General and Local Anesthetic Drugs

Question 1

Anesthetics primarily act on the… (2)

Answer 1

Synapse:

• presynaptic: release of NTs.
• postsynaptic: frequency/amplitude of impulses exciting the synapse.

Question 2

What inhibitory channels do general anesthetics activate? (2)

Answer 2

Cl- channels (GABA-A and glycine receptors).

K+ channels.

Question 3

What excitatory channels do general anesthetics inhibit? (3)

Answer 3

AChR (mAChR and nAChR)
EAA (AMPA, kainite, NMDA)
Serotonin

Question 4

What is the “driving force” for uptake of inhaled anesthetics?

Answer 4

Alveolar concentration, which is driven by inspired air concentration and alveolar ventilation.

Question 5

What is the blood:gas coefficient?

What is the relationship between the coefficient and rate of anesthetia onset?

Answer 5

It defines the relative affinity of an anesthetic for the blood compared with that of inspired gas (i.e. blood solubility).

Inverse - agents with low blood solubility reach high arterial pressure very quickly, and vice-versa.

Question 6

What is the blood:brain coefficient?

Does this vary much between drugs?

Answer 6

It defines the relative affinity of an anesthetic for the brain compared to blood.

It is relatively similar for all inhaled anesthetics; anesthetics are more soluble in the brain.

Question 7

What is the blood:gas partition coefficient, brain:blood partition coefficient and MAC for NO?

Answer 7

Blood:gas - 0.47 (low)
Brain:blood - 1.1 (low)
MAC - >100% (high)

Incomplete anesthetic; rapid onset and recovery.

Question 8

What is the blood:gas partition coefficient, brain:blood partition coefficient and MAC for Halothane?

Answer 8

Blood:gas - 2.3 (high)
Brain:blood - 2.9 (high)
MAC = 0.75% (low)

Medium rate of onset and recovery.

Question 9

What is MAC?

What is meant by a MAC >100%?

How much MAC in NO is sufficient for surgical anesthesia for most people?

Answer 9

Minimal Alveolar Concentration = measurement of anesthetic potency.

MAC >100% = if 100% of inspired air is the anesthetic, less than 50% of subjects would be anesthetize and other agents are needed to achieve full surgical anesthesia.

Using NO to produce 40% MAC in combo with 70% of a volatile agent’s MAC would equal 110% MAC and is sufficient in most people.

Question 10

What are the common side-effects of inhaled anesthetics?

What side-effect is specific to Halothane?

Which agents may cause renal toxicity?

Answer 10

Nausea and vomiting.

Hepatitis: symptoms onset within 2 days to 3 weeks after exposure (nausea, myalgia, rash, eosinophilia, jaundice and elevated LFTs).

Agents that are metabolized to products including fluoride ions (enflurane and sevoflurane).

Question 11

What causes malignant hyperthermia?

What is the antidote?

Answer 11

Succinylcholine in combo with volatile anesthetics may cause malignant hyperthermia.

Dantrolene.

Question 12

IV anesthetics are the preferred mechanism of anesthesia is most cases because…

Answer 12

They are highly lipophilic and preferentially partition into highly perf used lipophilic tissues (brain and spinal cord) - quick onset of action.

Question 13

What are the important IV anesthetic drugs? (5)

Answer 13

Etomidate
Ketamine
Midazolam
Propofol
Fentanyl

Question 14

Which IV anesthetics are known to have a slow onset? (2)

Answer 14

Midazolam

Fentanyl

Question 15

Which IV anesthetics are considered to have a rapid onset? (2)

Answer 15

Etomidate

Propofol

Question 16

Which IV anesthetic drug is considered to be moderately rapid in onset? (1)

Answer 16

Ketamine

Question 17

What is the MOA of Propofol?

What is Propofol made from?

Which adverse-effects may ensue? (3)

Answer 17

Targets GABA-A and acts as an agonist.

It is an emulsion with soybean oil, glycerol and lecithin (egg yolk component).

Allergic reactions (due to lethicin), hypotention and respiratory depression.

Question 18

What is the MOA of Etomidate?

How does its rate of LOC and recovery rate compared to Propofol?

Which patients is it useful to use?

What are the usual adverse-effects? (1)

Why is it rarely used via continuous infusion?

It undergoes…

Answer 18

Enhances actions of GABA on GABA-A receptors.

Patients with poor CV +/- respiratory symptoms because it causes minimal CV and respiratory depression.

Endocrine: adrenocortical suppression by inhibiting 11b-hydroxylase (cholesterol to cortisol conversion).

4-8 hour suppression after induction limits its usefulness for continuous infusion.

Extensive liver and plasma biotransformation.

Question 19

What is the MOA of Ketamine?

What does it cause?

What does it stimulate?

It is the only IV anesthetic to…

Answer 19

NMDA-receptor antagonist; similar to PCP.

Dissociative anesthetic state: catatonia, amnesia, analgesia +/- LOC.

Stimulates the SNS.

Produce profound anesthesia.

Question 20

What is the MOA of Dexmedetomidine?

Its sedative effect resembles…

What is used for mostly?

Answer 20

Alpha-2 adrenergic agonist in the locus caeruleus and spinal cord.

It resembles a physiologic sleep state.

Short-term sedation of incubated and ventilated patients in the ICU or as an adjunct to general anesthesia.

Question 21

Which drug classes are considered to be anesthesia adjuncts? (3)

Answer 21

Opioids
Barbiturates
Benzodiazepines

Question 22

What is the general MOA of local anesthetics?

What chemical classes are these drugs? (2)

Answer 22

Blockage of voltage-gated Na+ channels and inhibit the spread of APs across nerve axons.

Amides (if the drug name has > 2 “i’s” the drug is an amide).
Esters (1 “i”)

Question 23

What are the 2 major forms of adverse-effects of local anesthetics?

What are adverse-effects in the following?
CNS (high vs. low concentrations)
CV
Allergy

Answer 23

Toxicity following systemic absorption + direct neurotoxicity.

CNS: sleepiness, light-headedness, visual/auditory disturbances (low conc.); nystagmus, fasciculations, convulsions (high conc.; may pre-medicate w/ benzo).
CV: decrease CV conduction rate, force of contraction and arteriolar dilation leading to systemic hypotension.
Allergic: reactions to ester-types are most common due to metabolism of allergy-causing compounds.

Question 24

Benzocaine is used on as a…

Answer 24

Topical agents - poor water solubility.

Question 25

Bupivacaine is used for…

Answer 25

Producing prolonged anesthesia.

Question 26

Cocaine is used for…

Answer 26

Topical anesthesia of the URT.

Question 27

Dibucaine is only available as…

Answer 27

A topical cream for skin use due to its toxicity associated with injection.

Question 28

Procaine is primarily used for…

Answer 28

Infiltration anesthesia (local anesthesia produced by injection of the anesthetic solution directly into the area of terminal nerve endings).

Question 29

What are the inhaled anesthetics? (6)

Answer 29

Desflurane
Isoflurane
Enflurane
Sevoflurane
Halothane
NO

Question 30

What about Propofol’s PKs makes it a good choice for IV anesthesia?

Answer 30

Averages 30 sec onset of action and has a 3-10 min duration of action (dose-dependent).
There is also rapid recovery and patients are able to ambulated shortly after use.
Its PKs allow for short-duration general anesthesia (outpatient possible) as well as continuous infusion and sedation (ICU setting).