Pharmacodynamics

Question 1

Do all (or almost all) of the receptors for a drug have
to be bound to a drug for the drug to exert its
maximum effect?

Answer 1

No, there are typically far more receptors than needed for a
drug to exert its maximum effect. It is quite possible for a drug
to exhibit its maximum effect at very low drug concentrations
with numerous receptors still available.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 169.

Question 2

Where in the cell are most drug receptors located?

Answer 2

Most are proteins bound in the cell membrane. A few, however,
are located in the cytoplasm or nucleoplasm.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 169.

Question 3

Does the ionized or non-ionized form of a drug

confer its clinical effect?

Answer 3

In solution, the non-ionized form of a drug is considered to
confer pharmacologic activity, because it is in the non-ionized
form that the drug is able to pass through lipid soluble biologic
membranes to reach its point of action.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 62.

Question 4

How will the chronic administration of an antagonist
affect the number and sensitivity of the receptors it
antagonizes?

Answer 4

When chronically exposed to an antagonist, the receptors
upregulate, which means that both the number of receptors and
their sensitivity both increase.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 59.

Question 5

What is the occupancy theory?

Answer 5

The Occupancy Theory states that the magnitude of a drug’s
effect is proportional to the number of receptors it occupies.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 55.

Question 6

How does the overabundance of receptors for a drug
affect the dosing of an agonist for that receptor
compared to an antagonist for that receptor?

Answer 6

Because a drug can exert its maximum effect and still leave a
large number of receptors available, an agonist can exert its
effects at low concentrations. An antagonist, however, must
bind to a much larger number of receptors and requires higher
concentrations to do so. For example, acetylcholine (agonist)
only needs to bind to about 25% of the available nicotinic
cholinergic receptors in the neuromuscular junction to produce
a muscle contraction. A nondepolarizing muscle relaxant
(antagonist), however, must block 75% of the receptors to exert
a significant reduction in muscle fiber contractility.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 169.

Question 7

What are the two major scenarios by which drug
receptors bind to a drug and exert their effect. What
are they?

Answer 7

The two major ways in which a drug can bind to a receptor and
cause a change in cellular function are ionophores (ion
channels) and G-proteins.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 54-55.

Question 8

What is the difference between an agonist, an

antagonist, a partial agonist, and an inverse agonist?

Answer 8

A drug that has an affinity for a receptor but lacks efficacy
(meaning that it is unable to produce the conformational change
in the receptor necessary to elicit the response in the tissues for
which the receptor is designed) is an antagonist. An agonist
has both affinity and efficacy. A partial agonist can bind with the
receptor and has some efficacy, but it cannot elicit the maximal
tissue response. An inverse agonist can bind with the receptor,
but results in the opposite reaction of an agonist.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 60.

Question 9

What does the term LD50 mean?

Answer 9

The LD50 is the dose that is lethal in half of the population.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 57.

Question 10

What does the term C50 mean?

Answer 10

The C50 represents the site concentration at which a drug
exhibits half of its maximal effect.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 667.

Question 11

Is the binding of acetylcholine to a cholinergic
receptor an example of a G-protein mediated
mechanism or an ionophore?

Answer 11

It is an ionophore because an ion channel is affected by the
binding of acetylcholine to the cholinergic receptor. When
acetylcholine binds to the receptor, a sodium channel is opened
which allows the influx of Na+.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 169.

Question 12

Is the gamma-aminobutyric acid (GABA) receptor an
example of an ionophore or a G-protein mediated
receptor?

Answer 12

The GABA receptor is an ionophore. The binding of drugs or
neurotransmitters to a GABA receptor opens a chloride
channel, allowing the influx of chloride into the cell.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 169.

Question 13

What is meant by steady-state with regards to drug

concentration?

Answer 13

Steady-state is the point at which the plasma concentration of a
drug is in equilibrium with all other tissues is the body.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 171.

Question 14

With regards to drug-receptor complexes, what is

desensitization?

Answer 14

When receptors are exposed to an agonist more than normal,
they become desensitized. This means that the binding of the
agonist to the receptor exerts a lower-intensity response than
normal.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 169-170

Question 15

What is a pharmacodynamic interaction and what
are some common examples that would apply to
anesthesia?

Answer 15

A pharmacodynamic interaction is the effect one drug has on
the performance of another drug. It can be antagonistic or
synergistic. For example, cholinesterase inhibitors increase the
amount of acetylcholine, which antagonizes the effect of
nondepolarizing muscle relaxants. Hypnotics and narcotics act
on separate receptors, but have a synergistic effect which
increases the clinical effect of both drugs.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 174.

Question 16

Which would provide information about the steadystate
plasma concentration of a drug, a doseresponse
curve or a concentration-response curve?

Answer 16

The steady-state plasma concentration (CPss50) is determined
by a concentration-response curve using a continuous infusion
of a drug.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 171.

Question 17

What would be the effects of calculating the dose of
a drug for an extremely obese patient based on his
total body weight? Ideal body weight? Lean body
mass?

Answer 17

Dosing based on total body weight can lead to large doses and
prolonged duration of action in obese patients. Ideal body
weight, because it does not take into account the adipose
compartment, can lead to under-dosing. Dosing based on lean
body mass is advantageous because it takes into account
height and total body weight. Calculations based on lean body
mass have been used accurately to predict drug levels for
remifentanil in both lean and obese patients.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 676-
679.

Question 18

What is the function of the GABA-a receptor and how

is it similar/dissimilar to the acetylcholine receptor?

Answer 18

The GABA-a receptor allows the inward flow of chloride through
the central pore of the protein channel. Chloride (and therefore
GABA-a) transmits an inhibitory signal. The acetylcholine
receptor functions in a manner similar to the GABA receptor,
but utilizes sodium to accomplish the transduction of an
excitatory signal.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 54-55.

Question 19

What are the characteristics of G-protein receptors?

Answer 19

G-protein receptors utilize secondary messengers such as
cyclic GMP or cyclic AMP to transduce a signal. They can
activate phospholipase C and activate OR deactivate adenylyl
cyclase. Their resulting effect is the modulation of ligand
channels, but they are not ligand-gated receptors.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 54-55.

Question 20

What information does a dose-response curve

provide?

Answer 20

The slope of a dose-response curve demonstrates the rate of
increasing effect with an increased dose. The dose-response
curve also demonstrates the efficacy, or maximal effect of a
drug as well as the potency (ED50). A dose-response curve
can also demonstrate variability in drug effect if it measures
multiple subjects.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 170.