UNIT II

CHAPTER 4
PHARMACOTHERAPEUTICS,
PHARMACODYNAMICS &
PHARMACOKINETICS

ASHA RUSSEL
ASST.SCIENCE TUTOR ‘A’
Pharmacotherapeutics
• Pharmacotherapeutics is the achievement of the
desired therapeutic goal from drug therapy.

• Essentially, it is the clinical purpose—the indication—

for giving a drug.

• The desired pharmacotherapeutics can be to induce a

cure or prevent a problem.

• Nurses do need to question all orders if the intended

pharmacotherapeutics of a drug does not correlate
with the patient’s reason for receiving drug therapy.
 Pharmacokinetics
• Pharmacokinetics is the movement of the drug
particles inside the body.

 Absorption is the movement of the drug from the site

of administration into the bloodstream.
 Distribution is the movement of the drug into the
cells.
 Metabolism is the conversion of the drug into
another substance or substances.
 Excretion is the removal of the drug.
 Absorption
• Several variables affect the completeness & rate of drug
absorption:
1. Depends on the route of administration
 Drugs that are administered orally generally take the longest
to be absorbed.
 Drugs given parenterally are absorbed more rapidly than
drugs given orally.
 Intramuscular absorption is somewhat more rapid than
subcutaneous absorption.
 Drugs that are administered intravenously are placed
directly into the bloodstream.
 Absorption

2. Affected by the speed at which the drug dissolves

 Absorption (cont.)
3. Large surface areas increase the rate of
absorption.
4. Blood flow also affects the rate of absorption—
the greater the volume of blood flow, the faster
the rate of absorption.
 Absorption (cont.)
5. Lipid solubility also alters absorption.
6. pH also affects absorption.
 Distribution
• The distribution of a drug throughout the body
depends on three factors: blood flow to the tissues,
the drug’s ability to leave the blood, and the drug’s
ability to enter cells.

• The drug is transported to the tissues and cells

through the circulatory system.

• Healthy individual – all tissues well perfused - easy

distribution of drug molecules.

• Pathophysiologic changes in vascular system –

impaired distribution of drug molecules.
 Protein-Binding
• Protein binding of drugs affects the distribution of a
drug.
• When the drug is bound to protein, it is unable to pass
through the capillary walls.
• The bonds will dissolve in time, and the drug
molecules will become free and active.
• Drug dosages are calculated by the drug manufacturer
based on the protein-binding characteristics of the
drug.
• When the patient has a lower-than-expected protein
level, the distribution of the drug is altered.
The Effects of Administering Protein-Bound Drugs
 Blood–Brain Barrier
• The capillary bed that services the brain is different
from other capillary beds.
• Instead of wide spaces between the cells in the
capillary walls, the cells are packed tightly together.
• This structure prevents drug molecules, and other
foreign substances, from passing through and entering
the brain.
• The purpose of the blood–brain barrier is to keep
toxins and poisons from reaching the brain.
• At times, the mechanism will prevent treatment of a
problem.
 Placental Membrane
• The placental membrane separates the maternal circulation from
the fetal circulation.

• It is not a barrier like the blood–brain barrier.

• Any drug that can pass through a membrane can pass through the
placenta.

• In order to pass through the placenta, a drug must be lipophilic,

not ionized, and not protein bound.
 Metabolism

• Metabolism of drugs occurs primarily in the liver.

• Some metabolism also occurs in other tissues (small
intestine mucosa, lungs, kidney, brain, olfactory mucosa and
skin)
• Physiologic factors that impair the functioning of the
liver decrease the ability of the liver to metabolize drugs.
• When drugs are metabolized, they are changed from
their original form to a new form.
• Metabolism is sometimes referred to as
biotransformation.
• Drugs are generally metabolized from substances that are
lipophilic into substances that are hydrophilic.
Metabolites

• A product of metabolism is called a metabolite.

