General Anesthetics DSA Flashcards
Anesthetic state produced by general anesthetics
- unconsciousness
- amnesia
- analgesia
- attenuation of autonomic reflexes to noxious stimulation
- immobility in response to noxious stimulation (skeletal muscle relaxation)
monitored anesthesia care–what is it?
- sedation-based anesthetic techniques
- used for diagnostic and minor therapeutic surgical procedures
- without general anesthesia
monitored anesthesia care–drugs used
- midazolam (premedication–for anxiolysis, amnesia, mild sedation)
- propofol infusion (deep sedation)
- opioid analgesic or ketamine–added to minimize discomfort
conscious sedation–what is it?
- used by nonanesthesiologists
- patient retains the ability to maintain a patient airway and is responsive to verbal commands
conscious sedation–drugs used/reversible by?
-benzodiazepines and opioid anelgesics (fentanyl)–reversible by specfic R antagonist drugs; glumazenil and naloxone, respectively
deep sedation–what is it?
- transition from deep sedation to general anesthesia is fluid
- loss of protective reflexes, inability to maintain a patent airway, lack of verbal responsiveness to surgical stimuli
deep sedation drugs used
- IV –sedative hypnotics propofol and midazolam
- sometimes in combination with opioid analgesics or ketamine (depending on level of pain)
ICU-sedation–what is it? Drugs?
- patients who require mechanical ventilation for long periods
- sedative–hypnotic drugs and low doses of IV anesthetics
primary inhibitory ion channels for anesthetic action
- Cl channels (GABAa, glycine receptor)
- K channels
excitatory ion channel targets
- Ach (nAChR and mAChRs)
- EAAs (AMPA, NMDA receptors)
- serotonin (5HT2 and 3 Rs)
inhaled anesthetics types
- volatile anesthetics
- gaseous anesthetics
volatile anesthetics
Gaseous anesthetics?
HEIDS
- halothatne, enflurane, isoflurane, desflurane, sevoflurane
- low vapor pressure so high boiling points–liquid at room temperature
Gaseous: Nitrous oxide; high vapor pressure so low boiling points–gas at room temp
driving force for uptake of an inhaled anesthetic
alveolar concentration
2 factors that determine how quickly the alveolar concentration changes
- inspired concentration or partial pressure
- alveolar ventilation (increases in either direction will increase the rate of rise in alveoli–accelerate induction)
partial pressure in alveoli–expressed as
Fa (alveolar concentration)/Fi (inspired concentration)
-faster Fa/Fi approaches 1=faster anesthesia will occur
blood: gas partition coefficient–what is it? relationship?
- affinity of an anesthetic for blood compared with that of inspired gas (ie blood solubility)
- inverse relationship beteween blood:gas coefficient values and rate of anesthesia onset
agents with low blood solubility–onset of action
- NO, desflurane
- reach high arterial Pressure rapidly–results in rapid equilibration with brain
- fast onset of action
Agents with high blood solubility–onest of action
- halothane
- reach high arterial Pressure slowly–results in slow equilibration with brain
- slow onset of action
fastest onset of action (low blood solubility) to slowest onset o f action (high blood solubility)–drugs
-NO
-Desflurane
-Sevoflurane
-Isoflurane
-Enflurane
-Halothane
(NO, DSIEH)
increase in pulmonary blood flow (increase CO)- causes what?
- increases uptake of anesthetic and decrease the rate by which Fa/Fi rises-decreases the rate of induction of anesthesia (Fa decreases bc of the increased pulmnonary blood flow–dilutes the drug in alveoli)
- will increase uptake of anesthetic into blood–but will be distributed and diluted into all tissues (not just the CNS)
the slower the rate and extent of tissue uptake–does what to alveolar-venous partial pressure?
-greater the difference in anesthetic gas tensions bw arterial and venous blood–more time it will take to achieve equilibrium with brain tissue
larger alveolar-venous partial pressure differences means?
-less drugs are returning for elimination, which may increase the time for awakening
depression of respiration by opioid analgesics–does what to onset of anesthesia
-slows onset of anesthesia of inhaled anesthetics if ventilation is not assisted
increasing pulmonary blood flow (CO)–does what to rate of increase in arterial concentration
-slows rate of increase in arterial concentration of anesthetic because a larger volume of blood is exposed to anesthetic
what organs have higher immediate concentration of anesthetics
- brain, heart, liver, kidneys, splanchnic bed
- highly perfused (receive 75% of resting CO)
what tissues do anesthetics accumulate more slowly of anesthetics
- muscle and skin
- only recieve 1/5 of resting CO
major route of elimination from body of inhaled anesthetics
lungs
insoluble in blood and brain–rate of elimination?
faster
minimal alveolar concentration (MAC)–what is it?
-concentration of inhalation anesthetics that prevents movement in response to surgical stimulation in 50% of subjects (measures potency)
a dose of 1 MAC does what?
-prevents movement in response to surgical incision in 50% of patients
MAC values greater than 100%
-other agents must be supplemented to achieve surgical anesthesia (NO)
4 stages of increasing depth of CNS depression
- 1-stage of analgesia
- 2-stage of excitement
- 3-stage of surgical anesthesia
- 4-stage of medullary depression
stage 1
(analgesia)
- analgesia without amnesia
- with amnesia at end of stage
stage 2
(excitement)
- delirious
- respiration is irregular
- retching and vomiting may occur if patient is stimulated
- regular breathing is established at end of stage
stage 3
(surgical anesthesia)
-begins with regular breathing; extends to complete cessation of spontaneous respiration
stage 4
(medullary depression)
-severe depression of vasomotor depression center in medulla and respiratory center
inhaled volatile anesthetics–effects on CV system
-decrease mean arterial pressure in direct proportion to their alveolar concentration
Heart rate effects?
