Drug Interaction

DRUG INTERACTION
TEHREEM ARSHAD
INTRODUCTION
• A drug interaction is a change in the action or side effects of a drug caused by concomitant
administration with a food, beverage, supplement, or another drug.
• Every time a drug is administered with any other prescription medicine, OTC medicine, food item, or
herb, we expose ourselves to the risk of a potentially dangerous interactions.
• The risk of a drug-drug interaction increases with the number of drugs used.
• The drug whose activity is effected by such interaction is called as “Object Drug” and the agent which
precipitates such an interaction is called as the “Precipitant”.
• Drug interactions are thus- •Mostly undesirable •Rarely desirable (beneficial)
• for ex. Enhancement of activity of penicillin when administered with probenecid
CAUSES OF DRUG INTERACTIONS
• There are many causes of drug interactions.

• For example, one drug may alter the pharmacokinetics of another. Alternatively, drug
interactions may result from competition for a single receptor or signaling pathway.
• Main factors contributing to drug interactions are-
• Multiple drug therapy Multiple prescribers Multiple pharmacological effects of
drug Multiple diseases / illness Poor patient compliance Advancing age of patient
Drug related factors
TYPES OF DRUG INTERACTIONS
• Important types of drug interactions are:

• 1. Drug-drug interactions
• 2. Drug -food interactions
• 3. Drug-chemical interactions
• 4. Drug-laboratory test interactions
• 5. Drug-disease interactions
The net effect of a drug- interaction is:
• Generally quantitative – increased or
decreased effect.
• Seldom qualitative – rapid or slower
effect.
• Precipitation of newer or increased
adverse effect.
MECHANISMS OF DRUG INTERACTIONS
• Behavioral drug-drug interaction: (altered compliance)

• When one drug alters the patients behavior to modify compliance with another drug. For
ex. - a depressed patient taking an antidepressant drug may become more compliant to the
drug as symptoms improve.
• Pharmaceutic drug-drug interactions: (outside the body) It is a

physicochemical interaction that occurs when drugs are mixed with i.v. infusions causing
precipitation or inactivation of active principles before it is administered. For ex.-
precipitation of sodium thiopentone within an intravenous dose.
Pharmacokinetic drug-drug interactions : (altered concentration or
effect)
These interactions occur when one drug changes the systemic
concentration of another drug, altering how-much or how-long, it is
present at the site of action.
Pharmacodynamic drug-drug interactions
It occur when interacting drugs have either additive effects (overall effect
increased) or opposing effects (overall effect decreased or even cancelled
out).
PHARMACODYNAMIC INTERACTIONS
• When two drugs are used together, their effects can be additive (the result
is what you expect when you add together the effect of each drug taken
independently), synergistic (combining the drugs leads to a larger effect
than expected), or antagonistic (combining the drugs leads to a smaller
effect than expected). There is sometimes confusion on whether drugs are
synergistic or additive, since the individual effects of each drug may vary
from patient to patient. A synergistic interaction may be beneficial for
patients, but may also increase the risk of overdose.
Both synergy and antagonism can occur during different phases of the interaction
between a drug, and an organism.
For example, when synergy occurs at a cellular receptor level this is termed agonism,
and the substances involved are termed agonists.
On the other hand, in the case of antagonism, the substances involved are known as
inverse agonists. The different responses of a receptor to the action of a drug has
resulted in a number of classifications, such as "partial agonist", "competitive agonist"
etc. These concepts have fundamental applications in the pharmacodynamics of these
interactions
PHARMACOKINETIC INTERACTIONS
• Modifications in the effect of a drug are caused by differences

