ADVENTIST

MEDICAL CENTER
COLLEGE
SCHOOL OF NURSING

Daverly M. Cañeda, R.N.,

M.N.
 NURSING CARE
MANAGEMENT 106
NRSG (206a)

PHARMACOLOGY
"The fear of the Lord is
the beginning of
knowledge; fools despise
wisdom and instruction"
Proverbs 1:7
Implication of Pharmacology
to Nursing

1. Responsible for drug administration

2. Responsible for the administration of

medications that they direct others to give.

3. Ethical and legal responsibilities

Drugs and the body

Pharmacodynamics and
Pharmacokinetics
 Definition of terms
absorption: what happens to a drug from the time it enters
the body until it enters the circulating fluid; intravenous
administration causes the drug to directly enter the circulating
blood, bypassing the many complications of absorption from
other routes
active transport: the movement of substances across a cell
membrane against the concentration gradient; this process
requires the use of energy
chemotherapeutic agents: synthetic chemicals used to
interfere with the functioning of foreign cell populations,
causing cell death; this term is frequently used to refer to the
drug therapy of neoplasms, but it also refers to drug therapy
affecting any foreign cell
Definition of terms
critical concentration: the concentration a drug must reach in
the tissues that respond to the particular drug to cause the
desired therapeutic effect
distribution: movement of a drug to body tissues; the places
where a drug may be distributed depend on the drug’s
solubility, perfusion of the area, cardiac output, and binding of
the drug to plasma proteins
enzyme induction: process by which the presence of a
chemical that is biotransformed by a particular enzyme system
in the liver causes increased activity of that enzyme system
excretion: removal of a drug from the body; primarily occurs in
the kidneys, but can also occur through the skin, lungs, bile, or
feces
 Definition of terms
first-pass effect: a phenomenon in which drugs given orally
are carried directly to the liver after absorption, where they may
be largely inactivated by liver enzymes before they can enter
the general circulation; oral drugs frequently are given in higher
doses than drugs given by other routes because of this early
breakdown
glomerular filtration: the passage of water and water-soluble
components from the plasma into the renal tubule
half-life: the time it takes for the amount of drug in the body to
decrease to one half of the peak level it previously achieved
hepatic microsomal system: liver enzymes tightly packed
together in the hepatic intracellular structure, responsible for the
biotransformation of chemicals, including drugs
 Definition of terms
loading dose: use of a higher dose than what is usually used
for treatment to allow the drug to reach the critical concentration
sooner
passive diffusion: movement of substances across a
semipermeable membrane with the concentration gradient; this
process does not require energy
pharmacodynamics: the study of the interactions between the
chemical components of living systems and the foreign
chemicals, including drugs, that enter living organisms; the way
a drug affects a body
pharmacogenomics: the study of genetically determined
variations in the response to drugs
 Definition of terms
pharmacokinetics: the way the body deals with a drug,
including absorption, distribution, biotransformation, and
excretion
placebo effect: documented effect of the mind on drug therapy;
if a person perceives that a drug will be effective, the drug is
much more likely to actually be effective
receptor sites: specific areas on cell membranes that react with
certain chemicals to cause an effect within the cell
selective toxicity: property of a chemotherapeutic agent that
affects only systems found in foreign cells without affecting
healthy human cells (e.g., specific antibiotics can affect certain
proteins or enzyme systems used by bacteria but not by human
cells)
 PHARMACOKINETICS
Is the process of drug movement to achieve drug
action (McCuistion)

The way the body deals with a drug, including

absorption, distribution, biotransformation
(metabolism), and excretion (Karch)

“Fate of drug”
 PHARMACOKINETICS

• Absorption
 How the drug is moved into blood stream from the site of
administration ?
• Distribution
 How much drug is moved to various body tissues / organs ?
Depends on blood flow through tissue

• Metabolism
 How the drug is altered – broken down ?

• Excretion
 How much of the drug is removed from the body ?
Liberation is the first step in the process by which medication enters the
body and liberates the active ingredient that has been administered. The
pharmaceutical drug must separate from the vehicle or the excipient that
it was mixed with during manufacture.
 PHARMACOKINETICS
The study of what the body does to the drug

In clinical practice, pharmacokinetic considerations include

the onset of drug action (how long it will take to see the
beginning of the therapeutic effect), drug half-life, timing of
the peak effect (how long it will take to see the maximum
effect of the drug), duration of drug effects (how long the
patient will experience the drug effects), metabolism or
biotransformation of the drug, and the site of excretion.
  The figure below shows the processes by which a drug
is handled by the body.
DRUG ACTION
A tablet or capsule taken by mouth goes through three phases:

1. Pharmaceutic
2. Pharmacokinetic
3. Pharmacodynamic

Parenteral:
subcutaneous (subQ),
intramuscular (IM), or ► no pharmaceutic phase
intravenous (IV) routes
Approximately 80% of drugs are taken by mouth.
The Pharmaceutic phase (dissolution) is the first phase of
drug action.
Disintegration is the breakdown of a tablet into smaller
particles.
A drug in solid form (tablet or capsule) must disintegrate
into small particles to dissolve into a liquid, a process known
as Dissolution. Drugs in liquid form are already in solution.

Figure below displays the pharmaceutic phase of a tablet.

