Anesthesia

PHS 310
Week 6
Objectives of
lecture
1 2 3 4
Explain basic Explain broad Study classification Describe major
principles of mechanisms of of features of
general anesthesia action general anesthetics anesthetic drugs
 Anesthesia
• For patients undergoing surgical or medical procedures, different
levels of sedation can provide important benefits
• to facilitate procedural interventions. These levels of sedation
range from anxiolysis to general anesthesia and can create:
• Sedation and reduced anxiety
• Lack of awareness and amnesia
• Skeletal muscle relaxation
• Suppression of undesirable reflexes ‫قمع ردود الفعل غير المرغوب فيها‬
• Analgesia
General anesthesia

• General anesthesia is a reversible state of central nervous

system (CNS) depression, causing loss of response to and
perception of stimuli. ، ‫مما تسبب في فقدان االستجابة للمحفزات وإدراكها‬.

• Because no single agent provides all desired objectives, several

categories of drugs are combined to produce the optimum level
of sedation required (adjunct agents)
‫المواد االفيونيه‬
 Adjunct
agents
• H2 blockers to reduce gastric acidity
• Benzodiazepines (e.g., diazepam) to relieve anxiety and facilitate amnesia
• Nonopioids or opioids (e.g., fentanyl) for analgesia
• Antihistamines to prevent allergic reactions
• Antiemetics to prevent nausea
• Anticholinergics (e.g., atropine) to prevent bradycardia and secretion of fluids into the
respiratory tract
• Neuromuscular blockers to provide muscle relaxation.
Pre-medications facilitate smooth induction of anesthesia and lower required anesthetic
doses.
 Anesthesia
• General anesthetics • Local anesthetics
• Inhaled anesthetics • Amides
• Halothane • Lidocaine
• Isoflurane • Prilocaine (dental anesthetic)
• Desflurane • Bupivacaine
• Sevoflurane • Mepivacaine
• Nitric oxide • Ropivacaine
• IV • Esters
• Propofol • Procaine
• Barbiturates (thiopental) • Chloroprocaine
• Benzodiazepines • Tetracaine
• Opioids (fentanyl)
• Etomidate
• Ketamine
• Dexmedetomidine
General anesthesia

Inhaled anesthetics
Inhalation and/or (except for nitrous
intravenous (IV) oxide) are
injection halogenated
hydrocarbons
 Stages of anesthesia

General anesthesia has three stages: induction, maintenance, and

recovery.
• Induction is the time from administration of a potent anesthetic
to development of effective‫المستمر‬
anesthesia
‫التخدير‬
(IV anesthetic)
• Maintenance provides sustained anesthesia (inhaled anesthetic)
‫وقف‬
• Recovery is the time from discontinuation of anesthetic until
‫ وعي‬consciousness and protective reflexes return.

 Rapid induction and recovery.

Depth of anesthesia
‫االثاره‬
• Depth of anesthesia is the degree
‫هذيان‬
to which the CNS is depressed
Inhalation anesthetics
 Inhalation anesthetics
• Inhaled gases are used primarily for maintenance of anesthesia after
administration of an IV agent
• Depth of anesthesia can be rapidly altered by changing the inhaled
concentration. Inhalational agents have very sharp dose–response
curves and very narrow therapeutic indices, so the difference in
concentrations causing surgical anesthesia and severe cardiac and
respiratory depression is small.
• Require close monitor
• No antagonists exist
Potency
‫اللسان وسقف الفم‬
Measured by minimum alveolar concentration (MAC)

MAC= concentration that prevents movement in 50%

of patients in response to standardized stimulus
‫تحفيز موحد‬

Expressed as the percentage of gas in a mixture

required to achieve that effect
‫عكسيا‬
Potency is inversely related to MAC (small for
potent
anesthetics)
 Pharmacokinetics

