!general Anesthetics Flashcards
Inhaled general anesthetics
Desflurane Enflurane Halothane Isoflurane NO Sevoflurane
IV anesthetics
Dexmedetomidine Diazepam Etomidate Fentanyl Fospropofol Ketamine Lorazepam Methohexital Midazolam Propofol Thiopental
General anesthesia produce an anesthetic state. What is the anesthetic state
Collection of component changes in behavior or perception that include:
Unconsciousness
Amnesia
Analgesia
Attenuation of autonomic reflexes to noxious stimulation
Immobility in response to noxious stimulation (skeletal muscle relaxation)
Can a single drug achieve all 5 effects of anesthetic state
No -we use combinations of IV and inhaled drugs to take advantage of the favorable properties of each agent while minimizing their adverse effects (sedatives, neuromuscular blocking agents, local anesthetics, and analgesics may be used in addition to general anesthetics)
Monitored anesthesia care
A sedation based anesthetic technique utilized for diagnostic and/or minor therapeutic surgical procedures; typically involves the use of midazolam for premedication (to provide anxiolysis, amnesia, and mild sedation) followed by a titrated propofol infusion (to provide moderate to deep levels of sedation)
Conscious sedation
Used primarily by nonanesthesiologists where the patient retains the ability to maintain a patient airway and is responsive to verbal commands; benzodiazepines and opoid analgesics (fentanyl) are usediul bc they are reversible by receptor antagonists (flumazenil and naloxone)
Deep sedation
Similar to a light state of general(IV) anesthesia involving decreased consciousness from which the patient is not easily aroused; accompanied by a loss of protective reflexes , and inability to maintain a patient airway, and lack of verbal responsiveness to surgical stimuli; propofol and midazolam are often used, sometimes in combination with potent opoid analgesics or ketamine, depending on the level of pain associated with the surgery or procedure
ICU sedation
Patients require mechanical ventilation for prolonged periods
MOA general anesthetic action
Most general anesthetics cause CNS depression by facilitating chloride channel activation (GABA and glycine receptors) some reduce activity of excitatory ion channels, AMPA receptors, kainite receptors, and NMDA
Inhaled anesthetics
Volatile and gaseous
Volatile anesthetics
Halothane, enflurane, isoflurane, desflurane, sevoflurane
Low vapor pressures and thus high boiling points so that they are liquirds at room temperature and sea level ambient pressure
Gaseous anesthetics
NO
High vapor pressures and low boiling points and are in gas at room temperature
Inhaled anesthetics are absorbed through gas exchange in __ into the blood where the anesthetic is distributed throughout the body
Alveoli
The rate at which an inhaled anesthetic is absorbed is dependent upon the ____ of anesthetic in the inspired air, the ___ rate, and drug ___ in air, blood and CNS
Concentration
Ventilation
Solubility
What is the blood gas partition efficient
Relative affinity of an anesthetic for the blood compared with that of inspired gas
There is an __ relationship between blood gas partition. Coefficient values and the rate of anesthesia onset
Inverse
Agents with __ blood solubility (NO, desflurane) reach high arterial pressure rapidly, which in turn results in rapid equilibration with the brain and fast onset of action
Low
Agents with _ blood solubility (halothane) reachhigh arterial pressure slowly, which in turn results sin slow equilibration with the brain and a slow onset of action
High
Brain blood partition coefficient values for the inhaled anesthetics are relatively similar and indicate that all agents are more soluble in the brain than in the blood
Ok
NO Blood:Gas and Brain:blood
.47
1.1
NO MAC
> 100%
Metabolism NO
Non
Othe NO
Incomplete anesthetic; rapid onset and recovery
Desflurane blood:gas and brain:blood
.42
1.3
Desflurane MAC
6-7%
Desflurane metabolism
Other desflurane
Low volatility ; poor induction agent ; rapid recovery
Sevoflurane blood:gas and brain:blood
.69
1.7
Sevoflurane MAC
2%
Metabolism sevoflurane
2-5
Comment sevoflurane
Rapid onset and recovery
Isoflurane blood gas and brain blood
1.4, 2.6
MAC isoflurane
1.4%
Metabolism isoflurane
<2%
Comment isoflurane
Medium rate of onset and recovery
Enflurane blood gas and brain blood
1.8 1.4
MAC enflurane
1.7
Enflurane metabolism
