Objectives:

Discuss the following:

1. Drugs and the body

2. Toxic Effects of Drugs
3. Nursing Management
Assessing a patient’s response to drug therapy is an
ongoing nursing responsibility.
With increasing movement of health care into the
community, nurses are gaining more responsibilities and
opportunities to collaborate with patients in safe
medication administration and use.
To adequately assess, plan intervene, and evaluate drug
effects, the nurse must have knowledge of the
pharmaceutic, pharmacokinetic and pharmacodynamic
phases of drug action.
The word pharmacology is derived from two Greek words:

pharmakon, which means “medicine,”

and logos, which means “study”

Thus, pharmacology is most simply defined as the study of

medicine.

Pharmacology is an expansive subject ranging from

understanding how drugs are administered, to where they
travel in the body, to the actual responses produced.
To learn the discipline well, nursing students must acquire a
broad knowledge base from various foundation areas such
as anatomy and physiology, chemistry, microbiology, and
pathophysiology.
DRUGS AND THE BODY
A tablet or capsule taken by mouth
goes through three phases-
1. Pharmaceutic
2. Pharmacokinetic
3. Pharmacodynamic
…as drug actions occur.
Pharmaceutic phase
The first phase in drug action.
Disintegration – breakdown of a tablet
into smaller particles
Dissolution – dissolving of the smaller
particles in the GI fluid before absorption.
Approximately 80% of drugs are taken by
mouth.
Tablets are not 100% drug.
Fillers and inert substances, generally
called excipients, are used in drug
preparation to allow drug to take on a
particular size and shape and to
enhance drug dissolution.
Drugs in liquid form are more rapidly available for GI
absorption than solid ones.
Generally, drugs are both disintegrated and absorbed
faster in acidic fluids with a pH of 1 or 2 rather than in
alkaline fluids.
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
in the small intestine.
Pharmacokinetic phase
Pharmacokinetics is the process of drug
movement to achieve drug action.
The nurse applies knowledge of
pharmacokinetics when assessing the
patient for possible adverse drug
effects.
Pharmacokinetic phase
Four processes:

