General Anesthetics Flashcards
What is MAC?
Minimal alveolar concentration
Define MAC
50% of patients do not respond to a surgical stimulus (reach stage III anesthesia) - ED50
A _____ (higher / lower) MAC means the drug is more potent.
Lower
Which drug is the least potent of all the general anesthetics?
Nitrous oxide (105.0)
Which drug is the most potent of all the general anesthetics?
Methoxyflurane (0.16)
*****What is blood-gas partition coefficient?
ratio of drug gas dissolved in blood ( ionized) to free gas (nonionized)
*****If the blood-gas partition coefficient is higher then the onset is _____ (fast / slow). Why?
Slow because it indicates the drug is more ionized and dissolved in blood (water) and is unable to cross BBB.
*****Which inhaled general anesthetic onset is fastest (lower blood-gas partition coefficient number)?
Nitrous oxide (0.47)
*****Which inhaled general anesthetic onset is slowest (higher blood-gas partition coefficient number)?
Halothane (2.3)
*****What are the properties of a drug with a lower blood-gas partition coefficient (4 total)?
Less soluble in blood (nonionized higher), crosses BBB, arterial tension rises quickly, fast onset of action
*****What are the properties of a drug with a higher blood-gas partition coefficient (4 total)?
Highly soluble in blood (ionized higher), does not cross BBB, arterial tension rises slowly, slow onset of action
What are the two main side effects of nitrous oxide?
- Increased intracranial pressure (by increasing cerebral blood flow) 2. megaloblastic anemia (inhibitis vitamin B12 dependent enzyme methionine synthase because nitrous oxide oxidizes cobalt/metal)
Due to nitrous oxide’s side effect of increasing ICP, what conditions are contraindicated? What can you do in these conditions to help prevent this side effect?
Open head trauma, cerebral edema, and brain tumor; put patient on artificial respiratory support (intubated)
What kind of surgery is nitrous oxide most used in?
Dentistry
What are the three main side effects of halothane?
Decrease CO, liver dysfunction (very HY, can cause massive heptocyte death), and malignant hyperthermia
Which general anesthetics drugs can cause malignant hyperthermia?
Volatile anesthetic gases i.e. halothane, sevoflurane, desflurane, isoflurane, enflurane or the depolarizing muscle relaxants suxamethonium / succinylcholine* and decamethonium
All inhaled general anesthetics have the potential side effect of causing _____ and are therefore contradicted in open head trauma, cerebral edema, and / or brain tumor patients unless on artificial respiratory support (intubated)?
Increase ICP
Which IV anesthetic drugs can you use on in open head trauma, cerebral edema, and / or brain tumor patients because they reduce ICP?
Barbiturates Thiopental and Methohexital, Propofol (all other IV anesthetics increase ICP and cannot be used)
What IV general anesthetic drugs have a similar MOA as barbiturates?
Propofol and Etomidate
What is the structure and MOA of the dissociative anesthetic Ketamine?
Phencyclidine (PCP, dissociative anesthetic), NMDA receptor antagonist causing stimulation
What are the potential side effects of stimulation due to Ketamine?
HTN, tachycardia, ICP increase, and emergency phenomenon
Name the drug groups (6 total) and drugs within these groups that are intravenous general anesthetics.
- Barbiturates: thiopental, methohexital 2) dissociative: ketmaine 3) opiods: morphine, fentanyl 4) BZDs: midazolam, diazepam 5) Propofol 6) Etomidate
Name the drug groups (2 total) and drugs within these groups that are inhaled general anesthetics.
- Gaseous: NO / nitrOUS oxide 2) volatile liquids: Halothane and -fluranes
What is the “emergency phenomenon” that can be caused by Ketamine?
Hallucinations, disorientation, and nightmares a couple hours post-surgery
Which IV anesthetics are used for both induction and maintenance of anesthesia?
Propofol and fentanyl are the only two used for BOTH induction and maintenance of anesthesia (all others are only for induction).
Etomidate qualifies as a maintenance anesthetic (PK elimination fast) for continuous IV infusion but is only used for induction anesthesia. Why?
Prolonged administration can cause adrenal suppression (reduce adrenal hormone) due to inhibition 11b-hydroxylase in the adrenal cortex.
