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Pharmacology (Dustin, Ben) > B1-2: Inhalation Anesthetics. IV Anesthetics. Neurolept Analgesia. Perioperative meds. > Flashcards

B1-2: Inhalation Anesthetics. IV Anesthetics. Neurolept Analgesia. Perioperative meds. Flashcards

1
Q

What is general anesthesia?

A

Reversible loss of consciousness, arousal, memory, and pain sensation + inhibition of autonomic reflexes and skeletal tone

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2
Q

What are 5 aims of general anesthetics?

A
  • Analgesia (loss of pain sensation)
  • Loss of consciousness
  • Inhibition of sensory and somatic reflexes
  • Amnesia (loss of memory)
  • Skeletal muscle relaxation

(No single drug provides all, so several drugs are usually given - including some local anesthetics)

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3
Q

How does a general anesthetic’s lipid solubility influence its potency?

What method is used to quantify the potency in the inhaled anesthetics?

A
  • Anesthetics are more potent in proportion to their lipid solubility (Lipid Theory, Meyer-Orton correlation). Lipid-soluble drugs can cross BBB to enter CNS
  • Minimum Alveolar Concentration (MAC) is used to measure potency in inhalation anesthetics. This is median effective dose (ED50) to eliminate movement after surgical incision. Lower MAC = more lipid soluble = more potent.
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4
Q

What are Protein Theory and Binding Theory in regards to anesthetics?

[This seems kind of dumb to me but it’s in lecture]

A
  • Protein Theory: basically receptor theory. Anesthetics inhibit enzymes, e.g. GABA-A.
  • Binding Theory: anesthetics bind to the hydrophobic parts of ion channels (probably because they are also hydrophobic)
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5
Q

What are the general targets for anesthetics?

A
  • Ligand-gated ion channels (ligand being a neurotransmitter), e.g. Inhibitory ion channels (GABA-A and Glycine), or Excitatory (Ach, Glutamate [AMPA, NMDA], 5-HT…)
  • K+ Channels
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6
Q

What are the two liquid types of inhaled anesthetics?

A
  • Ethers (Diethylether = historical. Others end in flurane: Enflurane, Isoflurane, Desflurane, Sevoflurane, Methoxyflurane)
  • Halogenated hydrocarbons: Halothane (can also include Chloroform, Ethylchloride)
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7
Q

What are 2 examples of gas anesthetics?

A
  • Nitrous Oxide

- Xenon gas

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8
Q

What are those details about Ether Day that we had to memorize for basics of surgery again?
(date, context..)

A

October 16, 1846.

Dr. John Collins used it to remove a neck tumor in Boston.

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9
Q

What are the 4 stages of anesthesia?

A
  1. Analgesia: less pain sensation due to spinothalamic tract activity ↓
  2. Excitation: Delirium. Still has response to pain stimuli. Involuntary movement, irregular breathing, incoherent speech. Should shorten this period with rapid-acting IV agents.
  3. Surgical Anesthesia / “Tolerance.” No reflexes, regular breathing. Ideal for surgery.
  4. Asphyxia / Medullary Paralysis: Respiratory depression. May have bradycardia, cardiac arrest.
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10
Q

What are some external factors that can lower the MAC or increase the MAC of inhaled anesthetics?

A
  • Lower MAC: any inhibitory thing. Hypothermia, hypoxia, anemia, older age, other anesthetics or depressants
  • Increase MAC: stimulants, younger age
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11
Q

What are 4 factors that affect the onset and recovery from an inhaled anesthetic?

A
  • Solubility in blood (lower solubility = faster)
  • Concentration in inhaled air (higher concentration = faster) + exposure time
  • Breathing rate (note that opiates slow respiratory rate, slowing the onset)
  • Partial pressure gradient of anesthetic btwn arterial and venous blood (if it gets stuck in tissues outside CNS)
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12
Q

How do you measure the solubility of an inhaled anesthetic?

A

Solubility (S) = Blood : Gas partition coefficient. Relative affinity for blood compared to air.

