Nothing

1. Anesthetics
GK

5. Local anesthetics (LAs) are drugs that block the sensation of pain in the
region where they are administered. LAs act by reversibly blocking
the sodium channels of nerve fibers, thereby inhibiting the conduction of
nerve impulses.
Nerve fibers that carry pain sensation have the smallest diameter and are the
first to be blocked by LAs. Loss of motor function and sensation of touch and
pressure follow, depending on the duration of action and dose of the LA
used.
LAs can be infiltrated into skin/subcutaneous tissues to achieve local
anesthesia or into the epidural/subarachnoid space to achieve regional
anesthesia(e.g., spinal anesthesia, epidural anesthesia).

6. All local anesthetics have a similar chemical structure,
which consists of three components: aromatic portion,
intermediate chain, and amine group. Structurally, all
local anesthetics include a lipophilic group joined by an
amide or ester linkage to a carbon chain, which, in turn,
is joined to a hydrophilic group.
The intermediate chain, which connects the aromatic
and amine portions, is composed of either an ester or
an amide linkage.
This intermediate chain can be used in classifying local
anesthetics into esters and amides.
Ester-type local anesthetics have a very short plasma
half-life. They are metabolized by plasma
butyrylcholinesterase. In patients with decreased or
atypical cholinesterase, the plasma levels of these
anesthetics may be higher than usual.

12. Some LAs (lidocaine, prilocaine, tetracaine) are effective on topical application and are used
before minor invasive procedures (venipuncture, bladder catheterization,
endoscopy/laryngoscopy).
LAs are divided into two groups based on their chemical structure.
The amide group (lidocaine, prilocaine, mepivacaine, etc.) is safer and, hence, more
commonly used in clinical practice.
The ester group (procaine, tetracaine) has a higher risk of causing allergic reactions or
systemic toxicity and is therefore reserved for patients with known allergies to drugs of the
amide group.
Local anesthetic systemic toxicity may result from intravascular injection or administration
of LA that exceeds the maximum recommended local anesthetic dose. Toxicity may affect
the CNS (e.g., tinnitus, seizures) or cardiovascular system (e.g., arrhythmias, cardiac arrest).

19. •Clinical applications:
• Topical anesthesia (e.g., lidocaine, tetracaine, prilocaine)
• Infiltration anesthesia
• Skin surgery (e.g., skin biopsy)
• Epidural anesthesia
• Spinal anesthesia
•Pharmacology
• LAs have a lipophilic group linked with a hydrophilic group by a hydrocarbon chain
chain
• Bind to the inner portion of voltage-gated sodium channels of the nerve fibers
→ reversible blockage of sodium channels → inhibition of nerve excitation and
impulse conduction (pain signals)
•Adverse effects
• Allergy (acute anaphylaxis or delayed pruritic rash)
• Cross-reactivity between amide group and ester group agents is very rare.
• If a patient has an allergy to one group, prescribe agents from the other group.
group.
• Local anesthetic systemic toxicity (LAST)
• Methemoglobinemia (mostly with benzocaine)

