UNDESIRABLE DRUG EFFECTS

SIDE EFFECTS

Drug effect

Changes that take place in the body as a result of drug action

Slowing down or speeding up processes

Destroying certain cells or parts of cells

Replacing substances that the body lacks or fails to produce

The desired principal effect of any drug is to modify body

function in such a manner as to alleviate symptoms caused
by the patients illness.
In addition, a drug may also elicit unwanted effects that in
turn may cause complaints, provoke illness, or even lead to
death.
Overdosage (A). When the drug is administered in a higher dose
than is required for the principal effect; this directly or indirectly
affects other body functions.

For instance, morphine, given in the appropriate dose,

affords excellent pain relief. However, in excessive doses, it
inhibits the respiratory center and makes apnea imminent.
Difference between the therapeutic and toxic doses - margin
of safety or therapeutic index - indicates the risk of toxicity
when standard doses are exceeded.

Increased sensitivity (B). If

certain body functions develop
hyperreactivity,
unwanted
effects can occur even at normal
dose levels. For instance, aspirin
provokes the bronchial asthma
attack.
Undesired
effects
can
occur
because the drug does not
specifically act on the targeted
(diseased) tissue or organ. For
instance,
the
neuroleptic
chlorpromazine
is
able
to
interact with several different
receptor types. Thus, its action is
neither
organspecific
nor
receptor-specific.

The consequences of lack of selectivity can

often be avoided if the drug does not
require the blood route to reach the target
organ but is, instead, applied locally, as in
the administration of parasympatholytics in
the form of eye drops or in an aerosol for
inhalation (ipratropium bromidum).

Unknown action (C)

It is more difficult to detect unwanted effects that arise from
an unknown action. For instance, fetal damage after intake
of a hypnotic thalidomide, fibrosis after antimigraine
drugs.
REMEMBER!
With every drug use, unwanted effects must be taken into
account. Before prescribing a drug, the physician should
therefore do a risk-benefit analysis.

DRUG ALLERGY (D) THE IMMUNE SYSTEM NORMALLY FUNCTIONS

TO INACTIVATE AND REMOVE HIGH-MOLECULAR WEIGHT FOREIGN
MATTER TAKEN UP BY THE ORGANISM.
IN THE CASE OF PENICILLIN G, DURING INITIAL CONTACT WITH
THIS DRUG, IMMUNE SYSTEM IS SENSITIZED: LYMPHOCYTES OF THE TTYPE AND B-TYPE PROLIFERATE IN LYMPHATIC TISSUE. USUALLY, THESE
PROCESSES REMAIN CLINICALLY SILENT.

During
the
second
contact,
antibodies are already present
and memory cells proliferate
rapidly. A detectable immune
response occurs the allergic
reaction.
This
can
be
of
severe
intensity, even at a low dose
of the antigen.

FOUR TYPES OF ALLERGIC REACTIONS CAN BE DISTINGUISHED:

Type 1, (Immediate drug allergy), anaphylactic

reaction. Drug-specific antibodies (of the IgE type)
localized on the surface of mast cells. Subsequent
binding of the drug provides the stimulus for the mast
cell degranulation with release of histamine and other
allergic mediators prostaglandins, and leukotrienes.
These endogenous substancies (autacoides) mediate a
wide range of cellular responses, including contraction of
airway smooth muscle, stimulation of secretions, dilation
and increased permeability of the capillaries, and
stimulation of sensory nerve endings.

In the most severe form, a life-threatening anaphylactic shock

develops, accompanied by

hypotension,

bronchospasm (asthma attack),

laryngeal edema,

urticaria,

stimulation of gut musculature, and spontaneous bowel

movements.

Type 2, cytotoxic reaction. Drugantibody (IgG) complexes

adhere to the surface of blood cells and activate the
complement and, finally, can destroy the cell membranes
and thereby cause cell death. Type 2 reactions include
hemolytic
anemia
from
methyldopa,
lupus
erythematosus from hydralazine or procainamide
and etc.
Type 3, immune-complex vasculitis (serum sickness,
Arthus reaction). Drugantibody complexes, that involve Yg
M and Yg G, and possibly Yg E antibodies, precipitate on
vascular walls, complement is activated, and an
inflammatory reaction is triggered.

Symptoms may include

fever,

exanthema,

swelling of lymph nodes,

arthritis,

nephritis, and

neuropathy.

Stevens-Jonson syndrome, associated with

therapy may result from type 3 mechanisms.

sulfonamide

Type 4 allergy is a cell-mediated reaction that can

occur from topical application of drugs, it results in
contact dermatitis.

CUTANEOUS REACTIONS (E)

Cutaneous reactions are a common form of drug adverse reaction. They
vary from harmless to lethal. For instance, StevenJohnson syndrome (SJS,
erythema multiforme, Fig.35.) and toxic epidermal necrolysis (TEN or Lyell
syndrome, Fig.34.) with apoptosis of keratinocytes and bullous detachment
of the epidermis from the dermis.
Toxic epidermal necrolysis (TEN or Lyell syndrome)

Its

course is dramatic and outcome not rarely fatal.

Mentioned reactions result from use of penicillins and
sulfonamides. Lyell syndrome is more severe and
lethality is 40%.

StevenJohnson syndrome (SJS, erythema multiforme)

Man, 65 year. Breast cancer. The tumor is induced by

therapeutic doses of synthetic estrogens.

Drug Toxicity in Pregnancy and Lactation (F)

Drugs taken by the mother can be passed on transplacentally
or via breast milk and can adversely affect the unborn or
the neonate.
Pregnancy.
Eny type of therapy during pregnancy and the neonatal
period requires special consideration.

AMINOGLICOSIDES

(EXAMPLE, GENTAMICIN) MAY CAUSE

NEUROLOGIC DAMAGE, AMONG THEM IS AUDITORY NERVE
DAMAGE.
TETRACYCLINES

CAUSE TOOTH ENAMEL DYSPLASIA AND

INHIBITION OF BONE GROWTH.

Sulfonamides, by displacing bilirubin from serum albumin

may cause kernicterus in the neonate.

Chloramphenicol may cause grey baby syndrome.

The fluoroquinolones are not recommended for use in

pregnancy or in small children because of possible effects
on growing cartilage.

A peculiar type of damage results from the synthetic

estrogenic agent diethylstilbestrol following its use during
pregnancy: daughters of treated mothers have an increased
incidence of cervical and vaginal carcinoma at the age of
about 20 years.

TERATOGENIC EFFECTS:
EMBRYOPATHY: Deformity resulting from disturbance of embryonic
development (during the third8th week of pregnancy).
FETOPATHY: Deformity resulting from disturbance of fetal development
(from the 9th week of pregnancy until birth).
EMBRYOTOXIC and FETOTOXIC injury: Any exogenous disturbance,
ranging from reversible injury to lethal injury.
TERATOGENIC injury: Embryotoxic and fetotoxic injuries that manifest
themselves as disturbed morphogenesis.
TERATOLOGIC DETERMINATION PERIOD: The period in which a
teratogenic agent must act in the sensitive phase of organ or tissue
development in order to cause a certain pattern of injury. The causative
agent may be either an intrinsic (i.e., genetic) factor or an extrinsic (i.e.,
environmental) factor.

TERATOGENIC EFFECT OF CARBAMAZEPIN IN PREGNANCY,

THAT INDUCES FOLIC ACID METABOLISM

Thalidomide embryopathy
tipical malformation
syndrome primarily occurring
in the form of limb
abnormalities following intake
of thalidomide in pregnancy

Schistochilia Orofacial
pathology

Disturbance of fetal
development