Drugs with high S have more affinity for blood, they get stuck there and cross the BBB less. Drugs with low S (e.g. Nitrous Oxide) quickly raise partial pressure in the CNS, causing fast induction and fast recovery

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13
Q

In what way are inhalation anesthetics eliminated the most?

Which inhalation anesthetics are metabolized more? Which are metabolized less? What is the danger of being metabolized?

A
  • Via exhalation by lungs.
  • Metabolized more: all the liquid anesthetics. Methoxyflurane > Halothane > Sevoflurane > Isoflurane > Desflurane. Have a risk of producing free radicals from metabolism.
  • Poorly-metabolized: Nitrous oxide, Xenon.
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14
Q

What are the advantages of Nitrous Oxide as an inhaled anesthetic?

A
  • Non flammable, cheap, doesn’t irritate airways
  • Fast induction and recovery due to very low S (S = 0.47)
  • No post-op vomiting, no irritation of airways
  • Decreases MAC of other narcotics (potentiation)
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15
Q

What are the DISadvantages of Nitrous Oxide as an inhaled anesthetic?

A
  • Hypoxia risk by replacing partial pressure of O2
  • No muscle relaxation
  • Increased pressure of closed cavitiies
  • Repeated dose: Megaloblastic anemia, leukopenia
  • Can be abused (may be an advantage if that’s what you’re into)

-Not really a disadvantage, but it has a high MAC (>100) meaning it’s not very potent (need higher dose)

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16
Q

What are the advantages of Halothane as an inhaled anesthetic?

A
  • Doesn’t irritate airways
  • Relaxes the uterus
  • Causes muscle relaxation (potentiates curare)
  • Non-flammable

-Not sure if it’s an advantage, but has a very low MAC (0.75). Use a high dose for induction, but lower dose for maintenance.

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17
Q

What are the DISadvantages of Halothane as an inhaled anesthetic?

A
  • Dose-dependent drop in BP, output, contraction, and TPR
  • Bradycardia (may use atropine to reverse)
  • Sensitization of myocardium to catecholamines, risk of arrhythmia
  • Malignant hyperthermia in predisposed patients (similar to succinylcholine)
  • Hepatotoxicity

-Relatively high S (2.3) -> more likely to remain outside of CNS compared to nitrous oxide

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18
Q

What are the advantages and disadvantages of Enflurane?

don’t think we need to know S and MAC numbers but they’re in the answer too

A

-Advantages: faster than halothane (but slower than isoflurane). Not irritating to resp tract

-Disadvantages: resp and circ depression but increases HR. Can cause epileptic seizures and malignant hyperthermia. Fluoride formed from metabolism, damaging kidney
(S = 1.8, MAC = 1.7)

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19
Q

What are the advantages and disadvantages of Isoflurane?

don’t think we need to know S and MAC numbers but they’re in the answer too

A

-Advantages: faster than enflurane. Rapid awakening, low metabolism. Preferred for neurosurgery

-Disadvantages: pungent (irritates resp system). Only suitable for maintenance. Coronary steal syndrome: less blood supply to coronaries (but no clinical consequence). HR increase. May cause arrhythmia.
(S = 1.4, MAC = 1.4)

20
Q

What are the advantages and disadvantages of Desflurane?

don’t think we need to know S and MAC numbers but they’re in the answer too

A
  • Advantages: Fast induction and recovery (very low S for a flurane). No renal toxicity or renal damage, only slightly metabolized. Preferred in overweight patients.
  • Disadvantages: Respiratory irritation, only suitable for maintenance. Increases HR.

(S = 0.42, MAC = 6-7)

21
Q

What are the advantages and disadvantages of Sevoflurane?

don’t think we need to know S and MAC numbers but they’re in the answer too

A

Advantage: fast induction and recovery (rapid elimination). Less irritation to resp tract. Use for induction and maintenance in children. No liver/kidney damage. Most commonly-used inhaled anesthetic (highly potent)

-Disadvantage: Metabolic rate is relatively high (+ possible nephrotoxic metabolite.. yes this goes against the advantages listed. I’m just copying the lecture slide)

(S: 0.69, MAC = 2)

22
Q

Of the inhaled anesthetics, which ones can cause arrhythmias?