8
Comments enflurane
Medium rate of onset and recovery
Halothane blood gas and brain blood
2.3 2.9
Halothane MAC
.75
Metabolism halothane
> 40
Halothane comments
Medium rate of onset and recovery
Why is induction of anesthesia slower with more soluble anesthetic agents
For a given concentration or partial pressure of the two anesthetic gases in the inspired air, it will take much longer for the blood partial pressure of the more soluble gas (halothane) to rise to the same partial pressure as in the alveoli
Since the concentration of the anesthetic agent in the brain can rise no faster than the concentration in the blood, the onset of anesthesia will be slower with halothane than with NO
The _, _, _, _ and _ _ are highly perfumed and receive over 75% of the resting CO and as a result have higher immediate concentrations of anesthetic
Brain Heart Liver Kidney Splanchnic bed
Although __ and _- constitute about 50% of the total body mass, anesthetics accumulate more slowly in these tissues than highly perfused tissues because they receive only 1/5 of the resting cardiac output
Skin muscle
Inhaled anesthetics that are relatively insoluble in the blood and brain are eliminated at faster rates than more soluble anesthetics; clearance of inhaled anesthetics via the _ is the major route of elimination from the body, although some agents are metabolized by the __ to varying degrees
Lungs
Liver
What is MAc
Minimal alveolar concentration required to prevent a response to a surgical incision (concentration of inhalation anesthetic that prevents movement in response to surgical stimulation in 50% of subjects (a measure of potency ED50))
How are MAC expressed
%, the % of the atmosphere that is anesthetic at the MAc (1 MAC of isoflurane is 1.4volume % while 1 MAC of halothane is .75 volume %)
A dose of 1 MAC of any anesthetic prevents movement in response to surgical incision in _% of patients
50%- individual patients may require .5-1.5 MAC
MAC values >100%
If 100% of inspired air is in the anesthetic, the MAC value would still be less tan 1 and other agents must be supplemented to achieve full surgical anesthesia (NO)
Since NO lacks the potency to produce surgical anesthesia, it is combined with what to produce a state of balanced general anesthesia
Volatile or IV anesthetics
Using NO to produce 50% MAC in combination with 70% volatile agent’s MA would yield _ % MAC, sufficient for surgical anesthesia in most patients
110
Inhaled volatile liquid anesthesia __ mean arterial pressure in direct proportion to their alveolar concentration;
Decrease
All inhaled anesthetics can increase __ atrial pressure in a dose related manner, most likely caused by depression of myocardial function;effects on heart rate are mixed
Right
Halothane can cause _, desflurane and isoflurane can __ heart rate
Bradycardia
Increase
Volatile anesthetics are respiratory __ (the body has a reduced response to increased levels of CO2
Depressants
Common side effects of inhaled anesthetics
Nausea and vomiting
Halothane may cause __ with or without previous exposure. What are symptoms of this
Hepatitis
Anorexia, nausea, myalgia, arthralgias, rash, eosinophilia, hepatomegaly, jaundice 2-3 days after exposure_
Enflurane and sevoflurane can cause __ toxicity due to fluoridated metabolites
Renal
In combination with —-, inhaled volatile anesthetics may cause malignant hyperthermia which consists of rapid onset tachycardia and hypertension, severe muscle rigidity, rhabdomyolysis, hyperthermia, hyperkalemia, and acid base imbalance with acidosis. What is the antidote
Succinylcholine
Dantrolene
No opoid IV anesthetics are widely used to facilitate rapid induction of anesthesia and have replaced inhalation as the preferred method of anesthesia induction in most settings (except what)
Pediatric
Balanced anesthesia with multiple drugs (inhaled anesthetics, sedative hypnotics, opoids, neuromuscular blocking drugs) is used to ___ unwanted side efffects
Minimize
IV anesthetics are highly ___ and preferentially partition into highly perfused lipophilic tissues (brain spinal cord) which accounts for their quick onset of action
Lipophillic
Etomidate
Rapid onset and moderately fast recovery
Provides CV stability, causes decreased steroidogenesis and involuntary muscle movements
Ketamine
Moderately rapid onset and recovery
CV stimulation, increased cerebral blood flow and emergence reactions that impair recovery
