KSMU

Department of clinical pharmacology

Adverse drug reactions (side effects of drugs ).
Treatment and prevention. The principles of
rational drug use in lactating and pregnant
women.

lecturer: M.D., Associated professor Julia luneva

 Adverse drug reaction
• Adverse drug reaction (ADR, or adverse drug effect) is
a broad term referring to unwanted, uncomfortable,
or dangerous effects that a drug may have.
• Adverse drug reactions can be considered a form of
toxicity; however, toxicity is most commonly applied to
effects of over ingestion (accidental or intentional) or
to elevated blood levels or enhanced drug effects that
occur during appropriate use (eg, when drug
metabolism is temporarily inhibited by a disorder or
another drug).
• Side effect is an imprecise term often used to refer to a
drug’s unintended effects that occur within the
therapeutic range.
• In the US, 3 to 7% of all hospitalizations are due
to adverse drug reactions.
• ADRs occur during 10 to 20% of hospitalizations;
about 10 to 20% of these ADRs are severe.
• These statistics do not include the number of
ADRs that occur in ambulatory and nursing home
patients.
• Although the exact number of ADRs is not
certain, ADRs represent a significant public health
problem that is, for the most part, preventable
• Incidence and severity of adverse drug
reactions vary by patient characteristics (eg,
age, sex, ethnicity, coexisting disorders,
genetic or geographic factors) and by drug
factors (eg, type of drug, administration route,
treatment duration, dosage, bioavailability).
Incidence is higher with advanced age and
polypharmacy
 To the development of side effects
predispose:
• age over 60 years or up to one month,
• gender-women are more likely to suffer,
• history of adverse reactions,
• liver diseases,
• kidney diseases.
 The main types of adverse reactions
1. Absolute and relative drug overdose.
2. Drug intolerance (hypersensitivity to drugs caused by:
• slowing down the destruction of drugs by enzyme systems
• or increasing the sensitivity of receptors to conventional
doses of drugs).
3. Direct side effects:
• local negative action of the drug.
• reflex negative action of the drug.
• negative resorptive action of the drug.
• drug addiction.
• drug resistance (reduced response of the organism to
regular use of drugs).
• teratogenic effect of drugs.
• blastomogenic effect of drugs.
 Classification of side effects
• Type A-frequent, predictable reactions
associated with the pharmacological activity
of drugs (can be observed in any individual)
• Type B-infrequent, unpredictable reactions
(found in sensitive people)
• Type C-reactions associated with long-term
therapy ("chemical")
• Type D-deferred
 Type A
• Toxicity associated with drug overdose
• Secondary (concomitant) pharmacodynamic
effects
• Secondary side effects (dysbacteriosis,
candidiasis)
• Toxicity associated with drug interactions
 Type A- mechanisms of development
• Pharmacokinetic mechanisms (kidney and
liver dysfunction, interaction with other drugs,
pharmacogenetic factors).
• Pharmacodynamic mechanisms (the disease
can change the reaction of the body to drugs,
which is not associated with changes in
concentration).
 Type B
• Unpredictable action.
• Does not depend on the dose.
• Less common.
• Often have serious consequences.
• Usually you need to stop taking drugs
 Type C
• this type with a long-term receiving the drug.
• It is possible to develop tolerance, withdrawal
syndrome, drug dependence ,cumulative
effects, suppression effects on hormone
production.
 Classification of Adverse drug reactions by
frequency of occurrence
• very often (≥1/10);
• frequently (from ≥1/100 to <1/10)
• infrequently (from ≥1/1000 to <1/100)
• rarely (from ≥1/10000 to <1/1000);
• very rare (≤1/10000),
• isolated cases (spontaneous post-marketing
messages).
 Drug Testing in Pregnancy: Safety and Efficacy

• The optimal dose of a drug used during pregnancy should maximize therapeutic
benefit while minimizing the risk of damage or toxicity to the mother, fetus, and
placenta. Obviously, too high a dose could cause toxic effects, out of proportion to
therapeutic benefits. Less obviously, too low a dose may deny women any benefits of
treatment, while still exposing them to some risk.
• Determining the best dose is difficult because a woman’s ability to metabolize and
excrete drugs, as well as her body’s response to drugs, changes dramatically over the
course of her pregnancy. A case in point is that most drugs are eliminated from the
body either by enzymes in the liver or by excretion into the urine, and the activity of
both of these processes can be increased by up to 50% in most pregnant women. This
fact is rarely taken into account.
• It is a basic principle of pharmacology that, when we weigh potential harms of a drug
treatment, we should do so at a dose and dosing interval that maximizes potential
benefit. Unfortunately, we lack this sort of dosing information for almost all drugs
prescribed to pregnant women.
• Most women will require one or more prescription drugs during pregnancy despite
the fact that almost no commonly used drugs have been tested specifically for their
use in pregnancy. Consequently, while we always have some information about fetal
safety (more often in animals than in humans), we know almost nothing about
maternal safety, about choosing the right dose for a pregnant woman, or about how
effective the drug will be during pregnancy.
RISK CATEGORIES FOR USING DRUGS DURING PREGNANCY
DEVELOPED BY THE AMERICAN FOOD AND DRUG
ADMINISTRATION — FOOD AND DRUG ADMINISTRATION):
 RISK CATEGORIES FOR USING DRUGS DURING
PREGNANCY

• category A-safe for the fetus.

• category B- safe for the fetus (in animal studies).
No human studies have been conducted.
• category C-dangerous for the fetus (in animal
studies). No human studies have been conducted.
• category D-dangerous for the fetus (human
studies).
• category X-dangerous for the fetus (in animal
studies) and (human studies).