20. Delivery techniques of local anesthetics
topical administration, infiltration, perineural, and neuraxial (spinal, epidural, or caudal) blocks.
Regional anesthesia: It makes a specific part of the body numb to relieve pain or allow surgical procedures to be
done. Local anesthetics are safer than general or systemic anesthetics;
Surface anesthesia: It is used during ocular tonometry, intubation, and endoscopic procedures. Tetracaine 2% and
lidocaine 2% to 4% are used
Infiltration anesthesia: The local anesthetic is injected directly into the skin or deeper structures to carry out
incision, excision, hydrocoele, incision and drainage of an abscess, etc. Lignocaine and bupivacaine are generally
used for infiltration anesthesia.
Field block: The local anesthetic is injected subcutaneously proximal to the site where anesthesia is desired. All
nerves distal to the site of injection are blocked. Lidocaine (1% to 2%) is used for intermediate duration of anesthesia
in dental extraction, operation on forearms, legs.
Nerve block: The local anesthetic is injected around a nerve plexus or a nerve trunk. This results in a large area of
anesthesia. Lidocaine is most commonly used apart from bupivacaine. Intercostal, sciatic, brachial plexus, facial, and
phrenic are commonly performed nerve blocks.
Spinal anesthesia: A single dose of the local anesthetic is injected into the subarachnoid space in the lower end of
the spinal cord (lumbar region). The site of action is nerve roots, resulting in loss of pain sensation and paralysis of
the lower abdomen and hind limbs. Lidocaine, bupivacaine, and tetracaine are most commonly used for spinal
anesthesia. Spinal anesthesia is associated with complications such as respiratory paralysis, hypotension, headache,
nausea, bradycardia, and septic meningitis. It is used during operations on lower limbs, pelvis, lower abdomen, etc.
Epidural anesthesia: The local anesthetic is injected into the epidural space where it acts upon the nerve roots and
relieves pain from large areas of the body by stopping pain signals traveling along the nerves in the spine. Epidural
anesthesia is used during labor to relieve pain or during a cesarean section.

22. Epidural anesthesia
Definition
•Local anesthetics with or without opioids and alpha-adrenergic agonists are
injected into the epidural space and act on the spinal nerve roots.
•Epidural anesthesia blocks several nerve roots around the site of injection
and barely affects the function of the nerve rootsabove and below
(segmental anesthesia).
Indications
•Used for a variety of surgeries of the lower body (e.g., cesarean
delivery, hernia repair, appendectomy, prostate and bladder
surgeries, knee surgery)
•During labor
•Perioperatively
•Chronic pain management (e.g., spinal stenosis, disk herniation)

23. Spinal anesthesia
Definition
•Local anesthetics with or without opioids and alpha-adrenergic agonists are injected into
the cerebrospinal fluid (CSF) in the lumbar spine and act directly on the spinal cord
•Combined spinal and epidural anesthesia (CSE)
• Combines the advantages of spinal anesthesia (rapid action, motoric block) with the advantages
of epidural anesthesia(favorable post-operative pain management via an epidural catheter)
• Plays a major role in obstetrics and orthopedics.
Indications
Used for a variety of lower extremity, lower abdominal, pelvic, and perineal procedures (e.g., cesarean
delivery, hip and knee replacement), e.g:
•Cesarean delivery: T4–6 (mamillary line)
•Pelvic, urethral, and renal pelvic surgery: T6–8 (xiphoid)
•Transurethral surgery including stretching of the bladder, vaginal birth, hip surgery: T10 (navel)
•Transurethral surgery without stretching of the bladder: L1 (inguinal ligament)
•Knee and foot surgery: L2/3
•Perineal surgery: S2–5

24. •Pain pathway: thermal, mechanical, or chemical stimuli → nociceptor stimulation → conversion of stimulus to an electric
signal (action potential) → neural conduction of electric signal to the CNS → perception of pain
•LAs bind to the inner portion of voltage-gated sodium channels of the nerve fibers → reversible blockage
of sodiumchannels → inhibition of nerve excitation and impulse conduction (pain signals) → local anesthesia in the area
supplied by the nerve
•LAs with 3° amine structure infiltrate membranes in their uncharged form, then bind to ion channels in their charged
form.
•The susceptibility of nerve fibers to LA depends on their firing rate, size, and myelination.
• Rapidly firing neurons are blocked more effectively than slow-firing neurons.
• Small diameter nerves are the first to be anesthetized.
• Myelinated nerves are blocked faster than unmyelinated nerves.
• Because size is thought to outweigh myelination, nerve fibers are blocked in the following order:
• Small myelinated fibers
• Small unmyelinated fibers
• Large myelinated fibers
• Large unmyelinated fibers
• Loss of sensation occurs in the following order:
• Pain
• Temperature
• Touch
• Pressure