• Drugs that are metabolized are generally changed into an inactive

form.

• Metabolism can convert a drug that has little or no therapeutic

effect in its original form into the active form.

• Drugs that are inactive until metabolized into an active form are
called prodrugs.

• An active metabolite may cause a different and potentially harmful

effect.
First-Pass Effect

• Drugs that are highly metabolized lose much of their

effectiveness during this first pass through the liver.
• This loss of effectiveness is called the first-pass
effect.
• Drugs that experience a high first-pass effect may need
higher oral doses to achieve a therapeutic level of
circulating drug.
 P4-50System

• Liver metabolism is predominantly achieved by specific

liver enzymes.
• These microsomal enzymes are called the cytochrome P-
450 system.
• The enzyme CYP3A4 is the most common and is
responsible for the metabolism of most drugs.
• Some drugs either induce or inhibit the P-450 system,
altering metabolism of other drugs.
• When a large quantity of one of these enzymes is present,
more metabolism can occur through this pathway.
• This increase in metabolism rapidly decreases the amount
of circulating drug.
 Excretion
• Excretion is the process of removing a drug, or its metabolites,
from the body.

• The most common route for drug excretion is through the

urine.

• Other routes include bile in the GIT, expired air from the lungs,
breast milk, sweat from the skin and saliva.

• Diseases and pathophysiologic changes in the kidney decrease

the effectiveness of the kidney in drug excretion.
 Processes Involved in Renal Excretion
• Three processes are involved in renal excretion of drugs.

• The first is glomerular filtration.

– Most drug particles pass easily through the spaces of the
capillary walls into the urine in the proximal tubule.
• The second process is passive tubular reabsorption.
– The drug particles will try to move from the area of greater
concentration to that of lesser concentration.
• The third process that affects excretion is active tubular
secretion.
– Active transport systems in the renal tubule work to move
some drugs from the blood into the urine.
 Factors That Affect Renal Excretion
• Drug excretion can be increased if the pH of the urine
encourages the drug to become an ion.

• Overuse of the active transport system also affects

excretion.
– As the transport system becomes overloaded, some of
the drug particles will remain in the blood until they can
be moved by the transport system.

• Two drugs can be given together to slow deliberately

the rate of excretion of one or both of the drugs.
 Factors that Affect Biliary Excretion
• A factor that affects excretion of drugs through bile is
enterohepatic recirculation.

• Drug molecules that are in the bile are reabsorbed.

• This process lengthens the time the drug is present in the

bloodstream and can produce an effect.
 Half-Life
• The combined processes of metabolism and excretion
are responsible for elimination of a drug from the body.

• The amount of time that is required to remove half

(50%) of the blood concentration of a drug is called
half-life.

• Drugs have various half-lives, based on their

pharmacologic properties.

• In one half-life, a set percentage of the drug molecules

present in the blood is eliminated.
 HALF- LIFE
• The time required for the body to eliminate
50% of the drug.
 Steady State
• The point at which the amount of drug being administered
and the amount being eliminated balance off.

• At four to five half-lives, steady state is achieved.

• Increasing the dose has no effect on how quickly steady state

can be achieved.

• Steady state is achieved based on the amount of time

required for four to five half-lives to occur.

