general anesthetics

Question 1

Nitrous oxide, N2O

Answer 1

Inhaled General Anesthetic (GA)
MAC = 105 %, by itself cannot achieve the desired depth of anesthesia
-analgesia at 20% conc. of inhaled air, sedation 30%-80%
-used in dentist’s offices
-Blood : gas partition coefficient = 0.47–rapid induction and recovery or emergence

Question 2

Isoflurane (Forane®)

Answer 2

Inhaled General Anesthetic (GA)
MAC = 1.2%, pungent
Blood:gas partition coefficient = 1.4
>99% eliminated unchanged via the lungs

Question 3

Enflurane (Ethrane®)

Answer 3

Inhaled General Anesthetic (GA)
MAC = 1.6%, sweet
Blood:gas partition coefficient =1.8
2–8 % metabolized in liver

Question 4

Desflurane (Suprane®)

Answer 4

Inhaled General Anesthetic (GA)
MAC = 6%
*Irritating gas – coughing, respiratory, secretions, must use IV GA to induce anesthesia
Blood : gas partition coefficient = 0.45
>99% eliminated unchanged via lungs
SEs: dec. in BP, CO is well preserved, dec. in vent. rate

Question 5

Sevoflurane (Ultane®)

Answer 5

Inhaled General Anesthetic (GA)
MAC 2%
alone is non-irritating to airways and may be used to induce anesthesia
Blood : Gas partition coefficient = 0.65
*>99% eliminated unchanged via lungs

Question 6

Propofol (Diprivan®)

Answer 6

IV General Anesthetic
Induction dose 1.5-2.5 mg/kg, duration of action 4-8 min
Not water soluble (may be dissolved in vegetable oil) – very fatty, caution in pts with high TG levels
*Most common induction agent of anesthesia in US
-Enhance effects of GABA at GABAA inhibitory receptors

Question 7

Etomidate (Amidate®)

Answer 7

IV General Anesthetic
Induction dose 0.2-0.4 mg/kg, duration of action 4-8 min
-Not water soluble (35% propylene glycol), Used for pts at risk for hypotension
-Used for induction and maintenance of anesthesia
-Enhance effects of GABA at GABAa inhibitory receptor, Activate receptor without GABA present
-Metabolized in liver, metabolites eliminated in urine

Question 8

Ketamine (Ketalar®)

Answer 8

IV General Anesthetic
Induction dose 0.5-1.5 mg/kg duration of action 10-15 min
-Water soluble (100 mg/ml preparation)
-Given IV also oral, rectal, IM
-Produces profound analgesia – no need for opioid co-administration
-Competitive antagonist of NMDA receptor
-Inhibition of voltage sensitive Na, K channels
-Metabolized in liver to norketamine (has further action on CNS), rapid clearance

Question 9

Midazolam (Versed®)

Answer 9

GA Adjunct, benzo
water soluble, no pain on injection, rapid onset (2 min, IV), rapid recovery

-benzos used for pre-op sedation (Midazolam» diazepam > lorazepam): dec. brain MR, BF, dec. BP, vent. rate

Question 10

Fentanyl (Sublimaze®)

Answer 10

GA Adjunct, opioid
Minimize vascular reflex to noxious, painful stimuli, induction for later intubation
30 min duration of action; used in terrorist situations
-μ opioid receptor agonist
SEs: N/V, dec. vent rate, dec. HR, dec. BP

Question 11

Dexmedetomidine (Precedex®)

Answer 11

GA Adjunct, α2 adrenergic agonist
dec. catecholamine release
-used for sedation in critically ill adults, off label use as GA
adjunct; IV use only, no amnesia
SEs: dec. BP, bradycardia, no change in vent rate, Useful in non-intubated patients

Question 12

Dantrolene (Dantrium®)

Answer 12

Ryanodine receptor inhibitor
tx for malignant hyperthermia
Also used to treat spasms and spastic disorders

Question 13

how are GAs dangerous

Answer 13

very narrow therapeutic index of 2 – 4 (LD50/ED50) and extremely fast acting

Question 14

3 requirements for anesthetic state

Answer 14

Amnesia – occurs through depressing neuronal activity in the hippocampus -benzos
Immobility in response to noxious stimulation –NMJ blockers
Attenuation of autonomic response to noxious stimulus (^HR, ^BP); -analgesic opioids (fentanyl)
*inhaled and IV GAs enhance all three
-balanced implies use of multiple classes to get to desired depth of anesthesia

Question 15

pre-op sx drugs
for sedation?
for slowing HR?
to prevent vomiting/acid reflux? regurgitation?

Answer 15

barbiturates, diazepam, midazolam for sedation

• Atropine to counteract bradyarrhythmia (blocks ACh)
• Serotonin receptor antagonist (Ondansetron) for vomiting
• Histamine R2 antagonist (Ranitidine) for acid reflux
• both these prevent regurgitation due to LES relaxes with musc. relaxers

Question 16

?? are used to induce anesthesia because they faster acting (~1 min) than inhaled GAs

Answer 16

Intravenous GAs

-inhaled also tast bad

Question 17

For maintenance of anesthesia, ?? are used.