25. •Factors that affect the efficacy of LA
• Use of vasoconstrictors (e.g., adrenaline) reduces bleeding and
systemic absorption of LAs, leading to a prolonged anesthetic effect.
• Inflamed/infected tissue: decreased efficacy of LAs
• LAs are composed of a lipophilic group and a hydrophilic group,
and permeability depends on which group is predominant.
• Because inflamed tissue has an acidic environment,
alkaline anesthetics are charged and
the hydrophilic group predominates → ↓ ability to penetrate the
nerve cell membranes → ↓ efficacy

30. Local anesthetic systemic toxicity (LAST)
LAST is a potentially fatal adverse event caused by dose-dependent LA blockade of sodium channels in the CNS and cardiovascular

31. Management
•Primary survey
• Call for help.
• Secure the airway and start 100% oxygen therapy.
• Treat acute seizures preferentially with benzodiazepines.
•Hemodynamic instability: Start lipid emulsion therapy.
• LAST-induced cardiac arrest: Provide ACLS with the following modifications.
• Administer low-dose epinephrine (≤ 1 mcg/kg).
• Treat shockable rhythms with amiodarone; avoid lidocaine.
• Consider cardiopulmonary bypass or ECMO early in refractory arrest.
• Shock: Low-dose epinephrine is the preferred vasopressor; avoid vasopressin.
• Tachyarrhythmias
• Amiodarone is the preferred antiarrhythmic.
• Avoid lidocaine, procainamide, CCBs, and beta blockers.
•Disposition
• Continuous cardiac monitoring for a minimum of:
• 4–6 hours following resolution of arrhythmia or shock
• 2 hours following seizure termination
• Admit all patients with ROSC after cardiac arrest to ICU.

32. •Definition: the loss of sensation to skin or mucosa by direct application of a local anesthetic
agent (e.g., in the form of a gel, ointment, spray, or patch)
•Indications: typically used for superficial and localized procedures, particularly in children
• Good for anesthetizing small lacerations, intact skin, or mucus membranes
• Common applications include minor wound repair, peripheral IV placement, and foley
catheter placement
•Choice of agent is based on the intended location, e.g.:
• Skin: eutectic mixture of local anesthetic (EMLA)
cream, lidocaine/epinephrine/tetracaine (LET) gel
• Ophthalmic: tetracaine, proparacaine
• Oropharyngeal: benzocaine spray, viscous lidocaine
• Genitourinary: viscous lidocaine
Topical Anesthesia

38. A. Induction
General anesthesia in adults is normally induced with an IV agent such
as propofol, producing unconsciousness in 30 to 40 seconds.
Often an IV neuromuscular blocker such as rocuronium, vecuronium, or
succinylcholine is administered to facilitate endotracheal intubation by
eliciting muscle relaxation.
For children without IV access, nonpungent volatile agents, such as
sevoflurane, are administered via inhalation to induce general
anesthesia.

40. Sugammadex
Sugammadex is a selective relaxant-binding agent that terminates the
action of both rocuronium and vecuronium.
Its three-dimensional structure traps the neuromuscular blocker in a
1:1 ratio, terminating its action and making it water soluble.
It is unique in that it produces rapid and effective reversal of both
shallow and profound neuromuscular blockade.
Sugammadex is eliminated via the kidneys.

41. Maintenance of anesthesia
After administering the induction drug, vital signs and response to
stimuli are vigilantly monitored to balance the amount of drug
continuously inhaled or infused to maintain general anesthesia.
Maintenance is commonly provided with volatile anesthetics,
although total intravenous anesthesia (TIVA) with drugs such as
propofol can be used to maintain general anesthesia.
Opioids such as fentanyl are used for analgesia along with
inhalation agents, because the latter alter consciousness but not
perception of pain.

