IV Anesthesia Flashcards
What is special about induction agents?
they have a short onset of action
List the induction agents used in IV anesthetics.
Thiopental
Propofol
Etomidate
List the additional agents (with longer onset of actions) used in IV anesthetics.
- Ketamine
- Diazepam, Lorazepam, Midazolam
- Morphine, Meperidine, Fentanyl, Remifentanil
What are the 4 components of achieving balanced anesthesia?
- Relieve Anxiety
- Relax Muscles
- Induce unconsciousness
- Prevent secretions
How does balanced anesthesia contrast with “neurolept” analgesia?
Use of neurolept analgesia produces pain relief and provides a state of indifference (patient is responsive to command but is not compromised by situational anxiety)
What agents are used for neurolept analgesia?
Droperidol
Fentanyl
What does droperidol do to the patient?
state of indifference, anti-emetic, anti-convulsant
What does fentanyl do for the patient?
analgesia
What do you add to droperidol and fentanyl to get neurolept ANESTHESIA?
N2O
What other combination can you use for neurolept analgesia in preparation for surgery (dry secretions + provide analgesia)?
- Atropine
- Opiate (morphine or meperidine)
What problem does the high level of lipid solubility pose for lipophillic (IV) anesthetics?
difficult to formulate them for injection
What are two “tricks” for making lipophillic anesthetics more soluble for injection?
- Adjust pH
- Use surfactant like propylene glycol or glycerol
- Use 2nd generation pro-drugs that yield same pharmacologically active product only once they are inside the body
What problems may adding surfactant to a lipophillic anesthetic pose?
can sometimes give rise to a direct toxicity to the lining of the vein into which it is being administered; this can sometimes be avoided by diluting the drug and giving it more slowly
What is the main MOA for IV anesthetics?
reinforcing the inhibitory action of GABA and glycine
Which two IV anesthetics also have aneffect on the NMDA receptor for glutamate?
Ketamine (major inhibition)
Propofol (minor inhibition)
List the IV anesthetics that are major inhibitors of GABA.
Barbiturates
Propofol
Etomidate
List the IV anesthetics that are major inhibitors of glycine.
Propofol
MOA of barbiturates.
prolong the binding of GABA to the receptor (increases the strength of the inhibitory effects of endogenous GABA, so increase efficacy)
MOA of benzodiazepines.
Produce only an allosteric change in receptor activity, that is to say, they shift the dose response curve for GABA binding to the left, the increase potency but not efficacy.
True or false: barbiturates and benzodiazepines both have a “ceiling effect”
FALSE: With increasing dose barbiturates produce greater and greater CNS depression, ultimately leading to coma and death.
True or false: it is just as easy to overdose on barbiturates as it is on benzodiazepines.
FALSE: benzodiazepines are much safer and difficult to overdose with unless combined with drugs or alcohol (CNS depressants).
What is the benzodiazepine antagonist that can rapidly reverse acute toxicities if they occur?
flumazenil
What neurotransmitter is used in the consciousness pathway that activates the thalamus?
Ach
What part of the brain is activated by Histamine, Serotonin, and GABA in the consciousness pathway?
cortex
How do inhaled anesthetics compare to IV induction agents in terms of onset?
When compared with the onset of anesthesia with an inhaled anesthetic, the effects of an IV induction agent are almost instantaneous.
Where do IV anesthetics distribute to in the body?
Out of plasma into high flow organs then re-distributes to other organs (eventually adipose tissue if dosage is high enough)
What is happening when a patient awakens after IV anesthetia?
Awakening of the patient is due only to drug re-distribution, the timescale is far too short for metabolism or excretion to have had a meaningful impact upon drug load in the body.
What is the rate-limiting step in final elimination of the drug following surgery?
release of drug from adipose tissue
What two IV anesthetics have half lives that increase dramatically with the duration of drug administration (due to accumulation and release from fat, metabolism and elimination)?
Diazepam
Thiopental
What is the barbiturate used in IV anesthesia?
Thiopental
MOA: Reinforce the inhibitory effects produced by endogenous GABA binding to its receptor system.
Etomidate
MOA: Reinforce the inhibitory effects produced by endogenous GABA binding to its receptor system (can function like GABA at high concentrations). Also can block the binding of glutamate to its receptor
Propofol
TOXICITY:
- Depress cerebral blood flow, cerebral O2 consumption and ICP.
- Slight increase in HR, inhibition of cardiac output.
- Inhibit respiratory rate and minute volume.
- Porphyria*
Thiopental
What affect does thiopental have on CYPs?
induction
TOXICITY:
- Depress cerebral blood flow, cerebral O2 consumption and ICP.
- Slight increase in HR, inhibition of cardiac output.
- Inhibit respiratory rate and minute volume.