1. Absorption
2. Distribution
3. Metabolism
4. Excretion
I. ABSORPTION
-movement of drug particles from the GI tract to body fluids by
passive absorption, active absorption and pinocytosis.
a. Passive Absorption
-occurs mostly by fusion (movement from higher to lower
concentration)
b. Active Absorption
-requires a carrier such as an enzyme or protein to move the drug
against a concentration gradient, energy is required.
c. Pinocytosis
-process by which cells carry a drug across their membrane by
engulfing the drug particles.
GI membrane is composed mostly of lipid (fat) and
protein, so drugs that are lipid soluble pass rapidly
through the GI membrane.
Water-soluble drugs need a carrier, either enzyme or
protein, to pass through the membrane.
Large particles pass through the cell membrane if they
are nonionized (have no positive or negative charge).
Certain drugs such as calcium carbonate and many of
the antifungals need an acid environment to achieve
greater drug absorption.
There are many factors that affect the drug
absorption.
Blood flow
-Poor circulation to the stomach as a result of shock,
vasoconstrictor drugs, or disease hampers absorption
Pain, stress and food 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.
Medication route can also affect drug absorption.
Drugs given by IM are absorbed faster in muscles that
have more blood vessels (e.g. deltoids) that in those
that have fewer blood vessels (e.g. gluteals).
Subcutaneous tissue has fewer blood vessels, so
absorption is slower in such tissue.
Some drugs do not go directly into the systemic circulation
following oral absorption but pass from the intestinal
lumen to the liver via the portal vein.
The process in which the drug passes to the liver first is
called the first-pass effect, or hepatic first pass.
In the liver, some drugs may be metabolized to an inactive
form that may then be excreted, thus reducing the
amount of active drug.
Some drugs do not undergo metabolism at all in the liver,
and other may be metabolized to drug metabolite, which
may be equally or more active than the original drug.
Bioavailability
-a subcategory of absorption.
-it is the percentage of the administered drug dose that reaches the
systemic circulation.
-For oral route of drug administration, bioavailability occurs after
absorption and first-pass metabolism.
-The percentage of bioavailability of oral route is always less than 100%,
but for the IV route, it is 100%.
-Oral drugs and first-pass hepatic metabolism may have a bioavailability of
only 20% to 40% on entering systemic circulation. To obtain desired effect,
the oral dose could be higher than the drug dose for IV use.
-Rapid absorption increases the bioavailability of the drug and can cause an
increase in drug concentration. Drug toxicity man result.
-Slow absorption can limit the bioavailability of the drug, thus causing a
decrease in drug serum concentration.
II. DISTRIBUTION
-process by which the drug becomes available to the body
fluids and body tissues.
-it is influenced by blood flow, the drug’s affinity to the
tissue, and the protein-binding effect.
-Volume of drug distribution (Vd) is dependent on drug
dose and its concentration in the body.
a. Protein Binding
b. Blood Flow
c. Body Tissue Affinity
Protein Binding
-As drugs are distributed in the plasma, many are bound
to varying degrees (percentages) with protein (primarily
albumin).
Greater than 89% bound to protein: highly protein-bound
drugs
61% to 89% are moderately highly protein bound
30% to 60% are moderately protein-bound
Less than 30% are low protein-bound drugs
Drug dose is prescribed according to the percentage in
which the drug binds to protein.
Protein Binding
-Patients with liver or kidney disease or those who are
malnourished may have an abnormally low serum albumin
level. This results in fewer protein-binding sites, which in
turn leads to excess free drug and eventually to drug
toxicity.
-Older adults are more likely to have hypoalbuminemia.
With some health conditions that result in a low serum
protein level, excess free drug or unbound drug goes to
nonspecific tissue binding sites until needed and excess free
drug in the circulation does not occur. Consequently, a
decreased drug dose is needed as there is not as much
protein circulated for the drug to bind to.
To avoid possible toxicity:
-check the protein-binding percentage of all
drugs to be administered
-should also check the patient’s plasma protein
and albumin levels
Blood-Brain Barrier (BBB) and Placental Barrier
-semipermeable membrane in the CNS that protects the
brain from foreign substances
-highly lipid-soluble drugs are able to cross the BBB
-drugs that are not bound to proteins and are not lipid
soluble are not able to cross the BBB, which makes it difficult
to distribute the drug
-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 should be checked which may cross
into breastmilk before administering to a lactating patient.
III. Metabolism or Biotransformation
-it is the process by which the body inactivates or
biotransforms drugs
-drugs can be metabolized in several organs; however, the
LIVER is the primary site of metabolism
-Most drugs are inactivated by liver enzymes and are then
converted or transformed by hepatic enzymes to inactive
metabolites or water-soluble substances for excretion.
-when the drug metabolism rate is decreased, excess drug
accumulation can occur and lead to toxicity.
Half-Life (t ½) of a drug
-the time it takes for one half of the drug
concentration to be eliminated
-metabolism and elimination affect the half-life of a
drug
-for example: with liver or kidney dysfunction, the
half-life of the drug is prolonged and less drug is
metabolized and eliminated. When the drug is taken
continually, drug accumulation may occur.
-by knowing the half-life, the time it takes for a drug
to reach a steady state of serum concentration can be
computed.
 HALF-LIFE OF 650 mg OF ASPIRIN
Number Time of Dosage Percentage
(t ½) Elimination (h) remaining (mg) Left

1 3 325 50
2 6 162 25
3 9 81 12.5
4 12 40 6.25
5 15 20 3.1
6 18 10 1.55
IV. Excretion or Elimination
-main route is through the kidneys (urine)
-other routes include bile, feces, lungs, saliva, sweat
and breast milk
-The kidney filters free unbound drugs, water-soluble
drugs, and drugs that are unchanged.
-The lungs eliminate volatile drug substances and
products metabolized to CO2 and H2O.
-The urine influences drug excretion. Acidic urine
promotes elimination of weak base drugs, and alkaline
urine promotes elimination of weak acid drugs.
PharmacoDYNAMIC phase
is the study of the way drugs affect the
body
Drug response can cause primary or
secondary physiological effect or both.
Primary Effect -desirable
Secondary effect - desirable or
undesirable
Example:
Dipenhydramine (Benadryl)
-an antihistamine

Primary Effect:
Treat symptoms of allergy
Secondary Effect:
CNS 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.
Some patients respond to a lower drug dose, whereas
others need a high drug dose to elicit desired response.
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.
Onset, Peak and Duration of Action
Important aspect of pharmacodynamics

Onset of action
-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
-length of time the drug has a pharmacologic effect.
 Onset, Peak and Duration of Action

Some drugs produce effects in minutes, but

others may take hours or days.

