Tisdale: General Anesthetics Flashcards
General Anesthesia
Description:
Reversible CNS depression resulting in a collection of “component” changes
Unconsciousness, analgesia, amnesia, immobility and attenuation of autonomic responses
Classes: (2)
Inhalation
Intravenous
Balanced Anesthesia:
Balanced Anesthesia: use of combinations of intravenous and inhaled drugs; takes advantage of favorable properties of each while minimizing adverse effects
Minimum Alveolar Anesthetic Concentration (MAC):
MAC: alveolar concentration required to eliminate the response to a standardized painful stimulus in 50% of patients (1 MAC=prevents response in 50% of patients)
Measure of INHALED anesthetic potency
Potency= ?
Potency= 1/MAC (inversely related); therefore, lower MAC= higher potency
Each anesthetic has a defined MAC, but may vary among different patients depending on the following factors
Increase MAC: (6)
- Young age
- Hyperthermia
- CNS hypo-osmolality
- Habituation to alcohol
- CNS stimulants (dextroamphetamine, cocaine)
- Physostigmine
Decrease MAC: (10)
- Old age
- Hypothermia
- CNS hyperosmolality
- Acute effects of alcohol
- CNS depression (benzodiazepines, barbiturates, propofol)
- Tranquilizers (chlorpromazine)
- CNS effects of local anesthetics
- Narcotics
- Pregnancy
- Alpha 2 adrenergic agonists (clonidine, dexmedetomidine)
Effect on height, weight or sex on MAC:
NOT effected by height, weight or sex
What is the main determinant of the potency of an anesthetic
Oil:Gas Partition Coefficient (Lipid Solubility): main determinant of the potency of an anesthetic
Minimum Alveolar Anesthetic Concentration (MAC)
Oil:Gas Partition Coefficient (Lipid Solubility):
High lipid solubility on recovery from anesthesia:
High lipid solubility delays recovery from anesthesia (agent accumulates gradually in body fat and produces a prolonged Hangover)
High lipid solubility = high oil:gas partition coefficient = low MAC = high potency
Minimum Alveolar Anesthetic Concentration (MAC)
Potency of an Intravenous Agent:
Free plasma concentration that produces loss of painful stimulus in 50% of patients
Mechanism of Action
Current Theory:
Unitary Theory of Anesthesia:
Protein Theory of Anesthesia:
Current Theory: current research indicates the mechanism of action is a combination of two historical theories
Unitary Theory of Anesthesia: change in membrane dimension and/or change in membrane physical state
Protein Theory of Anesthesia: GAs directly interact with proteins
Dual Process Model of Anesthesia
GAs POTENTIATE:
GAs POTENTIATE the action of endogenous agonists at INHIBITORY receptors (GABA, glycine; stabilize OPEN state)
- Decrease the EC50 and increase the maximum response
Dual Process Model of Anesthesia
GAs INHIBIT:
GAs INHIBIT the action of endogenous agonists at EXCITATORY receptors (no depolarization of post-synaptic membrane, no AP; non-competitive inhibitor)
- Decrease the maximum response while leaving the EC50 unchanged
Inhaled Anesthetics
Effects on the Cardiovascular System:
Effects on the Cardiovascular System: most prominent effect is DECREASE in systemic arterial BP
Inhaled Anesthetics
Effects on the Respiratory System:
Exception:
Effects on the Respiratory System: reduction/elimination of ventilatory drive and reflexes to maintain patent airway
o Exception: nitrous oxide
Inhaled Anesthetics
Effects on the Brain:
Effects on the Brain: INCREASE cerebral blood flow (increases cerebral blood volume and ICP)
Inhaled Anesthetics
Effects on the Kidney:
Filtration Fraction= ?
