PHARMACODYNAMICS

•Pharmacodynamics involves drug

actions on target cells and the
resulting alterations in cellular
biochemical reactions and functions
(i.e. “what the drug does to the
body”).
Drug response can cause a primary or
secondary physiologic effect or both.
• The primary effect is desirable, and
the secondary effect may be
desirable or undesirable
•E.g. DIPHENHYDRAMINE
(BENADRYL), an antihistamine
which primarily treat the symptoms of
allergy, and the secondary effect is
CNS depression that causes
drowsiness
 DOSE RESPONSE AND MAXIMAL
EFFICACY
•Dose response is the relationship
between the minimal versus the
maximal amount of drug dose needed
to produce the desired drug response
• Some patients respond to a lower
drug dose, whereas others need a
high drug dose to elicit the desired
response.
•For example, morphine and tramadol
hydrochloride (Ultram) are prescribed to
relieve pain.
•The pain relief with the use of tramadol
hydrochloride is not as great as it is with
morphine.
 POTENCY
•potency is a measure of drug activity
expressed in terms of the amount
required to produce an effect of
given intensity.
EFFICACY
•maximal effect that drug produces
irrespective of concentration (dose).
efficacy may be beneficial in the
determination of clinical effectiveness of
a drug.
ONSET, PEAK, AND
DURATION OF ACTION
•Onset of action is the time it
takes to reach the minimum
effective concentration (MEC)
after a drug is administered.
•Peak action occurs when the
drug reaches its highest blood or
plasma concentration.
• Duration of action is the length of
time the drug has a pharmacologic
effect
Some drugs produce effects in
minutes, but others may take hours
or days
RECEPTOR THEORY
•Drugs act through receptors by
binding to the receptor to
produce (initiate) a response or to
block (prevent) a response.
• The activity of many drugs is
determined by the ability of the
drug to bind to a specific receptor.
• The better the drug fits at the
receptor site, the more biologically
active the drug is. It is similar to the
fit of the right key in a lock.
• Most receptors, which are protein in
nature, are found in cell membranes.
• Drug-binding sites are primarily on
proteins, glycoproteins, proteolipids,
and enzymes.
 THERE ARE
FOUR RECEPTOR FAMILIES:
•(1) kinase-linked receptors,
•(2) ligand-gated ion channels,
•(3) G protein–coupled receptor systems, and
•(4) nuclear receptors. The ligand-binding
domain is the site on the receptor at which
drugs bind.
•Kinase-linked receptors. The
ligand-binding domain for drug
binding is on the cell surface. The
drug activates the enzyme (inside the
cell), and a response is initiated.
• Ligand-gated ion channels. The channel
spans the cell membrane and, with this
type of receptor, the channel opens,
allowing for the flow of ions into and out
of the cells. The ions are primarily sodium
and calcium.
• G protein–coupled receptor systems.
There are three components to this
receptor response: (1) the receptor, (2)
the G protein that binds with guanosine
triphosphate (GTP), and (3) the effector
that is either an enzyme or an ion
channel.
• Nuclear receptors. Found in the
cell nucleus (not on the surface) of
the cell membrane.
•With the first three receptor
groups, activation of the
receptors is rapid.
AGONISTS AND
ANTAGONISTS
•Drugs that produce a response
are called agonists, and drugs
that block a response are called
antagonists.
•E.g. Epinephrine (Adrenalin)
stimulates beta1 and beta2 receptors,
so it is an agonist.
•Atropine, an antagonist, blocks the
histamine (H2) receptor, thus
preventing excessive gastric acid
secretion.
 NONSPECIFIC AND
NONSELECTIVE DRUG EFFECTS
•Many agonists and antagonists lack specific
and selective effects. A receptor
produces a variety of physiologic responses,
depending on where in the body the
receptor is located.
•Cholinergic receptors are located in the
bladder, heart, blood vessels, stomach,
bronchi, and eyes. A drug that stimulates or
blocks the cholinergic receptors affects all
anatomic sites of location.
• Drugs that affect various sites are
nonspecific drugs and have
properties of non-specificity.
•Bethanechol (Urecholine) may be
prescribed for postoperative urinary retention
to increase bladder contraction. This drug
stimulates the cholinergic receptor located in
the bladder, and urination occurs by
strengthening bladder contraction.
•Because bethanechol affects the cholinergic
receptor, other cholinergic sites are also
affected. The heart rate decreases, blood
pressure decreases, gastric acid secretion
increases, the bronchioles constrict, and
the pupils of the eye constrict
• These other effects may be either
desirable or harmful. Drugs that
evoke a variety of responses
throughout the body have a
nonspecific response.
• Drugs may act at different receptors.
Drugs that affect various receptors are
nonselective drugs or have properties
of non-selectivity.
• Chlorpromazine (Thorazine) acts on the
norepinephrine, dopamine, acetylcholine,
and histamine receptors, and a variety of
responses result from action at these
receptor sites.
•Epinephrine acts on the alpha1,
beta1, and beta2 receptors
• Drugs that produce a response but
do not act on a receptor may act by
stimulating or inhibiting enzyme
activity or hormone production.
 CATEGORIES OF DRUG
ACTION
•(1) stimulation or depression
•(2) replacement
•(3) inhibition or killing of organisms, and
•(4) irritation
 STIMULATION OR DEPRESSION
•In drug action that stimulates, the rate of cell
activity or the secretion from a gland
increases.
•In drug action that depresses, cell activity and
function of a specific organ are reduced.
REPLACEMENT