API + excipients = Medication
Active pharmaceutical ingredient (API), is the term
used to refer to the biologically active component of
a drug product (e.g. tablet, capsule).
Fillers and inert substances, generally called
EXCIPIENTS are used in drug preparation to allow
the drug to take on a particular size and shape and to
enhance drug dissolution. Some additives in drugs,
such as the ions potassium (K) and sodium (Na) in
penicillin potassium and penicillin sodium, increase
the absorbability of the drug.
Drugs in liquid form are more rapidly available for GI absorption
than are solids.
Generally drugs are both disintegrated and absorbed faster
in acidic fluids with a pH of 1 or 2 rather than in alkaline fluids.
Alkaline drugs would become ionized and have difficulty
crossing cell membrane barriers. Both the very young and
older adults have less gastric acidity, therefore, drug
absorption is generally slower for those drugs absorbed
primarily in the stomach.
Enteric-coated drugs resist disintegration in the gastric acid
of the stomach, so disintegration does not occur until the
drug reaches the alkaline environment of the small intestine.
- Remain in the stomach for a long time
- Effect may be delayed in onset
- Should not be crushed - alter the place and time of
absorption of the drug
Food in the GI tract may interfere with the dissolution of
certain drugs. Some drugs irritate the gastric mucosa, so
fluids or food may be necessary to dilute the drug
concentration and to act as protectants.
 Critical Concentration
The amount of a drug that is needed to cause a therapeutic
effect is called the critical concentration.
Drug evaluation studies determine the critical concentration
required to cause desired therapeutic effect.
Recommended dose of a drug is based on the amount that
must be given to eventually reach the critical concentration

Too much of a drug → produce toxic (poisonous) effects

Too little → will not produce the desired therapeutic effects.
Loading Dose
Some drugs may take a prolonged period to reach a critical
concentration. If their effects are needed quickly, a loading
dose is recommended.
Example:
• Digoxin (Lanoxin)—a drug used to increase the strength of
heart contractions
• Xanthine bronchodilators (e.g., aminophylline, theophylline)
used to treat asthma attacks
Started with a loading dose (a higher dose than that usually
used for treatment) → critical concentration.
Maintained by using the recommended dosing schedule
 Dynamic Equilibrium
The actual concentration that a drug reaches in the body
results from a dynamic equilibrium involving several
processes:
• Absorption from the site of entry
• Distribution to the active site
• Biotransformation (metabolism) in the liver
• Excretion from the body
These processes are key elements in determining the amount
of drug (dose) and the frequency of dose repetition
(scheduling) required to achieve the critical concentration
for the desired length of time.
Dose, Dosing, Dosage, Maintenance
Dose, Loading Dose
Dose: The quantity of drug Dosing Interval - How
administered at one time often the drug should be
500mg of Paracetamol given (every 4 hrs)
Dosage: The amount of the Loading dose – Which
puts the plasma
drug that should be given
concentration in the
over time therapeutic range
500 mg Paracetamol TID Maintenance dose -
for 3 days Routine smaller doses/
recommended dose to
maintain the steady state
(Plateau)
 Absorption
Involves the way a drug enters the body and passes into the
fluids and tissues.
Absorption refers to what happens to a drug from the time it is
introduced to the body until it reaches the circulating fluids and
tissues.
Drug absorption is influenced by the route of administration.

Figure below shows the processes by which a drug is handled

by the body.
ROUTES OF DRUG ADMINISTRATION

How the drug is given

Enteral Parenteral Topical

(injectable)
1. Oral 1. Intravenous 1. Intranasal
2. Sublingual 2. Intramuscular 2. Inhalation
3. Rectal 3. Subcutaneous 3. Intravaginal
 DRUG DOSAGE FORMS

Tablets
Aerosol Capsule

Suspension Injection

Cream Infusion
Solution
Absorption Processes
• Absorption is the movement of drug particles from the GI
tract to body fluids by passive absorption, active absorption,
or pinocytosis.
• Most oral drugs are absorbed into the surface area of the
small intestine through the action of the extensive mucosal
villi. Absorption is reduced if the villi are decreased in
number because of disease, drug effect, or the removal of
small intestine.
 Absorption Processes
Passive absorption occurs mostly by diffusion (movement from
higher concentration to lower concentration). With the process of
diffusion, the drug does not require energy to move across the
membrane.
Active absorption/transport requires a carrier such as an
enzyme or protein to move the drug against a concentration
gradient. Energy is required for active absorption.
Pinocytosis is a process by which cells carry a drug across
their membrane by engulfing the drug particle
Filtration involves movement through pores in the cell
membrane, either down a concentration gradient or as a result
of the pull of plasma proteins. Filtration is another process the
body commonly uses in drug excretion.
GI membrane is composed mostly of lipid (fat) and protein
Drugs that are lipid soluble (pass rapidly)
Water-soluble drugs need a carrier (enzyme or protein)
Large particles (nonionized - have no positive or negative charge)
Weak acid drugs (aspirin - less ionized in the stomach) (pass easily and
rapidly)
Infant’s gastric secretions (higher pH - alkaline) absorb more penicillin.
Calcium carbonate and many of the antifungals need an acidic
environment
Food can stimulate the production of gastric acid.
Hydrochloric acid destroys some drugs such as penicillin G (large oral
dosage of penicillin)
Remember, drugs that are lipid soluble and nonionized are absorbed faster
than water-soluble and ionized drugs.
Drug Absorption of Various
Dosage Forms

