice
among the older inhalational agents for pediatric anesthesia.
 Other inhalational agents are effective in anesthesia
maintenance both for infants and children; however, most
of these agents have sufficiently unpleasant, pungent odor
that they should not be used for inhaled induction.
[isoflurane (Forane) and desflurane (Suprane) are
examples of agents which may be used in pediatric cases
for anesthesia maintenance, but because of their odor they
really cannot be used for mask induction.
 Concerns about halothane (Fluothane)'s use in children
have to do with the following hemodynamic characteristics:
 Halothane (Fluothane) is a myocardial depressant, an
effect which is particularly apparent in children,
especially in hypovolemic patients.
 The extent of cardiac depression can be
reduced if halothane (Fluothane) requirements
are reduced by concurrent administration of
other agents such as opioids or muscle
relaxants.
 Halothane (Fluothane) can sensitize the myocardium
to catecholamines, thus predisposing towards
arrhythmias. This effect is more likely to occur
 during "light" anesthesia or in the presence of
hypercarbia. When epinephrine is required, up to 10
ug/kg may be given in the normocarbic pediatric
patients without incurring significant risk.
 Alternatives to halothane (Fluothane) for mask induction in
pediatric patients: Sevoflurane (Sevorane, Ultane), an
inhalational agent with a non-pungent odor, is probably the
agent of choice for pediatric patients.
 Sevoflurane (Sevorane, Ultane) combines both rapid
induction and emergence, secondary to its low lipid
solubility, with very low myocardial depression --
even at high vaporizer output.
 Furthermore, there probably is a reduced likelihood
of cardiac arrhythmias with sevoflurane (Sevorane,
Ultane) compared halothane (Fluothane) in this
patient group.
○ Halothane (Fluothane), a nonflammable relatively potent
inhalational agent exhibits a low blood:gas partition coefficient,
predicting relatively rapid induction and recovery
○ This agent can be used to provide controlled hypotension
bleeding control
○ Intermediate solubility (blood) + high-potency result in rapid
onset/recovery from anesthesia (either alone or in combination
with nitrous oxide or injected opioids)
• Chemical Considerations: (see structure above)
○ Consequences of halogenated structure:
 Nonflammability
 Intermediate blood solubility
 Anesthetic potency
 Molecular stability
○ Carbon-fluorine: decreased flammability
○ Trifluorocarbon: molecular stability
○ Carbon-chlorine & carbon-bromine components (with retention of
a hydrogen atom) contributing to anesthetic potency
○ Decomposition concerns:
 susceptible to decomposition to: HCl, hydrobromic acid,
bromide and phosgene.
• amber-colored bottle storage + thymol (reduces
spontaneous oxidative decomposition)
 • Thymol: remaining in vaporizers, following halothane
(Fluothane) vaporization leading to malfunction of
temperature-compensating devices or vaporizer
turnstiles
• Halothane (Fluothane) anesthesia: provides unconsciousness
• Clinical Indication:
○ Halothane (Fluothane) is effective for general anesthetic
maintenance and may be an induction agent of choice in difficult
airway
• Systems Physiology:
○ CNS:
 Generalized CNS depression
 cerebrovascular dilation causes increased ICP
○ Cardiovascular:
 Halothane (Fluothane) causes a slight decrease in heart
rate, a decrease in mean arterial pressure (MAP)-- both
associated with its well-documented cardiac depressant
property.
 Halothane (Fluothane) may also sensitize the myocardium
to circulating catecholamines, explaining the pro-
arrhythmogenic property.
○ Pulmonary:
 Halothane (Fluothane) causes decreasing tidal volume with
increasing MAC, increasing respiratory rate with increasing
MAC
 Halothane (Fluothane) also promote significant
bronchodilation
○ Hepatic: fulminant hepatic failure (halothane hepatitis): Case
history for slides below: "Forty four year old lady had uterine
curettage for metrorrhagia. Eight weeks later she had
hysterectomy. Three days after hysterectomy she became
jaundiced. Seven days later she died in liver failure. Halothane
was used as anesthetic in both surgical procedures. The autopsy
showed massive liver necrosis. It appears that the liver damage
was mediated by an immunoreactive mechanism. Multiple
exposures increase the incidence of liver damage." DRUG-
INDUCED LIVER INJURY by Dr. Emilio Orfei
• Musculoskeletal: relaxation
• Contraindications:
 ○ Trigger to malignant hyperpyrexia
○ Recent halothane (Fluothane) exposure
• Drug-drug interactions:
○ Muscle relaxants potentiation
○ Reduced MAC with opioids, nitrous oxide & benzodiazepines
• Concerns:
○ Inadequate analgesia
○ May not provide adequate muscle relaxation
○ May not provide adequate suppression of visceral reflexes
○ Reversible reduction of GFR
Halothane Disadvantages
• unpredictable occurrence of hepatitis

• Status: infrequently used due to the availability of isoflurane (Forane),

enflurane (Ethrane) and desflurane (Suprane).

