Pharmacodynamics - Part 2

Learning objective: describe the main post receptor mechanism of G-protein coupled
receptors.
Answer: A
The postreceptor mechanism of G-protein coupled receptors (also called metabotropic
receptors) involves the regulation of an effector element, usually an enzyme or an ion channel.
The enzyme in turn regulates the synthesis of a second messenger. According to the receptor
involved and the G-protein that is activated, the intracellular concentration of the second
messenger can be increased or decreased. B) Regulation of gene transcription follows the
activation of intracellular receptors or Janus-kinase linked receptors, not of G-protein coupled
receptors.
C) Opening of ligand-gated chloride channels is brought about by the activation of GABA-A or
glycine receptors. These receptors are ionotropic, not metabotropic.
D) Opening of ligand -gated Na+ channels is brought about by nicotinic, NMDA, and AMPA
receptors. These receptors are ionotropic, not metabotropic.
E) Activation of G-protein coupled receptors leads in turn to activation, not inactivation, of Gprotein

Learning objective: calculate the equieffective dose of a new drug given to a patient, when
the old drug must be suspended because of adverse effects..
Answer: D
Since naproxen was therapeutically effective, the rationale is to start the therapy with an
equieffective dose of the new drug. Celecoxib is about 5 time more potent than naproxen so a
dose 5 time lower should be equieffective.
A, B, C, E) (see explanation above)

Learning objective: define the terms :ionotropic and metabotropic receptors.
Answer: B
Nicotinic cholinergic receptors are ligand-gated ion channels. Binding of an agonist to these
receptors causes a conformational change that opens the channel, allowing inward movement of
positively charged ions (mainly Na+). Therefore nicotinic receptors are called ionotropic.
All muscarinic cholinergic receptors are G-protein coupled, and are called metabotropic.
A, C, D) (see explanation above)

Learning objective: define the term “drug synergism”.
Answer: C
A drug interaction is defined synergism when the response elicited by combined drugs is
greater than the combined responses of the individual drugs. In other words the response
elicited by the combined drugs is more than simply additive. In the present case the effects of
the individual drugs are bacteriostatic, whereas the effect of the combined drugs is more than
an additive bacteriostatic effect (a bactericidal effect is greater than a bacteriostatic effect). The
interaction is therefore defined synergism.
A) Additive effect occurs when the response elicited by combined drugs is equal to the
combined responses of the individual drugs.
B) Potentiation occurs when a drug enhances the effect of another drug, but is devoid of that
effect when given alone.
D, E) These terms refer to a drug effect which increases in time, when the drug is chronically
given.

Learning objective: describe the placebo effect of a drug.
Answer: E
When a plasma level of a drug administered one hour previously is equal to zero, a
pharmacological effect of the drug is exceedingly unlikely. Therefore the pain relief must be due
to an effect which is independent from the pharmacological action of the drug and operates
through psychological mechanisms, i.e. a placebo effect. Placebo effects are in fact quite
common in therapy and
A, B, C) All these factors would have caused significant plasma levels of the drug.
D) A poor patient compliance cannot explain a good pharmacological effect.

Learning objective: explains the chemical antagonism between two drugs.
Answer: D
Antacid drugs are weak bases that react chemically with gastric hydrochloric acid to form
a salt and water. In this way gastric acidity is reduced. This acid-antacid antagonism does not
involve pharmacokinetic action or receptor occupancy but only a chemical combination between
two molecules. It is therefore defined chemical antagonism.
A, B, C) All these antagonism involve receptor occupancy.
E) Pharmacokinetic antagonism occurs when a drug prevents the absorption or stimulates the
elimination of the drug to be antagonized, so reducing its concentration at the site of action

Learning objective: explain the mechanism s of pharmacodynamic tolerance.
Answer: C
Tolerance can be defined as a state of decreased responsiveness to the action of a drug which
results from a prior exposure to that drug or to a related drug. Drug tolerance can involve a
decreased concentration of the drug at the site of action, due mainly to an increased
biotransformation of the drug (pharmacokinetic tolerance), or it can occur even when the
concentration of the drug at the site of action is not modified (pharmacodynamic tolerance). In
this latter case mechanisms can be either a decreased number of receptors (the most common),
a change in the postreceptor mechanisms, or a homeostatic adaptive changes that counteract
the drug effect.
A, B, D) These mechanisms can explain the pharmacokinetic, not the pharmacodynamic
tolerance.
E) A decreased, not increased, number of receptors can explain a pharmacodynamic tolerance.

