L5. General Anesthetics

Stages of Anesthesia: Stage 1

decreased awareness

Stages of Anesthesia: Stage 2

delirium and excitation

Stages of Anesthesia: Stage 3

surgical anesthesia

unconscious, no pain perception, has reflexes

Stages of Anesthesia: Stage 4

medullary paralysis

respiratory and cardiovascular depression

True / False: modern anesthetics act very rapidly and achieve deep anesthesia quickly

True

True / False: currently no one single anesthetic can achieve all the desired affects / goals of anesthesia

true

What are the goals of anesthesia?

Unconsciousness

Analgesia

Skeletal muscle relaxation

Inhibition of autonomic reflexes

Amnesia

What autonomic reflexes are inhibited with anesthesia?

Bronchospasm

Excess salivation

Arrhythmias

An ideal anesthetic drug should have --- and --- induction, but rapidly reversible upon discontinuation

rapid and smooth induction

Balanced anesthesia

combination of agents and techniques to produce different components of anesthesia

What are the mechanisms of action of general anesthetics?

ligand gated ion channels

sleep promoting neurons in hypothalamus

Molecular Target for Anesthetic Action: ligand gated ion channels

increase inhibitory synaptic activity

reduce excitatory synaptic activity

GABA receptors are ligand gated ---- ion channels

chlorine

What increases inhibitory synaptic activity?

Binding of GABA to receptors

What happens what GABA binds to ligand gated ion channels?

Chlorine is released

Neuron becomes hyper polarized

What are the 2 ways in which anesthetics reduce excitatory activity?

inhabit ionotropic glutamate receptors

inhibit nicotinic acetylcholine receptors

What are ionotropic glutamate receptors?

AMPA

NMDA

Kainate

ketamine blocks __ receptors

NMDA

NO blocks ____ receptors

potassium _____ excitatory synaptic activity

reduces

True / False: most inhaled anesthetics inhibit nicotinic acetylcholine receptors at moderate to high concentrations

true

Two types of general anesthetics

Inhaled

Intravenous

What are the general anesthetics that are inhaled?

Nitrous oxide

Sevoflurane

Desflurane

Isoflurane

Halothane

What are general anesthetics that are given IV?

Propofol

Ketamine

Etomidate

Fospropofol

Methohexital

What IV anesthetic is only used for ECT procedures as it excites the brain and causes seizures?

Methohexital

General anesthetics cause direct activation of sleep-promoting neurons in the ---- nucleus of the hypothalamus.

ventrolateral preoptic

What is the main advantage of inhaled anesthetics (nitrous oxide, sevoflurane, desflurane, isoflurane, halothane)?

can easily change blood concentration by altering gas mixture to achieve anesthesia / reduce toxicity

Minimum alveolar concentration (MAC)

alveolar concentration of gas at which 50% of patients become unresponsive to stimulus

The lower the minimum alveolar concentration --- more --- the drug

the more potent

True / False: the rate of induction of an anesthetic is related to the minimum alveolar concentration (MAC)

false - unrelated

What affects the rate of induction?

Blood : gas partition coefficient

What is a gas partition coefficient?

how soluble a gas is = how easily it will move between different tissues in the body

When is the rate of induction of an anesthetic faster?

when the anesthetic is less soluble

blood:gas partition coefficient is small

When is the rate of induction of an anesthetic slower?

When the anesthetic is more soluble

blood:gas partition coefficient is large

Why is the controlled rate of induction less when an anesthetic is less soluble?

It diffuses from the lugs to the bloodstream quicker

doesn't dissolve in the lungs

Why is the controlled rate of induction better when an anesthetic is more soluble?

it dissolves in the blood faster

takes longer to diffuse from lungs to bloodstream

Fa / Fi

Fraction in alveoli / Fraction inspired

A faster approach of Fa to Fi means a --- onset of action

quicker

---- soluble agents reach Fa = Fi more rapidly and thus induce anesthesia faster

Less soluble agents

---- agents reach Fa = Fi more slowly and thus induce anesthesia slower

More soluble agents

How does increasing the rate of ventilation increase the rate of induction?

increased ventilation = more drug is inhaled into the lungs at a given time

What does an increase in the rate of ventilation do to Fa / Fi?

helps bring Fa closer to Fi more quickly

What is the size of the partition coefficient if a drug is less soluble?

Partition coefficient is small

What is the size of the partition coefficient if a drug is more soluble?

partition coefficient is larger

What happens to the rate of exhalation / elimination of the drug by the lungs when the blood:gas partition coefficient is small?

less soluble

exhaled / eliminated faster

What happens to the rate of exhalation / elimination of the drug by the lungs when the blood:gas partition coefficient is large/

more soluble

exhaled / eliminated slower

Inhalation anesthetics are only metabolized to a small degree. What is the exception?

Halothane - metabolized in the liver

What inhaled anesthetics have smaller blood:gas partition coefficients (more readily inducible)?

Nitrous oxide

Desflurane

Sevoflurane

What inhaled anesthetics have larger blood:gas partition coefficients (less readily inducible)?

