Induction Agents (2) Flashcards
What neurotransmitters do most inhibitory neurons in the brain and spinal cord use?
GABA or glycine
What neurotransmitter do most excitatory neurons in the brain use?
Glutamate
What is the purpose of an IV induction agent?
Move the patient from a state of consciousness to a state of unconsciousness
Moving from a state of consciousness to unconsciousness should happen how?
Rapidly, smoothly, without dysphoria, reversibly, reliably, and in an autonomically stable fashion (no current agent meets all these requirements)
What chart describes the stages of anesthesia and is used to assess the depth of general anesthesia?
The Guedel chart (created in 1937)
In general when GABA receptors are stimulated there is a ________ in neuronal activity
Decrease
What receptor is inotropic, and associated with binding sites for benzodiazepines, propofol, and barbiturates?
GABA-A
What type of channel are GABA-A channels
Ionotropic chloride channels
What type of channels are GABA-B and what do they effect?
Metabotropic, when activated, GABA-B receptors cause potassium channels to open, allowing positively charged potassium ions to flow out of the neuron making it hyperpolarized
What type of channels are GABA-C channels and where are they located?
Ionotropic chloride channels, found primarily in the retina
All anesthetics except ketamine and etomidate (barbiturates have little or no effect) stimulate what receptors
Glycine
All anesthetics except ketamine stimulate what receptors?
GABA
Most excitatory neurons in the brain use glutamate as their neurotransmitter. What channels does glutamate modulate?
Sodium channels
What does NMDA stand for?
N-methyl-D-aspartate
What type of receptor is the NMDA receptor?
Excitatory glutamate receptor
Barbiturates work on what receptor and what subunit?
GABA-A (beta subunit)
Barbiturates are metabolized by what?
CYP2C9 and 3A4
Barbiturate metabolites are:
Almost all inactive, water soluble, and excreted in the urine
Barbiturates accelerate what related to blood?
Heme production; by stimulating D-aminolevulinic acid synthetase (acute porphyria risk)
If injected intra- arterially what risk do barbiturates have?
Venous thrombosis risk
Patients treated with barbiturates for seizure disorders metabolized drugs ___ x faster than expected (especially muscle relaxants)
2 x
Barbiturates have what GI risk/side effect
PONV risk
What drugs can cause exacerbations of Porphyria?
Barbiturates (in rare cases some antibiotics, birth control pills, ketamine, and etomidate)
What is Porphyria?
rare group of disorders that affect the body’s ability to produce heme. These patients are deficient in enzymes within the heme biosynthetic pathway.
What is the rate limiting enzyme in heme synthesis?
ALA (aminolevulinic acid)
How do you pronounce Porphyria?
poor fear ya
What genetic factors are involved with Porphyria?
Non sex linked autosomal dominant, variable expression (chromosome 11)
(Variable expression describes a range of symptoms that can occur in people with the same genetic condition)
What are triggers of Porphyria?
Drugs are the most important trigger but other triggers can include infection, fasting, stress, menstruation and hormonal fluctuations
Symptoms of Porphyria:
Symptoms usually occur as attacks that develop over several hours or days
~ Abd pain (severe) most common symptom
~ Cause, vomiting, constipation, pain in the back arms and legs, muscle weakness, urinary retention, palpitations, confusion, hallucinations, seizures
Why can barbiturates cause a Porphyria attack?
barbiturates accelerate heme production, so it can accelerate the Porphyria process
Methohexital onset:
15-30 seconds
Methohexital Peak:
within 1 minute
Methohexital E1/2T:
3-6 hr
Methohexital VD:
2 L
Methohexital Protein Binding:
75%
Methohexital PKA:
Ph 10 - 11 of 1% solution
Methohexital excretion:
Renal
Methohexital metabolism
Hepatic oxidation via CYP2C9 and 3A4
Methohexital DOA:
5-10 min
Methohexital Class / structure:
~ Sedative/hypnotic/barbiturate
~ 6 carbon ring with O at C2 (oxybarbiturate) branched chain at C5 (hypnotic properties) and methyl group on N (decrease in seizure threshold)
Methohexital MOA:
Acts on GABA-A (Beta subunit) increasing the duration of Cl- channels being open (hyper polarizes the neuron)
Methohexital Dose:
Dose: Induction: 1 - 1.5 mg/kg IVP or 50-120mg (avg 70mg) at 10mg (1ml of 1% solution) over 5 seconds Maintenance: 20-40mg IVP q4-7min PRN; or 3ml/min (1gtt/sec); PEDS: induction dose- 6.6-10mg/kg IM once (5% conc); rectal 25mg/kg using 1% soln
Methohexital SE:
SE: hypotension and tachycardia may occur post induction dose; histamine release, coughing, hiccoughing, movement, laryngospasm ↑PONV
Methohexital Cautions:
~Long hangover/impaired judgment ~Decreases seizure threshold (ECT) ~Hyperalgesia with lower doses ~Can induce enzymes –> accellerate metabolism of other drugs ~CONTRAINDICATED in pts at risk for porphyria ~Intra-arterial injection- venous embolism
Etomidate, Ketamein and Propofol onset time:
30-60 seconds
Etomidate DOA:
3-5 min
Etomidate Peak:
Within 1 min
Etomidate E1/2T:
2-5 hours
Etomidate VD:
Large 2.5 - 45. L/kg
Etomidate Protein binding:
75%
Etomidate PKA:
4.2 WB (99% non-ionized at physiologic pH)
Etomidate excretion:
2% excreted unchanged, 85% renal, 13% in bile
Etomidate class/structure:
Sedative/hypnotic, imidazole derivative (aromatic N ring) -predominately R (+) isomer for anesthetic effect (5x more potent than S(-) isomer)
Etomidate MOA:
Binds to GABA-A (beta subunit) enhancing affinity for neurotransmitter GABA increasing its duration which increased dependent chloride channel opening thus hyperoplarizing the neuron.
Etomidate SE:
SE: NO ANALGESIC EFFECT; can increase EEG activity (esp. in patients with seizure history) CV: MINIMAL CV effects, slight fall in PVR Resp: min depression of CO2 response GI HIGH INCIDENCE FOR PONV (30 - 40%) “vomidate”
Etomidate Catuions:
Cautions: Pain on injection site d/t propylene glycol, **INHIBITS enzyme 11 beta hydroxylase (adrenocorticall suppression [lasting 4 - 8 hours]; acute porphyrias; Relatively hight margin of saftey (30-fold difference: effective dose vs. lethal dose)
Etomidate metabolism:
hepatic ally by ester hydrolysis to ethyl alcohol
