2. General Anesthetic Drugs Pt. II Flashcards
General Principles
- Injectable general anesthetics are typically administered ____ to induce and in some instances to maintain general anesthesia.
- Typical scenario is to induce with an ____ agent and maintain anesthesia with gaseous agents
- Can use intravenous agents alone (total intravenous anesthesia) employing a ____ infusion with ____ boluses as needed to rapidly adjust anesthetic depth.
intravenously
intravenous
continuous
intermittent
Injectable Agents • Fentanyl and sufentanil – \_\_\_\_ • Diazepam and midazolam – \_\_\_\_ • Methohexital and thiopental – \_\_\_\_ • Propofol – \_\_\_\_ • Ketamine – \_\_\_\_ • INNOVAR = Fentanyl + droperidol –\_\_\_\_
opioids benzodiazepines barbiturates ultrashort acting nonbarbiturate dissociative anesthetic neuroleptic anesthesia
Barbiturates
- Thiopental
- Methohexital
____ therapeutic indices. Another way of looking at it is via graded dose response curves, barbiturates is very ____, benzos are pretty ____. Difficult to progress from sedative to GA or coma with ____, but pretty easy to do with barbiturates
low
steep
flat
benzos
Barbiturate General Properties 1
- ____ distribution into and out of brain
- ____ injections rapidly (within seconds) produce general anesthesia
- Peak brain concentrations reached in one minute with only ____% remaining in CNS at 30 minutes
- Drugs can also be given as ____ infusion over 30 seconds
- Thiopental solution is constituted at pH ____, so extravasation outside the vein can cause tissue ____
rapid bolus 10 slower 10-11 damage
Barbiturate General Properties 2
- Sleep times are ____ minutes with thiopental and ____ minutes with methohexital
- Both drugs can depress ____ – No ____ agent
- Barbiturates in general are ____ (actually increase a patients perception of pain) thus other agents must be on board for ____ control (local anesthetics, N2O etc)
- Methohexital popular among oral surgeons as part of an ____ sedation cocktail
10-20 5-7 respiration reversal hyperalgesic pain intravenous
Benzodiazepines
- diazepam
- midazolam
- triazolam
- flumazenil
- benzodiazepine ____
antagonist
Benzodiazepine General Principles 1
• In dentistry intravenous benzodiazepines usually employed for ____ sedation
• Can titrate to effect – midazolam approximately ____X more potent that diazepam
• ____ dose bolus injections especially with midazolam can induce general anesthesia
• Diazepam must be dissolved in ____ (non-water soluble). Burns on injection, can cause ____
• Midazolam is ____ soluble
• ____ effect at sedative dosages
• Much ____ therapeutic index than barbiturates; however injectable benzos occasionally cause respiratory ____ (reversal agent = flumazenil)
conscious 3 high propylene glycol venous phlebitis water anterograde amnesic higher depression
Patients recall of local anesthetic and surgery
He didn’t like like the people that did this. Recall of LA injection and recall of the 3rd molar surgery. He doesn’t know how they did the placebo, but they recalled the injection and the surgery.
Goes through midazolam, 20% recall injection, anterograde amnesia effect, 60% recall the surgery. in Midazolam + midazolam they were allowed to give more during the procedure. (Whereas midazolam alone they only have saline on the second) but less than 20%, and less than 40% recall of LA and surgery.
Midazolam plus fentanyl: shows the amnesia effect is all the ____
Adding methohexital or brevital: you do get an additional drop in recall of ____, but not really any for the surgery (compared to M + M)
midazolam
LA
Quantal Dose-Response and Therapeutic Index
Did this last year. How to calculate therapeutic index. Want to know how much Valium/diazepam is needed to knock someone out but still live to tell about it.
See some hyper responders, the mass middle, or Valium junkie rats. Curve converts to cumulative percent asleep with a certain dose. Eventually find the dose that at least 50%. This give ____, but that’s useless without knowing ____ (lethal dose for 50% of people)
ED50
LD50
The ratio isn’t quantitative to transfer to ____, but you can ____ infer a therapeutic index. Really low TI better be a wonder drug, cancer or life saving, not to treat acne.
