A.21

Question 1

Inhalational anesthetics

Answer 1

Nitrous oxide,
Isoflurane,
Desflurane,
Sevoflurane

Question 2

Nitrous oxide (N2O)

Answer 2

MOA: NMDA antagonist (reduced opening), increases opening of TREK-1 K+ channels,
weak general anesthetic on its own→ cannot produce surgical anesthesia, but has analgestic effect.
Can lead to diffusion hypoxia. Second gas effect;
Effect: Reduced neuronal excitability/CNS activity depression/unconciousness/anesthesia;
Kinetics: non-irritating for airways + cheap, rapid onset + recovery, analgestic+amnestic, no damage to cardiovascular respiratory or parenchymal tissues;
IND: surgical anesthesia→ used as a “carrier gas” for sevoflurane/desflurane, Analgesia (“laughing gas”)→ used to reduce pain in dental procedures and childbirth (in both used 50:50 v/v with O2);
SEs: hallucination and laughing, potential drug abuse (in case of analgesia use),
-Staff toxicity (→ prolonged exposure to N2O can lead to inhibition of protein and RNA synthesis → abortion +teratogenic effect, ↓ of methionine synthase activity→ megaloblastic anemia),
-Accumulates in body cavities (→ abdomen, chest, inner ear→ stretch bowels/gallbladder and cause rupture of cysts);
Solubility:0.47;
MAC: >100

Question 3

Isoflurane

Answer 3

MOA: potentiates GABA action on GABAA-Rs and opens K+ ch. (TREK) to reduce neuronal activity;
IND: suitable for maintenance of anesthesia, preferred in neurosurgery;
SEs: Respiratory depression, Respiratory irritation (=pungent), Coronary steal syndrome- no significant clinical importance HR↑, Malignant hyperthermia, ↓CO, ↓↓Vascular resistance ;
Solubility: 1.40;
MAC: 1.40;
Extra: Enflurane isomer, less risk of seizures

Question 4

Desflurane

Answer 4

MOA: potentiates GABA action on GABAA-Rs and opens K+ ch. (TREK) to reduce neuronal activity;
IND: suitable for maintenance
SEs: Respiratory depression, irritates respiratory system (pungent), Malignant hyperthermia, ↓CO, ↓↓Vascular resistance, ↑HR ;
Extra: rapid onset and recovery, need special equipment to administer (heated vaporizer), preferred in overweight patients, it is slightly metabolized (but no liver/renal damage);
Solubility: 0.42;
MAC: 6-7

Question 5

Sevoflurane

Answer 5

MOA: potentiates GABA action on GABAA-Rs and opens K+ ch. (TREK) to reduce neuronal activity;
IND: used for induction and maintenance (in children); SEs: Respiratory depression, less irritation to the respiratory tract, malignant hyperthermia, metabolic rate is relatively high (→possible nephrotoxic metabolite), ↓CO, ↓↓vascular resistance;
Extra: fast induction and recovery, most commonly used inhaled anesthetic;
Solubility: 0.69;
MAC: 2

Question 6

MAC

Answer 6

minimal alveolar concentration. the concentration of inhaled anesthetic at sea level that produces immobility in response to surgical stimuli in 50% of the patients (MAC is the index of potency!)

Question 7

diffusion hypoxia

Answer 7

occurs when N2O diffuses out of the blood and into the alveoli in large volumes→ dilutes the O2 in the alveoli→ reducing alveolar O2 tension→ hypoxia

Question 8

Second gas effect

Answer 8

increased concentration of a second agent due to the rapid diffusion on N2O in the alveoli (when we inhale a gas the cc of it in the alveoli is very high so it will diffuse fast into the capillaries)

Question 9

Coronary steal syndrome

Answer 9

a condition that occurs due to dilation of coronary arteries in the presence of coronary artery disease, which is when there’s a partial or complete blockage in the lumen of another coronary artery.

Question 10

Treatment of malignant hyperthermia

Answer 10

dantrolene administration to reduce Ca2+-release from the SR

Question 11

elimination of inhaled anesthetics

Answer 11

Inhaled anesthetics are mainly eliminated by the lungs or by metabolism by hepatic and tissue enzymes
Sevoflurane>isoflurane>desflurane>nitrous oxide

Question 12

Pharmacodynamics of inhaled anesthetics

Answer 12

Potency: Minimum Alveolar Concentration (MAC)
the concentration of inhaled anesthetics at sea level that produces immobility in response to surgical stimuli in 50% of the patients.

Question 13

Pharmacokinetics of inhalation anesthetics

Answer 13

The concentration of anesthetics in the brain depends on:
1. The partial pressure of the anesthetic gas in the inhaled air
2. Pulmonary ventilation rate and blood flow rate
3. Technical settings (plastic tube, flow rate etc)
4. Blood solubility (property of the anesthetic drug)
5. cardiac output
6. The difference in partial pressure between the alveoli and venous blood

Question 14

Solubility

Answer 14

blood:gas partition coefficient: :is the relative affinity of an anesthetic for the blood compared to air (index of solubility)
Inhaled anesthetics with low partition coefficients (<0.5) like desflurane and nitrous oxide:
show low solubility in the blood→ few molecules are required to raise its partial pressure quickly→ fast induction and recovery

Question 15

Partition coefficient (=solubility of the blood→property of the anesthetic)

Answer 15

-If the solubility is very high we need a LOT of gas to reach equilibrium (btw alveoli-blood-CNS).
- The blood is like an inactive container of the anesthetic and if solubility is high we need a huge amount of gas to dissolve it in the blood.
- If the solubility is low the uptake is low and the effect is higher

Question 16

stages → Signs of anesthesia

Answer 16

Stage 1: Analgesia→ loss of pain sensation}
Stage 2: Excitation}→ the patient appears delirious, HR and BP↑
Stage 3: Tolerance→ slowing of respiration, no reflex
Stage 4: Asphyxia→ medullary depression, severe CNS depression→ can proceed to death