Test 1: Basic Overview of IV Sedatives & Hypnotics

Question 1

Which came first, inhalation or IV agents?

Answer 1

Inhalation Agents

Question 2

What is an intravenous anesthetic?

Answer 2

A clinically available substance that when administered directly to the patient via the bloodstream can be used to induce or maintain a state of general anesthesia.

Question 3

What is Volume of Distribution?

Answer 3

The volume into which a drug distributes in the body at equilibrium before elimination starts.

Question 4

What is the equation for Volume of Distribution?

Answer 4

Vd = the amount of drug in the body at equilibrium before elimination starts / plasma concentration of the drug

Question 5

What are properties of drugs with a SMALL Vd?

Answer 5

-Bind to plasma binding proteins
-Poor lipid solubility
-Highly ionized (charged)
-Drug stays in the circulation (High plasma concentration)
-Elimination is faster

Question 6

What is the example drug with a SMALL Vd?

Answer 6

Muscle Relaxants (Vd = 0.3-0.5 L/kg)

Question 7

What are properties of drugs with a LARGE Vd?

Answer 7

-Unbound
-Highly lipid soluble
-Non-ionized (uncharged)
-Drug diffuses into tissues (Low plasma concentration)
-Long terminal half times

Question 8

What are the example drugs with a LARGE Vd?

Answer 8

Benzos (Vd = 2-2.5 L/kg) and Barbiturates

Question 9

What does “Protein bound” mean?

Answer 9

-Protein bound drugs do not leave the circulation
-Only free, unbound drugs diffuse across the capillary walls

Question 10

What is Induction?

Answer 10

The transition from a state of awareness to a loss of consciousness.

Question 11

What is a sedative?

Answer 11

An agent used to exert an anxiolytic effect by reducing anxiety and causing calmness.
-Degree of CNS depression should be the minimum consistent with therapeutic efficacy

Question 12

What is a Hypnotic?

Answer 12

An agent that causes drowsiness, as well as the onset and maintenance of sleep.
-More pronounced CNS depression than sedatives

Question 13

What is a Sedative-Hypnotic?

Answer 13

A drug class capable of anxiety relief (sedation) as well as inducing sleep (hypnosis). Classification is based on its clinical use, rather than chemical structure.

Question 14

What are the qualities of an Ideal IV Anesthetic?

Answer 14

-Rapid/Smooth onset and recovery
-Provides Analgesia
-Minimal CV and Resp Depression
-Water soluble aqueous base
-Anti-emetic action
-Bronchodilation
-Lack of toxicity or histamine release
-Advantageous pharmacokinetics/pharmacodynamics

Question 15

How much of total body water is intracellular fluid?

Answer 15

2/3

Question 16

How much of total body water is extracellular fluid?

Answer 16

1/3
-Composed of plasma and interstitial fluid

Question 17

How much of extracellular fluid is plasma?

Answer 17

1/5

Question 18

How much of extracellular fluid is interstitial fluid?

Answer 18

4/5

Question 19

How many liters of Total Body Water do we have?

Answer 19

42 Liters Total Body Water

28 L ICF + 14 L ECF

Question 20

A drug with a large Vd is found where?

Answer 20

In the ICF of organs and tissues

Question 21

A drug with a small Vd is found where?

Answer 21

In the plasma

Question 22

What is the 2 Compartment Model?

Answer 22

Drugs administered IV are distributed to the central compartment and then redistributed to the peripheral compartment; then back to the central compartment for elimination.
-IV Anesthetics go from bloodstream straight to the central compartment due to their lipophilic nature (can rapidly diffuse through the CNS). However, they are redistributed quickly to other parts of the body, causing a decrease in effects. IV anesthetics become inactive once they reach the peripheral compartment (ex: Muscles).

Because the VRG receives a disproportionate amount of blood flow, it equilibrates with the blood plasma more rapidly than any other tissue group.
-Drugs go straight to brain = fast on but also fast off

Question 23

What makes up the Central Compartment?

Answer 23

The “Vessel Rich Group” (VRG)
-Highly perfused tissues. Only 10% of body mass, but receives 75% of cardiac output
-Liver
-Kidneys
-Lungs
-Heart
-Brain

Question 24

What makes up the Peripheral Compartment?

Answer 24

Everything else.
-Gut
-Skeletal Muscle
-Adipose tissue
-Etc

Question 25

What is the 3 Compartment Model?