Answer 17

inhaled GAs

-constantly monitored, can be fine tuned, N2O typically used, reduces amount GA used

Question 18

other substances given during anesthesia

Answer 18

• fentanyl: reduce dose of GAs and blocks the noxious stimulus reflex in the ANS
• Succinylcholine or other NMJ blocking agents as needed (e.g. endotracheal intubation)

Question 19

may have this effect post-op

Answer 19

“Emergence excitement” is a condition where the half conscious patient exhibits restlessness, crying, moaning, and in extreme cases thrashing
-may have rebound HTN and tachycardia

Question 20

tx for post-op hypothermia/shivering

Answer 20

meperidine (12.5mg) to reduce the shivering threshold

Question 21

tx for post-op pain

Answer 21

NSAIDS for pain, avoid narcotics until sx drugs wear off

Question 22

real life example of balanced anesthesia

Answer 22

Oxygen + Desflurane
Propofol (induce anesthesia) 
Fentanyl (narcotic pain) 
Midazolam (tranquilizer sedative) 
Rocuronium (muscle relaxer)

Question 23

GA pharmacokinetics

Answer 23

• effect proportional to concentration in CNS
• GA diffusion from lung–>blood–>CNS determines rate of induction/recovery
• rate of induction for inhaled GAs not too important (IV GAs used for induction), rate of recovery is important (faster=better)
• High water (blood) solubility = slow induction

Question 24

Blood/gas partition coefficient is a measure of ??

Answer 24

water solubility

[GA] in blood / [GA] in lung; when gas is in equilibrium

Question 25

Compare speed of induction of N2O and halothane

Answer 25

N2O--- poorly soluble in blood (blood/gas partition coefficient = 0.47) --- rapid induction Halothane--- very soluble in blood (blood/gas partition coefficient = 2.3)----slow induction.

Question 26

minimum alveolar concentration (MAC)

Answer 26

measure of potency;the concentration of inhaled GA needed for 50% of patients to NOT respond to pain. -proportional to lipid solubility

Question 27

GA mechanism: inhibit neuronal activity by causing ??

Answer 27

1) neuronal hyperpolarization 2) inhibition of excitatory synapses 3) enhancing inhibitory synapses

Question 28

GA theories

Answer 28

Lipid theory: GAs swell lipid membranes causing a general alteration in ion channel conduction; Myer-Overton rule – potency correlates with its solubility in olive oil Specific protein - GA interaction theory: GAs interact specifically with ion channels/receptors; isoflurane +/- sterioisomers (same lipid solubility) have diff. MAC values, but GABAa receptor point mutations abolish effects of isoflurane and enflurane (it's a receptor not solubility thing) *GAs alter cell membranes and enhance inhibitory membrane- bound receptors (GABA) or inhibit excitatory membrane-bound receptors (e.g. NMDA)*

Question 29

how to determine DoA (depth of anesthesia)

Answer 29

EEG; analyzed by Bispectral (BIS) index | -scale of 100 (awake) to 0 (deep coma)

Question 30

N2O SEs

Answer 30

Air pockets (e.g. middle ear) may expand Can change blood pressure depending on what is co-administered Depresses ventillary response to hypoxia Does not trigger malignant hyperthermia

Question 31

Enflurane SEs

Answer 31

- Dec. BP, cardiomyocyte contractility, peripheral vasodilation (cerebral vasculature), no change in HR - *Produces electrical seizure activity, though no evidence, contraindicated for epileptics - Muscle relaxation enhanced with NMJ blockers - Decrease in vent. rate

Question 32

Isoflurane SEs

Answer 32

-Dec. in BP, vasodilation only (cerebral vasculature), CO maintained -Mild tachycardia -Decrease vent. response reflex to hypoxia/hypercapnia -Modest vasodilation in cerebral vasculature, however metabolic rate of brain is decreased -Preferred GA for neurosurgery -Muscle relaxation enhanced with NMJ blockers -Decreased renal blood flow

Question 33

Sevoflurane SEs

Answer 33

- Decrease in blood pressure, systemic vasodilation - No change in CO - Preferred GA for patients prone to myocardial ischemia - Renal effects - Sevoflurane and soda lime combine to produce “Compound A” which may cause short term renal damage. Because of this, the FDA recommends sevoflurane administered with fresh gas at a rate of 2 L/min; semi closed or open gas administration.

Question 34

Propofol SEs

Answer 34

Major decrease in BP, vasodilation and decrease myocardial contractility - Pain of injection, reduced with local anesthetic or inject in large vessel - *Decrease in vent rate* - (killed Michael Jackson) - Anti-emetic properties – very useful property for people given opioids - Does not cross placenta, safe for pregnant women

Question 35

Etomidate SEs

Answer 35

- Pain of injection, reduced with local anesthetic or inject in large vessel - Myoclonic movements, benzos co-admin to prevent - N/V - Inhibition of adrenal gland synthetic enzymes - No decrease in BP or CO

Question 36

Ketamine SEs

Answer 36

-No pain of injection – no need for local anesthetics -^cerebral blood flow, no change in brain metabolism -Emergence delirium (1 hour post emergence) -Hallucinations, vivid dreams, illusions (drug of abuse) -Benzos lessen the hallucinations -only modest decrease in vent. rate and is potent bronchodilator CV: ^BP, ^CO, ^HR- useful for pts at risk for hypotension -severe deterioration of the urinary bladder (after only 2-3 years of abuse (~5 grams injected per day))

Question 37

hypothermia as a sx complication

Answer 37

body temp is below 36°C - cold OR, room-temp IV fluids, many GAs cause vasodilation-->heat loss - ^chance cardiac arrest, unstable angina, MI

Question 38

malignant hyperthermia

Answer 38

-adverse reaction to inhaled GAs, high mort rate; core temp rapidly increases to over 42°C (108°F) due to uncontrolled muscle rigidity -complication of most inhaled GAs; not N2O and not succinylcholine (NMJ blocker) -ryanodine Ca2+ channels don't close-->uncontrolled muscle contraction-->heat generation. -Fatigued myocytes eventually lyse releasing K+-->fatal cardiac events. (KCl is the 3rd and final drug given in conventional lethal injection protocols)