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Pharmacology
DENTALELLE TUTORING
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CHAPTER THREE
ADVERSE REACTIONS
OBJECTIVES
• Define and explain the adverse reactions to
drugs.
• Explain the different types of adverse reactions
that can occur such as toxicity, allergic
reactions, side effects and idiosyncratic
responses.
• Describe common signs and symptoms of an
adverse drug reaction.
• Summarize dental hygiene considerations
that apply to drug action, handling and adverse
reactions.
Adverse Reactions
• Drugs cause good (therapeutic effect) and
bad effects (adverse effect) and this is because
drugs act on many tissues at the same time.
• Adverse effects can happen at usual therapeutic
doses.
CLASSIFICATIONS OF ADVERSE
REACTION
1. TOXIC REACTION:

The amount of the desired effect is excessive; dose related
 Predictable
 Dose-related
 Acts on target organs
 Extension of the drug’s pharmacologic effects
• E.G include: hypoglycemia with an oral hypoglycemic agent or insulin
* Drug
allergies are
not examples
of dose-related
response –
WHY?
2.



SIDE EFFECT:
Occurs when a drug acts on a non target organ, producing an
undesirable effect
Is dose related reaction
NOT part of the desired therapeutic outcome
Predictable
Dose-related
Acts on nontarget organs
E.G include: stomachache, headache,
nausea, vomiting, local effects
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IDIOSYNCRATIC REACTION:
Genetically related abnormal response
This is a reaction that is neither a side effect nor an
allergic reaction.
3.
•
•
•
•
•
Some are genetically determined abnormal reactions.
Some are due to an immunologic mechanism.
E.G: Eskimos metabolize certain drugs faster than other
populations; therefore, a larger dose of those drugs would be
needed in that population
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•
DRUG ALLERGY:
Immunologic response to drug
Can be mild as a rash or severe as anaphylaxis
Neither predictable or dose-related

1.
2.
3.
4.
Specific reactions:
Hives
Urticaria (rash, itching)
Inability to breath
Anaphylaxis
4.
•
•
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INTERFERENCE WITH NATURAL DEFENSE
MECHANISMS:
5.


The drug reduces body’s ability to fight
infection(eg. adrenocorticosteroids);
Drugs that interfere with the body’s defenses can
cause more infections
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EG: Treatment for Allergic Reaction
•
Mild Reaction – antihistamine
•
Anaphylactic reaction – epinephrine subcutaneously
•
True allergy vs. Side effect
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Remember
 When using a drug - The beneficial effect must be weighed
against its potential for adverse reactions
Clinical Manifestations of Adverse Reactions
1. Exaggerated Effect on Target Tissues

An extension of the therapeutic effect caused by:

overreaction of the sensitive patient
OR

a dose that is too large for the patient.

In cases of systemic diseases such as kidney or liver disease, the
disease may interfere with the metabolism or excretion of the drug
therefore, the action of the drug may be enhanced or prolonged.
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Clinical Manifestations of Adverse Reactions
2. Effect on Non-target tissues

Caused by a non-therapeutic action of the drug.

Reactions can occur at usual doses but appear more often at higher doses

A reduction in the dose of the drug will usually reverse the adverse reaction.
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Clinical Manifestations of Adverse Reactions
3. Effect on Fetal Development (Teratogenic Effect)


TERATOGENIC- comes from the Greek prefix terato-meaning
“monster” and the suffix-genic; meaning “producing” a malformed fetus.
There is a relationship between drugs and congenital abnormalities.
 eg. thalidomide an OTC drug was found to cause short arms and
legs in the exposed fetus. Used as a sedative/hypnotic & also used to
treat leprosy.
These drugs in dentistry are considered the ‘safest’ :
penicillin and erythromycin, acetaminophen (Tylenol), and
the local anesthetic lidocaine (Xylocaine).
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Clinical Manifestations of Adverse Reactions
Effect on Fetal Development (Teratogenic Effect)
• Early in pregnancy (first trimester) the organs in the fetus are
forming, which is considered the most critical time for
teratogenicity.
• Drugs taken during the 2nd and 3rd trimester stages may affect
the newborn, but the fetus is fully developed.
–
Fetal organogenesis has already occurred, therefore critical
stages in fetal development have passed.
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Clinical Manifestations of Adverse Reactions
4. Local Effect