Uptake and Distribution

1-Partial pressure (P)
• The principal objective of inhalation anesthesia is a constant and optimal brain partial
pressure (Pbr) of inhaled anesthetic (to create a partial pressure equilibrium between
alveoli [Palv] and brain [Pbr]). ‫عملية ومجدية‬ ‫أيقن‬
• Measuring the Palv is the most practical and feasible way to ascertain the Pbr for the
inhaled anesthetic concentration, but this necessitates adequate time for the two
‫يتطلب‬
compartments to reach equilibrium.
• Palveoli = Pblood = Pbr > steady state
• The partial pressure of an anesthetic gas that originates by pulmonary entry is the driving force moving
the gas from the alveolar space into the bloodstream (Pa), which transports the drug to the brain and
other body compartments.
 2- Solubility in
blood
• Is determined by a physical property of the anesthetic called the blood:gas partition
coefficient (the ratio of the concentration of anesthetic in the liquid [blood] phase to the
concentration of anesthetic in the gas phase when the anesthetic is in equilibrium between
the two phases
• Solubility of inhaled anesthetics determines > speed of induction and recovery
Anesthetic gas with low blood solubility > diffuses from the alveoli into the circulation
rapidly, little anesthetic dissolves in the blood.
• Rapid induction and recovery
• Higher blood/gas partition coefficient
• Slower induction and recovery
Solubilit
y
• Desflurane and sevoflurane (newer
agents) provide rapid onset and
recovery due to low blood solubility.
• Isoflurane > higher blood solubility
typically used only when cost is a
factor.
Mechanisms of
action
• 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.

• GABA is the main inhibitory neurotransmitters

Mechanisms of action

• Other mechanisms:
• Inhibition of the N-methyl-d-aspartate (NMDA) receptors.
 NMDA receptor is a glutamate receptor.
 Glutamate is the main excitatory neurotransmitter
• Examples of general anesthetic work on NMDA receptor > nitrous oxide and
ketamine
 Halothane

Prototype anesthetic
• Was anesthetic of choice.
• However, it has been replaced in most countries > due to adverse effects
and the availability of other anesthetics with fewer complications
Halothane

Pharmacokinetics
Metabolism > toxic metabolites > hepatic necrosis
All halogenated inhalation anesthetics > hepatitis, but at a much
lower incidence than with halothane
 Adverse
effects

• Cardiac effects:
• Cardiac arrhythmias (sensitize the heart to catecholamines)> halothane only.
• Halogenated anesthetics > concentration-dependent hypotension and
bradycardia.
• Liver and kidney
• Release of fluoride, bromide, and other metabolites of halogenated hydrocarbons
can affect these organs, especially if they accumulate with frequently repeated
administration of anesthetics.
Adverse
effects

Respiratory system
• Inhaled agents depress respiration (decrease spontaneous
ventilation) but also act as bronchodilators.
• IV anesthetics and opioids suppress respiration.
 Adverse
effects

• Malignant hyperthermia
• A rare life-threatening condition
• A severe and uncontrolled increase in skeletal muscle oxidative metabolism >
exceed the body’s capacity to supply oxygen, remove carbon dioxide, and
regulate temperature > eventually leading to circulatory collapse and death if
not treated immediately
• Susceptibility > inherited as an autosomal dominant disorder (genetic
disorder).
Malignant hyperthermia management

• Dantrolene
• Blocks release of Ca2+ from the muscle cells > reducing
heat production and relaxing muscle tone.
• D/C anesthetic and cool the patient.
Isofluran
e

• Little metabolism > not toxic to the liver or kidney.

• It has a pungent odor and stimulates respiratory reflexes
• (e.g., breath holding, salivation, coughing, laryngospasm) > not
used for inhalation induction.
• Higher blood solubility.
Desfluran
e

• It provides very rapid onset and recovery due to low blood

solubility.
• Its degradation is minimal and tissue toxicity is rare.
• Required a special machine for delivery.
• It stimulates respiratory reflexes > not used for inhalation
induction.
• It is relatively expensive and thus rarely used for
maintenance during extended anesthesia.
Sevofluran
e

• It has low pungent odor, allowing rapid induction without

irritating the airways.
• This makes it suitable for inhalation induction in pediatric
patients.
• It has a rapid onset and recovery due to low blood
solubility.
• It is metabolized by the liver > metabolites may be
nephrotoxic.
Characteristic
of some
inhaled
anesthesia
Nitrous
oxide