Can see a huge difference between ____ and LD50, TI = 40 (4000mg/100mg).
Drugs w/ TI > ____ are relatively safe.
humans
qualitatively
ED50
15
Graph of dosage of benzo, on a ____ scale, can see the TI.
log
Compare benzo to barbiturate.
The ED curve looks ____ for both, but the LD of barbiturates is shifted much ____ to the ED curve. 700/140 = TI = ____
Phenobarbital in humans has a TI around ____, and that’s the safest one. The other gets closer to 5.
TI(diazepam) = ____
similar closer 5 8-9 40
Molecular pharmacology differences between benzo and barbiturates/alcohols
- Benzodiazepines increase frequency of ____ channel openings
• Barbiturates and alcohols:
• increase duration of ____ channel opening
• physically open chloride channels w/o ____
• depress action of excitatory amino acids like ____
chloride
chloride
GABA
glutamate
Benzodiazepines General Principles 2
active metabolites with ____
Strategy: For intravenous or oral sedation/anxiolysis administer ____-acting benzodiazepines
without ____ metabolites. (midazolam, triazolam)
diazepam
short
active
Oral benzodiazepines have a ____ therapeutic index, however bad things occasionally ____, especially in a young child given high therapeutic doses!!!!
huge
happen
Oral midazolam
Three year old, 35 pound female in need of 5 stainless steel crowns and other work. Procedures are scheduled over 4 visits. Patient administered 16 mg (1 mg/kg) oral midazolam syrup. Thirty minutes later clinician hears a “choking/gagging sound, O2 saturation has dropped to 95. Clinician repositions head, initiates assisted breathing, activates 911. EMTs arrive, O2 saturation 98, child is spontaneously breathing (16/min) but unresponsive to verbal commands. Unable to establish intravenous access. Decide to intubate, several failed attempts, child goes into respiratory arrest. Transported to nearby hospital emergency room, given ____ (Romazicon®) 0.35 mg intravenously. Child awakens and makes a full recovery
Flumazenil dosing: ____ mg (____ IV, ____ IM or sublingual)
flumazenil
0.2-1
lower
high
Benzodiazepine General Principles 3
- Some benzodiazepines are substrates of the ____ system (CYP-3A4)
- Potential for adverse drug interactions especially with other agents that impair their metabolism especially following ____ administration
cytochrome P450
oral
Benzos are ____ substrates and there are certain drugs and ____ that can jack up blood levels of these.
Issues with barbiturates that they actually ____ some of the CYP450 enzymes and ____ blood levels of other drugs and make them sub therapeutic.
3A4
grapefruit juice
induce
reduce
Midazolam
Cool study. One glass of ____ increasing midazolam blood levels by almost 100%
grapefruit juice
Showed that antibiotic ____ can do the same thing to boost midazolam levels. So can ____
erythromycin
clarithromycin
Sublingual triazolam
Sublingual triazolam wasn’t being used properly.
Sublingual triazolam. The issue was that the way it was being used was that they were going beyond the MRD saying that they were titrating sublingually. Blood levels can keep ____ after you discharge a kid
Blood levels of triazolam still increasing at ____ hours
rising
3
Sublingual triazolam
8/10 adults reached at least ____ sedation levels
O2 sat> ____ in all
Level of sedation still increasing at ____ hours
Sedation keeps going down even after they stop the drug. This is what people used to advertise for sleep dentistry.
deep
96
3
Propofol
Very simple molecule. Don’t need to ____.
regurgitate
Propofol nuances
• Formulated in vehicle called ____ that contains soybean oil and egg lecithin so you must check for ____ to these components
• Also this vehicle contains no ____ – and is good medium for microbial growth so can’t ____
• Hurts when injected into ____ veins
• Ultra short acting –duration of effect is from a single
dose is ____ minutes
• Possesses anti-____ activity (unlike opioids, ketamine, barbiturates and inhalation agents)
• Respiratory ____ most serious side effect
• No ____ agent
intralipid allergies preservatives reuse small 4-8 emetic depression reversal