Which ones alter heart rate, and how?

A
  • Arrhythmias: Halothane, Isoflurane

- HR: decreases with Halothane, increases with Isoflurane and Desflurane

23
Q

How do the S and MAC values compare between Nitrous Oxide and Halothane?

A

N2O: Low S (0.47), extremely high MAC (>100). Low potency but doesn’t bind much in the blood.

Halothane: High S (2.3), low MAC (0.75). High potency but binds in the bloodstream more.

24
Q

Which general anesthetics act on GABA-A receptors?

A
  • All inhaled anesthetics
  • Barbiturates
  • Benzodiazepines (don’t cause general anesthesia, but facilitate)
  • Propofol
  • Etomidate
25
Q

What measurement is useful when trying to quantify how quickly a person recovers from IV anesthesia after it has been discontinued?

In which IV anesthetics is this time considered to be short?

A

-Context-Sensitive Half-Time: time required for blood/plasma concentration of anesthetic agents to decrease by 50% after discontinuation of IV anesthetic

Short in Propofol, Etomidate, and Ketamine. (Note that Propofol has less side effects than the other two and is used more)

26
Q

Which barbiturates are used in IV anesthesia?

A
  • Thiopental: potent and rapid onset, but have poor analgesia, cause nausea, have little muscle relaxation, cause hypotension and laryngospasm (risk of airway obstruction). If use repeated dose, has long recovery time. Causes cerebrovascular constriction, which may benefit patients with intracranial hypertension.
  • Methohexital: similar to Thiopental. It may also lower the threshold for seizures.

Barbiturates enter CNS quickly but then rapidly diffuse out of brain, then remain in body for a long time. Not used in many countries anymore, replaced by Propofol.

27
Q

What is the onset and duration of Propofol?

What are some of its advantages?

A
  • Rapid onset (30 seconds), short acting (5-10 minutes), rapid recovery (short context-sensitive half-time).
  • Antiemetic
  • [note that it is not analgesic]
28
Q

What are the disadvantages and adverse effects of Propofol?

A
  • Hypotension. Acts synergistically with opioids to lower BP.
  • Pain in the infusion site
  • Transient apnea after induction
  • Propofol infusion syndrome: after long application in higher doses, it can disturb lipid metabolism -> metabolic acidosis
  • Highly binds to proteins

[Note that propofol is unique in that it looks like milk because it’s infused with oils since it’s not very water-soluble.]

29
Q

What are some clinical uses of Propofol?

A
  • Induction of anesthesia, balance anesthesia, total intravenous anesthesia (TIVA)
  • Sedating mechanically-ventilated ICU patients (maybe use Fospropofol: water-soluble form)
  • Low doses to treat post-operative nausea/vomiting
30
Q

What are indications and advantages of Etomidate?

A
  • Used as induction agent. Better for hypovolemic patients than propofol. Also maybe useful in other cardiovascular disease patients.
  • Advantages: little effect on the heart and respiratory drive.
  • (note that it is not analgesic)
31
Q

What are the disadvantages of Etomidate?

A
  • Decreased plasma cortisol and aldosterone, which can persist for 8 hours. Etomidate should be used for only short periods of time for these reasons
  • Also tendency for injection site reactions and involuntary skeletal muscle contractions
32
Q

What is the mechanism of action of Ketamine?

  • What are its advantages?
  • How does it alter heart rate and respirations?
A
  • NMDA receptor antagonist
  • Produces both anesthesia and significant analgesia
  • Can be used for induction and maintenance alone, without other drugs
  • Rapid onset (but still minutes, slower than some others)
  • Can be given IM
  • Low protein-binding
  • Stimulates circulatory system (other usually inhibit it) - BP, HR, respiratory rate increase, bronchodilation. May be useful in patients with worse CO, asthmatics, etc.
33
Q

What are the disadvantages of Ketamine?

A
  • Inceases salivations
  • Dilates cerebral vessels -> increased ICP.
  • Unpleasant recovery, nightmares
  • Not totally a disadvantage but odd: Patient may appear to be awake or may even be in semi-conscious “dissociative” state, but won’t feel or be concerned about pain (stuck in the K hole).
  • Hallucinogen / drug of abuse (people are always robbing veterinarians to get their ket fix)
34
Q

Which Benzodiazepines are commonly used in anesthesia?