•Oral Preparations
–Liquids, elixirs, syrups Fastest
Suspension solutions 
Powders 
Capsules 
Tablets 
Coated tablets 
Enteric-coated tablets Slowest
Factors affecting absorption
▪Blood flow, pain, stress, hunger, fasting, food, and pH
▪Poor circulation to the stomach as a result of shock,
vasoconstrictor drugs, or disease hampers absorption.
▪ Pain, stress, and foods that are solid, hot, or high in fat can
slow gastric emptying time, so the drug remains in the stomach
longer.
▪ Exercise can decrease blood flow by causing more blood to
flow to the peripheral muscle, thereby decreasing blood
circulation to the GI tract.
▪ Drugs given IM are absorbed faster in muscles (e.g., deltoids,
gluteals).
Subcutaneous tissue absorption is slower in such tissue.
▪ Drugs given rectally are absorbed slower than drugs
administered by oral route
 FIRST PASS EFFECT
Most drugs given orally are affected by first-pass metabolism.
Drugs taken orally are absorbed from the small intestine directly into the
portal venous system. The portal veins deliver these absorbed molecules
into the liver, which immediately transforms most of the chemicals delivered
to it by a series of liver enzymes.
•Lidocaine and some nitroglycerins are not given orally because they have
extensive first-pass metabolism and therefore most of the dose would be
destroyed
•Nitroglycerin when given orally are totally inactivated in the liver.
100% first pass effect. Always given sublingually
Active

metabolites
Inactive (secreted)
 Prodrug

• A prodrug is a medication or compound that, after 

administration, is metabolized (i.e., converted within the
body) into a pharmacologically active drug.
• Administered in an inactive form
• After administration converted into their active form (usually in
liver)
• Designed to improve bioavailability
Examples
 Enalapril – Enalaprilate
 Ramipril - Ramiprilate
FIRST PASS EFFECT
Systems that affect the first pass
effect of the drug:

• Enzymes of the gastro intestinal

lumen
• Gut wall enzyme
• Bacterial enzymes
• Hepatic enzymes
 BIOAVAILABILITY
Bioavailability is a subcategory of absorption. It is the
percentage of the administered drug dose that reaches the
systemic circulation. Oral route of drug administration,
bioavailability occurs after absorption and first-pass
metabolism.
Oral route is always less than 100%, (20% to 40%)
IV route it is 100%.
To obtain the desired drug effect, the oral dose could be
higher than the drug dose for IV use.
Factors that alter bioavailability

(1) drug form (e.g., tablet, capsule, sustained-release,

liquid, transdermal patch, rectal suppository,
inhalation),
(2) route of administration (e.g., oral, rectal, topical,
parenteral),
(3) GI mucosa and motility,
(4) food and other drugs, and
(5) changes in liver metabolism caused by liver
dysfunction or inadequate hepatic blood flow.
DISTRIBUTION
Distribution is the process by which the drug
becomes available to body fluids and body tissues.
Drug distribution is influenced by:
1. Blood flow
2. Drug’s affinity to the tissue
3. Protein-binding effect.
Volume of drug distribution (Vd) is dependent on drug
dose and its concentration in the body. Drugs with a
larger volume of drug distribution have a longer half-
life and stay in the body longer.
 Protein Binding
• Most drugs are bound to some extent to proteins
in the blood to be carried into circulation.

• The protein-drug complex is relatively large &

cannot enter into capillaries & then into tissues
to react. The drug must be freed from the
protein’s binding site at the tissues.
 Protein Binding
• Tightly bound – released very slowly. these
drugs have very long duration of action (not
freed to be broken down or excreted) , slowly
released into the reactive tissue.

• Loosely bound – tend to act quickly and

excreted quickly

• Compete for protein binding sites – alters

effectiveness or causing toxicity when 2 drugs
are given together.
 Protein Binding
Drugs are bound to varying degrees (percentages) with protein (primarily
albumin).
> highly protein-bound drugs (greater than 89% bound to protein)
> moderately highly protein bound (61% to 89% bound to protein)
> moderately protein-bound (30% to 60% bound to protein)
> low protein-bound drugs less than 30%.
The portion of the drug that is bound is inactive because it is not available
to receptors, and the portion that remains unbound is free, active drug.
Only free drugs (drugs not bound to protein) are active and can cause a
pharmacologic response.
•Free form
– Pharmacologically active
•Bound form
– Pharmacologically inactive
 Causes of drug accumulation and possible
drug toxicity
A. Two highly protein-bound drugs are given concurrently
will compete for protein-binding sites, thus causing
more free drug to be released into the circulation.
Warfarin 99% protein bound + furosemide 95% protein bound
B. Low serum protein level decreases the number of protein-
binding sites and can cause an increase in the amount of
free drug in the plasma.
1. Liver or kidney disease (albumin released to urine)
2. Malnourished (less muscles)
3. Older adults (hypoalbuminemia)
4. Health conditions that result in a low serum protein level
Decreased drug dose is needed
Most anticonvulsants bind primarily to albumin.
Some basic drugs such as antidysrhythmics bind mostly to
globulins.
To avoid possible drug toxicity:
1. Checking the protein binding percentage of all drugs
administered to a patient is important.
2. Check the patient’s plasma protein and albumin levels.
Abscesses, exudates, body glands, and tumors hinder drug
distribution.
Antibiotics do not distribute well at abscess and exudate sites.
Some drugs accumulate in particular tissues such as fat, bone,
liver, muscle, and eye tissues.
Blood-brain barrier (BBB) is a semipermeable membrane in
the central nervous system (CNS) that protects the brain from
foreign substances. Highly lipid-soluble drugs cross the BBB.
Drugs that are not bound to proteins and are not lipid
soluble are not able to cross the BBB
During pregnancy, both lipid-soluble and lipid-insoluble
drugs are able to cross the placental barrier, which can affect
the fetus and the mother. During lactation, drugs can be
secreted into breast milk, which could affect the nursing infant.
Check which drugs may cross into breast milk before
administering to a lactating patient.
Drugs taken during pregnancy can lead to:

First trimester: spontaneous abortion

Second trimester: spontaneous abortion,
teratogenesis
Third trimester: alter fetal growth and
development
Metabolism or
Biotransformation
• is defined as the process by which drug is
converted by the liver to inactive compounds
through a series of chemical reactions.
Hepatic Enzyme System

Liver: primary site of metabolism

Hepatic Microsomal System (enzymes in the liver)
Phase I biotransformation oxidation, reduction, or hydrolysis
of the drug via the cytochrome P450 system of enzymes.
These enzymes are found in most cells but are especially
abundant in the liver
Phase II biotransformation involves a conjugation reaction
that makes the drug more polar and more readily excreted by
the kidneys.
Enzyme induction: the presence of a chemical that is
metabolized by a particular enzyme system often increases the
activity of that enzyme system.
Some drugs cannot be taken together effectively. The
presence of one drug speeds the metabolism of others,
preventing them from reaching their therapeutic levels.
Some drugs inhibit an enzyme system, making it less
effective
Drug that is metabolized by that system will not be broken
down for excretion ► blood levels of that drug will
increase ► toxic levels.
Liver disease - contraindication/caution ► not metabolized
► toxic levels develop quickly.
 Half-Life
Half life of a drug is the time it takes for the amount
of drug in the body to decrease to one-half of the
peak level it previously achieved.

e.g.

