Drug interactions occur when one drug alters the effect of another, potentially leading to adverse or beneficial outcomes. Factors influencing these interactions include the type of drugs, patient-related variables such as age and health status, and the manner in which drugs are administered. Understanding drug interactions is crucial for clinicians to avoid serious side effects and enhance therapeutic efficacy, particularly in patients with multiple prescriptions.

1. Drug Interaction

2. Introduction:
 Drug interaction refers to the process of alteration in effect of one drug
that occurs after co-administration of the another drug.
 It is an adverse or seldom a beneficial drug response produced.
 The effects of drugs may be modified by food, smoking, alcohol or
environmental pollutants.
The components of a drug interaction are:
 Precipitant drug:The drug which causes the interaction .
 Object drug:The drug which is affected by the interaction.

3. Causes of Drug Interactions (DIS)
 Improper knowledge of health care practitioner
 Inappropriate dose; high, low and both
 Polypharmacy
 Use of non prescriptive medicine
 Drug abuse
 Patient non-compliance
 Multiple prescriber.
 Multiple pharmacological effects.
 Individual variation of patients: Age, Genetic factor, Sex, Disease state,
Renal function, Hepatic functions,Alcohol consumption, Smoking,
Diet, Environment factor, Individual variation etc.

4. Factors affecting drug interaction
Drug related factor
 Narrow therapeutic index
 Drug formulation (presence of interacting excipients)
 Drugs chemical and physiochemical properties
 Drug potency
 Duration of therapy
 Drug dosage
 Drug concentration in blood and tissue
 Timing and sequence of administration of interacting drug
 Route of administration
 Rate and extent of drug metabolism
 Degree of protein binding of interacting drugs
 Volume of distribution of affected drug

5. Patient-Related Factors
 Body weight and size
 Quantity and activity of specific drug-metabolizing enzymes
 Inherent inter- and intraindividual variability in pharmacokinetics and
pharmacological response
 Age
 Gender
 Race
 Habit; Tobacco andAlcohol use
 Diet
 Underlying disease states and their severity
 Malfunction and disease of organs of drug elimination (eg,
liver,kidney)
 Polypharmacy

6.  Classification of DIs
A. Consequence wise
1. Beneficial drug interactions
 Frequency and severity of the object drug related side effects is
decreased, while the therapeutic effect is enhanced by the co-
administration
 Aspirin + Acetaminophen
 This combination is used for more antipyretic effect.
 (Levodopa + Carbidopa) Carbidopa is used along with levodopa to
minimize the systemic effect of levodo and to increase the anti
parkinsonian action.
 Co-trimoxazole (Sulfamethoxazole +Trimethoprim)
 This combination is used because microbes resistant to one can be
susceptible to the combination

7.  Antihypertensives:
 Beta-blockers and diuretics are given in combination, as they are more
effective when in combination.
 Antitubercular drug therapy:
 Combination therapy has proved to be much effective and is treating
tuberculosis.
 Isoniazid + Ethambutol + Rifampicin + Pyrazinamide Local Anesthetics
 Minerals
 Iron is given in combination withVitamin C since it increases the
absorption of Iron
 Antidotes
 These are given for antagonizing the drugs in over dosage/toxicity cases.

8. 2.Adverse drug interactions
Undesirable, unwanted and harmful alteration in the effect of
one drug by the presence of another drug, food, drink or
chemical agent

9. B) Site wise
1. In-vitro drug interactions
 These interactions occur during formulation and mixing of drug and
usually termed as incompatibilities.
I. Physical Interaction
 When two or more different chemicals/drugs are mixed, their physical
state or color may be changed, changes may occur to all the
constituents mixed together or of one component mixed.
 E.g. Heparin and Protamine when mixed together, such kind of
interactions are observed.
II. Chemical interaction
 During mixing of two or more chemicals/drugs produce altered
product due to chemical reaction among them.
 E.g. Dopamine and Sodium bicarbonate, Furosemide andAscorbic acid
are mixed together, such kind of interactions are observed.

10. 2. In-vivo drug interactions
Pharmacokinetic drug interactions
I. Drug interaction due to absorption
a.Adsorption, Chelation and other Complexing mechanisms
 Tetracycline andAntacids,Ca+ion forming insoluble complexes, chelates
that can't be absorbed from the mucosal layer of GIT.
 Some adsorbents may also cause the reduction in the absorption of drugs
e.g. Kaolin, Charcoal,Anion exchange resins.
b. Change in Gl- pH
 Weakly acidic drugs are best absorbed at low pH e.g. Salicylates.
 Antacids, Proton-pump inhibitors, H, blockers affect the absorption of
other drugs.