Nitrous Oxide

• Overview: Low-molecular weight

○ Oderless to sweet smelling
○ Nonflammable
○ Low-potency gas
○ Poor blood solubility (0.46)
 Low blood solubility allows rapid attainment of alveolar and
brain partial pressure
 • Most commonly administered in combination with opioids or volatile
anesthetics.
• With a MAC value of 105%, nitrous oxide, by itself is not suitable or
safe as a sole anesthetic agent.
• Effective analgesic.
• Minimal skeletal muscle relaxation
• Effective: Nitrous oxide in combination with thiopental for induction, a
skeletal muscle relaxant, and hyperventilation to reduce CO2
• Nitrous oxide can be used as an adjunct to other agents: For example,
using 70% nitrous oxide + oxygen significantly reduces MAC for
halothane, enflurane, and isoflurane.
• Despite the relative insolubility of nitrous oxide, large quantitities of
gas are rapidly absorbed due to its high inhaled concentration.
○ This concentration effect speeds induction as fresh gas is
literally drawn into the lung from the breathing circuit.
• Since nitrous oxide is often administered with a second gas, the
second gas effect also enhances the rate of induction
• If administration of nitrous oxide is abruptly discontinued, rapid
transfer of NO from blood and tissues to the alveoli decreases arterial
tension of oxygen. This process is diffusional hypoxia.
Nitrous Oxide Disadvantages
• No skeletal muscle relaxation
• Weak anesthetic
• Air pockets in closed spaces expand
• Post-anesthesia hypoxia (diffusion hypoxia)
• Not suitable as a sole anesthetic agent
Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology
In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,
(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman,
A.G.,eds) The McGraw-Hill Companies, Inc.,1996, p 319 - 321.
Stoelting, R.K., "Inhaled Anesthetics", in Pharmacology and Physiology in
Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 36-76

Desflurane (Suprane)
• Desflurane (Suprane) Overview:
○ Fluorinated methyl ethyl ether and, similar to isoflurane (Forane).
Substitution of a fluorine atom for chlorine (isoflurane)
○ Fluorination (compared to chlorination) results in:
 increased vapor pressure-- 3X (= decreased
intermolecular attraction)
• High vapor pressure would result in boiling at
operating room temperatures requires:
 implementation of new vaporizer technology
converts desflurane (Suprane) to a gas (heated
& pressurized electric vaporizer) which is
blended with fresh gas flow
 increased molecular stability
 decreased potency: 5 fold < isoflurane (Forane)
 Minor desflurane (Suprane) metabolism
○ Pungent odor --desflurane (Suprane) less likely to be used for
inhalation induction compared to halothane (Fluothane) or
sevoflurane (Sevorane, Ultane).
 Airway irritation, breath-holding, coughing, laryngospasm
is greater than 6% desflurane (Suprane) administered to
an awake patient.
 Significant salivation
○ Carbon monoxide:
 Secondary to desflurane (Suprane) degradation by strong
base present in carbon dioxide absorbants.
 Carbon monoxide concentration: desflurane (Suprane) >
enflurane (Ethrane) > isoflurane (Forane) {carbon
 monoxide produced by halothane (Fluothane) or
sevoflurane (Sevorane, Ultane): extremely small)
○ Solubility (blood: gas partition coefficient = 0.45) and potency
(MAC 6%):
 Rapid achievement of alveolar partial pressures required
for anesthesia along with rapid awakening
 Distinguishing features of desflurane (Suprane) and
sevoflurane (Sevorane, Ultane) compared to earlier volatile
anesthetics:
• Lower blood-gas solubility
• More rapid recovery from anesthesia
• Desflurane (Suprane) Systems Physiology:
○ CNS:
 Generalized depression
 Extremely rapid emergence
 Increased ICP
○ Cardiovascular:
 Vascular resistance
 MAP
 Heart rate (deep anesthesia); tachycardia with rapid
concentration change
○ Pulmonary:
 decrease tidal volume
 increase respiratory rate
 irritant
○ Gastrointestinal: nausea
○ Musculoskeletal:relaxation
• Desflurane (Suprane): Clinical Indications:
○ General anesthesia maintenance
○ Agent of choice when:
 Rapid emergence desirable
 Precise anesthetic depth control required
• Contraindications:
○ Trigger to malignant hyperpyrexia
• Drug-drug interactions:
 ○ Muscle relaxant effect potentiation
○ MAC with opioids, nitrous oxide, & benzodiazepines

Isoflurane [Forane]

• Isoflurane[Forane]: Overview:
○ Halogenated methyl ethyl ether
○ Non-flammable liquid (room temperature);pungent odor; ether-
like
○ Intermediate solubility (blood) + high-potency ® rapid onset &
recovery using isoflurane (Forane) alone or in combination with
nitrous oxide or opioids (injected)
○ Very high physical stability; no need to add preservatives e.g.
thymol
• Isoflurane anesthesia: results in unconsciousness
• Initially, until deeper levels of anesthesia are reached, isoflurane
stimulates airway reflexes with:
○ increases in secretions
○ coughing
○ laryngospasm. (greater with isofluorane than enflurane
(Ethrane) or halothane (Fluothane))
• Isoflurane[Forane]: Systems Physiology:
○ CNS:
 Generalized CNS depression; Rapid emergence
 Increased ICP
○ Cardiovascular:
  Little effect on cardiac output & decreased vascular
assistance & decreased MAP
 Increased heart rate
○ Gastrointestinal: nausea
○ Musculoskeletal: relaxation
• Contraindications: trigger to malignant hyperpyrexia
• Drug-drug interactions:
○ muscle relaxants potentiation
○ MAC with opioids, nitrous oxide, & benzodiazepines
• Isoflurane[Forane] Comparative Pharmacology
○ By contrast to enflurane (Ethrane) or halothane (Fluothane)
cardiac output is well maintained with isoflurane (Forane)
○ May provide adequate muscle relaxation greater than seen with
halothane (Fluothane);
○ Perhaps adequate for abdominal procedures. Otherwise, reduced
amounts of tubocurarine may be required
○ As with enflurane, isoflurane (Forane) relaxation of uterine
muscle is not desirable if uterine contraction is required to limit
blood loss.
○ Reversible reduction of GFR
○ Unlike enflurane (Ethrane), convulsive activity has not been seen
with isoflurane (Forane).
• Isoflurane Advantages
○ Rapid, smooth adjustment of depth of anesthesia with limited
effects on pulse or respiration
○ Depth of anesthesia is easily controlled
○ No hepatic and renal toxicity
○ Cerebral blood flow and intracranial pressure are readily
controlled.
○ Relaxation of skeletal muscles may be adequate for surgery
○ Arrhythmias are uncommon.
• Isoflurane Disadvantage: As with halothane (Fluothane), enflurane
(Ethrane), isoflurane (Forane) may cause malignant hyperthermia
• Isoflurane Status: Isoflurane (Forane) may be the most widely used
inhalational agent.
 Enflurane (Ethrane)

