IV Anesthetics: Sedatives and Hypnotics Flashcards
Review: What are the 5 A’s of surgical anesthesia?
Amnesia Anesthesia Analgesia Akinesia (not moving) Areflexia (lack of autonomic reflexes)
7 uses of sedatives and hypnotics other than general anesthesia for surgery? (probs not necessary to memorize)
ICU sedation Procedural sedation Seizure treatment Generalized anxiety disorder, panic disorder EtOH withdrawal Insomnia Muscle spasms
5-6 neurotransmitters that sedatives and hypnotics work on?
GABA/galanin Histamine Serotonin Norepinephrine Acetylcholine
What are the 2 major principles to think about in the pharmacokinetics of IV anesthetics?
Drug redistribution
Context-sensitive half time
Review: What makes up the well-vascularized central compartment (in pharmacokinetics)?
Brain, Heart, Kidney
What’s the difference between distribution and elimination half life? Which one matters more?
Distribution half life: Time it takes drug in central compartment to be reduced by 50%, due to distributing into other compartments, esp. muscle and fat.
Elimination half life: Time it takes total drug in body to be reduced by 50%.
Distribution half life is what actually matters, as that represents the drug being where it does its job.
What is context-sensitive half time? Why does it happen?
The longer you infuse a drug, the longer it takes to eliminate once to stop infusing it.
This happens because the drug accumulates in fat over time, which will be released when the infusion is stopped.
What do you do different with sedatives / hypnotics that have a context-sensitive half life that increases sharply with infusion duration?
Usually don’t give them IV. Better suited for PO, suppository, IM etc.
What’s the preferred drug of anesthesia induction?
Propofol
What’s the redistribution half life of propofol? (roughly)
2-8 minutes. Really short. Even though the elimination half life is 4 - 24 hours, the drug effect goes away very quickly.
Special fact about propofol metabolism?
It’s partially metabolized extrahepatic-ly, including in the lungs.
Is the central compartment for pharmacokinetics lareger in children vs. adults? How about older adults vs. young adults?
Largest in children. “Kids are all head.”
Smallest in older adults.
MoA of propofol? (roughly)
Potentiates GABA-A receptor. (Also affects alpha 2 adrenal receptors, NMDA glutamate receptors, and glycine receptors)
Does propofol cause analgesia?
No. It has no effect on pain, only consciousness. You need to give something else for that.
What’s the effect of propofol on blood pressure? How? (3 things) On heart rate?
Decreased blood pressure via.. - vasodilation - decreased sympathetic tone - myocardial depression (maybe) Heart rate is decreased.
3 respiratory effects of propofol?
Decrease tidal volume +/- increased RR. (hypopnea or apnea).
Decreased response to high CO2 / low O2.
Bronchodilation.
(note similarities to respiratory effects of inhaled anesthetics)
2 neurological effects of propofol?
Decreased metabolic rate -> “burst suppression”
Decreased cerebral blood flow -> “brain relaxation” (the brain actually shrinks, useful in neurosurgery)
Adverse effects of propofol? Name 4.
Pain on injection.
Propofol-related infusion syndrome (PRIS) = metabolic acidosis with long-term use.
Hypertriglyceridemia and pancreatitis (propofol is suspended in fat).
Decreased PMN chemotaxis.
2 absolute contraindications to propofol?
Allergy to propofol.
Allergy to egg protein.
Relative contraindications for propofol? (2 main ones)
Hemodynamic instability (due to cardiovascular effects).
Hx of awareness under anesthesia.
(and, Dr. Lane-Fall notes, using it on your own at home)
What killed Michael Jackson?
Taking too much propofol at home.
5 reasons why people abuse propofol?
Rapid onset/offset Potent hypnotic Increases dopamine in nucleus accumbens -> euphoria, feeling of well-being Sexual dreams Not scheduled by DEA (Don't do it.)
What’s the main reason why people opt for etomidate?