42. After cessation of the maintenance anesthetic drug, the patient is
evaluated for return of consciousness.
For most anesthetic agents, redistribution from the site of action (rather
than metabolism of the drug) underlies recovery.
Neuromuscular blocking drugs are typically reversed after completion
of surgery, unless enough time has elapsed for their metabolism.
The patient is monitored to assure full recovery of all normal
physiologic functions (spontaneous respiration, blood pressure, heart
rate, and all protective reflexes)
Recovery

43. 1.Stage I—Analgesia: Loss of pain sensation results from interference
with sensory transmission in the spinothalamic tract. The patient
progresses from conscious and conversational to drowsy. Amnesia and
reduced awareness of pain occur as stage II is approached.
2. Stage II—Excitement: The patient displays delirium and possibly
combative behavior. A rise and irregularity in blood pressure and
respiration occur, as well as a risk of laryngospasm. To shorten or
eliminate this stage, rapid-acting IV agents are given before inhalation
anesthesia is administered.
3. Stage III—Surgical anesthesia: There is gradual loss of muscle tone
and reflexes as the CNS is further depressed. Regular respiration and
relaxation of skeletal muscles with eventual loss of spontaneous
movement occur. This is the ideal stage of surgery. Careful monitoring is
needed to prevent undesired progression to stage IV.
4. Stage IV—Medullary paralysis: Severe depression of the respiratory
and vasomotor centers occurs. Ventilation and/or circulation must be
supported to prevent death.

46. •Thiopental
•Methohexital
Mechanism of action
•Enhanced GABA action → enhanced duration
of chloride channel opening and hyperpolarization of
postsynaptic neurons→ ↓ neuronal excitability in the
brain
•High potency, highly-lipid soluble → rapid onset of
action due to quick transfer across the blood-
brain barrier → brief recovery time due to redistribution
redistribution into skeletal muscles and adipose tissue
Effects
•Hypnotic effects
•↓ Intracranial pressure due to reduced cerebral blood
flow
•Little to no analgesic or muscle relaxant effects
Side effects
•Hypotension (dose-dependent)
•Respiratory
depression and/or apnea (dose-
dependent)
•Laryngospasm, bronchospasm (due
to histamine release)
•Myoclonus
•Painful injection
•Visual hallucinations
•Vivid dreams
•Bradycardia, arrhythmias
•Cytochrome P450 induction

47. Indications
•IV anesthesia induction (esp. short procedures with minimal pain and high risk of raised
intracranial pressure)
•Reduction of intracranial pressure for brain edema following trauma or surgery
•Sedation for electroconvulsive therapy (e.g., methohexital)
•Convulsion during or after anesthesia
Contraindications
•Hypersensitivity
•Severe cardiovascular decompensation; conditions in which a decrease in blood pressure
would be hazardous
•Porphyria
•Addison disease
•Liver or kidney disease
•Severe anemia
•Thyroid disorders
•Myasthenia gravis
•Asthma

49. Propofol
Propofol is an IV sedative/hypnotic used for induction and/or maintenance of
anesthesia. It is widely used and has replaced thiopental as the first choice for
induction of general anesthesia and sedation.
Because propofol is poorly water soluble, it is supplied as an emulsion containing
soybean oil and egg phospholipid, giving it a milk-like appearance.
Onset:
Induction is smooth and occurs 30 to 40 seconds after
administration.
Plasma levels decline rapidly as a result of
redistribution, followed by a more prolonged period of
hepatic metabolism and renal clearance.
The initial redistribution half-life is 2 to 4 minutes.
The pharmacokinetics of propofol are not altered by
moderate hepatic or renal failure.

50. Actions: Although propofol depresses the CNS, it occasionally contributes to excitatory
phenomena, such as muscle twitching, spontaneous movement, yawning, and hiccups.
Propofol
• Transient pain at the injection site is common.
• decreases blood pressure without significantly depressing the myocardium.
• It also reduces intracranial pressure, mainly due to decreased cerebral blood flow and oxygen
consumption.
• It has less of a depressant effect than volatile anesthetics on CNS-evoked potentials, making it
useful for surgeries in which spinal cord function is monitored.
• It does not provide analgesia, so supplementation with narcotics is required.
• Propofol is commonly infused in lower doses to provide sedation.
• The incidence of postoperative nausea and vomiting is very low secondary to its
antiemetic properties.