•Replacement drugs such as

insulin replace essential body
compounds.
 INHIBIT OR KILL ORGANISMS
•Drugs that inhibit or kill organisms interfere
with bacterial cell growth
•(e.g., penicillin exerts its bactericidal effects
by blocking the synthesis of the bacterial cell
wall)
 IRRITATION
•Drugs also can act by the mechanism of
irritation (e.g., laxatives irritate the inner
wall of the colon, thus increasing peristalsis
and defecation).
THERAPEUTIC INDEX AND
THERAPEUTIC RANGE (THERAPEUTIC
WINDOW)
•The therapeutic index (TI)
estimates the margin of safety of a
drug through the use of a ratio,
that measures the effective (therapeutic)
dose (ED) in 50% of people (ED50) and
the lethal dose (LD) in 50% of people
(LD50). The closer the ratio is to 1, the
greater the danger of toxicity.
• In some cases, the ED may be 25%
(ED25) or 75% (ED75). Drugs with
a low therapeutic index have a
narrow margin of safety
• Drug dosage might need
adjustment, and plasma (serum)
drug levels need to be monitored
because of the small safety range
between the ED and LD.
•Drugs with a high therapeutic index
have a wide margin of safety and less
danger of producing toxic effects
•Plasma (serum) drug levels do not
need to be monitored routinely for
drugs with a high TI.
THERAPEUTIC RANGE (THERAPEUTIC
WINDOW)
•The therapeutic range (therapeutic
window) of a drug concentration in plasma is
the level of drug between the minimum effective
concentration in the plasma for obtaining desired
drug action and the minimum toxic concentration
(the toxic effect).
•If the therapeutic range is narrow, such as for
DIGOXIN (0.5 to 1 mg/mL),
•the plasma drug level should be monitored
periodically to avoid drug toxicity.
Monitoring the therapeutic range is not
necessary if the drug is not considered highly
toxic.
PEAK AND TROUGH DRUG LEVELS

•Peak drug levels indicate the rate of

absorption of the drug
•Trough drug levels indicate the rate of
elimination of the drug.
• Peak drug level is the highest
plasma concentration of drug at a
specific time.
• Peak drug levels indicate the rate of
absorption.
•If the drug is given orally, the peak time might
be 1 to 3 hours after drug administration.
•If the drug is given IV, the peak time might
occur in 10 minutes.
•If a peak drug level is ordered, a blood sample
should be drawn at the proposed peak time,
according to the route of administration.
• The trough drug level is the lowest
plasma concentration of a drug, and it
measures the rate at which the drug is
eliminated. Trough levels are drawn
immediately before the next dose of drug
is given, regardless of route of
administration.
• Peak and trough levels are requested for
drugs that have a narrow therapeutic index
and are considered toxic, such as the
aminoglycoside antibiotics
Loading Dose
When immediate drug response is desired, a
large initial dose, known as the loading dose,
of drug is given to achieve a rapid minimum
effective concentration in the plasma