1
,2
,that we can describe the action or effect of drugs, compare the effects of different drugs, and
predict their pharmacological effects.
It is simplest to think that drug responses are directly related to the fraction of receptors that are
occupied, or bound, by a drug, so that 50% of the maximum response occurs at a blood level or
concentration at which a drug occupies 50% of its receptors. But depending on the number of
receptors in a tissue and the ability of drug binding to produce a change in the receptor
conformation, far fewer receptors (less than 10%) may be needed to produce a maximum effect.
2 types:
1. Quantal-Quantal effects are responses that may or may not occur (Box 2-3). For example,
seizures either occur or they do not. The same is true for pregnancy, sleep, and death.
2. Graded- biological effects that can be measured continually up to the maximum responding
capacity of the biological system. Most drug responses are graded.
Blood pressure
Heart rate
Diuresis
Bronchodilation
FEV1
Pain (scale 1–10)
Coma score
Receptors: agonists, antagonists
Antagonists are drugs that occupy receptors without stimulating them. Antagonists occupy a
receptor site and prevent other molecules, such as agonists, from occupying the same site and
producing a response. Antagonists produce no direct response. The response we see following
administration of antagonists results from their inhibiting receptor stimulation by agonists. For
example, beta blockers such as propranolol and atenolol act as antagonists at the beta-
adrenoceptor. Adrenergic nerve activity can raise heart rate, and patients with high heart rates
experience a significant drop in heart rate following administration of beta blockers. The same
administration may have little effect on patients who lack adrenergic nerve activity and already
have a lower heart rate. The effect of antagonists is dependent on the background receptor
, activity that it can block. Antagonists produce a shift in the concentration-effect relationship for
agonists acting at that same specific receptor as the antagonist; they make agonists for the same
receptor appear less potent. The effect of an antagonist is dependent on its blood levels and its
affinity for the receptor. Most antagonists in clinical use are competitive reversible antagonists,
and it is possible to overcome the antagonist effects with higher concentrations of the competing
agonist. A very small number of antagonist drugs (e.g., echothiophate, phenoxybenzamine) act
by irreversibly binding to the receptor; their antagonism remains until new receptors can be
produced by the cell.
Partial agonists are drugs that have properties in between those of full agonists and antagonists.
Partial agonists bind to receptors but when they occupy the receptor sites, they stimulate only
some of the receptors. This is sometimes called intrinsic activity. So they can act as part agonist
and part antagonist. Partial agonists would require all of the available receptors to produce their
full response, and the maximum response for a partial agonist is less than that for a full agonist.
The beta blockers acebutolol, penbutolol, and pindolol are partial agonists. Administration can
block the effects of adrenergic nerves on heart rate, but partial agonist activity keeps heart rate
from falling too low, as might occur following administration of a pure beta-adrenoceptor
antagonist. So beta blockers with intrinsic sympathomimetic activity control heart rate within a
range that is higher than the response to an antagonist and lower than the response to an agonist.
Pharmacokinetics:
Absorption- determined by the route of administration> IV is best and most absorbed. Oral is
most common. If oral, then the medication must pass through the stomach, intestines, then to the
Liver. This is called the first-pass metabolism. Because not all of the administered dosage may
be dissolved or absorbed or survive liver passage, only a fraction of an administered dosage
makes it to the bloodstream. This percentage of the administered dose that does enter the
bloodstream is called the bioavailability of the dosage form. Bioavailability can range from less
than 10% to more than 90% for oral dosing. When the bioavailability of an oral preparation is
low, a higher dose will be given so that the amounts reaching the bloodstream are similar. For
example, an oral dose of 500 mg of ciprofloxacin can be substituted for a 400 mg IV dose;
ciprofloxacin has about 80% oral bioavailability.
,2
,that we can describe the action or effect of drugs, compare the effects of different drugs, and
predict their pharmacological effects.
It is simplest to think that drug responses are directly related to the fraction of receptors that are
occupied, or bound, by a drug, so that 50% of the maximum response occurs at a blood level or
concentration at which a drug occupies 50% of its receptors. But depending on the number of
receptors in a tissue and the ability of drug binding to produce a change in the receptor
conformation, far fewer receptors (less than 10%) may be needed to produce a maximum effect.
2 types:
1. Quantal-Quantal effects are responses that may or may not occur (Box 2-3). For example,
seizures either occur or they do not. The same is true for pregnancy, sleep, and death.
2. Graded- biological effects that can be measured continually up to the maximum responding
capacity of the biological system. Most drug responses are graded.
Blood pressure
Heart rate
Diuresis
Bronchodilation
FEV1
Pain (scale 1–10)
Coma score
Receptors: agonists, antagonists
Antagonists are drugs that occupy receptors without stimulating them. Antagonists occupy a
receptor site and prevent other molecules, such as agonists, from occupying the same site and
producing a response. Antagonists produce no direct response. The response we see following
administration of antagonists results from their inhibiting receptor stimulation by agonists. For
example, beta blockers such as propranolol and atenolol act as antagonists at the beta-
adrenoceptor. Adrenergic nerve activity can raise heart rate, and patients with high heart rates
experience a significant drop in heart rate following administration of beta blockers. The same
administration may have little effect on patients who lack adrenergic nerve activity and already
have a lower heart rate. The effect of antagonists is dependent on the background receptor
, activity that it can block. Antagonists produce a shift in the concentration-effect relationship for
agonists acting at that same specific receptor as the antagonist; they make agonists for the same
receptor appear less potent. The effect of an antagonist is dependent on its blood levels and its
affinity for the receptor. Most antagonists in clinical use are competitive reversible antagonists,
and it is possible to overcome the antagonist effects with higher concentrations of the competing
agonist. A very small number of antagonist drugs (e.g., echothiophate, phenoxybenzamine) act
by irreversibly binding to the receptor; their antagonism remains until new receptors can be
produced by the cell.
Partial agonists are drugs that have properties in between those of full agonists and antagonists.
Partial agonists bind to receptors but when they occupy the receptor sites, they stimulate only
some of the receptors. This is sometimes called intrinsic activity. So they can act as part agonist
and part antagonist. Partial agonists would require all of the available receptors to produce their
full response, and the maximum response for a partial agonist is less than that for a full agonist.
The beta blockers acebutolol, penbutolol, and pindolol are partial agonists. Administration can
block the effects of adrenergic nerves on heart rate, but partial agonist activity keeps heart rate
from falling too low, as might occur following administration of a pure beta-adrenoceptor
antagonist. So beta blockers with intrinsic sympathomimetic activity control heart rate within a
range that is higher than the response to an antagonist and lower than the response to an agonist.
Pharmacokinetics:
Absorption- determined by the route of administration> IV is best and most absorbed. Oral is
most common. If oral, then the medication must pass through the stomach, intestines, then to the
Liver. This is called the first-pass metabolism. Because not all of the administered dosage may
be dissolved or absorbed or survive liver passage, only a fraction of an administered dosage
makes it to the bloodstream. This percentage of the administered dose that does enter the
bloodstream is called the bioavailability of the dosage form. Bioavailability can range from less
than 10% to more than 90% for oral dosing. When the bioavailability of an oral preparation is
low, a higher dose will be given so that the amounts reaching the bloodstream are similar. For
example, an oral dose of 500 mg of ciprofloxacin can be substituted for a 400 mg IV dose;
ciprofloxacin has about 80% oral bioavailability.