• Overview: Enflurane (Ethrane)

○ Halogenated, methyl ethyl ether
○ Clear, nonflammable volatile liquid (room temperature)
○ Pungent odor
• Intermediate solubility + high potency leads to rapid onset/recovery
(enflurane (Ethrane) alone or in combination with nitrous oxide or
opioids)
• Clinical Use: maintenance of general anesthesia
• Systems Physiology:
○ CNS: increased ICP secondary to increased cerebral blood flow
(CBF)
○ Cardiovascular:
 myocardial depressant
 decreased vascular resistance; decreased mean arterial
pressure (MAP), tachycardia
○ Renal:
 renal dysfunction
○ Gastrointestinal:
 nausea
○ Musculoskeletal:
 muscle relaxation
• Contraindications
○ Renal failure
○ Long cases
 ○ Trigger to malignant hyperpyrexia
○ Epilepsy*
* may promote seizures (at concentrations > 3%); epileptiform paroxysmal
spike occurrences
• Drug Interactions:
○ Potentiation: muscle relaxants
○ MAC with opioids, nitrous oxide & benzodiazepines

Sevoflurane (Sevorane, Ultane)

• Overview: sevoflurane (Sevorane, Ultane)

○ Fluorinated methyl isopropyl ether
○ Vapor pressure: similar to halothane (Fluothane) & isoflurane
(Forane) (conventional, unheated vaporizer may be used)
○ Blood: gas partition coefficient of sevoflurane (Sevorane, Ultane)
= 0.69; similar to desflurane (Suprane) allowing:
 rapid induction
 rapid recovery upon anesthetic discontinuation
○ Non-pungent, bronchodilation similar to isoflurane (Forane)
○ Least airway irritation among current volatile anesthetics,
thereby allowing direct anesthesia induction (like halothane
(Fluothane))
• Metabolism:sevoflurane (Sevorane, Ultane)
○ More likely to be metabolized (3%-5% metabolized) than
desflurane (Suprane)
○ Principal metabolites:
  inorganic fluoride (>than that seen following enflurane
(Ethrane))
 hexafluoroisopropanol (nontoxic)
○ No trifluoroacetylated liver proteins formed (no anti-
trifluoroacetylated liver protein antibodies)
 Such antibodies may be seen with halothane (Fluothane),
enflurane (Ethrane), isoflurane (Forane), desflurane
(Suprane); these agents, metabolized to reactive acyl
halide intermediates may produce:
 hepatoxicity
 cross-sensitivity between agents
○ Sevoflurane (Sevorane, Ultane) no carbon monoxide formation
following exposure to carbon dioxide and absorbants
○ Level of major sevoflurane (Sevorane, Ultane) metabolite, a
vinyl-ether derivative (Compound A) is significantly below
possible toxic levels, even with gas flows > 1 liter per minute
• Clinical Use:sevoflurane (Sevorane, Ultane)
○ First-line, excellent induction agent
○ Rapid emergence
○ Allows excellent anesthetic depth control
• Systems Physiology: sevoflurane (Sevorane, Ultane)
○ CNS:
 CNS depression (generalized)
 Rapid emergence
 Increased ICP
○ Cardiovascular:
 reduced vascular resistance
 decreased MAP (mean arterial pressure)
○ Pulmonary:
 Nonirritant
 Respiratory depression
○ Musculoskeletal:
 Muscle relaxation
• Contraindications/Issues:
○ Trigger to malignant hyperpyrexia
○ Long cases (fluoride accumulation)
 ○ Closed-circuit anesthesia
• Drug-drug interactions
○ Muscle relaxants effect potentiation
○ MAC decreases when sevoflurane is combined with opioids,
benzodiazepines, nitrous oxide