Local tissue irritation
– Occasionally, injectable drugs can
produce irritation, pain, and tissue
necrosis at the site of injection
– Topically applied agents can produce irritation at
the site of application
– Drugs taken orally can produce gastrointestinal
symptoms such as nausea
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Clinical Manifestations of Adverse Reactions
5. Drug Interaction
A drug interaction can occur when the effect of
one drug is altered by another drug
– Interactions may result in toxicity or lack of
efficacy
– Interactions may also produce beneficial effects
• The likelihood that a drug interactions would
occur increases with the number of drugs a patient
is taking
•
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Clinical Manifestations of Adverse Reactions
6. Hypersensitivity (Allergic Reaction)
 Occurs when the immune system of an
individual responds to the drug administered
or applied
 Neither dose dependent nor predictable
 Intensity increases with subsequent exposures
 May be life-threatening
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Hypersensitivity (Allergic Reaction)
• Drug allergy can be divided into 4 types of
reactions, depending on the type of antibody
produced or the cell mediating the reaction:
–
–
–
–
Type I: Immediate
Type II: Cytotoxic/Cytolytic
Type III: Immune
complex/Arthus/Serum sickness
Type IV: Delayed Hypersensitivity
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Hypersensitivity (Allergic Reaction)
HINT:
STUDY ALL
THE TYPES
OF
ALLERGIC
REACTIONS
TYPE I
• Mediated by immunoglobulin E (IgE)
antibodies
•
•
When a drug antigen binds to IgE antibody,
histamine, leukotrienes, and prostaglandins are
released, producing vasodilation, edema, and
inflammation
Anaphylactic shock or immediate
hypersensitivity reactions
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Hypersensitivity (Allergic Reaction)
TYPE I
•
The targets of this reaction are
• Bronchioles, resulting in anaphylactic
shock
• Respiratory system, resulting in asthma
• Skin, resulting in urticaria and dermatitis
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Hypersensitivity (Allergic Reaction)
TYPE I
• Because these reactions can occur quickly after drug
exposure, they are known as immediate
hypersensitivity reactions
–
Anaphylaxis is an acute, lifethreatening allergic reaction
characterized by hypotension,
bronchospasm, laryngeal edema, and
cardiac arrhythmias
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Hypersensitivity (Allergic Reaction)
TYPE II
• Complement-dependent reactions involving
IgG or IgM antibodies
• The antigen-antibody complex is fixed to a
circulating red blood cell, resulting in lysis
• hypersensitivity causes cytolytic reactions
• EG: penicillin-induced hemolytic anemia.
Clinical Manifestations of Adverse Reactions
Hypersensitivity (Allergic Reaction)
YPE III
• Mediated by IgG
• The drug antigen-antibody complex fixes complement
and deposits in the vascular endothelium
• Manifested as serum sickness;
• Includes urticarial skin eruptions, arthralgia (joint
pain), arthritis, fever…, with little or no lung
involvement
• EG: Can be caused by penicillins
Hypersensitivity (Allergic Reaction)
TYPE IV
• Delayed hypersensitivity reaction
• Generally manifested as skin eruptions
• Mediated by sensitized T-lymphocytes
and macrophages
– Examples include allergic contact
dermatitis; poison ivy
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Clinical Manifestations of Adverse Reactions
7. Idiosyncrasy


Neither a side effect nor an allergic reaction
May be genetically determined

Example: Primaquine-induced hemolytic
anemia: Approximately 10% of male African
Americans develop a severe hemolytic
anemia when given the antimalarial drug
primaquine. This is an example of a
genetically determined abnormal reaction
(idiosyncrasy).
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Clinical Manifestations of Adverse Reactions
8. Interference With Natural Defense
Mechanisms
•
A drug’s effect on the body’s defense
mechanisms can result in an adverse reaction
– Long-term systemic administration of
corticosteroids can result in decreased
resistance to infection
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Toxicologic Evaluation of Drugs
• LD50 – LETHAL DOSE:
–
dose of a drug that kills 50% of
experimental animals
Toxicologic Evaluation of Drugs
• ED50 – MEDIAN EFFECTIVE
DOSE:
–
dose required to produce a specified
intensity of effect in 50% of the
animals
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Toxicologic Evaluation of Drugs
 Therapeutic Index (TI)- LD50/ ED50
>10 needed to produce a therapeutically
useful drug

The therapeutic index is the ratio of the
LD50 to ED50. The smaller the ratio is, the
closer the LD50 is to the ED50 and therefore
the closer a deadly dose is to the
therapeutic dose.
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Toxicological Evaluation of Drugs
Therapeutic Index
Therefore,
the lesser the therapeutic index is, the greater
the toxicity will be.
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Toxicologic Evaluation of Drugs
CALCULATING THE THERAPEUTIC INDEX (TI)- LD50/ ED50
 EXAMPLE:
 In an assessment of drug action for a certain therapeutic agent, results
indicate that the ED50 is 20 mg/kg, and the LD50 is 400 mg/kg.
 What is the therapeutic index for this agent?
 One must divide the LD50 value by the ED50 value. The LD50 value (400)
divided by the ED50 value (20) equals 20.
 THEREFORE, in this example the TI is greater than 10 and is a
therapeutically useful drug
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