L18- General Anesthetics

Question 1

define the state of ‘General Anesthesia’

Answer 1

• loss of consciousness
• analgesia (no pain)
• amnesia (no memory)
• suppression of reflexes
• relaxation of skeletal muscle

Question 2

______ is when several drugs used in combination create a state of general anesthesia

Answer 2

balanced anesthesia

Question 3

what are the types of general anesthetics, include functions and lack of functions

Answer 3

IV agents- to initiate anesthetic state, rapid action

Inhaled agents- to maintain anesthetic state, slower action

• lacks analgesic effects – give opioid
• lacks skeletal muscle relaxation effects – give neuromuscular blocker

Question 4

list the inhaled anesthetics

Answer 4

Gases: N2O

Volatile halogenated hydrocarbons:

• halothane
• euflurane
• isoflurane
• desflurane
• sevoflurane
• methoxyflurane

Question 5

list the uses for IV anesthetics

Answer 5

Alone or in combination:

• achieve anesthesia
• component of balanced anesthesia
• sedation of ICU patients who will be mechanically ventilated for long periods

Question 6

list the uses for inhaled anesthetics

Answer 6

maintain anesthetic state after administration of IV agent

Question 7

list the IV anesthetics

Answer 7

• barbiturates
• propofol
• ketamine
• etomidate

Question 8

Inhaled Anesthetics:

• potency correlates with (1)
• rate of onset inversely correlates with (2)
• all will have a (3) effect on cerebral blood flow
• recovery from anesthetics results from (4)
• (5) are the common respiratory effects

Answer 8

1- liposolubility (more lipophilic => crosses BBB easier)
2- blood solubility (less lipophilic => less soluble => rapid onset of action)
3- inc cerebral perfusion
4- redistribution of anesthetics from brain
5- bronchodilation, dec minute ventilation (respiratory depression)

Question 9

describe the main MOA of inhaled anesthetics

Answer 9

• positive modulation of GABA and Glycine activity in brain and spinal cord (inc inhibitory mechanisms of CNS)
• direct interactions with ligand-gated ion channels
• inhibition of nAChR

Question 10

define MAC (inhaled anesthetics)

Answer 10

Minimum Alveolar Concentration

• concentration of inhaled anesthetic that results in anesthetic state / immobility in 50% of population
• expressed as % of alveolar gas in mixture

-therefore the lower the percentage, the less amount needed to achieve anesthetic state –> more potent agents (large % for low potent agents)

Question 11

describe the effect on MAC when inhaled anesthetics are used in combination

Answer 11

(minimum alveolar concentration)
-MAC values are additive when used together, but also lower the individual MACs of each other

-N2O is commonly used as a carrier gas to dec amount needed of other inhaled agents

Question 12

list the inhaled anesthetics in order of potency / MAC

Answer 12

(highest MAC / lowest potency / lowest liposolubility / highest blood solubility —–> low MAC / high potency / high liposolubility / low blood solubility)

• N2O
• desflurane
• sevoflurane
• enflurane
• isoflurane
• halothane
• methoxyflurane

Question 13

describe the Meyer-Overton correlation in relation to inhaled anesthetics

Answer 13

• potency can predicted by liposolubility
• λ(oil:gas) = partition coefficient measuring liposolubility; the higher λ => inc liposolubility => inc potency / dec MAC

Question 14

define λ(oil:gas)

Answer 14

partition coefficient- ratio of concentrations of compound in oil compared to concentration in alveolar gas

ex: λ = 19 –> anesthetic agent 19x more abundant in oil than in alveolar gas at equal partial pressures / equilibrium

Question 15

list the factors that effect induction of anesthetic agents

Answer 15

• solubility of anesthetic
• [agent] in inspired air
• pulmonary ventilation rate
• pulmonary blood flow
• arteriovenous concentration gradient

Question 16

describe how solubility in blood of inhaled anesthetics is measured and its relationship with speed of onset

Answer 16

-λ(blood:gas) correlates with blood solubility of agents — same order as λ(oil:gas)

• the higher λ => higher solubility => slower equilibrium at BBB –> slower onset of action
• the lower λ => lower blood solubility => rapid equilibrium at BBB –> rapid onset of action

Question 17

describe the relationship of potency and speed of onset of inhaled anesthetics

Answer 17

high potency —–> slower onset of action (higher liposolubility, higher blood solubility)

low potency —–> rapid onset of action (lower liposolubility, lower blood solubility)

Question 18

how does i) [anesthesia] in inspired air, ii) ventillation rate, and iii) pulmonary blood flow –> correlate with speed of onset