• Known as laughing gas

• Non-irritating
• Potent analgesic but a weak general anesthetic
• It is frequently used in dental clinics
• Low potency > combined with other more potent agents for
surgical anesthesia
• Poor solubility in blood > rapid induction and recovery.
Nitrous
oxide

• Does not depress respiration

• Moderate to no effect on the cardiovascular system
• The least hepatotoxic of the inhalation agents
• Therefore> it probably the safest of inhalation anesthetics
Intravenous anesthetics
 Intravenous anesthetics

•IV anesthesia cause rapid induction

Induction:
• The majority of cardiac output (CO) flows to the brain, liver, and kidney (“vessel-
rich organs”) > a high proportion of initial drug bolus is delivered to the cerebral
circulation > passes along a concentration gradient from blood into the brain.
• Unbound, lipid-soluble, nonionized molecules cross into the brain most quickly.
•Once the drug has penetrated the CNS, it exerts its effects.
Recovery
• Due to redistribution from sites in the CNS to other
tissues.
Intravenous anesthetics

Propofol:
• It is widely used and has replaced thiopental as the first choice
for induction of general anesthesia and sedation.
• No anlegesia effects
Barbiturate (thiopental) > many adveres effects no longer used in
some counteries.
Fentanyl > opioid analgesic
Intravenous anesthetics

Etomidate:
• Benefit> little to no effect on the heart and circulation> usually
only used for patients with coronary artery disease or
cardiovascular dysfunction.
• Its adverse effects include decreased plasma cortisol
and aldosterone levels
 Intravenous anesthetics

Ketamine:
• induces a dissociated state >patient is unconscious (but may appear to be
awake) and does not feel pain. This dissociative anesthesia provides sedation,
amnesia, and immobility.
• Stimulates sympathetic > increase increased blood pressure and
bronchodilation
• Benefit> cardiogenic shock and in asthmatic patients.
• Contrindiction > hypertensive and stroke patients.
• May be used illegally > dream-like state and hallucinations
Intravenous anesthetics

Dexmedetomidine
• Mechanism of action: α2 receptor agonist > sympatholytic
• Blunts undesirable cardiovascular reflexes
• No respiratory depression
Local
anesthetics
Local
anesthetics

• Produce loss of sensation to pain in a specific area of the body

without the loss of consciousness.
• Routes of administration: include topical administration, SQ,
epidural.
Mechanism of
Action
• Block nerve conduction of
sensory impulses and from
the periphery to the CNS.
• Block voltage-gated
Na+ channels > inhibit
action potential.
Local Anesthetics
types
 Esters
:
• These include:
• Cocaine
• Procaine
• Tetracaine
• Chloroprocaine

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 Amides
•: These include:
• Lidocaine
• Mepivicaine
• Prilocaine
• Bupivacaine
• Etidocaine

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Local
anesthetics
local anesthetic
Prila cream is a local anesthetic (numbing medication) containing lidocaine and prilocaine
Local
anesthetics
Metabolism:

Amides >primarily in the liver.

Esters > by plasma pseudo-cholinesterase> metabolite

para aminobenzoic acid (PABA)> causes allergy.
Local
anesthetics

Action: ‫مدة أقصر‬

• They cause vasodilation > rapid diffusion away from the site of
action and shorter duration when these drugs are administered
alone.
• By adding the vasoconstrictor epinephrine, the rate of local
anesthetic absorption and diffusion is decreased. This minimizes
systemic toxicity and increases the duration of action.
‫يتم تقليل االمتصاص واالنتشار‬
‫يقلل من السمية الجهازية ويزيد من مدة العمل‬.
Local
anesthetics

Allergic reactions
• Common adverse effect
• May be due to epinephrine added to the local anesthetic
• Rare with amide anesthetics and common with esters
• Allergy to one ester > avoid others (all produce metabolite
responsible to allergy)
 Systemic
toxicity

Local anesthetic may cause systemic toxicity by :

• all systemic toxic reactions associated with local anesthetics are the result of
over-dosage leading to high blood levels of the agent given.
• Neurotoxicity resulting from local effects produced by direct contact with
neural
elements.

CNS toxicity:
• Initial imbalanced brain excitement (seizure) followed by generalized CNS
depression (cardiac and respiratory depression)
Questions