20 mg of a drug with half-life of 2 hours, 10 mg of the

drug will remain 2 hours after administration. Two hours
later, 5 mg will be left (one-half of the previous level); in
2 more hours, only 2.5 mg will remain.
 Why to know half-life?

– To determine the appropriate timing for a

drug dose or
– determining the duration of a drug’s effect on
the body.
 Determining the Impact of
Half-Life on Drug Levels
• A patient is taking a drug that has a half-
life of 12 hours. You are trying to
determine when a 50-mg dose of the drug
will be gone from the body.
– In 12 hours, half of the 50 mg (25 mg) would be in
the body

– In another 12 hours (24 hours) half of 25 mg (12.5

mg) would remain in the body.
Determining the Impact of
Half-Life on Drug Levels
– After 36 hours, half of 12.5 mg (6.25 mg)
would remain
– After 48 hours, half of the 6.25 mg
(3.125 mg) would remain
– After 60 hours, half of the 3.125 mg
(1.56 mg) would remain
– After 72 hours, half of the 1.56 mg (0.78
mg) would remain
Determining the Impact of
Half-Life on Drug Levels
– After 84 hours, half of the 0.78 mg (0.39
mg) would remain
– Twelve more hours (for a total of 96
hours) would reduce the drug amount to
0.195 mg
– Finally,12 more hours (108 hours) would
reduce the amount of the drug into the
body to 0.097 mg, which is negligible
– Therefore, it would take 4 ½ to 5 days to
clear the drug from the body.
Excretion
• Is the elimination of drugs from the body
 Excretion or Elimination
Kidneys (urine) main route of elimination
Other routes include bile, feces, lungs, saliva, sweat, tears and
breast milk.
The kidneys filter free unbound drugs, water-soluble drugs, and
drugs that are unchanged.
The lungs eliminate volatile drug substances and products
metabolized to carbon dioxide (CO2) and water (H2O).
The urine pH influences drug excretion.
Urine pH varies from 4.5 to 8. Acidic urine promotes elimination
of weak base drugs, and alkaline urine promotes elimination of
weak acid drugs.
Example:
Aspirin, a weak acid, is excreted rapidly in alkaline
urine. If a person takes an overdose of aspirin,
sodium bicarbonate may be given to change the
urine pH to alkaline to promote excretion of the
drug. Large quantities of cranberry juice can
decrease urine pH, causing acidic urine and thus
inhibiting the elimination of aspirin.
Kidney disease glomerular filtration rate (GFR) slow or impaired
excretion. Drug accumulation with possible severe adverse drug
reactions can result. Decrease in blood flow kidneys can also alter
drug excretion.
Common tests used to determine renal function are
1. creatinine clearance (CLcr)
2. blood urea nitrogen (BUN)
BUN metabolic breakdown product of protein metabolism
Creatinine is a metabolic by-product of muscle that is excreted by
the kidneys.
Lower values: older adult and female patients (decreased muscle
mass)
GFR best test, expensive, not commonly used.
Decrease GFR → increase in serum creatinine level and decrease in
urine creatinine clearance
Drug dosage usually needs to be decreased
 PHARMACOGENETICS
Pharmacogenetics is the scientific discipline studying how the
effect of a drug action varies from a predicted drug response
because of genetic factors or hereditary influence.
Genetic factors can alter the metabolism of the drug in
converting its chemical form to an inert metabolite ► drug
action can be enhanced or diminished.
Some persons are less or more sensitive to drugs and their
drug actions because of genetic factors.
Example, African Americans do not respond as well as
Caucasians to some classes of antihypertensive medications
such as ACE inhibitors.
Tolerance and Tachyphylaxis
Tolerance refers to a decreased responsiveness over the
course of therapy.
Tachyphylaxis refers to a rapid decrease in response to the
drug. “acute tolerance.”
Drug categories that can cause tachyphylaxis include
narcotics, barbiturates, laxatives, and psychotropic agents.
Example, drug tolerance to narcotics can result in decreased
pain relief for the patient. If the nurse does not recognize the
development of drug tolerance, the patient’s request for more
pain medication might be interpreted as drug-seeking behavior
associated with addiction.
Prevention of tachyphylaxis should always be part of the
therapeutic regimen
Placebo Effect