Effects on the Kidney: DECREASE GFR and RBF and INCREASE filtration fraction (effects concentration dependent)
Filtration Fraction= GFR/RPF (renal plasma flow)
Inhaled Anesthetics
Effects on the Liver:
Effects on the Liver: DECREASE in hepatic blood (15-45% below baseline; concentration dependent decrease)
Malignant Hyperthermia
Description:
Description: autosomal dominant genetic disorder of skeletal muscles occurring in susceptible individuals undergoing general anesthesia with volatile agents and muscle relaxants (ie. succinylcholine)
o Rare but important cause of anesthetic morbidity and mortality
o Due to increase in free Ca++ concentration in skeletal muscle cells
Malignant Hyperthermia
Symptoms: (6)
Symptoms: rapid onset of o Tachycardia o HTN o Severe muscle rigidity o Hyperthermia o Hyperkalemia o Acid-base imbalance (acidosis)
Malignant Hyperthermia
Treatment:
Treatment: dantrolene
Nitrous Oxide
B:G:
O:G/MAC:
Nitrous Oxide: not used alone except for in dental procedures; only one that provides analgesia
o Low B:G: rapid induction/recovery
o Low O:G/MAC: low potency
Sevoflurane
B:G:
O:G/MAC:
Sevoflurane: expensive; becoming more popular in US for outpatient use; used in children (sweet odor)
o Low B:G: rapid induction/recovery
o A little higher O:G/MAC: a little more potent than N2O
Isoflurane
B:G:
O:G/MAC:
Isoflurane: most widely used inhalation anesthetic*; pungent odor
o Higher B:G: slower induction/recovery (medium)
o Higher O:G/MAC: higher potency
Halothane
B:G:
O:G/MAC:
Halothane: used for induction in children (non-pungent); not used in adults due to hepatotoxicity
o Higher B:G: slower induction/recovery (medium)
o Higher O:G/MAC: higher potency
Desflurane
B:G:
O:G/MAC:
Desflurane: most widely used for outpatient surgery; irritates airway
o Low B:G: rapid induction/recovery
o A little higher O:G/MAC: a little more potent than N2O
Blood:Gas Partition Coefficient:
Blood:Gas Partition Coefficient: main factor determining the rate of induction and recovery
- More rapidly a drug equilibrates in the blood, the more quickly it passes into the brain to produce anesthesia
Solubility
Low Solubility:
Low Solubility: low blood:gas partition coefficient –> equilibrate more rapidly
- With a low solubility agent, less has to be transferred via the lungs to the blood in order to achieve a given partial pressure
Solubility
High Solubility:
High Solubility: high blood:gas partition coefficient –> equilibrate more slowly
- Blood doesn’t want to give up gas
Blood Flow:
The greater the blood flow to a tissue, the faster the uptake of the anesthetic
Tissues with high blood flow will have a rapid rise in the partial pressure of the anesthetic
Uptake and Distribution
General:
Uptake and Distribution
General: the greater then blood flow to a tissue, the faster the uptake of the anesthetic by the tissue
Uptake and Distribution
Tissues with high blood flow/low capacity:
Examples:
Tissues with high blood flow/low capacity: rapid rises in the partial pressure of the anesthetic
Examples: brain, lung, heart and kidney
Uptake and Distribution
Tissues with medium blood flow/high capacity:
Examples:
Tissues with medium blood flow/high capacity: intermediate rates of rise in partial pressure
Example: skeletal muscles
Uptake and Distribution
Tissues with low blood flow/very high capacity:
Example:
Tissues with low blood flow/very high capacity: very slow rise in partial pressure
Example: adipose tissue
Uptake and Distribution
Role of % Body Fat:
Role of % Body Fat: people who take a highly lipid soluble drug and have high body fat will have a slower recovery (remain drowsy)
Pulmonary Ventilation
The greater the ventilation rate:
Hyperventilation:
The greater the ventilation rate, the more rapid the rise in alveolar and blood concentration of the agent and the more rapid the onset on anesthesia
Hyperventilation can increase the speed of induction in those drugs that have a slow onset (ie. high blood:gas partition coefficient)
Pulmonary Blood Flow