Learning objective: explain the mechanisms of pharmacodynamic tolerance.
Answer: D
The most common mechanism of pharmacodynamic tolerance is a receptor down-regulation,
that is a decrease receptor density. Other mechanisms can be homeostatic adaptive changes of
the organism that counteract the drug effect.
A) Tolerance due to increased metabolism of the drug is called pharmacokinetic tolerance.
B, C) These events would have increased, not decreased, the effects of morphine.
E) By definition pharmacodynamic tolerance refers to a decrease in time of the effect of a drug
whose concentration at the site of action remains the same

Learning objective: identify the drug parameter that is increased when a drug effect
undergoes tolerance.
Answer: B
Since by definition tolerance is a decreased responsiveness to the action of a drug, a higher
dose of that drug will be necessary to obtain the given effect in 50% of the population (median
effective dose) when tolerance has occurred..
A) The maximal efficacy refers to the maximum effect achievable, if the dose is taken to very
high levels. In tolerant subjects maximal efficacy may still be achieved, even if higher doses are
needed to obtain it.
C) The therapeutic index is the ratio between a toxic dose and an effective dose. Since the
effective dose is increased because of tolerance, the therapeutic index is expected to decrease
or to remain the same (if the toxic dose is also increased).
D) Actually potency (the dose of the drug needed to produce a given effect) is decreased when
tolerance has occurred.
E) Tolerance can be due to an increase metabolism of the drug. In this case however the half
life would be decreased, not increased.

Learning objective: identify the graded log dose-response curve from a graph..
Answer: D
A curve that reports the log of the dose on the x-axis (see the geometric scale) and the percent
of maximum effect on the y-axis is defined as a graded log dose-response curve.
A, B, C, E) All these curves report the percent of individuals responding on the y-axis.

Learning objective: explain the term “drug potentiation”.
Answer: B
Potentiation occurs when a drug enhances the effect of another drug, but is devoid of that effect
when given alone. Cimetidine is devoid of sedative effects but can increase the sedative effect
of diazepam by inhibiting diazepam metabolism in the liver.
A) Additive effect occurs when the response elicited by combined drugs is equal to the
combined responses of the individual drugs.
C) Synergism occurs when the response elicited by combined drugs is greater than the
combined responses of the individual drugs.
D, E) These terms refer to a drug effect which increases in time, when the drug is chronically
given.

Learning objective: explain the mechanism of pharmacokinetic tolerance.
Answer: C
If a drug can induce its own metabolism tolerance will occur, since the amount of available drug
decreases in time. This tolerance is called pharmacokinetic because it results from a
pharmacokinetic mechanism.
A) Tolerance is called pharmacodynamic when the drug effect decreases in time, but the
concentration of the drug at the site of action remains the same.
B) Tachyphylaxis is the name for a tolerance that develops very rapidly, in a matter of hours.
D) Tolerance is called crossed when the exposure to a drug leads to tolerance to it and also to
other drugs with similar chemical structure and/or similar pharmacological effects.
E) Sensitization (also called reverse tolerance) occurs when the response increases with the
repetition of the same dose of a drug.

Learning objective: calculate the duration of action of a drug, given sufficient data.
Answer: B
The given dose of acetaminophen is effective after 2 half-lives. Knowing that the plasma
concentration (Cp) of the drug becomes one half after each t½, it can be concluded that a Cp
corresponding to 125 mg of the drug is the minimum effective concentration. If a 1000 mg dose
is given, this minimum effective concentration will be reached after 3 t½ (Cp corresponding to
500 mg after 1 t½, corresponding to 250 after 2 t½, corresponding to 125 mg after 3 t½.). Since
every medication is effective in the body as long as the Cp is higher than, or equal to, the
minimum effective concentration, it can be concluded that a dose of 1000 mg will be effective
for approximately 6 hours.
A, C, D, E, F) (see explanation above)

Learning objective: explain the most likely consequence of chronic blockade of drug
receptors
Answer: C
When receptors are blocked chronically the number of those receptors may increase in time, a
process called up-regulation of receptors or sensitization or supersensitivity, since the effector
response will be greater than usual, if the blockade is abruptly removed.
A) By definition spare receptors are not involved in receptor activation or blockade.
B, E) Since the number of receptors increases in time, G-protein and second messengers , if
something, would increase, not decrease.
D) Receptor intrinsic activity refers to the amount of activation each receptor is able to produce
when bound by an agonist drug. If something, this amount would increase, not decrease.

Learning objective: identify the more potent between two drugs, given sufficient data.
Answer: D
Potency of a drug refers to the dose of that drug needed to obtain a given effect. Since 10 mg of
morphine are needed to get an analgesic effect equal to that given by 0.3 mg of buprenorphine,
morphine is less potent than buprenorphine.
Efficacy refer to the maximal effect produced by a drug. By definition partial agonists have a
maximal efficacy lower than that of full agonists. Since morphine is a full agonist and
buprenorphine a partial agonist at the same receptor, buprenorphine is less effective than
morphine.