Drugs for General Anesthetics (& N2O)

Question 1

What is general anesthesia?

Answer 1

Depression of CNS
Controlled state of unconsciousness
Amnesia
Inhibition of sensory and autonomic reflexes
Skeletal muscle relaxation

Question 2

What is an ideal anesthetic?

Answer 2

Smooth and rapid onset, rapid recovery, wide margin of safety, no adverse effect

Question 3

Why use balanced anesthesia?

Answer 3

Combine drugs to achieve ideal anesthetic.
1. preoperative sedatives (benzos), analgesic (topical and local), antimuscarinic

2. pre and intraoperative neuromuscular blocking drugs
3. IV and inhalation anethetics for surgery

Question 4

In dentistry, when is N2O used?

Answer 4

For incidental discomforts, but NOT a good substitute for local anesthesia.

Question 5

What is an IV anesthetic adjunct that has dissociative anesthetic effects?

Answer 5

Ketamine

Question 6

List 4 opiate IV anesthetic adjunct analgesics:

Answer 6

1. morphine
2. fentanyl
3. alfentanil
4. sufentanil

Question 7

What is the site of anesthetic action?

Answer 7

The hydrophobic (oily) portion of the cell.

Question 8

What determines the anesthetic’s potency?

Answer 8

Potency is directly proportionate to the oil:gas partition coefficient.
(increase oil:gas solubility, increase potency)

So, the more lipid soluble the drug, the more potent it is.

Measure potency as minimal alveolar concentartion (MAC).

NOTE: a small MAC = more potent! Less is needed!

Question 9

List 3 theories of anesthesia:

Answer 9

1. Membrane fluidity hypothesis.
2. Volume expansion hypothesis
3. Protein perturbation hypothesis –> MOST LIKELY

Question 10

What does the protein perturbation hypothesis state?

Answer 10

Anesthetics inhibit excitatory ion channel receptors (receptors of glutamate, NMDA, AMPA, nicotinic).

Also enhance inhibitory ion channel receptors (like receptors for GABA and glycine ).

Note that ion channels at the synapses are more likely to be involved.

Question 11

What all does N2O cause and what receptors does it target?

Answer 11

N2O:
Hypnosis +
Amnesia +
Analgesia ++
Immobility +

Receptors:
GABA +
Glycine +

(note does not affect NDMD or AMPA receptors)

Question 12

What is stage I of anesthesia?

Answer 12

Analgesia.
Patient is conscious and responsive. May have some amnesia.

–> This is the stage N2O stays!

Question 13

What is stage II of anesthesia?

Answer 13

Excitement or delirium.
Patient is delirious, has amnesia, reaches unconsciousness and higher blood pressures (sympathetic stimulation) at upper levels.

Can cause irregular respiration, vomiting, incontinence.

–> Too high of N2O can reach this stage.

Question 14

What is stage III of anesthesia?

Answer 14

Surgical anesthesia.
Patient has loss of protective reflexes, regular respiration returns.

Can’t reach this stage with N2O because MAC would need to be 105%.

Question 15

What is stage IV of anesthesia?

Answer 15

Medullary depression.

Respiration ceases, circulatory failure, coma, death.

Question 16

Uptake and distribution of inhaled anesthetics are determined by:

Answer 16

For rate on onset (and recovery):

1. Solubility is inversely related to the blood:gas partition coefficient. (lower blood solubility = faster rate of induction)
   - -> Note N2O has a very low solubility and thus is very rapidly absorbed.
2. Concentration in the inspired air. Increased conc = increased rate.
3. Pulmonary ventilation rate. Increase ventilation = increased rate. Not a factor for N2O.
4. Pulmonary blood flow (aka cardiac output, CO). Increase blood flow = slower rate. Note that a decreased CO can increase the uptake of anesthetic.

Question 17

What is the second gas effect?

Answer 17

When a 2nd anesthetic is given along with N2O, N2O can be given in a lower concentration with a more rapid onset.

(alveolar tension already exists, so less N2O is required to reach appropriate pressure).

Question 18

What is diffusion hypoxia?

Answer 18

Common with N2O.

Discontinue anesthetic. Gradient changes so that N2O is quickly taken from blood the lungs.
This dilutes the O2 in the lungs!

Question 19

What are the 3 compartment N2O is sent to?

Answer 19

1. Vessel rich group: brain, heart, kidney, liver, endocrine glands (initially high uptake)
2. Muscle group: also the skin. (slower and prolonged uptake).
3. Fat group: dominates! Enormous capacity to hold anesthetic, takes a long time to reach equilibrium.

Note that drugs with high tissue lipid solubility have prolonged recovery periods.

Question 20

What is elimination of inhaled anesthetic a function of?

Answer 20

A function of the cardiopulmonary status of the patient!

NOT controlled by the clinician.

Note that metabolism in liver can count for 20 - 50% of elimination of anesthetics. But, N2O isn’t metabolized, just exhaled back out.

Question 21

For the MAC at steady state, what are the compared levels in different compartments of the body?

Answer 21

MAC= min alveolar concentration. The measure of potency that results in immobility to noxious stimuli in 50% of patients.

MAC levels in the lung is equal to that of the brain.

The smaller the MAC, the more potent the drug.

Note that the MAC for N2O is 105%…so N2O can never be used as a sole anesthetic agent (noxious stimuli).

Question 22

Does N2O create a depression in cardiac function?

Answer 22

Just a light depression.

This is counteracted by a slight increase in sympathetic nervous system activity.

Question 23

How does N2O affect the respiratory system?

Answer 23

N2O has minimal effect on respiratory function in normal individuals.

Patients with severe chronic COPD may become hypoxic with low, sedative concentrations of N2O.

Question 24

How does N2O affect the brain?

Answer 24

N2O increases cerebral blood flow LESS than other anesthetics.

This is because they decrease the cerebral metabolic rate and increase cerebral vasodilation = increased cerebral blood flow = increased intracranial pressure.

So, use careful consideration for a patient with a head injury.

Question 25

Does N2O cause nausea and vomiting?

Answer 25

Not usually at the normal, lower concentrations.

Question 26

What do inhaled anesthetics do to the kidneys and liver?

Answer 26

All inhaled anesthetics decrease glomerular filtration rate, renal plasma flow, and hepatic blood flow.

Question 27

Can you ever use N2O as a single anesthetic agent?

Answer 27

No. Not potent enough.

BUT. Use with other more potent general anesthetic to lower their MAC and thus speed induction and recovery (2nd gas effect!!)

Question 28

What is the N2O procedure in dentistry?

Answer 28

1. 100% O2 for 2 - 3 minutes
2. Start at 20% N2O, monitor for 1 -2 minutes
3. Increase N2O by 5-10% until patient exhibits symptoms
4. After termination of N2O, give 100% O2 for at least 5 minutes to avoid diffusion hypoxia.

Note there will be a rapid onset of 3 - 5 minutes due to the low solubility.

Question 29

What max percentage of N2O gives analgesia?

Answer 29

40% is the max for analgesia.

At 20 - 40%, have numbness, analgesia, dissociation, euphoria

Question 30

Around 30- 50% what are symptoms?

Answer 30

Sweating, nausea, amnesia, increased sleepiness.

Question 31

What % of N2O can result in unconsciousness?

Answer 31

Greater than 50% can result in unconsciousness and light, general anesthesia.