- Halothane–causes bradycardia
- Desflurane and isoflurane–increases HR
Respiratory effects?
- respiratory depressants
- depression of mucociliary function in airway–can result in pooling of mucus and postoperative respiratory infections
May cause hepatitis
-halothane (2 days to 3 weeks after exposure)
May cause renal toxicity
- agents metabolized to products including fluoride ions
- enflurane, sevoflurane
may cause malignant hyperthermia; antidote??
- inhaled volatile anesthetics in combination with succinylcholine
- antidote=dantrolene
IV anesthetics are?
- highly lipophilic
- go into highly perfused lipophilic tissues (brain, spinal cord)
- quick onset of action
Most commonly used as parenteral anesthetic
propofol
Propofol–MOA, characteristics, metabolized
- rapid onset, recovery–able to ambulate quickly after use
- time of onset–15-30 seconds
- continuous infusions and maintenance of anesthesia, sedation in ICU, conscious sedation and short-duration general anesthesia outside operating room
- agonist for GABA receptors–Cl current
- metabolized in liver
- low hangover effect–high plasma clearance
context–sensitivity half life
contact sensitivity half life–drugs that increase dramatically and drugs that increase modestly
-describes the elimination half time after a continuous infusion; key factor of a drug to be used as a maintenance anesthetic; propofol–brief contact sensitivity half life–prompt recovery!
- diazepam and thioental–half lives increase dramatically with prolonged infusions
- Midazolam, ketamine, propofol, etomidate–half lives increase modestly (high to low half lives) MKPE
propofol CNS effects
- general suppression of CNS activity
- no analgesic properties
- decreases cerebral blood flow and cerebral metabolic rate for oxygen–which decreases intracranial pressure
- burst suppression in EEG–neuroprotective effect during neurosurgical procedures
Propofol CV effects
- produces the decrease in systemic blood pressure due to vasodilation (most pronounced compared with other agents)
- hypotensive effects–inhibits normal baroreflex response
propofol respiratory effects
- potent respiratory depressant
- effects similar to propofol
- onset and recovery prolonged
- less pain on administration
- adverse effects–paresthesias and pruritus–mostly limited to first 5 minutes of administration
Fospropofol–what is it? Effects?
- prodrug of propofol
- effects similar to propofol
- onset and recovery prolonged
- less pain on administration
- adverse effects–paresthsias and pruritus–mostly limited to first 5 minutes of administration
Etomidate–effects? MOA?
- hypnotic but not analgesic effects
- MOA–enhances GABA on GABA receptors
- minimal CV and respiratory depressions (useful in patients with impaired CV, resp systems)
- rapid loss of consciousness and less rapid recovery rate
- metabolized by liver and in plasma
Etomidate–CNS, CV, Resp, endocrine effects?
- CNS–potent cerebral vasoconstrictor, decreases cerebral blood flow and ICP
- CV–stability is maintained–minimal change in HR and CO
- endocrine–causes adrenocortical suppression by inhibiting 11B-hydroxylase (needed for cholestrol–>cortisol)
- suppression lasts 4-8 hours after induction dose
Ketamine–effects? MOA?
- NMDA Receptor Antagonist
- dissociative anesthetic state–catatonia, amnesia, analgesia, with or without loss of consciousness
- lacrimation and salivation increase upon administration
Ketamine–CNS, CV effects?
- increases cerebral blood flow and CMRO2 (don’t use in patients with intracranial pathology)
- unpleasant emergence reactions
- may induce a euphoric state
- increase systemic BP, HR, CO (stimulates Symp NS)
- direct myocardial depressant (masked by stimulation of Sympathetic NS)
Ketamine–only IV anesthetic to produce?
-analgesia, stimulation of SNS, bronchodilation, minimal respiratory depression
Dexmedetomidine–MOA? effect? used for?
- alpha-2 adrenergic agonist
- hypnosis and analgesic effects
- sedative effect–sleep state (act of endogenous sleep pathways)
- moderate decreases in HR and systemic vascular resistance and systemic blood pressure
- used for short term sedation of intubated and ventilated patients in an ICU setting or as an adjunct to general anesthesia
Anesthetic Adjuncts–used to?
-augment components of anesthesia, permitting lower doses of general anesthetics with fewer side effects
opioid analgesics–used with? MOA? common agents? Adjunct to?
- -in combo with benzodiazepines to achieve a general anesthetic state
- agonists and opiate receptors
- fentanyl, sufentanil, remifentanil, morphone (FSRM)
- adjunct to IV and inhaled anesthetics to provide perioperative analgesia
Barbituates–common agents? MOA? effects? used for?
- Thiopental, Metohexital
- lipophilic, quick plasma:brain equilibrium
- CNS depression
- Respiratory depression
- GABAa R agonist–increases the duration of channel opening
- preferred for thiopental for short ambulatory procedures due to its rapid elimination
- induces CYP450 enzymes
Benzodiazepines–common agents? MOA? antagonist? Used for?
- diazepam, lorazepam, midazolam
- GABAa Rec agonist–increases R sensitivity to GABA
- used in perioperative period–anxiolytic properties and produces anterograde amnesia
- antagonist–flumazenil
- Midazolam–drug of choice for parenteral administration–frequently administer IV before patients enter operating room because rapid onset, shorter elimination half life
- potent anticonvulsant properties
