General Anesthetics Flashcards
what are the 4 original stages of Anesthesia based on Ether?
- Analgesia (Loss of Pain Sensation)
- Excitement (Delirium & Disinhibition) – Most Dangerous Stage
- Surgical Anesthesia (Ideal Stage for Surgery)
- Medullary Depression (Dangerous Overdose Stage)
what happens during Stage 1:Analgesia (Loss of Pain Sensation)?
- patient is conscious but has decreased awareness of pain
- impaired consciousness begins, but the patient can still respond to stimuli.
- may experience amnesia, but reflexes and breathing remain normal
what happens during Stage 2: Excitement (Delirium & Disinhibition) – Most Dangerous Stage
- patient becomes delirious, excited, and uncoordinated
- amnesia is present, but reflexes are hyperactive
- irregular breathing, enhanced reflexes, and uncontrolled movements occur
- retching, vomiting, and incontinence may happen
- patients are prone to laryngospasm
what happens during Stage 3: Surgical Anesthesia (Ideal Stage for Surgery)
- patient is unconscious and does not perceive pain
- reflexes to pain may still be present, but the brain is not processing pain perception
- spinal cord responses cause increased blood pressure and tachycardia when pain is applied
- breathing is regular, and blood pressure is stable
what happens during Stage 4: Medullary Depression (Dangerous Overdose Stage)
- severe respiratory depression (or complete respiratory arrest)
- cardiovascular collapse (severe hypotension, bradycardia)
- loss of all reflexes
- patient requires immediate respiratory and cardiovascular support (mechanical ventilation and vasopressors) to prevent death
Goals of General Anesthesia?
- unconsciousness
- analgesia
- immobility, skeletal muscle relaxation without impairing breathing
- inhibition of autonomic reflexes that causes bronchospasm, excess salivation, arrhythmias
- amnesia
an ideal anesthetic drug should?
induce rapid and smooth induction, be rapidly reversible upon discontinuation, and possess a wide margin of safety.
what is balanced anesthesia?
combination of agents and techniques (e.g., premedication, regional anesthesia, and general anesthesia with one or more agents) is used to produce the different components of anesthesia
what are the two MOA for general anesthetics?
- altering ligand gated ion channel activity in neurons
- activate sleep-promoting neurons in the hypothalamus
how do Anesthetics increase inhibitory synaptic activity?
enhance the function of inhibitory neurotransmitters, particularly GABA (gamma-aminobutyric acid) to allow hyperpolarization of neurons through Cl- channels
or
activate potassium channels, leading to neuron hyperpolarization
what are the Anesthetics that enhance GABA-A activity?
- Inhaled anesthetics (e.g., isoflurane, sevoflurane)
- Barbiturates (e.g., thiopental)
- Etomidate
- Propofol (widely used for IV anesthesia).
how do Anesthetics reduce excitatory synaptic activity?
suppress excitatory neurotransmission, particularly by blocking glutamate activity through its ionotropic glutamate receptors (AMPA, Kainate, NMDA)
or
blocking acetylcholine activity through its nicotinic acetylcholine receptors
what are the Anesthetics that reduce excitatory synaptic activity?
- Ketamine blocks NMDA receptors
- Nitrous oxide inhibits glutamate activity
- Most inhaled anesthetics inhibit nicotinic acetylcholine receptors at moderate to high concentrations
General anesthetics cause direct activation of (Anesthetic hypnosis)?
sleep-promoting neurons in the ventrolateral preoptic nucleus of the hypothalamus.
- these neurons preferentially fire during natural sleep
what are the inhaled general anesthetics?
- Nitrous Oxide
- Sevoflurane
- Desflurane
- Isoflurane
- Halothane
what are the intravenous general anesthetics?
- Propofol
- Ketamine
- Etomidate
- Fospropofol
- **Methohexital
what is special about Methohexital?
an ultrashort-acting barbiturate that is primarily used for inducing anesthesia by exciting the brain, which helps facilitate seizure induction during electroconvulsive therapy (ECT)
what is the main advantage of Anesthetic Gases?
can be rapidly adjusted by changing the gas mixture which allows for fast induction, maintenance, and recovery from anesthesia and quick elimination via the lungs reduces systemic toxicity
what are three anesthetic gasses no longer used?
Ether, cyclopropane and enfluorane
what is Minimum Alveolar Concentration (MAC)?
the “dose” (potency) of an inhaled anesthetic needed to keep half of the patients completely unconscious and unresponsive to pain
**the lower the MAC the more potent the drug
what would increasing the ventilation rate due to the rate of induction for inhaled general anesthetics?
increase the rate of induction
the lower the blood:gas partition coefficient (decreased solubility) the
faster the induction rate
- less soluble anesthetics cause effects faster
the lower the solubility of a drug (blood:gas partition coefficient), the faster the
rate of elimination
how do inhaled general anesthetics affect the liver?
