Factors Affecting Drug
Activity
Chapter 11
Pages 252-264
Bell work 4/27

Can you think of three things that might
influence an individuals response to
medication?
Human Variability

Differences in age, weight, genetics, and
gender are factors that influence the
differences in response to medication among
people.
Age

Infants and Neonates

Drug distribution is different in a neonate and
infant because their organ systems are not fully
developed. They do not eliminate drugs as
efficiently as adults.
Age

Children



Children metabolize certain drugs more rapidly
than adults.
Metabolism rates increases between 1 year and
12 years (depends on age and drug).
After age 12 metabolism rates decline with age to
a normal adult level.
Age

Adult


Adults experience a decrease in many
physiological function after age 30.
Decreases in affects on drug activity are gradual.
Age

The elderly

Elderly typically consume more drugs than any
other age group due to chronic illness and
disease.
Gender




Women used to be excluded from drug studies. In
1993 the FDA stated that women will be included in
clinical drug trials.
Since then many studies have been completed and
show that men and women do show differences in
absorption, distribution, metabolism, and excretion
(ADME).
Gender based differences in drug response appear
to be related to hormonal fluctuations.
Gender differences may also be due to differences
in body composition.
Genetics


The field of study, pharmacogenetics,
defines the hereditary basis of individual
differences in absorption, distribution,
metabolism, and excretion (ADME)
processes.
The largest contributing factor to variability is
metabolism.
Body Weight

Dosage adjustments based on weight are
generally not made for adults who are slightly
overweight.

Weight is a factor in determining drug dosage
for infants, children, or obese patients.
Psychological Factors



Psychological factors can influence individual
responses to drugs.
When placebo drugs are given patients
receiving them can report therapeutic and
adverse effects.
Another factor can be patient’s willingness to
follow prescribed dosage regimens.
Bell work 4/30

Name two groups of people that need to have
adjustments in drug dosages?

What group of people metabolism drugs the
fastest?
Adverse Drug Reactions



Drugs generally produce a mixture of either
therapeutic (desired) or adverse (undesired)
effects.
An adverse effect is an unintended side effect
of a medication that is negative or in some
way injures a patient’s health.
Reactions may be rare or common, localized
or wide-spread, mild or severe depending on
the drug and the patient.
Common Adverse Reactions

Hypersensitivity or Allergy



Almost any drug, in any dose, can produce an
allergic or hypersensitive reaction in a patient.
The drug will interact with antibodies, releasing
histamine and other substances that produce
reactions that can range from mild rashes to
potentially fatal anaphylactic shock.
Allergic reactions can occur within minutes or
weeks after drug administration
Adverse Drug Reactions

Central nervous system (CNS):



Stimulation – agitation, confusion, disoriented
Depression – dizziness, drowsiness, sedation
Hepatotoxicity:


Hepititis
Necrosis


Hepatotoxic drugs include: acetaminophen, aspirin.
Gastrointestinal effects:


Anorexia, nausea, diarrhea
Ulcers, colitis
Adverse Drug Reactions

Nephrotoxicity:


Idiosyncrasy:


Chronic use of analgesics, sedatives, hypnotics,etc
Teratogenicity:


Coagulation, bleeding, bone marrow disorders
Drug dependence:


Unexpected reaction the first time a drug is given
Hematological effects:


Kidney failure - Gentamicin and ibuprofen
Ability of a substance to cause abnormal fetal
development
Carcinogenicity:

Ability of a substance to cause cancer
Bell Work 5/1, 5/2

What is a potentially fatal hypersensitivity
reaction that produces respiratory distress
and cardiovascular collapse?

What is an unexpected reaction the first time
a drug is given?
Drug – Drug Interactions



Taking more than one drug at a time can
cause a drug-drug interaction.
Drug – drug interactions can affect the
disposition (all processes of the ADME) of
any drug.
Therapeutic effects and side effects can be
decreased or increased when more than one
drug is taken.
Drug – Drug Interactions

See examples of drug-drug interactions on page 256-257

Common drug-drug interactions




Additive effects – when two drugs effects equal
to the sum of the individual effects
Synergism – two drugs produce greater effect
than the sum of the individual effects
Potentiation – one drug increases the activity of
another drug
Antidote – a drug given to block or reduce toxic
effects
Drug – Drug Interactions





Complex – decreased intestinal absorption of oral
drugs occurs when drugs complex to produce
nonabsorbable compounds
Displacement – a drug bound to a plasma protein
is removed when another drug of greater binding
potential binds to the same protein.
Inhibition – one drug with the elimination of a
second drug may intensify the effects of the
second drug
Induction – a drug causes more metabolic
enzymes to be produced, increasing metabolic
activity
Urinary excretion – some drugs are altered by
raising urinary pH and decrease renal absorption
Drug – Diet Interactions

Dietary intake may affect disposition of drugs.




Absorption - increased or decreased when food is in
the stomach. Generally absorption is decreased.
Distribution – a previously bound drug is displaced
and this increases the concentration of the drug in the
blood and this leads to an increased effect
Metabolism – high protein diets are associated with
increased drug metabolism and high carbohydrate
diets are associated with decreased metabolism.
Malnourished adults have a decreased metabolism
Excretion – high protein diet increases kidney
function.
Disease States

The disposition (ADME process) and effect of some
drugs can be influenced by diseases other than the
one that the drug is intended for.

Hepatic



Cirrhosis and obstructive jaundice decrease hepatic
metabolism and will diminish drug elimination
Viral hepatitis little change in disposition
Circulatory

Changes in blood flow can influence ADME and therefore
will have the potential to alter the effect of the drug
Disease States

Renal


Reduced renal function can effect the elimination of many
drugs and affect the plasma protein binding of drugs
Thyroid

Changes in thyroid function can effect many aspects of
absorption excretion and metabolism