Block 9 Pharm Pharmacodydamics W/Exp Part 1

Explanation
1) Learning objective: describe the main cell constituents that can act as drug receptors.
Answer: B
Ion channel proteins can function as receptors, since binding to those channels may cause the
opening of the channel (i.e. acetylcholine at nicotinic receptors). It is worth to note that, in this
case, the receptor is also the effector because a single molecule incorporates both the drug
binding site and the effector mechanism.
A) G-proteins are not receptors. They are coupled to many receptors and the activation of those
receptors in turn activates the G-protein.
C) cAMP is a second messenger, i.e a molecule that transmits and amplify signals received from
the receptor.
D, E ) Receptors are most often protein molecules.

Explanation
2) Learning objective: define the specific region of the receptor molecule at which the drug
binds.
Answer: B
Drugs acting on receptors bind to a specific region of the receptor molecule called receptor site
or, better, recognition site. In fact this is the region that has a high and selective affinity for the
drug and therefore can bind the drug with a chemical bond.
A) There is no activation region since the site of receptor molecule can bind the drug, but then
the drug can either activate or block the receptor.
C) Effectors are molecules that translate the drug-receptor interaction into a biological effect.
D) G-proteins are not part of the receptor but are separate proteins that can be activated by an
activated receptor.
E) Spare receptors are receptors that are not occupied by the drug even when a maximal
response is obtained.

Explanation
3) Learning objective: define the term stereo-selectivity
Answer: C
A peculiar property of receptors is stereo-selectivity, that is often they bind only one enantiomer
of a racemic pair.
A) Intrinsic activity refers to the ability of a drug (once bound to a receptor) to initiate changes
which lead to a biological response.
B) Affinity refers to the tendency of a drug to bind to a receptor.
D) Potency refers to the dose of a drug required to produce a given effect.
E) Variability refers to the fact that the number of receptors can vary with time.
F) Maximal efficacy refers to the maximal effect that can be produced by a drug

Explanation
4) Learning objective: define the term “affinity” of a drug.
Answer: D
The tendency of a drug to bind to a receptor is defined affinity. According to the occupation
theory binding to a receptor is driven by the law of mass action, that is the number of bound
receptors increases when the number of available drug molecules increases. Now suppose that
100 receptors are exposed to 1000 molecules of drug A or to 1000 molecules of drug B. Also
suppose that 10 molecules of drug A are able to bind to the receptors, but 40 molecule of drug B
are able to bind to the receptors. It can be concluded that receptor affinity of drug B is greater
than that of drug A.
A) Intrinsic activity refers to the ability of a drug (once bound to a receptor) to initiate changes
which lead to a biological response.
B) Potency refers to the dose of a drug required to produce a given effect (often the effect is
chosen as the 50% of drug's maximal effect). The lower the dose required to produce the effect,
the higher the potency
C) Efficacy refers to the maximal effect that can be produced by a drug.
E) Receptor activation is related to the drug intrinsic activity (the higher the intrinsic activity of a
drug , the higher the amount of receptor activation brought about by that drug).

Explanation
5) Learning objective: describe the different drug -receptor bonds.
Answer: E
In general drugs binding to receptors in a reversible way and therefore the chemical bond
between drug and receptor must be weak. A covalent bond is the strongest chemical bond (more
than 50 Kcal/mole) and is rare in pharmacology. Nevertheless some drugs can bind covalently
and this often results in an irreversible action (examples are the covalent bond between some
anticancer drugs and the DNA, between phenoxybenzamine and alpha receptors, between
organophosphates and cholinesterase).
A, B, C, D) The energy of all these chemical bonds is less than 10 Kcal/mole.

Explanation
6) Learning objective: explain why log dose- response curves can indicate the tipe of drugreceptor
interaction
Answer: A
When two drugs exhibit the same slope of the dose response curves the drugs most likely act at
the same receptor. Since they have the same maximal efficacy both drugs must be full agonists. .
B; C; D, E) (see explanation above)

Explanation
7) Learning objective: define the term “partial agonist”.
Answer: C
A drug which is able to activate only partially the receptor is defined a partial agonist. This
means that its intrinsic activity is higher than 0% and lower than 100%. Therefore when all
receptors in a system are activated by a partial agonist, the maximum effect of the drug will be
lower than the one produced by a full agonist, that is the maximal efficacy of a partial agonist is
by definition lower than that of a full agonist.
A) The intrinsic activity of a full agonist is by definition 100%.
B) The intrinsic activity of a pharmacological antagonist is by definition 0%.
D, E) These antagonisms are not related to the receptor theory and therefore they cannot be
related to the intrinsic activity.