• The full pharmacotherapeutic response of a particular drug

dose is measured when the drug has achieved steady state.
 Clearance
• The rate at which drug molecules disappear from the
circulatory system is effected by several factors.
• This rate is called clearance or clearance rate of a
drug.
• Renal excretion and hepatic metabolism are the
major modes of clearance.
• The gender of the patient can also alter the clearance
of some drugs.
• Even though a drug’s clearance is shown to be
statistically altered, this statistical difference does
not necessarily create a clinical difference.
 Pharmacodynamics
• Pharmacodynamics is the biologic, chemical, and
physiologic actions of a particular drug within the
body.
• The pharmacodynamics of a drug are responsible for
its therapeutic effects and sometimes its adverse
effects.
• The pharmacodynamics of a drug can be affected by
the age of the patient.
• Drugs cannot create new responses in the body; they
can only turn on, turn off, promote, or block a
response that the body is inherently capable of
producing.
 Drug–Receptor Interactions
• Most drugs create their effects in the body by attaching
to special sites, called receptors.
• At the receptor site, the drug is able to stimulate the
cell to act in a way that the cell is designed to act.
• Each type of receptor is responsible for producing a
particular effect in the cell.
• An agonist causes the cell to act.
• An antagonist or blocker are drug molecules that by
attaching to a receptor prevents something else from
attaching to the cell and thus blocks its action.
• If the drug is on the receptor, the other chemical
cannot also be on the receptor.
 Drug–Receptor Interactions
• A drug’s ability to stimulate its receptor is termed its
intrinsic activity.

• Drugs with high intrinsic activity cause strong

reactions from the receptor; drugs with low intrinsic
activity cause low reactions from the receptor.

• A drug with high affinity and high intrinsic activity is

able to produce a strong effect from a small amount of
drug.
Variables that Influence the Dose of a Drug
• Potency and Efficacy
– The level of the drug needed in the body to produce an
effect

• ED50, Maintenance and Loading Doses

– Maintenance dose—daily dose
– Loading dose—larger than usual dose to reach a
therapeutic effect quicker

• Therapeutic Index
– The difference between an effective dose and a toxic dose
 Potency and Efficacy
• A certain level of drug must be present in the body to
produce an effect at all.
• This level is called the minimum effective
concentration.
• The strength of the response to a drug increases
proportionately as more drug is given.
• The amount of a drug that must be given in order to
produce a particular response is called the potency of
a drug.
• How well a drug produces its desired effect is called
efficacy.
• The efficacy of a drug is related to its intrinsic activity.
 ED50, Maintenance and Loading Doses
• Because people are unique, how individuals respond to
a drug dose varies.
• The dose that is required to produce the therapeutic
response in 50% of the population is called the
effective dose 50% (ED50).
• The dose that is given consistently over time is called
the maintenance dose.
• Patients who are started on drug therapy using the
standard maintenance dose arrive at steady state after
four to five half-lives.
ED50, Maintenance and Loading Doses (cont.)
• For drugs that have long half-lives, achieving steady
state may take days or weeks.

• The patient’s medical condition may warrant

immediate and full drug effect, however in order to
maintain health or life
– If this is the case, a larger dose than usual is given
initially.
– This initial large dose is called a loading dose.
– The loading dose is computed so that after some of the
drug is eliminated, the drug concentration in the body is
still in the therapeutic range.
 Therapeutic Index
• The lethal dose is computed in a laboratory setting
and analyzed statistically.

• The point at which the dose would be fatal in 50% of

the population receiving that dose is called lethal
dose 50% (LD50).

• To determine the safety of a drug, the ED50 is

compared with the LD50.
 Therapeutic Index (cont.)
• The relation of ED50 to LD50 is called the therapeutic
index.
– TI = ED50 / LD50

• If the amount of a drug required to be the ED 50 is

similar to the amount that is the LD50, the
mathematical ratio of the two values will equal a
number close to one.

• When the ED50 and the LD50 do not differ by much, the
drug is considered to have a narrow therapeutic index.
Drug Dosage and Blood Concentration
• As drug levels within the body increase, the patient is
more likely to experience adverse effects from drug
therapy.

• To help determine whether a drug’s dose is sufficient to

be in the therapeutic range, but not so high as to cause
adverse effects, blood levels of the drug are often
measured.
 Drug Dosage and Blood Concentration
(cont.)
• Nurses need to monitor drug blood levels if samples
are drawn and notify the physician or nurse
practitioner if the level indicates that the blood levels
are not in the therapeutic range.

• The therapeutic range can only be considered an

average.