What is the property of all the IV anesthetics which allow for induction of anesthesia (onset fast)?
Lipid soluble
All the IV anesthetics can induce anesthesia because bypass stage _____ also known as the _____ stage or _____ period.
2, disinhibition, paradoxal paradoxical excitation
Which stage of anesthesia do you want to make as short as possible?
Stage 2
Why is Stage 2 of anesthesia called the paradoxal excitation period and what features is it characterized by?
This stage is termed paradoxical because the drug that is intended to induce unconsciousness induces excitation instead. Characteristic feature include purposeless or defensive movements, incoherent speech, euphoria or dysphoria, and an increase in beta activity on the EEG (13 to 25 Hz).
Propofol and Fentanyl cause induction like every other IV anesthetic. Why can they be used for maintenance anesthesia (continuous IV) as well unlike other IV anesthetics?
Due to their pharmacokinetics, Propofol and Fentanyl are eliminated after a couple of hours which allows the patient to recover sooner/quicker. Other IV anesthetics accumulate and are eliminated slowly which is not beneficial because want the patient to wake up as soon as possible after surgery to monitor for any problems.
What is the advantage of using Etomidate over other IV anesthetics and in what type of patient would this advantage be optimized?
Etomidate does not effect the CVS as much. There is minimal change in cardiac functions (BP and HR pretty stable). This drug is optimized for use in patients having poor cardiovascular status.
How do opioids increase ICP?
Opiods directly inhibit the respiratory center (do not exhale as strongly) causing increased CO2 in the and increased PCO2 in the entire body (including the brain). This leads to cerebral vasodilation. Vasodilation causes increased ICP.
What side effect do opiods cause on the chest and why?
Opioids cause chest rigidity by contracting the circular muscle.
What is the MOA of barbiturates?
Direct activation of GABA A receptor mediated by GABA ligand prolongs GABA-Cl- influx / opening DURATION
What is the MOA of BZDs?
Direct activation of GABA A receptor mediated by GABA ligand increases GABA-Cl- influx / opening FREQUENCY (potentiate Cl- current of GABA A receptor)
GABA ligand is a mediator of the mechanisms of action for both barbiturates and BZDs. What happens if the GABA ligand is not there?
Without GABA ligand binding, binding of the barbituate or BZD to the GABA A receptor will do nothing / have no effect.
Why does one dose of thiopental lose its function after 4 minutes?
After 4 minutes, the drug distributes out of the brain into the adipose tissue and skeletal muscle causing termination of anesthesia after one dose. DISTRIBUTION accounts for the loss of function NOT excretion by kidney or liver metabolism because < 4 minutes too fast for either of these to occur.
Within 1 to 4 minutes of giving induction anesthetic Thiopental, why do you need to have a continuous IV infusion of Propofol / Fentanyl or inhaled anesthetic ready?
After 4 minutes the brain’s dose concentration of Thiopental is lower than the minimum effective level allowing the patient to wake up.
The induction anesthetic Thiopental puts the patient in Stage 3 anesthesia for _____ minute.
< 1
What are the four stages of anesthesia?
1: Analgesia = decreased awareness of pain with some amnesia, can make conversation
2: Disinhibition = delirious and excited, reflexes enhanced, irregular respiration
3: Surgical anesthesia = patient unconscious, no pain reflexes
4: Medullary paralysis = severe respiratory and cardiovascular depression
A good anesthetic has a _____ MAC and _____ blood gas partition ratio.
low, low
Slide 2 depicts the relationship of substances / drugs and CNS depression. Describe the relationship between CNS depression and Drug A. Describe the relationship between CNS depression and Drug B.
The linear slope for drug A is typical of many of the older sedative-hypnotics including the barbiturates and alcohols, and is a graded dose-dependent depression relationship. Increase in dose higher than needed for hypnosis may lead to a state of general anesthesia. At even higher doses, may depress respiratory and vasomotor centers in the medulla leading to coma and death. Deviations from a linear dose-response relationship, as shown for drug B (BZDs and newer hypnotics with similar MOA), require proportionately greater dosage increments to achieve central nervous system depression more profound than hypnosis.