Explanation
8) Learning objective: calculate the response of two drugs present together in an in vitro
system, given sufficient data.
Answer: C
Since the two drugs have equal affinity for the same receptor, when both are present at the same
time in maximally effective concentrations, one half of the receptors will be occupied by the first
drug and one half by the second drug. Since the intrinsic activity of the first drug is 1.0, each
receptor occupied by this drug will be activated 100% and therefore the total response of one
half of the receptors will be 50% of the maximal response. By the same token, since the intrinsic
activity of the second drug is 0.25, each receptor occupied by this drug will be activated 25% and
so the total response of the other half of the receptors will be 12.5% of the maximal response.
Therefore the response of all receptors will be 50% +12.5%, that is 62.5 % of the maximal
response.
A, B, D, E) (see explanation above)

Explanation
9) Learning objective: define the terms potency and efficacy of a drug.
Answer: D
Drug effectiveness is measured by the maximal effect the drug can produce when the dose is
taken to high levels. In case of diuretics the maximal daily urine output (that is the urine output
that is no longer increased by increasing the dose) is a convenient measure of the effectiveness
of the drug. It is worth to note that efficacy is independent upon potency, which is measured by
the drug needed to get 50% of maximal effect. In fact in the present case the drug D is the most
effective but the least potent.
A, B, C, E) (see explanation above)

Explanation
10) Learning objective: predict the shift of log-dose effect curve a full agonist, when a fixed
dose of a partial agonist is given concomitantly
Answer: B
Since the two drugs have an intrinsic activity greater than zero they must be either full agonists
or partial agonists. Since the maximal efficacy of drug B is 100% drug B must be a full agonist.
As a rule, a partial agonist behaves as a competitive antagonist when given together with a full
agonist, that is higher doses of a full agonist are needed to get the same response. Therefore
the log dose-effect curve of the agonist will be shifted to the right.
A) A full agonist would shift to the left, not to the right, the log dose-effect curve of another
agonist. In fact lower doses of the agonist are needed to get the same response since some
receptors are already activated by the other agonist.
C, D) By definition competitive and irreversible antagonists are devoid of intrinsic activity
E) A functional antagonist acts on receptors different from those activated by the agonist.

Explanation
11) Learning objective: define the term “functional antagonism”.
Answer: C
Glucagon induced activation of glucagon receptors leads to an increase in heart contractility. By
blocking beta-1 receptors in the heart beta-blockers lead to a decrease in heart contractility.
When two drugs act on different receptors causing action in opposite directions, the antagonism
is defined functional (also called physiological).
A, B, D, E) (see explanation above)

Explanation
12) Learning objective: predict the shape of log-dose effect curve of an agonist when afixed
dose of irreversible antagonist is given concomitantly.
Answer: D
Irreversible antagonists bind to the receptor so tightly that the receptor is unavailable for binding
of agonist. After occupancy of some proportion of receptors by such an antagonist, the number
of remaining unoccupied receptors may be to low for the agonist(even at high concentrations) to
elicit a response comparable to the previous maximal response. Therefore an irreversible
antagonist will cause a downward shift of the maximum of the log dose effect curve, i.e. from C to
D.
A, B, C, E) (see explanation above)

Explanation
13) Learning objective: define the therapeutic window of a drug.
Answer: E
The interval between the minimum therapeutic dose (or plasma concentration) and the minimum
toxic dose (or plasma concentration) of a drug is defined therapeutic window. Since doses below
the minimum therapeutic dose are by definition ineffective ,and doses above the minimum toxic
dose are, by definition, toxic, this window defines the range of doses which have a high
probability of therapeutic success.
A) Intrinsic activity refers to the ability of a drug (once bound to a receptor) to initiate changes
which lead to a biological response.
B) Potency refers to the dose of a drug required to produce a given effect
C) Efficacy refers to the maximal effect that can be produced by a drug.
D) The therapeutic index is a ratio between an harmful dose and an effective dose of a drug . It
is (like the therapeutic window) an index of the safety of a drug, but is a single value and
therefore cannot predict the range of doses that are both safe and effective.

Explanation
14)Learning objective: describe the drug parameters that can be determined from a quantal
log-doThe cumulative frequency distribution of subjects showing a desired effect is called quantal log
dose response curve. From this curve, the dose that can produce that effect in 50% of
individuals (called median effective dose) can be read on the abscissa.
A) Affinity is the tendency of a drug to bind to a receptor. It can be measured by plotting the
fraction of receptors bound by drug, against the log of the concentration of drug. It cannot be
measured with a quantal log dose-response curve.
C, D) The therapeutic index is a ratio between the toxic (TD50) and the effective (ED50) dose of a
drug. The therapeutic window is the interval between the minimum effective dose (ED1) and the
minimum toxic dose (TD1). In order to measure these variables, two quantal log dose-effect
curves are needed.
E) Maximal efficacy is the maximal effect a drug can produce. It can be measured with a grade
log dose-effect curve, but not with a quantal log dose-effect curve.se effect curve

Explanation
15) Learning objective: explain the meaning of irreversible antagonist
Answer: D
Drug that can bind a receptor but has no intrinsic activity is defined pharmacological antagonist.
These antagonists can be competitive (when they can be displaced from the receptor by an
appropriate concentration of the agonist) or irreversible (when they cannot be displaced,
whatever the concentration of the agonist).
A, B, C, E) (see explanation above)