Induction Drugs Flashcards
Midazolam Elimination (beta) Half-Life
2-4 hours
Etomidate Elimination (beta) Half-Life
2-5 hours
Propofol Elimination (beta) Half-Life
1-5 hours
Ketamine Elimination (beta) Half-Life
2-3 hours
Dexmedetomidine Elimination (beta) Half-Life
2-2.6 hours
Diazepam vs Lorazepam Elimination (beta) Half-Life
Diazepam: 20-50 hours
Lorazepam: 10-16 hours
Volume of Distribution (what it means if its large vs small)
How extensively a drug distributes throughout the body
- Large (>0.6L/kg): Drug is widely distributed, likely lipid soluble
- Small (<0.4L/kg): Drug contained in plasma, likely water soluble (too ionized to pass through membranes into the tissues)
Volume of Distribution of Propofol vs Midazolam
Propofol: 2-8L/kg
Midazolam: 1-1.7L/kg
Protein binding of drugs, when its significant, what populations to worry in
Drugs bound to protein in circulation (primarily albumin) aren’t free to act on receptors/aren’t active
Significant when >90% of drug is protein bound, any change in protein/albumin level will drastically change the active level of the drug in the body
Populations: Malnutrition, severe liver and kidney disease, last trimester of pregnancy
Reason someone falls asleep so quickly after Propofol and why they wake up so quickly (where it goes)
Rapid distribution to the brain = why they fall asleep so quickly
Redistribution = why they wake up so fast, redistributes from brain -> vital organs -> muscle -> fat
GABA receptor (what it does, which drugs work here)
#1 inhibitory receptor in the brain When receptor binds it opens a Cl channel, Cl goes into the cell and hyperpolarizes it Drugs: Benzodiazepines, Propofol, Etomidate, Barbiturates, and inhalation agents?
NMDA receptor (what it does, which drugs work here)
Excitatory receptor in the brain
Activated by agonist glutamate and co-agonist glycine when voltage changes displace Mg from the ion channel
Drugs: Ketamine is an antagonist to glutamate
Mechanism of action (receptor type) of benzos, Propofol, Etomidate, ketamine, and precedex
GABA mimetic -Benzos, Propofol, Etomidate NMDA receptor antagonist/Glutamate antagonist -Ketamine Presynaptic alpha 2 receptor agonist -Precedex
Propofol use for asthmatics
Many generic formulations have sulfites, which shouldn’t be given to asthmatics (Product should be labeled as containing them)
Diprivan (Astra Zeneca brand name) doesn’t contain them and is safe to use for these patients
Propofol use in patients allergic to soy/eggs
No evidence that it should be avoided
Some other countries labeling warns against it but US doesn’t
Propofol induction dose, onset, duration
Induction dose: 1-3mg/kg
Onset: <30 seconds
Duration: 3-8 minutes
Etomidate induction dose, onset, duration
Induction dose: 0.2-0.3mg/kg
Onest: <30 seconds
Duration: 5-10 minutes
Midazolam induction dose, onset, duration
Induction dose: 0.2-0.4mg/kg
Onset: 30-60 seconds
Duration: 15-30 minutes
Ketamine induction dose, onset, duration
Induction dose: 1-2mg/kg
Onset: 45-60 seconds
Duration: 10-20 minutes
Precedex induction dose, onset, duration
Induction dose: 1mcg/kg over 10 mins, gtt 0.2-0.7mcg/kg/hr
Onset: 2-5 minutes
Duration: 10-30 minutes
Excitatory activity of induction drugs (what/why, what drugs it happens with)
Myoclonia/involuntary muscle movements
- Happens when they’re in stage 2, “uneven distribution” to CNS, certain parts of the brain are inhibited before others
- Propofol: +
- Etomidate: +++
- Ketamine: ++
Flumazenil (Alpha and beta half lives, dosing)
Distribution half-life: 7-15 minutes
Elimination half-life: 45 minutes (faster than benzos, might need redosing)
-Give in 0.2 mg increments, max 1mg/20mins
Induction drug and opioid effect on CBF/CMR
All decrease CBF and CMR except ketamine increases CMR
- Remifentanil may cause very slight increase/no change in CMR
- Other opioids cause no change or decrease in CBF
Mechanisms for decreased BP (5)
- CNS depression
- Direct cardiac depression
- Decreased SVR
- Baro-receptor depression
- Hormonal changes
Induction drug effect on respiratory system
Propofol and Etomidate cause dose dependent decrease in respiratory drive
Ketamine maintains reflexes and respirations, is a significant bronchodilator (because of catecholamine release)
Propofol infusion syndrome
Associated with long-term high-dose infusions (hasn’t occurred in anesthesia)
Current theory
-Propofol inhibits intracellular energy production by inhibiting transport of long chain fatty acids into the cell and inhibiting the mitochondrial respiratory chain
Associated with significant morbidity/mortality
Unique properties of ketamine
- Produces dissociative amnesia
- Increased CMRO2, CBF, ICP
- Increased IOP, nystagmus
- Analgesic (only induction drug that does this)
- Increases BP/HR
- Bronchodilator
- Maintains airway reflexes and RR
- Increases salivation and respiratory secretions
- Increases muscle tone
- Emergence delirium, nightmares, hallucinations (~5% of the time)
Etomidate effect on corticosteroid synthesis
Biosynthesis of cortisol and aldosterone are blocked because Etomidate inhibitos 11-beta-hydroxylase, which is the rate limiting enzyme in their production
Etomidate and ketamine effect on PONV
Increase recovery nausea and vomiting
Dexmedetomidine mechanism of action
Highly selective alpha 2 presynaptic adrenergic receptor agonist
-Has sedative, anxiolytic, analgesic, and sympatholytic properties (without also causing respiratory depression)
Dexmedetomidine and postop shivering
Can be used to stop shivering (currently use Demerol which is a narcotic and can increased N/V)
Porphyria (and which drugs aren’t allowed for these patients)
Deficiency in enzyme activity in the biosynthesis of heme molecules
- The rate limiting enzyme in heme production (ALA synthase 2) is induced by Etomidate
- Patients with acute intermittent porphyria can’t control how much heme is in the body and can’t tolerate increased levels
- Drugs not allowed: Etomidate, ketamine, ketorolac, amiodarone, calcium channel blockers
Droperidol
Butyrophernone drug class (same as Haldol, antipsychotics, tranquilizers)
- Blocks dopamine in the brain, produce CNS depression, tranquility, cataleptic immobility
- Has a black box warning for arrhythmias, have to get a 12 lead before giving to check QT
- Prevents pruritis from opioids
- Used not for antiemetic properties (equal effect as ondansetron but more cost effective)