Answer 18

SIMPLE:
i) inc [anesthetic] in inspired air => inc rate of induction

ii) inc ventilation rate => inc rate of induction
iii) inc pulmonary blood flow (inc CO) => dec rate of induction [inc blood volume exposed to anesthetic –> inc blood capacity –> tension rises slowly (equilibrium takes longer)]

Question 19

how does arteriovenous concentration gradient correlate with speed of onset for inhaled anesthetic agents

Answer 19

Definition: gradient = [anesthetic]arteries - [anesthetic]veins

• gradient is reflection of solubility in tissues
• inc gradient = inc uptake of drug in tissues => slower rate of onset of drug and slower recovery

Question 20

Elimination of Inhaled Anesthetics:

• most anesthetic is eliminated via (1)
• recovery from agents with low blood and tissue solubility mirrors (2) process (low potency, rapid action)
• recovery from agents with high blood and tissue solubility depends on (3) (high potency, slow action)

Answer 20

1- reverse process of uptake –> exhalation

2- anesthetic induction, regardless of duration of anesthetic administration (time in = time out, ex. N2O)

3- duration of anesthetic administration - anesthetic accumulates in fat (time in «< time out, ex. methoxyflurane)

Question 21

Most inhaled anesthetics have a (1) effect on the heart with a (2) effect to CVS overall.

(3) agents reduce MAP via (4) process and have little effect on (5).

Answer 21

1- depress cardiac contractility
2- dec MAP

3- halothane, enflurane
4- myocardial depression
5- PVR

Question 22

(1) anesthetic agents are preferred in patients with impaired myocardial function because they only produce (2) CVS effects.

Answer 22

1- isoflurane, desflurane. sevoflurane

2- vasodilation, minimal effects on CO

Question 23

______ lowers BP less than all the other inhaled anesthetics

Answer 23

N2O (nitrous oxide)

Question 24

Use of (1) inhaled anesthetic may lead to ventricular arrhythmias due to (2) process. This effect is minimal with use of (3) agents.

Answer 24

1- halothane
2- inc myocardial sensitization to cathecholamines
3- isoflurane, desflurane, sevoflurane

Question 25

- (1) general respiratory effects of inhaled anesthetics - (2) have the largest effects - (3) have the least effects

Answer 25

1- respiratory depression: bronchodilator, dec minute ventilation 2- isoflurane, enflurane 3- nitrous oxide

Question 26

(1) is the main CNS effect seen by use of inhaled anesthetics, therefore it is contraindicated in (2) cases. (3) has the smallest (1) effect.

Answer 26

1- inc ICP via inc cerebral perfusion 2- Pts w/ raised ICP via brain tumor or head injury 3- nitrous oxide

Question 27

______ inhaled anesthetic at high enough concentrations may cause tonic-clonic movements

Answer 27

enflurane

Question 28

describe the additional effect nitrous oxide has compared to other inhaled agents + the contraindications due to this effect

Answer 28

-N2O exchanges with N2 in air-containing cavities in body --> N20 escapes faster than N2 --> inc volume and or pressure of body cavities Contraindications: pneumothorax, obstructed middle ear, air embolus, obstructed bowel lop, intraocular air bubble, pulmonary bulla, intracranial air

Question 29

Use of (1) anesthetic may lead to hepatotoxicity where (2) is the treatment

Answer 29

1- halothane 2- possibly severe and life threatening --> no specific Tx --> possibly liver transplant

Question 30

Use of (1) anesthetic may lead to nephrotoxicity due to (2) action / effects.

Answer 30

1- methoxyflurane 2- via fluoride release during metabolism

Question 31

(1) is a potentially fatal genetic skeletal muscle disorder if the patient is exposed to (2) or (3) which apart of balanced anesthesia.

Answer 31

1- malignant hyperthermia - one the main causes of death due to anesthesia 2- halothane 3- succinylcholine (skeletal muscle relaxant)

Question 32

The trait for predisposition for malignant hyperthermia is inherited in (1) fashion. It usually consists of a defect in (2) which normally has (3) function, but now has (4) function.