Psychological benefit from a

compound that may not
have the chemical structure
of a drug effect
Factors Influencing Drug Effects
• Factors Affecting the Body’s Response to a Drug
• Weight
• Age
• Gender
• Physiological factors—diurnal rhythm, electrolyte balance, acid–base balance,
hydration
• Pathological factors—disease, hepatic dysfunction, renal dysfunction,
gastrointestinal dysfunction, vascular disorders, low blood pressure
• Genetic factors
• Immunological factors—allergy
• Psychological factors—placebo effect, health beliefs, compliance
• Environmental factors—temperature, light, noise
• Drug tolerance
• Cumulation effects
• Interactions
 Weight
The recommended dose of a drug
is based on drug evaluation
studies and is targeted at a 150-
pound person.
People who are much heavier
may require larger doses
People who weigh less than the
norm may require smaller doses
Toxic effects may occur at the
recommended dose if the person
is very small.
 Age
Age is a factor primarily in children
and older adults.
Children immature systems for
handling drugs (pediatric doses,
convertions)
Older adults physical changes
aging process → less effective
absorption, distribution, less
efficient perfusion, altered
biotransformation or metabolism
less effective excretion.
Gender
IM injections - men have more vascular
muscles than in women (effects sooner
in men)
Women have more fat cells than men
do, drugs that deposit in fat may be
slowly released and cause effects for a
prolonged period.
Example:
Gas anesthetics have an affinity for
depositing in fat and can cause
drowsiness and sedation sometimes
weeks after surgery.
Women who are given any drug should
always be questioned about the
possibility of pregnancy
 Physiologic Factors
• Physiological differences such
as diurnal rhythm of the nervous
and endocrine systems, acid–
base balance, hydration, and
electrolyte balance can affect
the way that a drug works on
the body and the way that the
body handles the drug.
• If a drug does not produce the
desired effect, one should
review the patient’s acid–base
and electrolyte profiles and the
timing of the drug.
 Pathological Factors
Drugs are usually used to treat
disease or pathology. However, the
disease that the drug is intended to
treat can change the functioning of the
chemical reactions within the body
and thus change the response to the
drug.
Example:
• GI disorders can affect the
absorption of many oral drugs.
• Vascular diseases and low blood
pressure alter the distribution
• Liver or kidney diseases affect
biotransformation and excretion
Genetic Factors
Lack certain enzyme systems
necessary for metabolizing a drug
Overactive enzyme systems that cause
drugs to be broken down more quickly.
Differing metabolisms or slightly
different enzymatic makeups that alter
their chemical reactions and the effects of
a given drug.
Trastuzumab (Herceptin) treat breast
cancer ‒ tumor expresses human
epidermal growth factor receptor 2—a
genetic defect seen in some tumors
Blood test to check for specific genetic
markers that would indicate that a patient
would metabolize warfarin (Coumadin),
an oral anticoagulant
 Immunological Factors
People can develop an allergy to
a drug. After exposure to its
proteins, a person can develop
antibodies to a drug. With future
exposure to the same drug, that
person may experience a full-
blown allergic reaction.
Sensitivity to a drug can range
from mild (e.g., dermatological
reactions such as a rash) to more
severe (e.g., anaphylaxis, shock,
and death).
 Psychological Factors
Placebo effect, Health Beliefs,
Compliance

Patient’s attitude/ personality

about a drug has been shown to
have an effect on how that drug
works

Nurse’s positive attitude,

combined with additional comfort
measures, can improve the
patient’s response to a
medication.
 Environmental Factors
Quiet, cool, nonstimulating
environment
Sedating drugs → relax or to decrease
tension. Reducing external stimuli to
decrease tension and stimulation help the
drug be more effective
Temperature
Antihypertensives that work well during
cold, winter month → too effective in
warmer environments (natural
vasodilation) → heat loss → ↓ed blood
pressure.
Nurses look for possible changes in
environmental conditions.
 Drug Tolerance
When tolerance occurs the drug
no longer causes the same
reaction. Increasingly larger
doses are needed to achieve a
therapeutic effect.
Example is morphine, an opiate
used for pain relief.
Giving the drug in smaller doses or
in combination with other drugs
Cross-tolerance—or resistance to
drugs within the same class or
similar classes—may also occur
in some situations.
 Cumulation
If a drug is taken in successive
doses at intervals that are
shorter than recommended, or if
the body is unable to eliminate a
drug properly, the drug can
accumulate in the body, leading
to toxic levels and adverse
effects.
This can be avoided by following
the drug regimen (strict
compliance)
 Interactions
At the site of absorption: One drug prevents or accelerates
absorption of the other drug
Example:
Antibiotic tetracycline is not absorbed from the GI tract if
calcium or calcium products (milk) are present in the stomach.
During distribution: One drug competes for the protein-
binding site of another drug, so the second drug cannot be
transported to the reactive tissue
Example:
Aspirin competes with the drug methotrexate (Rheumatrex) for
protein-binding sites. Because aspirin is more competitive for
the sites the methotrexate is bumped off, resulting in increased
release of methotrexate and increased toxicity to the tissues.
During biotransformation: One drug stimulates or blocks the
metabolism of the other drug.
Examples:
Warfarin (Coumadin), an oral anticoagulant, is biotransformed
more quickly if it is taken at the same time as barbiturates,
rifampin, or many other drugs. Because the warfarin is
biotransformed to an inactive state more quickly, higher doses
will be needed to achieve the desired effect.
St. John’s wort may experience altered effectiveness of several
drugs that are affected by that herb’s effects on the liver.
Digoxin, theophylline, oral contraceptives, anticancer drugs,
drugs used to treat HIV, and antidepressants are all reported to
have serious interactions with St. John’s wort.
During excretion: One drug competes for excretion with the
other drug, leading to accumulation and toxic effects of one of
the drugs.
Example:
Digoxin (Lanoxin) and quinidine are both excreted from the
same sites in the kidney. If they are given together the
quinidine is more competitive for these sites and is excreted,
resulting in increased serum levels of digoxin, which cannot
be excreted.
At the site of action: One drug may be an antagonist of the
other drug or may cause effects that oppose those of the other
drug, leading to no therapeutic effect.
Examples:
Antihypertensive drug (lowers BP) + antiallergy drug
(increases blood pressure) → loss of the antihypertensive
effectiveness of the drug.