- reduce hepatic (liver) blood flow by 15–45% (usually reversible)
- Most inhaled anesthetics undergo minimal liver metabolism, meaning they are primarily eliminated through the lungs (Halothane is an exception)
how do inhaled general anesthetics affect the kidneys?
- reduce glomerular filtration rate (GFR) and renal plasma flow, leading to a temporary decrease in kidney function (usually reversible)
what are the advantages of Nitrous Oxide?
Good analgesia (used in asthmatics)
Rapid onset and recovery
Safe and non-irritating
Can be used in pregnant people
what are disadvantages of Nitrous Oxide?
Incomplete anesthetic
Low potency
No muscle relaxation
hypoxia (above 75%)
what are the clinical uses for Nitrous Oxide?
- Sole Agent for Sedation and Analgesia → Used alone for dental procedures, minor surgeries, and labor pain relief.
- Adjunct to General Anesthesia → Used in combination with other anesthetics to reduce their required dose and side effects.
what are the abuse potentials for Nitrous Oxide?
- Recreational Abuse: causes euphoria, dizziness, depersonalization, and altered sound perception
- Long-Term Abuse Effects: neurological Damage: Chronic use can lead to brain damage and sensory neuropathies due to B12 deficiency
what are the advantages of Sevoflurane (most commonly used)?
- Potent anesthetic with rapid onset and recovery.
- Ideal for mask induction (non-pungent, smooth induction, especially in pediatrics)
what are the disadvantages of Sevoflurane?
- Interacts with soda lime in anesthesia machines, producing compound A, which may be nephrotoxic (toxic to the kidneys) *fresh gas (not recycled) should be used
- Minimal Liver Metabolism (3%) but No Known Hepatotoxicity or Nephrotoxicity
what are advantages for Desflurane?
- Highly potent anesthetic.
- Minimal effects on cardiac output
- Rapid onset and recovery
- Extremely Low Liver Metabolism
- Preferred for Outpatient Surgery
what are the disadvantages for Desflurane?
- Airway irritation: can cause laryngospasm during induction
- Pungent Odor – Not Suitable for Mask Induction
- Requires special heated vaporizer
- Greenhouse Gas – Stays in the Atmosphere for Years
what are the advantages for Isoflurane?
- Potent and safe anesthetic.
- Less decrease in cardiac output compared to halothane.
- Good muscle relaxation
- Minimal liver metabolism (no metabolic toxicities)
- used on a wide rage of patients (less common in children)
what are disadvantages of Isoflurane?
- Medium rate of onset and recovery
- Pungent Odor – Not Ideal for Mask Induction
- greenhouse gas
what are advantages of Halothane?
- Potent anesthetic
- Not pungent: Useful for mask induction
- low cost (used in low income countries)
what are disadvantages of Halothane?
- Slow Induction and Recovery (High Blood Solubility)
- Hepatic toxicity: over 20% undergoes liver metabolism
- Malignant hyperthermia
- Arrhythmias
Halothane induced Malignant Hyperthermia
- a genetic disorder of skeletal muscle, a
rare, but important, cause of anesthetic morbidity and mortality - causes hyperthermia, muscle rigidity, rapid onset of tachycardia and hypercapnia, hyperkalemia, and metabolic acidosis
what other drugs can trigger malignant hyperthermia?
isoflurane and succinylcholine
what causes Malignant hyperthermia?
mutations of the ryanodine receptor
(type 1), located on the sarcoplasmic reticulum where triggering agents cause calcium release from the SR and increase intracellular calcium concentration in the skeletal muscle
what would you give to a patient who is experiencing triggered malignant hyperthermia?
Stop the triggering agent, give dantrolene, treat fever, acidosis and arrhythmia
- Dantrolene: decreases the amount of calcium released from the sarcoplasmic reticulum leading to muscle relaxation
Halothane induced Hepatotoxicity
can cause hepatic necrosis due to
Immune response
Halothane induced Arrhythmias
sensitizes the heart to catecholamines
what are the general properties of IV anesthetic agents?
- highly lipophilic, allowing rapid brain penetration and quick onset
- short-lived initially due to redistribution from the brain to other tissues
- prolonged infusions lead to drug buildup in fat, which can delay recovery
what are advantages of Propofol
- Rapid Induction and Recovery
- Potent Anesthetic but No Pain Relief (No Analgesia)
- Minimal Residual Effects (no grogginess)
what are disadvantages of Propofol?
