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Drug interaction
Bashir Alsiddig Yousef
B. Pharm., MSc. Molecular Medicine, Ph.D. Pharmacology
Department of Pharmacology
Email: bashiralsiddiq@outlook.com
2017 - 2018
Introduction
• Drug interaction is one of the factors that can alter the response to drugs is the
concurrent administration of other drugs.
• Many patients, especially the elderly, are treated continuously with one or more
drugs for chronic diseases such as hypertension, heart failure, osteoarthritis and
so on. Acute events (e.g. infections, myocardial infarction) are treated with
additional drugs.
• The potential for drug interactions is therefore substantial, and poly-pharmacy is
an important factor to consider when prescribing in this group.
• Drugs can also interact with other dietary constituents (e.g. grapefruit juice,
which down-regulates expression of CYP3A4 in the gut) and herbal remedies
(such as St John's wort).
• There are several mechanisms by which drugs may interact.
• The administration of one drug (A) can alter the action of another (B) by one of
two general mechanisms:
1. Modification of the pharmacological effect of B without altering its
concentration in the tissue fluid (pharmacodynamic interaction)
2. Alteration of the concentration of B that reaches its site of action
(pharmacokinetic interaction).
• Combined pharmacodynamics with pharmacokinetic interactions also may
happen between two drugs when used concurrently.
• For such interactions to be important clinically, it is necessary that the
therapeutic range of one drug is narrow (i.e. that a small reduction in effect will
lead to loss of efficacy and/or a small increase in effect will lead to toxicity).
Consequences of Drug Interactions
• Their effect on patients can vary greatly, from no untoward effects to the most
extreme result of severe morbidity or death.
• Physicians face medical-legal liability if a poor patient outcome is the result of a
known drug interaction.
• Health care facilities face increased consumption of resources and increased
costs for diagnosing and treating patients with significant drug interactions.
(One study found that hospitalized patients who received interacting drugs had a
longer and more costly hospitalization than patients who did not experience such
interactions).
• The pharmaceutical industry faces loss of investment, time, and financial
resources if a drug is removed from the market, as well as potential litigation.
Risk Factors
• Use of multiple prescribers and/or multiple pharmacies increases the odds that
health professionals will have incomplete medical and drug information available
to them, and raises the chance that a potential drug interaction may go
undetected.
• Specific populations are at increased risk of experiencing drug interactions. For
example, the elderly patients.
• The genetic makeup of an individual determines his or her complement of
metabolizing enzymes and other proteins. Patients classified as slow metabolizers
appear to be at less risk for drug interactions than extensive metabolizers or
ultra-rapid metabolizers.
• Number of chronic illnesses, increased drug usage to manage those illnesses,
and age-related physiologic changes (e.g., decreased renal function, decreased
protein binding), are at higher risk for drug interactions and adverse events.
• Obese patients have altered levels of metabolizing enzymes, making them
more susceptible to drug interactions, as do malnourished patients.
• Other populations at risk include critically ill patients, patients with
autoimmune disorders, and transplant recipients.
• Drugs with a narrow therapeutic index, a steep dose-response curve, or
potent pharmacologic effects have been associated with greatest risk for
significant drug interactions.
Risk Factors for Drug Interactions
DRUG INTERACTIONS
CLASSIFIED AS:
ENHANCED EFFICACY
A) USEFUL
WITHOUT TOXICITY
TOXICITY
B) HARMFUL
EFFICACY