A time-response curve evaluates the three

parameters of drug action.
 Drug effects

Side Effects
Adverse Reactions
Toxic Effects
Side Effects
-are psychologic effects not related to desired drug
effects
-can be desirable and/or undesirable side effects
-sometimes called adverse reactions in literatures and in
speaking, but they are different
-the occurrence of expected undesirable side effects is
not a reason to discontinue therapy
NURSING MANAGEMENT:
-teaching patients to report any side effects
Examples of Side Effects
Adverse Drug Reactions (ADR)
-severe than side effects
-range of untoward effects (unintended and
occurring at normal doses) of drugs that cause
mild to sever side effects
-always undesirable

NURSING MANAGEMENT:
-should always be reported and documented
because they represent variances from planned
therapy
Examples of Adverse Drug Reactions
Toxic Effects or Toxicity
-can be identified by monitoring plasma (serum)
therapeutic range of the drug
-when the drug level exceeds the therapeutic
range, toxic effects are likely to occur from over
dosing or drug accumulation
NURSING MANAGEMENT:
-should always be reported and documented
because they represent variances from planned
therapy
Examples of Toxic Effects
Drug Interactions
Drug interactions
Drug-Diet Interactions

Food also may decrease absorption by combining with a

drug to form an insoluble drug–food complex.

In other instances, however, certain drugs or dosage

forms are better absorbed with certain types of meals.
Drug interactions
Drug-Diet Interactions

Food may alter the absorption of oral drugs. In many

instances, food slows absorption by slowing gastric
emptying time and altering GI secretions and motility.

When tablets or capsules are taken with or soon after

food, they dissolve more slowly; therefore, drug
molecules are delivered to absorptive sites in the small
intestine more slowly
Drug interactions
Drug-Drug Interactions

The action of a drug may be increased or decreased by

its interaction with another drug in the body. Most
interactions occur whenever the interacting drugs are
present in the body; some, especially those affecting the
absorption of oral drugs, occur when the interacting drugs
are given at or near the same time.
Drug interactions
Drug-Drug Interactions

Increased Drug Effects

Interactions that can increase the therapeutic or adverse

effects of drugs are as follows:
a. Additive Effects
b. Synergism or potentiation
c. Inference
d. Displacement
Additive effects
Additive effects occur when two drugs with
similar pharmacologic actions are taken.

Example: ethanol + sedative drug

→increased sedation
Synergism or potentiation
Synergism or potentiation occurs when two drugs
with different sites or mechanisms of action
produce greater effects when taken together than
either does when taken alone.

Example: acetaminophen (non-opioid analgesic) +

codeine (opioid analgesic) →increased analgesia
Interference
Interference by one drug with the metabolism or
elimination of a second drug may result in intensified
effects of the second drug.
Example: cimetidine inhibits CYP 1A, 2C, and 3A
drug-metabolizing enzymes in the liver and therefore
interferes with the metabolism of many drugs
When these drugs are given concurrently with
cimetidine, they are likely to cause adverse and toxic
effects.
Displacement
Displacement of one drug from plasma protein-
binding sites by a second drug increases the
effects of the displaced drug. This increase occurs
because the molecules of the displaced drug,
freed from their bound form, become
pharmacologically active.
Example: aspirin (an anti-inflammatory/ analgesic/
antipyretic agent) + warfarin (an anticoagulant)
→increased anticoagulant effect
Drug interactions
Drug-Drug Interactions

Decreased Drug Effects

Interactions in which drug effects are decreased

are grouped under the term antagonism.
Example 1
In some situations, a drug that is a specific antidote is
given to antagonize the toxic effects of another drug.
Example: naloxone (a narcotic antagonist) +
morphine (a narcotic or opioid analgesic) → relief of
opioid induced respiratory depression. Naloxone
molecules displace morphine molecules from their
receptor sites on nerve cells in the brain so that the
morphine molecules cannot continue to exert their
depressant effects.
Example 2
Decreased intestinal absorption of oral drugs
occurs when drugs combine to produce
nonabsorbable compounds.
Example: aluminum or magnesium hydroxide
(antacids) + oral tetracycline (an antibiotic)
→binding of tetracycline to aluminum or
magnesium, causing decreased absorption and
decreased antibiotic effect of tetracycline