51. Side effects
•Hypotension (dose-dependent)
•Respiratory depression (dose-dependent)
•Anaphylaxis (esp. in patients with allergies to soy or egg products )
•Pain on injection
•Propofol infusion syndrome
• Etiology: high doses and prolonged administration of propofol
• Clinical features: severe metabolic acidosis, rhabdomyolysis, renal
failure, and/or cardiac failure (often fatal)
• Diagnostics: Patients undergoing prolonged propofol treatment
should have triglycerides monitored at least every 3 days, as
increased triglyceride levels correlate with development of propofol
the presence in the blood of an abnormally high
concentration of emulsified fat.

56. Mechanism of action
•Not fully understood. Propofol is thought to act as
as
an agonist on GABAA receptors and sodium channe
els of the reticular formation.
Effects
•Hypnotic effects
•Antiemetic
•Antipruritic
•Anticonvulsant
•Bronchodilation
•↓ Intracranial pressure
•No analgesic or muscle relaxant effects
Indications
•Standard for anesthesia induction
•Total intravenous
anesthesia (TIVA)
• A technique for induction
and maintenance of general
anesthesia using IV drugs alo
ne.
• Propofol is the drug of
choice, especially for patients
with an intermediate to high
risk of postoperative nausea
and vomiting (PONV).

57. Etomidate
Etomidate is a hypnotic agent used to induce anesthesia, but it lacks
analgesic activity.
Its water solubility is poor, so it is formulated in a propylene glycol
solution. Induction is rapid, and the drug is short-acting.
Among its benefits are little to no effect on the heart and systemic
vascular resistance.
Etomidate is usually only used for patients with cardiovascular
dysfunction or patients who are acutely critically ill.
It inhibits 11-β hydroxylase involved in steroidogenesis, and adverse
effects may include decreased plasma cortisol and aldosterone
levels. Etomidate should not be infused for an extended time, because
prolonged suppression of these hormones is dangerous.
Injection site pain, involuntary skeletal muscle movements, and nausea
and vomiting are common.

58. Mechanism of action
•Acts on the GABA receptors in the reticular formation
•Rapid onset and recovery
Effects
•Hypnotic effects
•↓ Intracranial pressure
•Anticonvulsant effects
•Little to no effect on the cardiovascular system
•No analgesic or muscle relaxant effect
Side effects
•Transient acute adrenal insufficiency (due to adrenal cortex suppression → reduced cortisol production)
•Postoperative nausea and vomiting
•Painful injection (avoid by administering an opioid prior to injection)
•Myoclonus
Indications
Anesthesia for patients with hemodynamic instability
Of all the IV anesthetics, etomidate has the least impact on
the cardiovascular system.

59. Ketamine
 Ketamine, a short-acting anti-NMDA receptor anesthetic and analgesic, induces a dissociated state in
which the patient is unconscious (but may appear to be awake) with profound analgesia.
 Ketamine stimulates central sympathetic outflow, causing stimulation of the heart with increased blood
pressure and CO. It is also a potent bronchodilator.
 Therefore, it is beneficial in patients with hypovolemic or cardiogenic shock as well as asthmatics.
Conversely, it is contraindicated in hypertensive or stroke patients.
 The drug is lipophilic and enters the brain very quickly.
 Like the barbiturates, it redistributes to other organs and tissues.
 Ketamine has become popular as an adjunct to reduce opioid consumption during surgery.
 Of note, it may induce hallucinations, particularly in young adults, but pretreatment with
benzodiazepines may help.
 Ketamine may be used illicitly, since it causes a dream-like state and hallucinations similar to
phencyclidine (PCP).