The greater the pulmonary blood flow:
Result of increased blood flow:
The greater the pulmonary blood flow (ie. greater CO) the SLOWER the equilibration (this effect is larger in more blood soluble gases)
Increased blood flow exposes larger volume of blood to the anesthetic –> takes longer for the anesthetic and blood to equilibrate
Elimination
Termination of anesthesia:
Termination of anesthesia: occurs by redistribution of the drug from the brain to the blood and elimination of the drug through:
- The lung
- Metabolism by enzymes in the liver and tissue
Elimination
Recovery:
Recovery: occurs in reverse sequence from those of the stages of induction (redistributes down a partial pressure gradient)
Elimination
Factors Affecting Rate of Recovery: (3)
Rate of recovery is faster in anesthetics with low blood:gas partition coefficients
Rate of recovery is proportional to duration of anesthesia (since partial pressure of anesthetic in muscle and fat increases with duration)
Rate of recovery accelerated by increased ventilation
Intravenous Anesthetics
Onset of Action:
Onset of Action: much faster than any inhaled agent (highly lipid soluble and easily cross BBB)
o When administered, transported through vascular system to heart and then distributed to the brain and highly vascular tissues (peaks in 1 minute)
o Low blood flow to body fat, so redistribution to adipose tissue occurs later
Intravenous Anesthetics
Duration of Action:
Duration of Action: short (2-5 minutes)
o Recovery is sufficiently rapid to allow use for outpatient procedures
Intravenous Anesthetics
Use:
Use: induction (followed by administration of inhalation anesthetic)
o Balanced Anesthesia: combination of inhaled and intravenous anesthetics
Intravenous Anesthetics
Structure:
Structure: small, hydrophobic substituted aromatic or heterocyclic compounds (hydrophobicity plays a key role in pharmacokinetics)
Intravenous Anesthetics
Agents: (6)
Barbiturates Benzodiazepines Opiods Propofol Etomidate Ketamine
Barbiturates
Agents: (3)
Agents:
- Sodium thiopental
- Thiamylal
- Methohexital
Barbiturates
Use:
Use: ultra-short acting barbiturates are capable of producing anesthesia within seconds
- Rate of removal slow due to accumulation in body fat (highly lipid soluble)
Benzodiazepines
Agents: (3)
Agents:
- Diazepam
- Lorazepam
- Midazolam
.
Benzodiazepines
Use:
Use: often given for anxiolytic and anterograde amnesic properties
- Administered 15-60 minutes before induction to calm patient and obliterate memory of induction
- May also be used for intraoperative sedation
Opioids
Agents: (2)
Morphine
Fentanyl
Opioids
Use:
Use: ability to produce analgesia
- Duration of action 30-60 minutes after a single bolus
- Poor amnesics
Propofol
Use:
Onset:
Use: most popular IV anesthetic
- Good choice for ambulatory surgery (rapid recovery)
- Good for prolonged sedation in patients in critical care settings
Onset: rapidly acting (half-time of blood-brain equilibration is 1-3 minutes)
Propofol
Recovery:
Metabolism:
Recovery: rapid (patients able to ambulate earlier after general anesthetic)
Metabolism: rapidly in the liver
Etomidate
Use:
Use: primarily used in patients at risk for hypotension (does not cause significant cardiac or respiratory depression)
Etomidate
Issues: (2)
Metabolism:
Issues:
- High incidence of pain on injection (acidic solution; co-administered with lidocaine)
- High incidence of postoperative N/V
Metabolism: extensive hepatic metabolism as well as in the plasma
Ketamine
General:
Use:
General: analog of PCP (can cause hallucination and irrational behavior)
Use: induction and maintenance, usually in combination with a sedative drug
Ketamine
Mechanism:
Dissociative Anesthesia:
Mechanism: non-competitive antagonist of the NMDA receptor
Dissociative Anesthesia: characterized by catatonia, amnesia and analgesia without LOC
Ketamine
Onset:
Issues:
Metabolism:
Onset: rapid acting and produces profound analgesia
Issues: only IV anesthetic that produces dose-related cardiovascular stimulation
Metabolism: liver