Antidiabetic medication + herb ginseng → lowers blood

glucose levels → hypoglycemia and loss of blood glucose
control
 Pharmacodynamic Interactions
(McCuistion)
Takes place when one drug alters the action of
another drug.
Some are helpful but often produce adverse
effects.
 Common Drug Interactions
Additive drug effect- takes place when 2 drugs
are given together & double the effect is
produced. (1 + 1 = 2)
(Desirable effect)
codeine + aspirin = increased pain relief
Common Drug Interactions
Additive drug effect (desirable effect)

e.g. furosemide (diuretic) + propranolol (adrenergic

blockers/ beta blockers) = lower BP
 Common Drug Interactions
Additive drug effect (undesirable effect)

e.g. alcohol + aspirin = gastric bleeding

 Common Drug Interactions
Additive drug effect (undesirable effect)

e.g. hydralazine + nitroglycerine = severe

hypotension
 Common Drug Interactions
Antagonistic effect- when drugs with antagonistic
effects are administered together, one drug
reduces or blocks the effect of the other
(1 + 1 = 0)
e.g. Protamine sulfate to counteract Heparin toxicity
Naloxone to counteract Morphine overdose
 Common Drug Interactions
Synergistic Effect and Potentiation when
two or more drugs are given together, one
drug can have a synergistic effect on
another (1 + 1 = 3)
Undesirable effect
e.g. alcohol + diazepam (sedative-hypnotic) = increased
CNS depression
Common Drug Interactions
Synergistic Effect and Potentiation

e.g. Use of two cytotoxic drugs to reduce individual

dosing, thereby decreasing side effects
 Common Drug Interactions
Synergistic Effect and Potentiation
Some antibiotics have enzyme inhibitor added to the
drug to potentiate the therapeutic effect.
Bacterial beta-lactamase (enzymes produced by
bacteria) inactivates the drugs and causes bacterial
resistance. Sulbactam and clavulanate inhibits
bacterial enzyme activity. e.g. ▪ ampicillin with
sulbactam
▪ amoxicillin with clavulanate
 Common Drug Interactions
Incompatability occurs when 2 drugs mixed together in a
syringe produce a chemical reaction so they cannot be
given.
E.g.
Protamine sulfate and vitamin K
Phenytoin can precipitate if mixed with 5% glucose
 Drug-Nutrient Interactions
Examples:
Monoamine oxidase inhibitor (MAOI) and antidepressant
drug taken with tyramine rich foods such as cheese, wine,
organ meats, beer, yogurt, sour cream or bananas.
Tyramine is a potent vasoconstrictor, when taken with
MAOI it could result to hypertensive crisis.
Foods must be avoided when taking MAOI
Grapefruit alters/ inhibit metabolism of many drugs these
could result to serious adverse reactions
 Examples of foods high in tyramine
• Strong or aged cheeses, such as aged cheddar, Swiss and
Parmesan; blue cheeses such as Stilton and Gorgonzola;
and Camembert. Cheeses made from pasteurized milk are
less likely to contain high levels of tyramine — for example,
American cheese, cottage cheese, ricotta, farmer cheese and
cream cheese.
• Cured meats, which are meats treated with salt and nitrate or
nitrite, such as dry-type summer sausages, pepperoni and
salami.
• Smoked or processed meats, such as hot dogs, bologna,
bacon, corned beef or smoked fish.
• Pickled or fermented foods, such as sauerkraut, kimchi,
caviar, tofu or pickles.
• Sauces, such as soy sauce, shrimp sauce, fish sauce, miso
and teriyaki sauce.
• Soybeans and soybean products.
• Snow peas, broad beans (fava beans) and their pods.
• Dried or overripe fruits, such as raisins or prunes, or
overripe bananas or avocados.
• Meat tenderizers or meat prepared with tenderizers.
• Yeast-extract spreads, such as Marmite, brewer's yeast or
sourdough bread.
• Alcoholic beverages, such as beer — especially tap or
homebrewed beer — red wine, sherry and liqueurs.
 Drug-Laboratory Interactions
Drugs often interfere with clinical laboratory testing by:

1. Cross-reaction with antibodies

2. Interference with enzyme reactions
3. Alteration of chemical reactions
This may lead to missed or erroneous clinical diagnosis
Drug-Induced Photosensitivity
Drug-induced photosensitivity reaction is a skin reaction
caused by exposure to sunlight.
Photoallergic reaction: An allergic reaction caused by drugs
in which ultraviolet exposure changes the structure of the
drug so that it is seen by the body's immune system as an
invader. The allergic response causes inflammation of the skin
Phototoxic reaction: This is the most common reaction and
usually occurs when a drug you're taking (whether by mouth
or topically applied) is activated by exposure to UV light and
causes damage to the skin that can look and feel like a
sunburn or a rash.
How to avoid photosensitivity reactions

