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Which compound has a pH of 10-11 and why?
Barbiturates, due to the inclusion of sodium carbonate which prevents precipitation of free acids by atmospheric carbon dioxide
Where does Ketamine work?
Old theory: functionally dissociates thalamocortical and limbic systems
New theory: binds noncompetitively to the phencyclidine recognition site on the NMDA receptor (inhibiting activation of the receptor)
What are the steps in treating intra-arterial injection of barbiturates?
1. LEAVE THE IV IN!
2. Remove any restrictive garments (on the patient)
3. Inject papaverine or procaine to inhibit smooth muscle spasm
4. Heparinize unless contraindicated
5. If necessary, perform sympathetic block of brachial plexus and/or stellate ganglion to relieve pain and dilate collateral circulation
What are two things that can adversely affect rectal barbiturate administration?
2. Incorrect catheter placement, leading to inadequate absorption
Which class of drugs has an antianalgesic effect and how can the anesthetist counteract this?
Barbiturates, supplement with fentanyl
What effects do barbiturates have on the CV system?
Transient reduction in CO, increase in HR, hypotension secondary to vasodilation
How do barbiturates affect the respiratory system?
Decreased ventilatory response to hypercarbia and hypoxemia, decreased minute volume and tidal volume (all dose dependent)
How do barbiturates exacerbate acute intermittent porphyria?
They stimulate the activity of a mitochondrial enzyme which accelerates the production of heme
You're in the OR and your patient begins to seize. What is the first drug you can grab?
Midazolam (0.1mg/kg IV for suppression of seizure activity)
How is midazolam buffered in the bottle?
Its benzene ring is open in the bottle, making it water soluble with a pH of 3.5. In the body the ring closes and the drug becomes lipid soluble.
What six properties do benzodiazepines have?
Hypnotic, sedative, anxiolytic, muscle relaxant (at higher doses), amnestic (anterograde), anticonvulsant
What is the mechanism of action of benzodiazepines?
Bind to alpha subunit of GABA receptor, enhancing inhibitory effect of GABA (inhibition is due to increased influx of chloride ions into the cell, increasing the polarization of the nerve cell so ability to promote a signal is decreased)
How protein-bound are benzodiazepines? Who needs caution with administration?
90-98% protein bound, leaving 2-10% free drug. Use caution with debilitated patients with low plasma proteins.
Which factor impacts the rate of biotransformation most?
Patient age. The older the patient, the less drug needed. 30 is the peak of physiological function. :(
Which population needs the most caution when administering benzodiazepines and why?
Elderly, because benzos are dependent on hepatic microsomal enzyme activity, hepatic blood flow, protein binding, and lipid solubility. Elderly patients have slow drug absorption, decreased plasma protein, decreased hepatic blood flow, decreased metabolism, decreased CO, and decreased circulation time (??? this was in his slide... doesn't he mean INcreased circ time?)
Does diazepam create active metabolites?
Yes, demethylation yields oxazepam, which is pharmacologically active.
Benzodiazepines have long half-lives. Why is this important?
It's important to consider for elderly patients, as well as for dosing intervals.
What effect does enterohepatic circulation have on diazepam?
Produces a secondary peak in plasma concentration within 6-12 hours
What effects do benzos have on the CNS?
Dose-related decrease in CBF, ICP, and CMRO2, and increase in seizure threshold.
How do benzos affect the respiratory system?
Dose-related decrease in hypoxic drive/response to CO2, decreased ventilation (higher doses)
How do benzos affect the CV system?
No actual CV effect, but a decrease in HR and BP may occur due to anxiolysis
What is the problem when you combine the half-life of romazicon with the half-life of benzos?
Sedation can return. Patient should be monitored for 120 minutes after giving romazicon.
How is ketamine metabolized?
The hepatic microsomal enzyme is responsible for the biotransformation of ketamine.
Does ketamine form an active metabolite?
Yes, ketamine is demethylated into norketamine, which is 20-30% pharmacologically active
How does ketamine affect the CNS?
Produces profound analgesia, a dissociative state of amnesia, and a cataleptic state (eyes open, pupils reactive to light, corneal reflexes intact, lacrimation and blinking)
Agree or disagree?: Ketamine increases CBF?
Agree, but only transiently. Increases by 60-80%, and returns to normal in 20-30 minutes
What effects does ketamine have on the CV system?
It is an all-around circulatory stimulant: increases BP, CO, HR, CVP, myocardial contractility, and myocardial O2 consumption.
What causes the transient changes in CV after a dose of ketamine?
Sympathetic nervous system stimulation
Ketamine is contraindicated in which patients?
CHF, CAD, uncontrolled HTN, neuro, cerebral aneurysms.
What patients are the exception to the ketamine CV rule?