- Anti-emetic*
Propofol
What is propofol infusion syndrome?
fatal cardiovascular and organ-systems failure of unknown etiology with protracted use
TOXICITY:
- Depress cerebral blood flow, cerebral O2 consumption and ICP.
- NO side effects with heart*
- Inhibit respiratory rate and minute volume.
- Inhibition of Steroidogenesis→ fatalities in elderly
Etomidate
Which IV anesthetic is NOT used in the ICU?
Etomidate
MOA: physical occulsion of the glutamate channel
Ketamine
What are the major ways in which ketamine’s toxicity differs from the other IV anesthetics?
- INCREASE in cerebral blood flow, NO EFFECT on cerebral O2 consumption, and INCREASE in ICP
- INCREASE HR, CO and MAP
- NO effect on respiratory system
- Analgesic
- Bronchodilatory
- Hallucinations
What does it mean when you call ketamine a “dissociative anesthetic”?
Analgesic that preserves pharyngeal and laryngeal reflexes (patients can be unconscious with eyes open)
How do you treat ketamine hallucinations?
benzodiazepine
Why aren’t benzodiazepines used to produce unconsciousness?
they have a long onset of effect
What do benzodiazepines do to a patient?
- Anticonvulsant
- Antiemetic
- NO ANALGESIA
What are the 3 most commonly used benzodizapeines in IV anesthesia?
Diazpeam
Lorazepam
Midazolam
Metabolism of midazolam.
Rapidly inactivated (halflife is 2-4 hours)
Metabolism of diazepam.
3 active metabolites (halflife is 20-40 hours)
Metabolism of lorazepam.
conugated for elimination
What happens when venodilation (decreased venous return) or reduced CO occur with administration of a benzodiazepine?
immediate compensation by increasing HR and myocardial contractility. Also, blood is shunted from the spleen and intestines into the portal system to increase venous return
When would the net effect of benzodiazepines be a depressant?
When compensatory reactions to venodilation and reduced CO cannot occur due to things like cardio-active drug preventing increases in HR or contractility or hemorrhage preventing blood mobilization from the periphery
List some advantages of opioid therapy.
- Absence of direct effects on the heart
- Maintenance of regional blood flow autoregulation
- Decreased airway reflexes (facilitates intubation)
- Pain relieved but patient arousable
- Non-organotoxic (no malignant hyperthermia)
List some disadvantages of opioid therapy.
- Incomplete amnesia
- Histamine-related reactions
- Increased blood requirements
- Prolonged respiratory depression in ICU
- CV instability (bradycardia, hypo- or hypertension; addition of N2O results in CV depression)
Which opioid is favored for a 20 minute procedure?
fentanyl (short duration of action, onset in seconds, no N/V)
Which opioid is favored for long lasting analgesia?
Morphine (poor BBB penetration but longer duration of action)
List the CV effects of opiates.
Dependent on speed of injection and presence of other CV agents.
- Hypotension (secondary to histamine release)
- Hypertension (reflex with light analgesia)
- R-A-A effect
- Intense pressor effect with naloxone
List the respiratory effects of opiates.
dose dependent respiratory depression due to unresponsiveness to CO2 in carotid bodies (reversible with naloxone or nalmefene)
List the other toxicities of IV opiates.
- Muscle rigidity (wooden chest)
- Increased ICP
- N/V, constipation, miosis
What is the overdose triad for opiates?
Pinpoint pupils
Decreased respiration
Coma
How does remifentanil differ from other opioid agents?
Remifentanil is an ultra-short acting drug that must be given by IV infusion. AND you must give analgesic coverage prior to terminating remifentanil infusion
True or false: effects of remifentanil are cumulative.
FALSE
What causes malignant hyperthermia?
Succinylcholine and volatile anesthetics leads to intracellular calcium release from the SR
Who gets malignant hyperthermia?
most commonly in young men as a result of genetic predisposition
What genetic predisposition exists for malignant hyperthermia?
Several genetic loci are implicated, most especially that of the ryanodine receptor (RYR1)
What is the presentation of a patient with malignant hyperthermia?
heat generation, increase (X 2-3) in end tidal CO2, total body rigidity, unexpected tachycardia and tachypnea, respiratory and metabolic acidosis
OR
unexpected cardiac arrest
How do you treat malignant hyperthermia?
- Stop giving trigger agent
- Cool patient
- Acid-base support (hyperventilate with O2)
- Dantrolene
MOA of dantrolene.
permits the calcium to be repackaged back into the sarcoplasmic reticulum
DDI of dantrolene
CCBs (which interfere with calcium entry at the cell surface)
Prognosis for malignant hyperthermia.
in young males with undiagnosed cardiomyopathy (50% mortality)