1. Using sunscreen (SPF > 15)

2. Avoiding excessive sunlight exposure
especially at the height of the daylight hours
3. Wearing protective clothing (long sleeves)
4. Wear wide brimmed sun hat
Pharmacodynamics
 PHARMACODYNAMICS
• Is the study of the interactions between the
chemical components of living systems and the
foreign chemicals, including drugs, that enter
those systems. All living organisms function by a
series of complicated, continuous chemical
reactions. (Karch)
• Is the study of the effects of drugs on the body
(McCuistion)
• “What the drug does to the body”
Drugs act within the body to mimic the actions of the
body’s own chemical messengers.
 Drugs usually work in one of four
ways:
1. To replace or act as substitutes for missing
chemicals
2. To increase or stimulate certain cellular activities
3. To depress or slow cellular activities
4. To interfere with the functioning of foreign cells,
such as invading microorganisms or neoplasms
leading to cell death (drugs that act in this way are
called chemotherapeutic agents).
(KARCH)
 Mechanism of Drug Action
1. Stimulation
2. Depression
3. Irritation
4. Replacement
5. Cytotoxic action
6. Antimicrobial action
7. Modification of the immune status
(MCCUISTION)
Stimulation: drug that stimulates enhances intrinsic activity (e.g.,
adrenergic drugs that increases heart rate, sweating and respiratory rate
during fight-or-flight response
Depression: Depressant drugs decrease neural activity and bodily
functions (e.g., barbiturates and opiates)
Irritation: Drugs that irritate have a noxious effect, such as
astringents, laxatives irritate the inner wall of the colon, thus
increasing peristalsis and defecation. This can occur on all types of
body tissues in the body and may result in inflammation, corrosion and
necrosis of cells
Replacement: drugs may be used for replacement when there is
deficiency of natural substances like hormones ,metabolites or
nutrients ,e.g., insulin in diabetes, iron in anemia ,vitamin C in scurvy.
Cytotoxic action: drugs selectively kill invading parasites
or cancers.
Antimicrobial action: drugs prevent, inhibit, or kill
infectious organism
Modification of immune status: vaccines and sera act by
improving our immunity while immune-suppressants act
by depressing immunity, e.g., glucocorticoids, interferons
and methotrexate
 Basics of Drug Action
Drug Action – the cellular processes involved in the drug
and cell interaction
Drug Effects – the physiologic reaction of the body to the
drug
Desired action – the expected response of a medication
Side effects –known and frequently experienced, expected
reaction to drug.
Adverse reaction –unexpected, unpredictable reactions
that are not related too usual effects of a normal dose of the
drug.
Primary Effects - drug’s desired or therapeutic effect
Secondary Effects – all other effects whether desirable or
undesirable.
An example of a drug with a primary and secondary
effect is diphenhydramine (Benadryl), an
antihistamine. The primary effect of diphenhydramine
is to treat the symptoms of allergy, and the secondary
effect is a central nervous system depression that
causes drowsiness. The secondary effect is
undesirable when the patient drives a car, but at
bedtime it could be desirable because it causes mild
sedation.
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.
Two concepts further describe this relationship.
Potency refers to the amount of drug needed to elicit a
specific physiologic response to a drug. A drug with high
potency, such as fentanyl, produces significant therapeutic
responses to a lower concentrations: a drug with low potency,
such as codeine, produces minimal therapeutic response at
low concentrations. The point at which increasing a drug’s
dosage no longer increases the desired therapeutic response
is referred to as maximal efficacy.
5mg of fentanyl relieves pain as effectively as 10 mg of
codeine, therefore fentanyl is twice as potent as codeine.
Some patients respond to a lower drug dose, whereas others
need a high drug dose to elicit the desired response. The drug
dose is usually adjusted to achieve the desired drug response.
All drugs have a maximum drug effect (maximal efficacy).
For example, morphine and tramadol hydrochloride (Ultram)
are prescribed to relieve pain. The maximum efficacy of
morphine is greater than tramadol hydrochloride,
regardless of how much tramadol hydrochloride is given. The
pain relief with the use of tramadol hydrochloride is not as
great as it is with morphine.
 Therapeutic Index and Therapeutic Range
(Therapeutic Window)
The safety of drugs is a major concern.
Effective/Therapeutic Dose (ED/TD) amount of drug that produces a
therapeutic/ effective response in 50 % of the people taking it.
Toxic/Lethal Dose (TD/LD) amount of drug that produces adverse effects in
50 % of the people taking it.
Therapeutic index (TI) estimates the margin of safety of a drug through the
use of a ratio that measures the effective (therapeutic) dose (ED) and the
lethal dose (LD). It is the difference between the ED and the LD. The closer
the ratio is to 1, the greater the danger of toxicity. The higher the TI, the
safer the drug is considered to be, in general nonprescription drugs have
much higher TIs than prescription drugs.
Drugs with a low therapeutic index have a narrow margin of safety. Drugs
with a high therapeutic index have a wide margin of safety and less danger of
producing toxic effects. Drugs with a narrow therapeutic index – such as
warfarin, digoxin and phenytoin – require close monitoring to ensure patient
safety.
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/ therapeutic effect.

Some drugs produce effects in minutes, but others may take

hours or days
 Therapeutic Drug Monitoring
Peak drug levels indicate the rate of absorption of the drug.
Trough drug levels indicate the rate of elimination of the drug.
Peak and trough levels are requested for drugs that have a
narrow therapeutic index and are considered toxic, such as the
aminoglycoside. If the peak is too low no therapeutic effect is
achieved.
Peak drug level is the highest plasma concentration of drug at
a specific time.
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 he next dose of drug is given,
regardless of route of administration.
Maintenance Dose versus Loading Dose

Maintenance dose the amount
of a medication administered to
maintain a desired level of the
medication in the blood.
Loading Dose a doses of
medication, often larger than
subsequent doses,
administered for the purpose of
establishing a therapeutic level
of the medication.
 Loading and Maintenance 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. After a large initial dose, a prescribed dosage per
day is ordered.

Example:
Digoxin (Digitek, Lanoxicaps, Lanoxin), a digitalis
preparation, requires a loading dose when first prescribed.
Digitalization is the process by which the minimum effective
concentration level for digoxin is achieved in the plasma
within a short time.
IMPORTANCE OF LOADING DOSE