- No analgesia
- Can cause significant blood pressure drop (hypotension) due to vasodilation
- poorly soluble: can cause pain on injection
- decreases cerebral metabolism
- causes respiratory depression
what are the clinical uses of Propofol?
- Induction and Maintenance of General Anesthesia
- Ideal for Same-Day (Outpatient) Surgeries
- Used in ICUs for Sedation
what is Fospropofol?
water-soluble prodrug of propofol (too expensive, not much used)
what is the advantage and disadvantage for Methohexital?
- rapid indiction and redistribution induces stage 3 anesthesia quickly but prolonged use and accumulation in fat tissue delays recovery, leading to extended drowsiness (grogginess)
*only used during electroconvulsive shock treatment
what are the pharmacological characteristics of Ketamine?
- good analgesic
- produces amnesia
- excites the heart: increases heart heart, cardiac output and blood pressure
- causes bronchodilation
- produces a state of dissociative anesthesia
what are the clinical uses of Ketamine?
- pediatric patients
- patients at risk for hypotension and bronchospasm (asthmatics)
- cardiac patients
what are the side effects of Ketamine?
- increases cerebral blood flow
- hallucinations can occur after emergence that are sometimes reoccurring
- A drug of abuse: Long term use causes bladder damage
what is the MOA for Benzodiazepines?
increasing the activity of GABA-A receptors, which are inhibitory neurotransmitter receptors in the brain
what are the pharmacological characteristics of Benzodiazepines?
- causes sedation reduced anxiety and induces amnesia
- reduces the doses needed to reach anesthesia when used with drugs like propofol
- High doses will induce hypnosis and unconsciousness
- poor analgesics
which benzodiazepine is the most commonly used and why?
Midazolam is the most commonly used because of its short half-life
- Can be injected or given orally or rectally
what are the side effects of Benzodiazepines?
- prolonged recovery (especially with long-acting benzodiazepines)
- respiratory depression: can cause hypoventilation and apnea
- hypotension: blood pressure reduction due to CNS depression
Flumazenil
- competitive benzodiazepine antagonist at the GABA_A receptor used to reverse benzodiazepine-induced sedation and respiratory depression.
what are Opioids?
the primary analgesic agents used in major surgery that act primarily as μ-opioid receptor (mu-opioid receptor) agonists in the central nervous system (CNS) and spinal cord.
pharmacokinetics of each of the main opioids used
- Morphine has the longest duration of action
- Remifentanil has the shortest half-life
- Fentanyl is most commonly used, intermediate half life, most prolonged by infusion, lipophilic
- sufentanil, and alfentanil all have intermediate half-lives and vary in duration of action after infusion
what are the pharmacological characteristics of Opioids?
- excellent analgesics
- potency: Sufentanil (1000) > remifentanil (300) >
fentanyl (100) > alfentanil (15) > morphine (1) - full anesthesia when given in high enough doses
- lower doses- used in combination with a
sedative - state of sedation analgesia - not good at causing amnesia
what are the clinical uses of Opioids?
- relieve pain during and after surgery
- used as adjunct to reduce the amounts of other anesthetics needed
- in high doses can be used as the primary anesthetic agent, especially in cardiac surgery
- Remifentanil is used in briefly painful short
procedures
what are the side effects of Opioids?
- prolonged respiratory depression
- constipation
- drug of abuse
what is the MOA of Dexmedetomidine?
acts on α₂-adrenoceptors in the central nervous system (CNS), particularly in the brainstem (locus coeruleus) and spinal cord to exert hypnosis, analgesia, and sedation effects
how does Dexmedatomidine exert hypnosis, analgesia, and sedation?
- Hypnosis: Induced by inhibition of norepinephrine in the locus coeruleus, mimicking natural sleep.
- Analgesia: Provided via spinal cord α₂-receptor activation, reducing pain transmission.
- Sedation: Arousal is suppressed, but patients remain responsive to stimuli (cooperative sedation).
what are the pharmacological characteristics of Etomidate?
- stage III anesthesia - no analgesia
- minimal effect on the cardiovascular system
- mild respiratory depression
when is Etomidate used?
- rarely used
- for anesthetic induction, but not maintenance
what are the major side effects of Etomidate?
- increase in death rate attributed to suppression of adrenocorticosteroids (common after repeated use)
- nausea and vomiting.
what are the minor side effects of Etomidate?
- injection can be very painful
- causes myoclonic movements (can be suppressed by opioids and benzodiazepines)