Isoflurane

Halothane

What is the pharmacological effects of inhaled general anesthetics on the liver?

depresses blood flow by 15 - 45%

liver metabolism low for all inhaled agents except halothane

What is the pharmacological effects of inhaled general anesthetics on the kidneys?

depresses glomerular filtration rate

Which inhaled anesthetics are potent anesthetics:

- nitrous oxide

- deslurane

- sevoflurane

- isoflurane

- halothane

- deslurane

- sevoflurane

- isoflurane

- halothane

Which inhaled anesthetics can be used in asthmatics?

- nitrous oxide

- deslurane

- sevoflurane

- isoflurane

- halothane

nitrous oxide

Which inhaled anesthetics SHOULD NOT be used in asthmatics?

- nitrous oxide

- deslurane

- sevoflurane

- isoflurane

- halothane

desflurane

Which inhaled anesthetics are pungent and cannot be used with mask induction?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Desflurane and isoflurane

Nitrous oxide can be used in --- and ---

asthmatics and pregnant woman

Which inhaled anesthetics have a rapid onset and recovery?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Nitrous oxide

Desflurane

Sevoflurane

Why does nitrous oxide, desflurane, and sevoflurane have more rapid onset and recovery compared to isoflurane and halothane?

Smaller blood:gas partition coefficient

Of the inhaled anesthetics that have rapid onset and recovery, which has the most rapid onset and recovery?

- nitrous oxide

- desflurane

- sevoflurane

Nitrous oxide

Disadvantages of nitrous oxide?

Incomplete anesthesia

Hypoxia

No muscle relaxation

How is nitrous oxide used?

In combination with other general anesthetics

Nitrous oxide

- adverse effects

incomplete anesthesia

hypoxia

What happens if nitrous oxide is abused?

depersonalization

brain damage

peripheral sensory neuropathy

Which inhaled anesthetic is most commonly used?

- nitrous oxide

- deslurane

- sevoflurane

- isoflurane

- halothane

Sevoflurane

Which inhaled anesthetics are not pungent and can be used with mask induction?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

nitrous oxide

sevoflurane

halothane

What is sevoflurane commonly used for?

Same day surgery

Sevoflurane interacts with ----

Why is this important?

soda lime of re-breathing apparatus

can form compound that is toxic to the kidneys

What should be used with sevoflurane?

fresh gas - not recycled gas

Recovery for desoflurane is --- as fast as isoflurane

twice as fast

Desflurane

- adverse effects

airway irritation

bronchospasm / laryngospam

What is desflurane commonly used for?

Outpatient surgery

What is the benefit of using isoflurane?

less reduction in cardiac output

What inhaled anesthetic agent is used in cardiac surgery?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Isoflurane

What inhaled anesthetic agent provides skeletal muscle relaxation?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Isoflurane

Which inhaled anesthetic is not good for children?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Isoflurane

Which inhaled anesthetic has the highest solubility in blood?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Halothane

Which inhaled anesthetic has the lowest solubility in blood?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Nitrous oxide

Halothane undergoes ---- liver metabolic

>20

What inhaled anesthetic can be used for inhalation anesthesia in children (mask induction) because it is not pungent?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Halothane

What inhaled anesthetic is used in low income countries because of relatively low cost?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Halothane

What is the major side effect of halothane?

malignant hyperthermia

hepatotoxicity

What is the treatment for malignant hyperthermia?

stop halothane

give dantrolene

How does dantrolene fix malignant hyperthermia?

decreases the amount of Ca released from the sarcoplasmic reticulum

What drugs are the most likely to trigger malignant hyperthermia?

Succinylcholine

Halothane

Isoflurane

Which inhaled anesthetic is least likely to trigger malignant hyperthermia?

- nitrous oxide

- desflurane

- sevoflurane

- isoflurane

- halothane

Desflurane

Ketamine is a ---- receptor antagonist

NMDA

What is an advantage of intravenous anesthetics?

rapid onset of action

What is a disadvantage of intravenous anesthetics?

Harder to lower blood level

Intravenous agents are highly ---

lipophilic

How do intravenous agents work?

First distributed into brain and spinal cord

then redistributed to muscle and fat

Following prolonged intravenous anesthetic infusion, there is a build up in which portion of the body? Why?

Fat because intravenous agents are lipophilic

True / False: even after prolonged infusion the half time of propofol is relatively short

true

What are the advantages of propofol?

Less distribution to muscle and fat

Less grogginess

What is the induction time of propofol?

Rapid

Is propofol potent?

Yes potent

- can be used for stage 3 anesthesia = unconscious, no pain perception, skeletal reflexes present

Does propofol provide analgesic effects?

No anelgesia

What is the adverse effect of propofol?

Hypotension

Cerebral metabolism

Respiratory depression

Compared with thiopental propofol causes greater --- and less likely to induce ----

causes greater hypotension

less likely to induce bronchospasm

What are the clinical uses of propofol?

Same day surgery

Sedative in ICU

Propofol can be used in the --- and --- of anesthesia

induction and maintenance