1. Propofol (INN, marketed as Diprivan by AstraZeneca) is a short-acting,

intravenously administered hypnotic agent. Its uses include the induction
and maintenance of general anesthesia, sedation for mechanically ventilated
adults, and procedural sedation. Propofol is also commonly used in
veterinary medicine. Propofol is approved for use in more than 50 countries,
and generic versions are available.
Pharmacology
Propofol is highly protein-bound in vivo and is metabolised by conjugation in
the liver.[4] Its rate of clearance exceeds hepatic blood flow, suggesting an
extrahepatic site of elimination as well. It has several mechanisms of action,
[5][6][7]
both through potentiation of GABA-A receptor activity, thereby slowing
the channel closing time,[8][9][10] and also acting as a sodium channel blocker.
[11][12]
Recent research has also suggested the endocannabinoid system may
contribute significantly to propofol's anesthetic action and to its unique
properties.[13]
The elimination half-life of propofol has been estimated to be between 2 and
24 hours. However, its duration of clinical effect is much shorter, because
propofol is rapidly distributed into peripheral tissues. When used for IV
sedation, propofol typically wears off in minutes. Propofol is versatile; the
drug can be given for short or prolonged sedation as well as for general
anesthesia. Its use is not associated with nausea as is often seen with opioid
medications. These characteristics of rapid onset and recovery along with its
amnestic effects[14] have led to its widespread use for sedation and
anesthesia.
EEG research upon those undergoing general anesthesia with propofol finds
that its effect upon the loss of consciousness links to its causing a prominent
reduction in the brain's information integration capacity at gamma wave
band frequencies.[15]
Contraindications and interactions
The respiratory effects of propofol are potentiated by other respiratory
depressants, including benzodiazepines.[16]
Adverse effects
Aside from low blood pressure (mainly through vasodilatation) and transient
apnea following induction doses, one of propofol's most frequent side effects
is pain on injection, especially in smaller veins. This pain can be mitigated by
pretreatment with lidocaine.[17] Patients show great variability in their
response to propofol, at times showing profound sedation with small doses. A
more serious but rare side effect is dystonia.[18] Mild myoclonic movements
are common, as with other intravenous hypnotic agents. Propofol appears to
be safe for use in porphyria, and has not been known to trigger malignant
hyperpyrexia.
It has been reported that the euphoria caused by propofol is unlike other
sedation agents, "I even remember my first experience using propofol: a
young woman who was emerging from a MAC anesthesia looked at me as
though I were a masked Brad Pitt and told me that she felt simply wonderful"
—C.F. Ward, M.D.[19]
Propofol has reportedly induced priapism in some individuals.[20][21]
Propofol infusion syndrome
Another recently described rare, but serious, side effect is propofol infusion
syndrome. This potentially lethal metabolic derangement has been reported
in critically-ill patients after a prolonged infusion of high-dose propofol in
combination with catecholamines and/or corticosteroids

2. Sodium thiopental, better known as Sodium Pentothal (a trademark of

Abbott Laboratories), thiopental, thiopentone sodium, or trapanal, is a rapid-
onset short-acting barbiturate general anaesthetic. It is an intravenous ultra-
short-acting barbiturate. Sodium thiopental is a depressant and is sometimes
used during interrogations—not to cause pain (in fact, it may have just the
opposite effect), but to weaken the resolve of the subject and make him or
her more compliant to pressure.[3] Thiopental is a core medicine in the World
Health Organization's "Essential Drugs List", which is a list of minimum
medical needs for a basic health care system.[