60. Mechanism of action
•NMDA receptor antagonist
•Belongs to the arylcyclohexylamines class
•Rapid onset
Effects
•Dissociative anesthesia: unique anesthetic state with analgesia, intact spontaneous breathing, amnesia, and
no complete loss of consciousness
•Strong analgesia
•Bronchodilation
•Sympathomimetic effects: ↑ blood pressure, ↑ heart rate, ↑ cardiac output
•Increases cerebral blood flow
Side effects
•Nystagmus
•↑ Oxygen demand and ↑ pulmonary arterial pressure
•↑ Intracranial pressure due to increased cerebral blood flow
•Acute psychotomimetic effects: disorientation, hallucinations, vivid dreams,
nightmares, and/or abnormal EEG (concomitant administration of benzodiazepines is recommended to
avoid these effects)
•Rapid injection or high doses can lead to respiratory depression.
•↑ Salivation

61. Indications
•Ideal emergency anesthetic for polytrauma patients and other
patients with risk of hypotension (no cardiovascular depression)
depression)
•Treatment-resistant asthma
•Short painful procedures (e.g., fracture reduction)
•Treatment-resistant depression

63. Because of their analgesic property, opioids are commonly
combined with other anesthetics.
The choice of opioid is based primarily on the duration of
action needed. The most commonly used opioids are
fentanyl and its congeners, sufentanil and remifentanil
because they induce analgesia more rapidly than
morphine. They may be administered intravenously,
epidurally, or intrathecally.
Opioids are not good amnestics, and they can all cause
hypotension and respiratory depression, as well as nausea
and vomiting. Opioid effects can be antagonized by
naloxone.
Opioids – for analgesia

64.  Intravenous anesthetics are a group of fast-acting compounds that are used to induce a
state of impaired awareness or complete sedation.
 Commonly used intravenous anesthetics include propofol, etomidate, ketamine,
and barbiturates (e.g., thiopental).
 Propofol is the standard drug for induction of anesthesia and etomidate is most commonly
used in cases of hemodynamic instability.
 Ketamine plays a key role in emergency medicine because of its strong
dissociative, sympathomimetic, and analgesic effects.
 The barbiturate thiopental reduces intracranial pressure, making it useful in patients with
high intracranial pressure and/or head trauma.
 While the characteristics and side effects of intravenous anesthetics are highly dependent
on the substance involved, they all share a strong hypnotic effect.

65. Inhalational anesthetics are used for the induction and maintenance of general
anesthesia as well as sedation. The exact mechanisms by which they act are
still unknown.
The most common inhalational anesthetics are sevoflurane, desflurane,
and nitrous oxide.
Of these, sevoflurane is the most common because of its rapid onset of action
and the fact that patients recover quickly from it.
Inhalational anesthetics cause respiratory depression, a decrease in arterial
blood pressure and cerebral metabolic demand, and an increase in cerebral
blood flow. While side effects differ based on the substance
(e.g., halothane can cause hepatotoxicity), the most common side effect is
nausea.

79. Common features of inhalation anesthetics
Modern inhalation anesthetics are nonflammable, nonexplosive
agents, which include nitrous oxide and volatile, halogenated
hydrocarbons.
These agents decrease cerebrovascular resistance, resulting in
increased brain perfusion. They cause bronchodilation but also
decrease both respiratory drive and hypoxic pulmonary
vasoconstriction (increased pulmonary vascular resistance in poorly
oxygenated regions of the lungs, redirecting blood flow to better
oxygenated regions).
Movement of these gases from the lungs to various body
compartments depends upon their solubility in blood and tissues, as
well as on blood flow. The following factors play a role in induction
and recovery.