What are their advantages?

A
  • Midazolam: commonly used in induction, ultra-short acting
  • Diazepam and Lorazepam: longer-acting, used as premedication / sedatives.

-Potentiate other anesthetics, less side effects or risks, have an antidote in case of overdose (Flumazenil: BDZ antagonist)

35
Q

Which α2 agonists are used in anesthesia?

Why are they useful?

A
  • Clonidine (for delirium tremens patients) and Dexmedetomidine
  • Advantage: sedative effects, blunt the cardiovascular responses of anesthetics, don’t cause significant respiratory depression. Lowering BP may be useful if patient has hypertension, but don’t use these if they have hypotension. May be useful in ICU for intubated/ventilated patients.
36
Q

Which opioids are often used in anesthesia?

Why are they useful?

A
  • Fentanyl and similar drugs (sufentanil, etc). Induce analgesia more rapidly than morphine.
  • Provide analgesic effect that may otherwise be missing in anesthesia. While they can cause hypotension, respiratory depression, muscle rigidity, nausea, and vomiting, they also can be easily reversed with the opioid antagonist Naloxone.
37
Q

What is “Balanced Anesthesia?”

What are some drugs that could be used?

A

Combination of IV and inhaled anesthetic agents that uses their advantages while minimizes the side effects of individual drugs. Fast induction from IV drugs + maintenance by inhaled agents (easy to titrate)

For analgesia use N2O or fentanyl, for autonomic stabilization maybe use atropine, for muscle relaxation maybe use pancuronium, for unconsciousness maybe use halothane and/or propofol.

38
Q

What drug can be used for Total Inhalation Anesthesia?

In which kinds of patients?

A
  • Sevoflurane for both induction and maintenance

- Used in pediatrics

39
Q

What is TIVA and what order is it given in?

A

TIVA = Total IntraVenous Anesthesia

  1. Hypnosis via short-acting drug (especially Propofol)
  2. Analgesia via short-acting opioids like (Remi)Fentanyl
  3. Muscle relaxaton via short or intermediate-acting drugs like Atracuronium, Vecuronium, Mivacurium, or Midazolam
40
Q

What are the advantages of TIVA?

A
  • Avoid toxicity of inhaled anesthetics
  • Less nitrous oxide problems
  • Preferred in neurosurgery
  • Less waste
41
Q

What are the disadvantages of TIVA?

A
  • Expensive
  • Need very good IV access
  • Often causes hypotension
  • “Awareness about IV infusion fails” - not sure wtf this means, bad English on the slide
42
Q

What is Neuroleptic Analgesia / Neuroleptanalgesia?

Which drugs are used in this technique?

A
  • Combination of antipsychotic/tranquilizer “neuroleptic” drug + a strong analgesic. Creates detached, pain-free state for operations.
  • Usually use droperidol + fentanyl (but this is rarely done today)
43
Q

What is Neuroleptic Anesthesia?

What drugs are used for this?

A
  • Same as neuroleptic analgesia but also has an anesthetic

- Droperidol + Fentanyl + Nitrous Oxide

44
Q

What drugs are good for causing anxiolysis/sedation and amnesia before a surgery?

A

Benzodiazepines (e.g. Diazepam). Patients can still respond to commands, and doesn’t significantly impact respiration unless other drugs are also given.

45
Q

What are some drugs that are commonly given perioperatively?

A
  • Antiemetics (prevent aspiration during surgery)
  • Antacids
  • Antibiotics
  • Analgesics
  • Parasympatholytics like Atropine to prevent side-effects of bradycardia
  • Sympatholytics, e.g beta blockers to stop the increased sympathetic tone during intubation
  • Sedatives like Benzodiazepines

(Can remember AAAAABB: Antiemetic, Antacid, Antibiotic, Analgesics, Atropine, Beta Blockers, Benzos)

Pharmacology (Dustin, Ben) (17 decks)

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