Methohexital
Rapid onset and rapid recovery
Preferred over thiopental for short ambulatory procedures
Midazolam
Slow onset and recovery; flumazenil reversal available
Used in balanced anesthesia and conscious sedation; provides CV stability and marked amnesi
Propofol
Rapid onset and rapid recovery
Used in induction and for maintence ; can cause hypotension ; has useful antiemetic action
Thiopental
Rapid onset and rapid recovery (bolus dose)-slow recovery following infusion
Standard induction agent; causes CV depression avoid in porphyrias
Fentanyl
Slow onset and recovery; naloxone reversal available
Opoid used in balanced anesthesia and conscious sedation; produces marked analgesia
Propofol MOA
Targets GABAA as an agonist and potentials the Cl current (other receptors likely involved)
Pharmacokinetics propofol
Rapidly metabolized int he liver (phase 1 and II reactions (glucuronide and sulfate conjugates)) with extensiveextrahepatic metabolism (lung tissue may account for elimination of up to 30% of a bolus dose) rapid rate of onset, rapid recovery, and patients are able to ambulated quickly after use (low hangover effect) time of onset is 15-30 seconds as determined by time to unconsciousness
PK properties propofol allow for continuous infusions and maintence of anesthesia, sedation in the ICU, conscious sedation and short duration general anesthesia in locations outside te operating room
Ok
Poor solubility in water and is formulated as an emulsion containing soybean, oil, glycerol, and lecithin (yolk egg), making allergic reactions possible in susceptible patients (solution appears milky white and slightly viscous)
Ok
What are drug half life’s dependent on
Rate of redistribution of drug, amount accumulated in fate and drugs metabolic rate
Called context sensitive half lif e
__ ___ and ___ increase only modestly with prolonged infusions
Etomidate, propofol, ketamine
__ an d___ increase dramatically with prolonged infusion
Diazepam
Thiopental
CNS effects propofol
General suppression of CNS activity even though excitatory effects such as twitching or spontaneous movement are occasionally observed during induction; no analgesic properties; decreases cerebral blood flow and the cerebral metabolic rate for oxygen which decreases intracranial pressure and intraocular pressure
Cardiovascular effects:
compared with other induction agents produces the most pronounced decres]ase in systemic blood pressure due to profound vasodilation in both arterial and venous circulation leading to reductions in preload and afterload; hypotensive effects are augmented by inhibition of the normal baroreflex response
Cardiovascular effects propofol
Compared with other induction agents produces the most pronounced decrease in systemic blood pressure due to profound vasodilation in both arterial and venous circulation leading to reductions in preload and afterload; hypotensive effects are augmented by inhibition of the normal baroreflex response
Respiratory effects propofol
Potent respiratory depressant; generally produces apnea after an induction dose
Why premeditate with opoid or coadminister lidocaine before propofol
Pain on injection is common
Fosprofol
Water soluble prodrug of propofol that is rapidly metabolized by alkaline phosphatase, producing propofol, phosphate, and formaldehyde (metabolized by aldehyde dehydrogenase int he liver and in erythrocytes)
Effects of fospropofol
Similar to propofol, and formaldehyde (metabolized by aldehyde DH in the liver and in erythrocytes)
There is __ pain when administer fospropofol than propofol
Less
Common adverse effects fosopropofol
Paresthesia (including perineal discomfort or churning sensation) and pruritus (including genital , perineal, and generalized pruritus) are mostly limited to the first 5 minutes of administration and usually described as mild moderate in intensity (mechanism is unknown; no pretreatment are helpful)
Etomidate MOA
Enhances the actions GABAA a=on GABA A receptors
Effects etomidate
Hypnotic but not analgesic effects
Causes etomidate on CV and respiratory
Minimal CV and respiratory depression useful in patients with impaired CV and respiratory systems
Etomidate produces rapid loss of ___ and less rapid recovery rate compared to propofol
Consciousness
Etomidate metabolism
Liver and in plasma
CNS effects etomidate
Potent cerebral vasoconstrictor; decreases cerebral blood flow and ICP