81. General effects
•Anesthesia
•Sedation/narcosis
•↓ Respiration
•↓ Arterial blood pressure
•Myocardial depression
•↓ Cerebral metabolic demand
•↑ Cerebral blood flow
•↑ ICP
•Postoperative: nausea and
vomiting

83. Potency is defined quantitatively as the minimum alveolar concentration
(MAC), which is the end-tidal concentration of inhaled anesthetic needed to
eliminate movement in 50% of patients exposed to a noxious stimulus.
MAC is the median effective dose (ED50) of the anesthetic, expressed as the
percentage of gas in a mixture required to achieve that effect. Numerically,
MAC is small for potent anesthetics such as isoflurane and large for less
potent agents such as nitrous oxide. Thus, the inverse of MAC is an index of
potency.
Nitrous oxide alone cannot produce general anesthesia because any
admixture with a survivable oxygen percentage cannot not reach its MAC
value. The more lipid soluble an anesthetic, the lower the concentration
needed to produce anesthesia and, therefore, the higher the potency.
Factors that can increase MAC (make the patient more resistant) include
hyperthermia, drugs that increase CNS catecholamines, and chronic ethanol
abuse.
Factors that can decrease MAC (make the patient more sensitive) include
increased age, hypothermia, pregnancy, sepsis, acute intoxication,
concurrent IV anesthetics, and α2-adrenergic receptor agonists (clonidine
and dexmedetomidine).

86. Nitrous oxide (“laughing gas”) is a nonirritating potent sedative that is unable to create a state of general
anesthesia.
It is frequently used at concentrations of 30% to 50% in combination with oxygen to create moderate sedation,
particularly in dentistry.
Nitrous oxide does not depress respiration and maintains cardiovascular hemodynamics as well as muscular
strength.
Nitrous oxide can be combined with other inhalational agents to establish general anesthesia, which lowers the
required concentration of the combined volatile agent.
This gas admixture further reduces many unwanted side effects of the other volatile agent that impact
cardiovascular output and cerebral blood flow.
Nitrous oxide is poorly soluble in blood and other tissues, allowing it to move very rapidly in and out of the body.
This can be problematic in closed body compartments because nitrous oxide can increase the volume
(exacerbating a pneumothorax) or pressure (sinus or middle ear pressure);
it replaces nitrogen in various air spaces faster than the nitrogen leaves.
Its speed of movement allows nitrous oxide to retard oxygen uptake during recovery, thereby causing “diffusion
hypoxia.” This can be overcome by delivering high concentrations of inspired oxygen during recovery.

87. Mechanism of action
No specific receptor has been identified as the locus to create a state of general
anesthesia.
The fact that chemically unrelated compounds produce unconsciousness argues
against the existence of a single receptor, and it appears that a variety of molecular
mechanisms may contribute to the activity of anesthetics.
At clinically effective concentrations, general anesthetics increase the sensitivity of
the γ-aminobutyric acid (GABAA) receptors to the inhibitory neurotransmitter GABA.
This increases chloride ion influx and hyperpolarization of neurons. Postsynaptic
neuronal excitability and, thus, CNS activity are diminished.
Unlike other anesthetics, nitrous oxide and ketamine do not have actions on GABAA
receptors. Their effects are mediated via inhibition of N-methyl-d-aspartate (NMDA)
receptors. [Note: The NMDA receptor is a glutamate receptor, which is the body’s
main excitatory neurotransmitter.]
Receptors other than GABA that are affected by volatile anesthetics include the
inhibitory glycine receptors found in the spinal motor neurons. Additionally,
inhalation anesthetics block excitatory postsynaptic currents found on nicotinic
receptors. However, the mechanisms by which anesthetics perform these
modulatory roles are not fully understood.

91. Halothane
is a noninflammable, nonirritant, photosensitive volatile agent with a sweet smell. It is a liquid at room temperature
and it is administered with a special vaporizer at a concentration of 2% to 4% for induction followed by 0.5% to 1%
for maintenance.
A precise control of the concentration of halothane is essential as it can cause direct effect on heart by interfering
with calcium, thus causing depression of myocardial contractility.
Dose-dependent fall in blood pressure is known during halothane anesthesia.
It directly suppresses respiratory centers, thereby reducing ventilatory response to blood carbon dioxide levels.
Decreased alveolar ventilation can cause increase in arterial CO2 levels without compensatory increase in
ventilation.
Therefore, continuous arterial gas monitoring is essential during its usage.
Halothane dilates cerebral blood vessels and increases cerebral blood flow which in turn causes increased
intracranial pressure, especially in patients with other susceptible comorbid conditions in the brain. It causes
relaxation of skeletal muscle and potentiates the actions of competitive neuromuscular blockers.