Uses
Anesthesia
Thiopental is an ultra-short-acting barbiturate and has been used commonly
in the induction phase of general anesthesia. Its use in the United States and
elsewhere has been largely replaced with that of propofol. Following
intravenous injection the drug rapidly reaches the brain and causes
unconsciousness within 30–45 seconds. At one minute, the drug attains a
peak concentration of about 60% of the total dose in the brain. Thereafter,
the drug distributes to the rest of the body and in about 5–10 minutes the
concentration is low enough in the brain such that consciousness returns.
A normal dose of thiopental (usually 4–6 mg/kg) given to a pregnant woman
for operative delivery (caesarian section) rapidly makes her unconscious, but
the baby in her uterus remains conscious. However, larger or repeated doses
can depress the baby.
Thiopental is not used to maintain anesthesia in surgical procedures
because, in infusion, it displays zero-order elimination kinetics, leading to a
long period before consciousness is regained. Instead, anesthesia is usually
maintained with an inhaled anesthetic (gas) agent. Inhaled anesthetics are
eliminated relatively quickly, so that stopping the inhaled anesthetic will
allow rapid return of consciousness. Thiopental would have to be given in
large amounts to maintain an anesthetic plane, and because of its 11.5–26
hour half-life, consciousness would take a long time to return.[6]
In veterinary medicine, thiopental is also used to induce anesthesia in
animals. Since thiopental is redistributed to fat, certain breeds of dogs,
primarily the sight hounds can have prolonged recoveries from thiopental
due to their lack of body fat and lean body mass. Thiopental is always
administered intravenously, as it can be fairly irritating; severe tissue
necrosis and sloughing can occur if it is injected incorrectly into the tissue
around a vein.
Medically induced coma
In addition to anesthesia induction, thiopental was historically used to induce
medical comas. It has now been superseded by drugs such as propofol.
Thiopental has a long Context Sensitive Half Time (CSHT) meaning infusions
saturate peripheral compartments (fat, muscle etc). When the infusion is
stopped, the drug re-distributes from the peripheral tissues back into the
blood, prolonging the effect.
Thiopental also exhibits zero order kinetics at higher doses. The rate of
clearance becomes fixed which slows elimination from the body.
Patients with brain swelling, causing elevation of the intracranial pressure,
either secondary to trauma or following surgery may benefit from this drug.
Thiopental, and the barbiturate class of drugs, decrease neuronal activity
and therefore decrease the production of osmotically active metabolites
which in turn decreases swelling. Patients with significant swelling have
improved outcomes following the induction of coma. Reportedly, thiopental
has been shown to be superior to pentobarbital[7] in reducing intracranial
pressure.
Euthanasia
Thiopental is used intravenously for the purposes of euthanasia. The
Belgians and the Dutch have created a protocol that recommends sodium
thiopental as the ideal agent to induce coma followed by pancuronium
bromide.[8]
Intravenous administration is the most reliable and rapid way to
accomplish euthanasia and therefore can be safely recommended. A
coma is first induced by intravenous administration of 20 mg/kg
thiopental sodium (Nesdonal) in a small volume (10 ml physiological
saline). Then a triple intravenous dose of a non-depolarizing
neuromuscular muscle relaxant is given, such as 20 mg pancuronium
dibromide (Pavulon) or 20 mg vecuronium bromide (Norcuron). The
muscle relaxant should preferably be given intravenously, in order to
ensure optimal availability. Only for pancuronium dibromide (Pavulon)
are there substantial indications that the agent may also be given
intramuscularly in a dosage of 40 mg.[8]
Lethal injection
Along with pancuronium bromide and potassium chloride, thiopental is used
in 35 states of the U.S. to execute prisoners by lethal injection. A very large
dose is given which places the subject into a rapidly induced coma.
Executions using the three drug combination are usually effective in
approximately 10 minutes, but have been known to take several times this
length. The use of thiopental alone is hypothesized to cause death in
approximately 45 minutes.[citation needed] The use of sodium thiopental has been
the cause of current Supreme Court challenges to the lethal injection
protocol, after a study in the medical journal the Lancet, where autopsy
studies on executed inmates revealed that there was not a high enough
concentration of thiopental in their blood to have caused unconsciousness.
The exclusion of physicians participating in executions is partly to blame for
inept administration of the drugs.[citation needed]
Truth serum
Thiopental is still used in some places as a truth serum.[3] The barbiturates as
a class decrease higher cortical brain functioning. Some psychiatrists
hypothesize that because lying is more complex than telling the truth,
suppression of the higher cortical functions may lead to the uncovering of
the "truth". However, the reliability of confessions made under thiopental is
dubious; the drug tends to make subjects chatty and cooperative with
interrogators, but a practiced liar or someone who has a false story firmly
established would still be quite able to lie while under the influence of the
drug.[9]
Psychiatry
Psychiatrists have used thiopental to desensitize patients with phobias,[10]
and to "facilitate the recall of painful repressed memories."[11] One
psychiatrist who worked with thiopental is Professor Jan Bastiaans, who used
this procedure to help release trauma in victims of the Nazis.[12]
Metabolism
As with all lipid soluble anaesthetic drugs, the short duration of action of STP
is almost entirely due to its redistribution away from central circulation
towards muscle and fat tissue. Once redistributed the free fraction in the
blood is metabolised in the liver. Sodium thiopental is mainly metabolized to
pentobarbital,[13] 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid,
and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.[14]
Dosage
The usual dose range for induction of anesthesia using thiopental is from 3 to
7 mg/kg; however, there are many factors that can alter this. Premedication
with sedatives such as benzodiazepines or clonidine will reduce
requirements, as do specific disease states and other patient factors.
Side effects
As with nearly all anesthetic drugs, thiopental causes cardiovascular and
respiratory depression resulting in hypotension, apnea and airway
obstruction. For these reasons, only suitably trained medical personnel
should give thiopental in an environment suitably equipped to deal with
these effects. Side effects include headache, emergence delirium, prolonged
somnolence and nausea. Intravenous administration of sodium thiopental is
followed instantly by an odor sensation, sometimes described as being
similar to rotting onions. The hangover effects may last up to 36 hours.
Although molecules of thiopental contain one sulfur atom, it is not a
sulfonamide, and does not show allergic reactions of sulfa/sulpha drugs.
Drug interaction
Co-administration of pentoxifylline and thiopental causes death by acute
pulmonary oedema in rats. This pulmonary oedema was not mediated by
cardiac failure or by pulmonary hypertension but was due to increased
pulmonary vascular permeability.[15]

Ketamine is a drug used in human and veterinary medicine developed by

Parke-Davis (today a part of Pfizer) in 1962. Its hydrochloride salt is sold as
Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as
an NMDA receptor antagonist[2]. At high, fully anesthetic level doses,
ketamine has also been found to bind to opioid μ receptors and sigma
receptors.[citation needed] Like other drugs of this class such as tiletamine and
phencyclidine (PCP), it induces a state referred to as "dissociative
anesthesia"[3] and is used as a recreational drug.
Ketamine has a wide range of effects in humans, including analgesia,
anesthesia, hallucinations, elevated blood pressure, and bronchodilation.
 Ketamine is primarily used for the induction and maintenance of
[citation needed]

general anesthesia, usually in combination with some sedative drug. Other

uses include sedation in intensive care, analgesia (particularly in emergency
medicine), and treatment of bronchospasm. It is also a popular anesthetic in
veterinary medicine.
3. Ketamine is a chiral compound. Most pharmaceutical preparations of
ketamine are racemic; however, some brands reportedly have (mostly
undocumented) differences in enantiomeric proportions. The more active
enantiomer, (S)-ketamine, is also available for medical use under the brand
name Ketanest S.[4] Ketamine is a core medicine in the World Health
Organization's "Essential Drugs List", which is a list of minimum medical
needs for a basic health care system.
Medical use
Indications for use as an anaesthetic:
• Paediatric anaesthesia (as the sole anaesthetic for minor procedures or
as an induction agent followed by muscle relaxant and endotracheal
intubation)
• Asthmatics or patients with chronic obstructive airway disease
• Emergency surgery in field conditions in war zones
• To supplement spinal / epidural anaesthesia / analgesia utilizing low
doses