in the absorption, transport, distribution, metabolism or
excretion of one or both of the drugs compared with the
expected behavior of each drug when taken individually. These
changes are basically modifications in the concentration of the
drugs. In this respect, two drugs can be homergic if they have
the same effect in the organism and heterergic if their effects are
different.
Absorption interactions Some drugs, such as the prokinetic agents
increase the speed with which a substance passes through the intestines.
If a drug is present in the digestive tract's absorption zone for less time
its blood concentration will decrease. The opposite will occur with drugs
that decrease intestinal motility. The absorption of some drugs can be
drastically reduced if they are administered together with food with a
high fat content. This is the case for oral anticoagulants and avocado
Transport and distribution interactions The main interaction
mechanism is competition for plasma protein transport. In these cases
the drug that arrives first binds with the plasma protein, leaving the
other drug dissolved in the plasma, which modifies its concentration.
The organism has mechanisms to counteract these situations (by, for
example, increasing plasma clearance), which means that they are not
usually clinically relevant. However, these situations should be taken
into account if other associated problems are present such as when the
method of excretion is affected
Metabolism interactions: Many drug interactions are due to alterations in drug
metabolism. Further, human drug-metabolizing enzymes are typically activated through
the engagement of nuclear receptors. One notable system involved in metabolic drug
interactions is the enzyme system comprising the cytochrome P450 oxidases CYP450
Cytochrome P450 is a very large family of haemoproteins (hemoproteins) that are
characterized by their enzymatic activity and their role in the metabolism of a large
number of drugs. Of the various families that are present in human beings the most
interesting in this respect are the 1, 2 and 3, and the most important enzymes are
CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. The majority of the
enzymes are also involved in the metabolism of endogenous substances, such as steroids
or sex hormones, which is also important should there be interference with these
substances. As a result of these interactions the function of the enzymes can either be
stimulated (enzyme induction) or inhibited (enzyme inhibition)
Enzymatic inhibition If drug A is metabolized by a cytochrome P450 enzyme and
drug B inhibits or decreases the enzyme's activity, then drug A will remain with high
levels in the plasma for longer as its inactivation is slower. As a result, enzymatic
inhibition will cause an increase in the drug's effect. This can cause a wide range of
adverse reactions. Enzymatic induction If drug A is metabolized by a cytochrome
P450 enzyme and drug B induces or increases the enzyme's activity, then blood
plasma concentrations of drug A will quickly fall as its inactivation will take place
more rapidly. As a result, enzymatic induction will cause a decrease in the drug's
effect.
EXCRETION INTERACTIONS
• Renal excretion Only the free fraction of a drug that is dissolved in the blood plasma can be
removed through the kidney. Therefore, drugs that are tightly bound to proteins are not
available for renal excretion, as long as they are not metabolized when they may be eliminated
as metabolites. Creatinine clearance is used as a measure of kidney functioning but it is only
useful in cases where the drug is excreted in an unaltered form in the urine. The excretion of
drugs from the kidney's nephrons has the same properties as that of any other organic solute:
passive filtration, reabsorption and active secretion. In the latter phase the secretion of drugs is
an active process that is subject to conditions relating to the saturability of the transported
molecule and competition between substrates. Therefore, these are key sites where interactions
between drugs could occur.
Bile excretion is different from kidney excretion as it always involves
energy expenditure in active transport across the epithelium of the bile
duct against a concentration gradient. This transport system can also be
saturated if the plasma concentrations of the drug are high. Bile
excretion of drugs mainly takes place where their molecular weight is
greater than 300 and they contain both polar and lipophilic groups .
CONCLUSION
• It is possible to take advantage of positive drug interactions. However, the negative

interactions are usually of more interest because of their pathological significance, and also
because they are often unexpected, and may even go undiagnosed. By studying the
conditions that favor the appearance of interactions, it should be possible to prevent them,
or at least diagnose them in time.
• The factors or conditions that predispose the appearance of interactions include:
Old age Polypharmacy Genetic factors Hepatic or renal diseases Serious diseases
Drug dependent factors like Narrow therapeutic index, Steep doseresponse curve, Saturable
hepatic metabolism.

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DRUG INTERACTION

• There are many causes of drug interactions.

• Important types of drug interactions are:

• Behavioral drug-drug interaction: (altered compliance)

• Pharmaceutic drug-drug interactions: (outside the body) It is a

• Modifications in the effect of a drug are caused by differences

• It is possible to take advantage of positive drug interactions. However, the negative

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