ADVENTIST

MEDICAL CENTER
COLLEGE
SCHOOL OF NURSING

Daverly M. Cañeda, R.N.,

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

PHARMACOLOGY
"The fear of the Lord is
the beginning of
knowledge; fools
despise wisdom and
instruction"
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
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.
Liquid form (dissolutirapidly available for GI absorption
Solids Form (disintegrate)
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
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 → 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.
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.
 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
Active

metabolites
Inactive (secreted)
 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%, (205 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.
 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.
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
Example:
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.
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, 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).
Creatinine is a metabolic by-product of muscle that is excreted by the
kidneys. The creatinine clearance test compares the level of
creatinine in the urine with the level of creatinine in the blood.
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)
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 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.