Patient has hemodynamic instability / undergoing cardiac surgery.
How is etomidate different from propofol in its effects? (name 4-5)
Causes adenocortical suppression. Minimal to moderate cardiovascular effects. Minimal to moderate respiratory effects. Can cause seizures. Worse nausea/vomiting than propofol.
What are the 2 major adverse effects of etomidate?
Nausaea/vomiting (moreso than propofol).
Adrenal suppression.
1 absolute and 3 relative contraindications for etomidate?
Absolute: Allergy to etomidate.
Relative:
-adrenal insufficiency
-critical illness, especially septic shock
-history of post-operative nausea/vomiting
What anesthetic is also used for lethal injection?
Thiopental.
What class of drug is thiopental a member of? (or, at least, is friends with?) What’s their common MoA?
Barbituates. Potentiate GABA receptors by stabilizing the open conformation of the Cl- channel.
What’s worth of note about the metabolism of thiopental? (2 things)
It induces it the enzymes that biotransform it, thus may need to give higher doses after giving for a long duration.
Exhibits zero-order kinetics “at supratherapeutic doses” -> linear elimination.
To people with which rare condition must you never give thiopental?
People with acute intermitted porphyria. (we didn’t even cover this in MDTI)
Physiological effects of thiopental (and a similar drug, methohexital)?
Very similar to propofol.
Except- methohexital is more predisposing to seizures.
4 adverse effects of thiopental?
Garlic/onion taste. (must be a similar enough sulfur-containing molecule)
Tissue irritation, possibly necrosis.
Stimulation of porphyrin formation.
Anti-analgesic effect.
Absolute contraindications to thiopental? (name 2)
Allergy to thiopental.
Acute intermittent porphyria.
Relative contraindications for thiopental? (name 2)
Hemodynamic instability. (like propofol)
Questionable IV access (i.e. you don’t want this irritating stuff getting into tissues)
Which street drug is ketamine most like? Which receptor do they act on?
Most like PCP. Both antagonist NMDA receptor.
How is the distribution half life of ketamine compare to the other sedatives / hypnotics discussed?
At 11 - 16 minutes, it’s slightly longer (but still not that long).
What’s special about the metabolism of ketamine?
One of its metabolites, norketamine, has desirable analgesic effects.
MoA of ketamine? (more than one thing)
Primarily: NMDA antagonist. But it's dirty also has affects on... GABA (+) Nicotinic AChR (-) 5HT-3 (+) <- a serotonin receptor Opiate receptors (+)
Does ketamine decrease sympathetic tone?
No. It increases it - can actually cause hypertension and tachycardia.
Does ketamine suppress respiration?
No. Which makes it nice for additional pain relief without using opioids.
What are 4 undesirable affects of ketamine?
Dysphoria.
++ salivation and lacrimation. (makes intubation a pain)
Sympathetic simulation -> increased myocardial work.
Increased ICP. (bad for neurosurgery)
Absolute contraindication for ketamine?
Ketamine allergy. (if there’s only one, it must be that)
Relative contraindications for ketamine? *(name 4)
Psychosis
Extremely compromised myocardial function
Inability to tolerate tachycardia, hypertension.
Intracranial hypertension.
What drugs can mitigate the dissociative effects of ketamine?
Benzodiazepines.
What drug reverses the effects of benzodiazepines?
Flumazenil
What drug reverses the effects of opiods?
naloxone / naltrexone
How are alpha-2 adrenoreceptor antagonists (dexmedetomidine and clonidine) useful?
Inducing actual sleep / sedation during which the patient can respond / be aroused. Useful for awake craniotomy.
What effect do dopamine antagonists (droperidol and haloperidol) have? (very simply)
Induce catatonia - people don’t move. But they are conscious and remember.
What’s the sedative in Tylenol PM?
diphenhydramine aka Benadryl. (due to its antihistamine activity?)
What hypnotic / sedative is great if you don’t want / get get IV access?
Ketamine.