Answer 25

-Describes the behavior of an IV anesthetic infusion.
-The drug being administered begins in the Central Compartment and then distributes peripherally.
-As the peripheral compartment begins to saturate, an appropriate blood concentration can be maintained with a lower infusion rate.
-The longer you run an infusion, the more you prolong wake-up. Want to hit a steady state where you’re only replacing what is being eliminated.
-Ex: Start with large bolus at the beginning to rapidly fill compartments, then start drip at a lower rate

Question 26

What is Context Sensitive Half-Time?

Answer 26

The time it takes to achieve a 50% reduction in concentration after stopping a continuous infusion.
-Important because, with some drugs, the longer you keep it on, the longer it takes for a patient to wake up.
-Can introduce a shorter acting drug to wean off of a longer acting one towards the end of the case.
-Long CS 1/2 time = Fentanyl
-Short CS 1/2 time = Propofol

Question 27

What are the 5 effects caused by General Anesthesia?

Answer 27

1) Unconsciousness
2) Amnesia
3) Analgesia
4) Suppression of Stress Response (inhibition of autonomic reflexes)
5) Sufficient Immobility (skeletal muscle relaxation)

Question 28

What is the most important determinant of awakening?

Answer 28

Redistribution to inactive, poorly perfused tissues is the most important determinant of awakening

Question 29

What is the primary binding site for the majority of IV anesthetics?

Answer 29

GABAA Receptor.
y– aminobutyric acid type A
-Endogenous neurotransmitter = GABA
-Primary binding site for the majority of IV anesthetics
-Most abundant inhibitory receptor in the brain
-Broadly distributed throughout the CNS
-Regulate neuronal excitability, mediate unconsciousness
-Ligand-gated ion channels

Question 30

What are the functions of the GABA A Receptor?

Answer 30

Thalamic Circuits
-Sensory Processing
-Attention

Hippocampal Networks
-Memory

Thalamocortical Circuits
-Consciousness
-Awareness

Question 31

Describe how IV Anesthetics work on the GABA Receptor (general overview)?

Answer 31

GABA is a major inhibitory transmitter in the central nervous system (CNS).

-The GABA A receptor, which is a ligand-gated ion channel receptor, is activated by the binding of the neurotransmitter GABA.
-This binding of GABA to the GABA A receptor initiates the movement of chloride (Cl−) through ion channels into the cell.
-This results in hyperpolarization of the postsynaptic cell membrane and the inhibition of neuronal cell excitation.

Question 32

Which subunits of GABA do Benzos act on?

Answer 32

Benzodiazepines are thought to interact with GABAA receptors between the α and γ subunits

Question 33

Which drugs interact with the β subunits of GABA?

Answer 33

Propofol, etomidate,and barbiturates

Question 34

What is the NMDA Receptor?

Answer 34

N-methyl-D-aspartate type
-Endogenous neurotransmitters: Glutamate & Glycine
-Excitatory receptor
-Mediates excitatory postsynaptic currents of prolonged duration
-Location: Presynaptic, Postsynaptic, Extrasynaptic
-Effected by: Xenon, Nitrous Oxide (N2O), and Ketamine
-Ligand gated ion channel (also sensitive to voltage across the membrane containing the receptor)

Question 35

What are the Non-NMDA Receptors?

Answer 35

AMPA Receptors & Kainate receptors also mediate fast excitatory impulses but have little anesthetic sensitivity

Question 36

What is important to know about the NMDA Receptor before it can be occupied by an Antagonist?

Answer 36

-NMDA Receptors required not only a presynaptic release of a neurotransmitter (ligand), but also the voltage across the membrane containing the receptor.
-Mg2+ blocks the channel until membrane depolarization occurs
-Channel must first be activated before occupied by antagonist

Question 37

How does the NMDA receptor work?

Answer 37

L-glutamate, an amino acid, is probably the most important excitatory neurotransmitter in the CNS.
-At the NMDA receptor, it causes the opening of the ion channel.
-A rapid influx of Na + , Ca 2+ , and K + results in the depolarization of the normally negative postsynaptic membrane that initiates the action potential.

Question 38

How does Ketamine cause its effects at the NMDA Receptor?

Answer 38

Ketamine is a noncompetitive antagonist at this receptor.
-Depresses medial thalamic nuclei, leading to the blockage of afferent pain signals to the thalamus and cortex.
-Afferent impulses are transmitted to cortical regions of the brain but are not interpreted, so responses to visual, auditory, and pain stimuli are inappropriate.
-Although cortical association areas are depressed, the limbic system, which is thought to cause excitatory behavior, is simultaneously activated.