92. Halothane causes uterine smooth muscle relaxation.
Although it is useful for the manipulation of fetus orientation, it is not
used due to its action of inhibiting uterine contraction during parturition.
Therefore, it is not used for vaginal delivery.
More than 60% of the inhalationally administered halothane is
eliminated through lungs on recovery within 24 hours.
The rest of halothane is metabolized by liver.
Trifluoroacetic acid is a major metabolite which can cause hepatic
injury (halothane-induced hepatic necrosis).
This syndrome of hepatic necrosis is reported in 1 in 10,000 patients
and it is referred to as “halothane hepatitis.”

93. Isoflurane
Isoflurane, like other halogenated gases, produces dose-dependent hypotension predominantly from
relaxation of systemic vasculature.
Hypotension can be treated with a direct-acting vasoconstrictor, such as phenylephrine.
Because it undergoes little metabolism, isoflurane is considered nontoxic to the liver and kidney.
Its pungent odor stimulates respiratory reflexes (breath holding, salivation, coughing, laryngospasm), so
it is not used for inhalation induction.
With a higher blood solubility than desflurane and sevoflurane, isoflurane takes longer to reach
equilibrium, making it less ideal for short procedures;
however, its low cost makes it a good option for longer surgeries.

94. Desflurane
Desflurane provides very rapid onset and recovery due to low blood solubility.
This makes it a popular anesthetic for short procedures.
It has a low volatility, which requires administration via a special heated
vaporizer.
Like isoflurane, it decreases vascular resistance and perfuses all major tissues
very well.
Desflurane has significant respiratory irritation like isoflurane so it should not be
used for inhalation induction. Its degradation is minimal and tissue toxicity is
rare. Higher cost occasionally prohibits its use.

95. Sevoflurane
 Sevoflurane has low pungency or respiratory irritation.
 This makes it useful for inhalation induction, especially with
pediatric patients who do not tolerate IV placement.
 It has a rapid onset and recovery due to low blood solubility.
 Sevoflurane has low hepatotoxic potential, but compounds
formed from reactions in the anesthesia circuit (soda lime)
may be nephrotoxic with very low fresh gas flow that allows
longer chemical reaction time.

99. General side effects
•Postoperative nausea and vomiting
•Risk of malignant hyperthermia (except nitrous oxide)
•Postoperative shivering
Side effects of specific substances
•Nitrous oxide
• Can diffuse into gas-filled body compartments and cause expansion of the gas present there → potential damage to
organs/tissues
• Causes mild myocardial depression and increases pulmonary vessel resistance
•Desflurane: sympatho-adrenergic reaction → ↑ blood pressure and ↑ heart rate
•Sevoflurane: interacts with soda lime → nephrotoxic breakdown products (known as compounds A–E)
•Methoxyflurane: nephrotoxic
•Enflurane: proconvulsive
•Halothane: hepatotoxic → halothane hepatitis
• Pathophysiology: underlying mechanism not fully understood
• Clinical features
• Occurs 2 days to 3 weeks after halothane exposure
• Signs of acute hepatitis (e.g., jaundice, fever, vomiting, hepatomegaly)
• Rash, arthralgias
• Diagnostics: diagnosis of exclusion
• Possible laboratory findings: ↑ eosinophils, ↑ serum transaminases , ↑ bilirubin, ↑ alkaline phosphatase
• Biopsy shows massive centrilobular hepatic necrosis
• Treatment: depending on the severity of liver damage, ranges from supportive treatment to liver transplantation