Answer 32

1- AD 2- RYR1 (ryanodine receptor gene) 3- regulates RYR release of Ca in response to depolarization of sarcomere 4- unregulated release of Ca from SR in skeletal muscle

Question 33

list the signs and symptoms of malignant hyperthermia

Answer 33

- tachycardia, hypertension - severe muscle rigidity - hyperthermia - hyperkalemia, acidosis

Question 34

______ is used to treat and reverse malignant hyperthermia, include mechanism

Answer 34

dantrolene: blocks Ca release from SR - reduces body T - restores electrolyte and acid-balance

Question 35

describe the pathogenesis of malignant hyperthermia

Answer 35

- genetic predisposition + agent inc skeletal depolarization administered i) inc Ca release from SR ii) inc muscle contraction --> *generates heat iii) inc aerobic metabolism => inc CO2 + O2, ATP depletion iv) anerobic metabolism => worsens acidosis via lactate production v) energy stores depleted vi) muscle fibers die => hyperkalemia + myoglobinuria

Question 36

(1) is the most reliable test to establish risk / susceptibility to malignant hyperthermia. A sample of (2) is taken and a positive is indicated by (3).

Answer 36

1- Caffeine-Halothane muscle contracture test 2- muscle via thigh 3- contracture in response to halothane and caffeine

Question 37

Prolonged exposure to (1) agent decreases the activity of (2) to cause (3), a hematotoxicity.

Answer 37

1- N2O 2- methionine synthase 3- megaloblastic anemia Note- occupational hazard in poorly ventilated dental suits

Question 38

(1) are the ultra-short acting barbiturates used for (2) purpose. Recovery from (1)/(2) can occur do to (3- explain), although elimination of (1) requires (4).

Answer 38

1- thiopental, methohexital (IV anesthetics) 2- induction of anesthesia for short surgical procedures 3- redistribution from brain --> other tissues: 1st- brain, liver, kidneys; 2nd- muscle; 3rd- skin 4- hepatic metabolism

Question 39

Barbiturates other effects: - (1) effect on brain/skull - (2) effect on sensory system - (3) effect on lungs, therefore contraindicated with (4) patients

Answer 39

1- dec ICP 2- hyperalgesia (no analgesia effects) 3- apnea, cough, chest wall spasm, laryngospasm, bronchospasm 4- asthma

Question 40

Propofol: - (1) main use - (2) additional useful effect - lacks (3) effect

Answer 40

1- induction and maintenance of anesthesia (IV anesthetic) 2- anti-emetic, postoperative vomiting is very uncommon 3- no analgesia

Question 41

(1) is the prodrug of propofol. Propofol is normally (rapidly/slowly) metabolized by the liver.

Answer 41

1- fospropofol 2- rapid metabolism in liver

Question 42

list the main AEs of propofol

Answer 42

- potent respiratory depression - dec ICP - hypotension via dec PVR (contraindication in susceptible patients)

Question 43

(1) is used for anesthetic induction of patients at risk for hypotension. (1) lacks (2) effects. In compared to other anesthetics it has minimal effects on (3). (1) will also reduce (4) and is associated with (5) as other adverse effects.

Answer 43

``` 1- etomidate 2- analgesic 3- CVS, respiratory (depression) 4- ICP 5- n/v ```

Question 44

(1) produces dissociative anesthesia, characterized by (2). (1) has (3) as its MOA. (1) is the only IV anesthetic that has (4) properties and stimulates (5).

Answer 44

1- ketamine 2- catatonia (disturbed movements and behavior as seen in schizophrenia), amnesia, analgesia +/- LOC 3- NMDA receptor (glutamate) blockade 4- analgesic 5- CVS --> therefore good for people in shock

Question 45

Ketamine AEs: - raises (1) - causes 'emergence phenomenon', define as (2) and can be prevented or reduced by using (3)

Answer 45

1- ICP 2- sensory and perceptual illusions, vivid dreams 3- sedatives: diazepam, midazolam, propofol

Question 46

describe the classic Neuroleptic-Opiod combination and how it might cause neurolept analgesia and then neurolept anesthesia

Answer 46

(neurolept --> sedation, opioid --> analgesia) -*fentanyl + droperidol --> neurolept analgesia -fentanyl + droperidol + 65% N2O in O2 --> neurolept anesthesia = balanced anesthesia

Question 47

Adjuncts to anesthesia: - (1) are for anxiolytic and anterograde amnesic effects, typically given pre-surgery - (2) are for analgesia - (3) are to achieve muscle relaxation

Answer 47

1- benzodiazepines 2- opioids 3- neuromuscular blockers (succinylcholine)

Question 48

Adjuncts for anesthesia: - (1) is the typical anti-emetic given in order to avoid (2) as complications - (3) is the typical anti-muscarinic given for its (4) effects, to prevent (5), and protect (6)

Answer 48

1- odansetron 2- prevent aspiration of stomach contents (--> choking, obstructions, ect) 3- scopolamine 4- amnesic effects 5- prevent salivation / bronchial secretions 6- protect heart from bradycardia (via inhalation anesthetics and neuromuscular blockers)