11. c.Alteration in gastric motility
 Opiates (Morphine, Codiene, Pethidine) reduce gastric motility thus
decrease absorption of another drug by decreasing gastric emptying
 Metocloperamide increases gastric emptying thus increase absorption of
another drug
d.Alteration in normal flora of GIT
 10% Digoxin is inactivated by gut bacteria. Introduction of broad-
spectrum antibiotics decrease the gut bacteria, hence increasing the
levels of Digoxin

12. II. Drug interaction due to distribution
a. Drug displacement/Protein binding interaction
 Reduction in the extent of plasma protein binding of one drug caused
by the presence of another drug, resulting in an increased free or
unbound fraction of the displaced drug
 If a patient taking Phenytoin is given another drug that displaces it from
its binding sites, free or unbound drug increases.
b. Receptor binding
 Binding sites are significant in interactions
 e.g. Quinidine displaces Digoxin from binding sites in skeletal muscle
increasing serum concentration of Digoxin

13. III. Drug interaction due to Metabolism
 The concurrent administration of more than one drug may lead to an
alteration in metabolic rates.
Enzyme Induction
 Certain drugs induce enzyme systems causing more metabolism of drug
 Approximately 400 drugs and chemicals are enzyme inducers in animals
and humans. Phenobarbital, Phenytoin, Carbamazepine, Rifampicin are
enzyme inducers of clinical significance
Enzyme Inhibition
 Certain drugs inhibit enzyme system causing less metabolism of drug,
This likely results in increased serum concentration of the object drug
and if the drug has narrow therapeutic index, the toxicity occurs very
soon
 Ciprofloxacin and Norfloxacin inhibit CYP1A2 and ha been reported to
increase plasmaTheophyllin levels.

14. IV. Drug interaction due to Elimination
 Most drugs are eliminated either through the bile or through urine.
 Interactions occur when drugs interfere with kidney pH, active
transport mechanism or blood flow.
Changes in urinary pH
 A change in glomerular filtration rate (GFR), tubular secretion,
reabsorption, urinary pH etc can alter elimination of the same drug.
 Urine alkalization and acidification is used as a mean of increasing the
elimination of drug in the poisoning with Salicylates &Amphetamine
Changes in active renal tubular excretion
 Competition at the same active transport system in tubules may occur
with certain drugs
 Methotrexate toxicity is seen in patients concurrently treated with
NSAIDs due to this process

15. II. Pharmacodynamic drug interactions
 In this process one drug induces a change in patient's response
towards drug without altering the object drug's pharmacokinetics, are
known as pharmacodynamic drug interactions.
Types of pharmacodynamic drug interactions
I.Additive reactions (A+A= 2A)
 If the effect of one drug doubles, on co-administering the similar dose
of another drug, it is said to be showing additive effect.
 Two drugs with similar pharmacological effects when given together,
the effect may be additive
II. Synergestic reactions (A+A=>2A)
 If the effect of one drug becomes more than double, on co-
administering the similar dose of another drug, it is said to be showing
synergistic effect.

16. III.Antagonistic reactions (A + A =<A)
 If the effect of one drug becomes less than the effect of the single
drug, on co administering the similar dose of another drug,
 Agonist and antagonist competition for the same receptor site
 antagonists may be used to reverse the effect of another drug at the
receptor site e.g. Opioid vs. Naloxone, Benzodiazepine vs. Flumezinil
IV. Indirect pharmacodynamic interactions
 There are many indirect pharmacodynamic interactions of potential
clinical significance.
 Eg. MAOIS and SSRIS, MAOIS andTCAS are responsible for
serotonin syndrome. It is caused by excessive serotonin activity in
CNS which causes confusion, fever, shivering, ataxia, diarrhea,

19. Clinical Significance of DIs
 Drugs that have small therapeutic index so that relatively small
quantitative changes at the target site, will lead to substantial changes in
effect, eg lithium
 Drugs that are exhibit saturable metabolism when small interference with
kinetics may lead to large alteration of plasma concentration, eg phenytoin
 Drugs that are used long-term, where precise plasma concentrations are
required, egantiepilepsy drugs, lithium
 When drugs that may interact are used to treat the same disease, for this
increases their chance of being given concurrently, e.g. theophylline and
salbutamol given for asthma may cause cardiac arrhythmia
 In patients with significantly impaired liver or kidney function, for these
are the principal organs that terminate drug action
 In the elderly, for they tend to have multiple pathology, may receive several
drugs concurrently, and are specially susceptible to adverse drug effects