10 ml bottles of ketamine (veterinary use)

Severe:Impairs all senses, especially:
• Sight
• Balance
• Sense of time
Cardiovascular:
• Partial depressant
Gastrointestinal:
• Nausea
Musculoskeletal:
• Relaxant
Neurological:
• Analgesia
Respiratory:
• Partial depressant/stimulant
In medical settings, ketamine is usually injected intravenously or
intramuscularly,[17] but it is also effective when insufflated, smoked, or taken
orally.[18]
Since it suppresses breathing much less than most other available
anaesthetics,[19] ketamine is still used in human medicine as an anesthetic,
however, due to the hallucinations which may be caused by ketamine, it is
not typically used as a primary anesthetic, although it is the anaesthetic of
choice when reliable ventilation equipment is not available. Ketamine tends
to increase heart rate and blood pressure. Because ketamine tends to
increase or maintain cardiac output, it is sometimes used in anesthesia for
emergency surgery when the patient's state of fluid volume status is
unknown (e.g., from traffic accidents). Ketamine can be used in podiatry and
other minor surgery, and occasionally for the treatment of migraine. There is
ongoing research in France, the Netherlands, Russia, Australia and the US
into the drug's usefulness in pain therapy, depression suppression, and for
the treatment of alcoholism[20] and heroin addiction.[21]
In veterinary anesthesia, ketamine is often used for its anesthetic and
analgesic effects on cats, dogs, rabbits, rats, and other small animals.
Veterinarians often use ketamine with sedative drugs to produce balanced
anesthesia and analgesia, and as a constant rate infusion to help prevent
pain wind-up. Ketamine is used to manage pain among large animals, though
it has less effect on bovines. It is the primary intravenous anesthetic agent
used in equine surgery, often in conjunction with detomidine and thiopental,
or sometimes guaifenesin.
Ketamine may be used in small doses (0.1–0.5 mg/kg·h) as a local
anesthetic, particularly for the treatment of pain associated with movement
and neuropathic pain.[22] It may also be used as an intravenous co-analgesic
together with opiates to manage otherwise intractable pain, particularly if
this pain is neuropathic (pain due to vascular insufficiency or shingles are
good examples). It has the added benefit of counter-acting spinal
sensitization or wind-up phenomena experienced with chronic pain. At these
doses, the psychotropic side effects are less apparent and well managed
with benzodiazepines.[23] Ketamine is a co-analgesic, and so is most effective
when used alongside a low-dose opioid; while it does have analgesic effects
by itself, the higher doses required can cause disorienting side effects.[23] The
combination of ketamine with an opioid is, however, particularly useful for
pain caused by cancer.[24]
The effect of ketamine on the respiratory and circulatory systems is different
from that of other anesthetics. When used at anesthetic doses, it will usually
stimulate rather than depress the circulatory system.[25] It is sometimes
possible to perform ketamine anesthesia without protective measures to the
airways. Ketamine is also a potent analgesic and can be used in sub-
anesthetic doses to relieve acute pain; however, its psychotropic properties
must be taken into account. Patients have reported vivid hallucinations,
"going into other worlds" or "seeing God" while anesthetized, and these
unwanted psychological side-effects have reduced the use of ketamine in
human medicine. They can, however, usually be avoided by concomitant
application of a sedative such as a benzodiazepine.[23]
Low-dose ketamine is recognized for its potential effectiveness in the
treatment of complex regional pain syndrome (CRPS), according to a
retrospective review published in the October 2004 issue of Pain Medicine.[26]
Although low-dose ketamine therapy is established as a generally safe
procedure, reported side effects in some patients have included
hallucinations, dizziness, lightheadedness and nausea. Therefore nurses
administering ketamine to patients with CRPS should only do so in a setting
where a trained physician is available if needed to assess potential adverse
effects on patients.[27]

Examples of epidural anesthesia

Clexane - General Information:

Clexane, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant. It
has the highest negative charge density of any known biological molecule. Clexane acts as an
anticoagulant, preventing the formation of clots and extension of existing clots within the blood.
While heparin does not break down clots that have already formed, it allows the body's natural
clot lysis mechanisms to work normally to break down clots that have already formed. Clexane
binds to and accelerates the activity of antithrombin III. By activating antithrombin III, heparin
preferentially potentiates the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the
conversion of prothrombin to thrombin, so heparin s inhibition of this process results in
decreased thrombin and ultimately the prevention of fibrin clot formation.
Pharmacology:
Clexane is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine
and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty
thousand. Clexane occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates.
Clexane is a well known and commonly used anticoagulant which has antithrombotic properties.
Clexane is indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary
embolism, and also for the prophylaxis of ischemic complications of unstable angina and non-Q-
wave myocardial infarction, when concurrently administered with aspirin. Clexane inhibits
reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in
vivo. Clexane acts at multiple sites in the normal coagulation system. Small amounts of Clexane
in combination with antithrombin III (Clexane cofactor) can inhibit thrombosis by inactivating
activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active
thrombosis has developed, larger amounts of heparin can inhibit further coagulation by
inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Clexane also
prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing
factor.
Clexane for patients
Clexane Interactions
Drug Interactions:
a. Drugs Enhancing Heparin Effect:
Oral anticoagulants: Heparin sodium may prolong the one-stage prothrombin time. Therefore,
when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours
after the last intravenous dose or 24 hours after the last subcutaneous dose should elapse before
blood is drawn if a valid prothrombin time is to be obtained.
Platelet inhibitors: Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen,
indomethacin, dipyridamole, hydroxychloroquine and others that interfere with platelet-
aggregation reactions (the main hemostatic defense of heparinized patients) may induce bleeding
and should be used with caution in patients receiving heparin sodium.
The anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III
(human) in patients with hereditary antithrombin III deficiency. Thus in order to avoid bleeding,
reduced dosage of heparin is recommended during treatment with antithrombin III (human).
b. Drugs Decreasing Heparin Effect:
Digitalis, tetracyclines, nicotine, or antihistamines may partially counteract the anticoagulant
action of heparin sodium. Heparin Sodium Injection should not be mixed with doxorubicin,
droperidol, ciprofloxacin, or mitoxantrone, since it has been reported that these drugs are
incompatible with heparin and a precipitate may form.
Drug/ Laboratory Tests Interactions
Hyperaminotransferasemia: Significant elevations of aminotransferase (SGOT [S-AST] and
SGPT [S-ALT]) levels have occurred in a high percentage of patients (and healthy subjects) who
have received heparin sodium. Since aminotransferase determinations are important in the
differential diagnosis of myocardial infarction, liver disease and pulmonary emboli, rises that
might be caused by drugs (heparin sodium) should be interpreted with caution.
Clexane Contraindications
Heparin sodium should not be used in patients:
• With severe thrombocytopenia.
• In whom suitable blood coagulation tests e.g. the whole-blood clotting time, partial
thromboplastin time, etc. cannot be performed at appropriate intervals (this
contraindication refers to full-dose heparin; there is usually no need to monitor
coagulation parameters in patients receiving low-dose heparin sodium).
 • With an uncontrollable active bleeding state, except when this is due to disseminated
intravascular coagulation.
Additional information about Clexane
Clexane Indication: For anticoagulant therapy in prophylaxis and treatment of venous
thrombosis and its extension, for prevention of post-operative deep venous thrombosis and
pulmonary embolism and for the prevention of clotting in arterial and cardiac surgery.
Mechanism Of Action: The mechanism of action of heparin is antithrombin-dependent. It acts
mainly by accelerating the rate of the neutralization of certain activated coagulation factors by
antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin
is well correlated to the inhibition of factor Xa. Clexane interacts with antithrombin III,
prothrombin and factor X.
Drug Interactions: Aspirin Association of ASA/Clexane increases risk of bleeding
Drospirenone Increased risk of hyperkaliemia
Food Interactions: Adequate calcium intake is recommended, needs increased with long term
use, supplement recommended.
Generic Name: Heparin
Synonyms: Alpha-Heparin; Heparin sodium; Heparin sodium preservative Free; Heparin sodium
salt; Heparin sulfate; Heparinate; Heparinic acid; Low molecular weight heparin sodium;
Sodium heparin
Drug Category: Fibrinolytic Agents; Anticoagulants; Heparins
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Heparin: Ariven; Arteven; Bemiparin; Calcilean; Calciparine;
Certoparin; Clexane; Clivarin; Clivarine; Dalteparin; Depo-Heparin; Eparina [DCIT]; Fluxum;
Fragmin A; Fragmin B; Fraxiparin; Hed-Heparin; Hepalean; Heparin Cy 216; Heparin Leo;
Heparin Lock Flush; Hepathrom; Leparan; Lipo-Hepin; Liquaemin; Liquaemin Sodium;
Liquemin; Multiparin; Novoheparin; Pabyrin; Parnaparin; Parvoparin; Pularin; Reviparin;
Sandoparin; Sublingula; Thromboliquine; Vetren; Vitrum AB;
Absorption: Some oral absorption but lack of anticoagulant effect. Rapidly taken up by
endothelial cells with remainder bound to plasma proteins.
Toxicity (Overdose): Heparin sodium - Mouse, median lethal dose greater than 5000 mg/kg.
Another side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an
immunological reaction that makes platelets form clots within the blood vessels, thereby using
up coagulation factors
Protein Binding: Very high, mostly to low-density lipoproteins
Biotransformation: Liver and the reticulo-endothelial system are the sites of biotransformation.
Half Life: 1.5 hours
Dosage Forms of Clexane: Solution Intravenous
Liquid Irrigation
Solution Subcutaneous
Liquid Intravenous
Solution Intraperitoneal
Chemical IUPAC Name: 6-[5-acetamido-4,6-dihydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-3-
[5-(6-carboxy-4,5-dihydroxy-3-sulfooxyoxan-2-yl)oxy-6-(hydroxymethyl)-3-(sulfoamino)-4-
sulfooxyoxan-2-yl]oxy-4-hydroxy-5-sulfooxyoxane-2-carboxylic acid
Chemical Formula: C26H42N2O37S5
Heparin on Wikipedia: http://en.wikipedia.org/wiki/Heparin
Organisms Affected: Humans and other mammals

Levophed - General Information:

Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and
autonomic neurotransmitter. Levophed is the principal transmitter of most postganglionic
sympathetic fibers and of the diffuse projection system in the brain arising from the locus
ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
[PubChem]
Pharmacology:
Noradrenaline acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction.
Its effect in-vitro is often limited to the increasing of blood pressure through antagonising alpha-
1 and alpha-2 receptors and causing a resultant increase in systemic vascular resistance.
Additional information about Levophed
Levophed Indication: Mainly used to treat patients in vasodilatory shock states such as septic
shock and neurogenic shock and has shown a survival benefit over dopamine. Also used as a
vasopressor medication for patients with critical hypotension.
Mechanism Of Action: Levophed functions as a peripheral vasoconstrictor (alpha-adrenergic
action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-
adrenergic action).
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Norepinephrine
Synonyms: L-noradrenaline; Arterenol; L-Norepinephrine; Norepinephrine; Noradrenaline
Drug Category: Adrenergic alpha-Agonists; Sympathomimetics; Vasoconstrictor Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Norepinephrine: Levophed;
Absorption: Not Available
Toxicity (Overdose): In high dose and especially when it is combined with other vasopressors,
it can lead to limb ischemia and limb death.
Protein Binding: Not Available
Biotransformation: Not Available
Half Life: Not Available
Dosage Forms of Levophed: Solution Intravenous
Liquid Intravenous
Insert, extended release Intrauterine
Tablet Oral
Chemical IUPAC Name: 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol
Chemical Formula: C8H11NO3
Norepinephrine on Wikipedia: http://en.wikipedia.org/wiki/Norepinephrine
Organisms Affected: Humans and other mammals

Isocaine HCL - General Information:

A local anesthetic that is chemically related to bupivacaine but pharmacologically related to
lidocaine. It is indicated for infiltration, nerve block, and epidural anesthesia. Isocaine HCL is
effective topically only in large doses and therefore should not be used by this route. (From
AMA Drug Evaluations, 1994, p168)
Pharmacology:
Mepivicaine is a local anesthetic of the amide type. Mepivicaine as a reasonably rapid onset and
medium duration and is known by the proprietary names as Carbocaine and Polocaine.
Mepivicaine is used in local infiltration and regional anesthesia. Systemic absorption of local
anesthetics produces effects on the cardiovascular and central nervous systems. At blood
concentrations achieved with normal therapeutic doses, changes in cardiac conduction,
excitability, refractoriness, contractility, and peripheral vascular resistance are minimal.
Isocaine HCL for patients
When appropriate, patients should be informed in advance that they may experience temporary
loss of sensation and motor activity, usually in the lower half of the body, following proper
administration of caudal or epidural anesthesia. Also, when appropriate, the physician should
discuss other information including adverse reactions listed in this package insert.
Isocaine HCL Interactions
Isocaine HCL Contraindications
Mepivacaine is contraindicated in patients with a known hypersensitivity to it or to any local
anesthetic agent of the amide-type or to other components of mepivacaine solutions.
Additional information about Isocaine HCL
Isocaine HCL Indication: For production of local or regional analgesia and anesthesia by local
infiltration, peripheral nerve block techniques, and central neural techniques including epidural
and caudal blocks.
Mechanism Of Action: Local anesthetics block the generation and the conduction of nerve
impulses, presumably by increasing the threshold for electrical excitation in the nerve, by
slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action
potential. In general, the progression of anesthesia is related to the diameter, myelination, and
conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as
follows: pain, temperature, touch, proprioception, and skeletal muscle tone.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Mepivacaine
Synonyms: Mepivacaina [INN-Spanish]; DL-Mepivacaine; Mepivacaine HCL; mepivacaine
hydrochloride; Mepivacainum [INN-Latin]; Mepivicaine; S-Ropivacaine Mesylate
Drug Category: Anesthetics, Local
Drug Type: Small Molecule; Approved
Other Brand Names containing Mepivacaine: Arestocaine HCL; Carbocain; Carbocaine;
Isocaine HCL; Polocaine; Polocaine-MPF; Scandicain; Scandicaine; Scandicane; Scandonest
Plain;
Absorption: Absorbed locally. The rate of systemic absorption of local anesthetics is dependent
upon the total dose and concentration of drug administered, the route of administration, the
vascularity of the administration site, and the presence or absence of epinephrine in the
anesthetic solution.
Toxicity (Overdose): The mean seizure dosage of mepivacaine in rhesus monkeys was found to
be 18.8 mg/kg with mean arterial plasma concentration of 24.4 µg/mL. The intravenous and
subcutaneous LD 50 in mice is 23 mg/kg to 35 mg/kg and 280 mg/kg respectively.
Protein Binding: Mepivacaine is approximately 75% bound to plasma proteins. Generally, the
lower the plasma concentration of drug, the higher the percentage of drug bound to plasma.
Biotransformation: Rapidly metabolized, with only a small percentage of the anesthetic (5
percent to 10 percent) being excreted unchanged in the urine. The liver is the principal site of
metabolism, with over 50% of the administered dose being excreted into the bile as metabolites.
Half Life: The half-life of mepivacaine in adults is 1.9 to 3.2 hours and in neonates 8.7 to 9
hours.
Dosage Forms of Isocaine HCL: Solution Subcutaneous
Solution Infiltration
Liquid Infiltration
Chemical IUPAC Name: N-(2,6-dimethylphenyl)-1-methylpiperidine-2-carboxamide
Chemical Formula: C15H22N2O
Mepivacaine on Wikipedia: http://en.wikipedia.org/wiki/Mepivacaine
Organisms Affected: Humans and other mammals