CV effects etomidate
CV system stability is maintained even after bolus injections minimal change in heart rate and cardiac output
Respiratory depressant effects are less pronounced impaired to barbiturates
For etomidate
Endocrine effects etomidate
Causes adrenocortical suppression by producing a dose dependent inhibition of 11b-hydroxylase (necessary for the conversion of cholesterol to cortisol); suppression lasts 4-8 hours after induction dose; limited use as continuous infusion
Ketamine MOA
NMDA receptor antagonist
What does ketamine cause
Dossociative anesthetic state characterized by Catalonia, amnesia, and analgesia with or without loss of consciousness (eyes ramain open with slow nystagmic gaze)
Structure ketamine
Similar to phencyclidine PCP
Why premedication of anticholinergic with ketamine use
Lacrimation and salivation are increased upon administration
CNS effects ketamine
Increases cerebral blood flow and not recommended for use in patients with intracranial pathology, espicially increased ICP; unpleasant emergence reactions after administration are the main factor limiting ketamine use (vivid colorful dreams, hallucinations, out of body experiences, increased and distorted visual, tactile, and auditory sensitivity) may induce a euphoric state, which explains the potential for abuse
CV ketamine
Can increase systemic blood pressure, heart rate, and cardiac output, presumably by centrally mediated sympathetic stimulation
Ketamine is the only IV anesthetic to produce analgesia, stimulation of the sympathetic nervous system, bronchodilator, and minimal respiratoy depression
Ok
Dexmedetomidine MOA
Alpha 2 adrenergic agonist that produces hypnosis presumably from stimulation of alpha 2 receptors in the locus caeruleus and analgesic effects at the level of the spinal cord
Effect dexmedetomidine
More completely resembles a physiologic sleep state through activation of endogenous sleep pathways
Infusion dexmedetomidine
Moderate decreases in heart rate and systemic vascular resistance and systemic bp, bradycardia may require treatment
What is dexmedetomidine used for
Short term sedation of incubated and ventilated patients in an ICU setting or as an adjunct to general anesthesia
What are anesthetic adjuncts used for
Augment specific components of anesthesia, permitting lower doses of general anesthetics with fewer side effects
What have opoid analgesics been used in combination with
Large doses of benzodiazepines to achieve a general anesthetic state
Common IV opoid analgesics
Fentanyl, sufentanil, remifentanil, and morphine
MOA opoid analgesics
Agonists at opiate receptors
Due to adverse effects (what are they?) opiates are often used as premedicationa Nd as an adjunct to both IV and inhaled anesthetics to provide perioperative analgesia
Impaired ventilation, tolerance after surgery, awareness during anesthesia
Examples of barbiturates
Thiopental and methohexital
Barbiturates are highly ___ and quick plasma:brain equilibrium
Lipophillic
Barbiturates cause dose dependent CNS depression ranging from _ to _
Sedation to general anesthesia
Side effect barbiturates
Respiratory depression
MOA barbiturates
Acts on the GABAA receptor to increase the duration of channel opening (agonist) and enhances inhibitory NT
Methohexital may be preferred over thiopental for short ambulatory procedures due to its rapid elimination
Over Barbiturates
Barbiturates induce ___ enzymes
P450
Barbiturates are replaces now by ___
Propofol induction agents
Benzodiazepines examples
Diazepam, lorazepam, midazolam
MOA benzodiazepines
Acts on GABAA receptor to increase receptor sensitivity to GABA (agonist) and enhances inhibitory NT
When are benzodiazepines used
In the perioperative period bc of their anxiolytics properties and ability to produce anterograde amnesia; actions can be terminated by the antagonist flumazenil
Benzodiazepine an be terminated by antagonist
Flumazenil
__ is water soluble )__ and __ are not and is not considered the drug of choice for parenteral administration
Midazolam
Diazepam and lorazepam
Midazolam is given IV when
Before patients enter the OR bc it has a more rapid onset, shorter elimination half life (2-4hrs) and steeper dose response curve than other benzodiazepines
Benzodiazepines have potent __ properties . What can they treat
Anticonvulsant
Status epilepticus, alcohol withdrawal, local anesthetic induced seizures