1. To attend quick plasma level.

2. Attain quick action
3. The main importance of loading dose is
average plasma concentration at a
steady state as quickly as possible.
4. In some cases loading dose helps to get
therapeutic effect quickly
RECEPTOR SITES
Many drugs are thought to act at specific areas on cell
membranes called receptor sites. The receptor sites react
with certain chemicals to cause an effect within the cell. In
many situations, nearby enzymes break down the reacting
chemicals and open the receptor site for further stimulation.
To better understand this process, think of how a key works in
a lock. The specific chemical (the key) approaches a cell
membrane and finds a perfect fit (the lock) at a receptor site
The interaction between the chemical and the receptor site
affects enzyme systems within the cell. The activated enzyme
systems then produce certain effects, such as increased or
decreased cellular activity, changes in cell membrane
permeability, or alterations in cellular metabolism.
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) cell membrane-embedded enzymes
(2) ligand-gated ion channels
(3) G protein–coupled receptor systems
(4) transcription factors
The ligand-binding domain is the site on the
receptor at which drugs bind.
1. Cell membrane-embedded enzyme. 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.
2. Ligand-gated ion channels. The channel
crosses 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.
3. 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. The system works as shown in
the figure below.
4. Nuclear/Transcription receptors. Found
in the cell nucleus on DNA (not on the
surface) of the cell membrane. Activation of
receptors through the transcription factors is
prolonged. With the first three receptor
groups, activation of the receptors is rapid.
 Drug Attachment
Medication chemically binds to specific sites called
“receptor sites”

Agonist-chemical fits at receptor site well. Drugs

Enhance
Antagonist- a chemical blocks another chemical from
getting to a receptor. Drugs Block
Partial agonist - attach to the receptor but only produce
a small effect. Drugs Diminish
Affinity – attraction between a drug and a receptor
High Affinity – drug will bind easily to the receptor
Low Affinity – requires a higher concentration of the drug
to get a therapeutic response
Drug Potency – amount of drug required to produce a
therapeutic response
Efficacy (Intrinsic activity) - Inherent ability of the drug to
induce a physiological response
Some drugs interact directly with receptor sites to cause the same activity
that natural chemicals would cause at that site. These drugs are
called agonists. For example, insulin reacts with specific insulin-receptor
sites to change cell membrane permeability, thus promoting the movement
of glucose into the cell.
MAO an enzyme involved in removing the neurotransmitters
norepinephrine, serotonin and dopamine in the brain
Norepinephrine is a naturally occurring chemical in the body that acts as
both a stress hormone and neurotransmitter (a substance that sends
signals between nerve cells). It's released into the blood as a stress
hormone when the brain perceives that a stressful event has occurred
Serotonin is a chemical that has a wide variety of functions in the human
body. It is sometimes called the happy chemical, because it contributes to
wellbeing and happiness. It is mainly found in the brain, bowels, and blood
platelets.
Other drugs act to prevent the breakdown of natural chemicals that are
stimulating the receptor site. For example, monoamine oxidase inhibitors
(MAOIs) block the breakdown of norepinephrine by the enzyme MAO.
(Normally, MAO breaks down norepinephrine, removes it from the receptor
site, and recycles the components to form new norepinephrine.) The
blocking action of MAO inhibitors allows norepinephrine to stay on the
receptor site, stimulating the cell longer and leading to prolonged
norepinephrine effects. Those effects can be therapeutic (e.g., relieving
depression) or adverse (e.g., increasing heart rate and blood pressure).
Selective serotonin reuptake inhibitors (SSRIs) work similarly to MAO
inhibitors in that they also exert a blocking action. Specifically, they block
removal of serotonin from the nerve synapse, allowing it to remain in the
synapse longer, leading to further stimulation of receptor sites. This action
leads to prolonged stimulation of certain brain cells, which is thought to
provide relief from depression.
Some drugs react with receptor sites to block normal stimulation, producing
no effect. For example, curare (a drug used on the tips of spears by
inhabitants of the Amazon basin to paralyze prey and cause death)
occupies receptor sites for acetylcholine, which is necessary for muscle
contraction and movement. By blocking the action of acetylcholine at this
receptor site, curare prevents muscle stimulation, causing paralysis.
Curare is said to be a competitive antagonist of acetylcholine
Still other drugs react with specific receptor sites on a cell and, by reacting
there, prevent the reaction of another chemical with a different receptor
site on that cell. Such drugs are called noncompetitive antagonists. For
some drugs the actual mechanisms of action are unknown. Speculation
exists, however, that many drugs use receptor site mechanisms to bring
about their effects.
 Nonspecific and Nonselective Drug Effects
Drugs that affect various sites are nonspecific drugs
and have properties of nonspecificity. 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
Drugs may act at different receptors. Drugs that
affect various receptors are nonselective drugs or
have properties of nonselectivity. 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
 DRUG-ENZYMES INTERACTIONS
Drugs also can cause their effects by interfering with
the enzyme systems that act as catalysts for various
chemical reactions. Enzyme systems work in a
cascade fashion, with one enzyme activating another,
and then that enzyme activating another, until a
cellular reaction eventually occurs. If a single step in
one of the many enzyme systems is blocked, normal
cell function is disrupted. Acetazolamide (Diamox) is
a diuretic that blocks the enzyme carbonic
anhydrase, which subsequently causes alterations in
the hydrogen ion and water exchange system in the
kidney, as well as in the eye.
 SELECTIVE TOXICITY
Ideally, all chemotherapeutic agents would act only on
enzyme systems that are essential for the life of a
pathogen or neoplastic cell and would not affect
healthy cells. The ability of a drug to attack only those
systems found in foreign cells is known as selective
toxicity. Penicillin, an antibiotic used to treat
bacterial infections, has selective toxicity. It affects
an enzyme system unique to bacteria, causing
bacterial cell death without disrupting normal human
cell functioning.
 SELECTIVE TOXICITY
Unfortunately, most other chemotherapeutic
agents also destroy normal human cells,
causing many of the adverse effects
associated with antipathogen and
antineoplastic chemotherapy. Cells that
reproduce or are replaced rapidly (e.g., bone
marrow cells, gastrointestinal [GI] cells, hair
follicles) are more easily affected by these
agents. Consequently, the goal of many
chemotherapeutic regimens is to deliver a
dose that will be toxic to the invading cells
yet cause the least amount of toxicity to the
host.