Those who are catecholamine depleted (then ketamine will act as a myocardial depressant)
What respiratory side effects are associated with ketamine?
Minor and/or transient decrease in tidal volume (accentuated with larger doses or concomitant opioid), increased salivation
Can a person anesthetized with ketamine protect their own airway?
Theoretically, yes. Ketamine preserves the laryngeal, pharyngeal, cough, sneeze, and swallow reflexes
How does etomidate work?
Depresses the RAS and mimics the inhibitory effects of GABA, producing a hypnotic CNS effect
Agree or disagree?: Etomidate is water soluble?
Disagree, it is lipid soluble and results in extensive redistribution to organs and tissues after one minute
How is etomidate metabolized?
By hepatic microsomal enzymes and produces plasma esterases via hydrolysis, resulting in inactive metabolites
Does etomidate have analgesic properties?
No, due to its inability to block afferent pain stimulus to the thalamus
_________ ________ is a distinct disadvantage of etomidate which produces ________ ________
Excitatory phenomenon; muscle tremors
Agree or disagree?: Etomidate produces profound CV changes with normal doses. With higher doses?
Disagree. Changes to HR, SV, and CO are minimal. With higher doses, significant decrease in BP and CO occur.
What effect does etomidate have on respiration?
Dose dependent respiratory depression, including increased RR, decreased MV, apnea followed by hyperventilation
When a patient has an egg allergy on their chart, can you give propofol?
Yes, because allergy is usually to the egg protein (egg white), and propofol contains egg phosphatide (yolk)
What are two ways to minimize the pain of propofol injection?
1. Use a large vein (like the antecubital)
2. Pretreat with lidocaine 1% 1mL IV
Agree or disagree?: You can mix lidocaine with propofol in the same syringe to minimize injection pain.
Disagree. This can result in coalescence of oil droplets, destabilizing the propofol.
How long is propofol good for after drawing it out of the vial?
Six hours, as long as sterile technique was used
Ideally, propofol should be pushed at a rate of ___________
40mg in 10 seconds for healthy patients, 20mg in 10 seconds for elderly patients
Agree or disagree?: Propofol is a great choice for induction in pediatrics under three years old, pregnancy, labor and delivery, and lactating ladies
Disagree. While propofol can be used for induction over three years of age and maintenance over 2 months of age, it is not recommended for the other populations listed due to transfer to fetus/infant through blood/breast milk.
My patient woke up after like eight minutes after I gave a bolus of propofol. Why?
Propofol rapidly redistributes from the central compartment to the peripheral compartment, decreasing the plasma concentration in 8-10 minutes.
My patient woke up with a wicked hangover. Is it because I gave him propofol?
No, propofol has less hangover effect compared to other agents secondary to high plasma clearance
The pharmacokinetics of propofol are affected by _______________
Age, debilitating conditions, cardiac compromise, and weight
Describe the effects of propofol on the CNS
Decreases CMRO2, CBF, ICP, and CPP, making it a good choice for neuro anesthesia
Describe the effects of propofol on the CV system?
Decreases MAP, SBP, SVR, and CO due to negative inotropic properties (up for debate), causes arterial and venous vasodilation, and inhibits normal baroreceptor responses, making it a bad choice for cardiac anesthesia (but it's still the best thing we have)
What effects does propofol have on respiration?
More respiratory depression than is seen with pentothal, can cause apnea, more depression of upper airway reflexes than is seen with pentothal, minimal bronchial tone alteration (good for asthmatics)
Generic propofol contains what bacterial retardant, and why is it bad?
Metabisulfate, which can trigger an asthma attack
What makes propofol a good antiemetic?
It possesses antidopaminergic qualities, which depress the CRTZ, decrease glutamate and aspartate in the olfactory cortex, and reduces serotonin concentrations in the area postrema
Your patient is vomiting, but you've already given them propofol, zofran, and decadron. What else can you try?
Reglan, because their stomach may be full of blood
Propofol infusion syndrome causes what muscle-wasting condition? How long does it take?
Rhabdomyolysis, after a propofol infusion lasting 3-4 days
What are the three conditions that propofol infusion syndrome causes?
Myocardial failure, metabolic acidosis, and rhabdomyolysis
What is thought to cause propofol infusion syndrome?
Large lipid load associated with prolonged infusion
What is the chemical structure of Precedex, and to which other drug is it related?
Imidazole derivative; etomidate
Agree or disagree?: Precedex is FDA approved for anesthesia
Disagree. This is an "off-label" use. Only approved for short term use in ventilated ICU patients.
Why do we care about Precedex? What's so great about it?
Produces a more "natural" sleep state than other sedatives, produces less respiratory depression, and produces only moderate changes in SVR and HR
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