This document discusses therapeutic incompatibility, also known as drug interactions. It defines therapeutic incompatibility as a change in therapeutic response to one or more drugs that is unintended by the prescriber. The mechanisms of drug interactions are divided into pharmacokinetic and pharmacodynamic categories. Pharmacokinetic interactions involve changes in absorption, distribution, metabolism, or excretion of a drug due to another drug or substance. Pharmacodynamic interactions occur when drugs interact at receptor sites, resulting in synergism, antagonism, or additive effects. Several examples of each type of interaction are provided. Reasons for therapeutic incompatibility include prescription errors, improper storage, and patient noncompliance.

1. SHITAL TRIVEDI
ASSISTANT PROFESSOR,
Department of pharmaceutical technology,
L.J.INSTITUTE OF PHARMACY
Subject: Pharmaceutics
SEMESTER 1
Therapeutic Incompatibility

2. Therapeutic Incompatibility
• Definition:
• Change in therapeutic response or intensity of response of one
or more drugs that is unintended by the prescriber is called
therapeutic incompatibility. (It is also called drug interactions)

3. Mechanisms of therapeutic incompatibility
• Mechanism can be divided into two groups:
1. Pharmacokinetic interactions:
Change in absorption, distribution, metabolism and excretion of one
drug in presence of another drug/food/other factors.
2. Pharmacodynamic interactions:
These are related to the altered pharmacological activity of the
interacting drugs due to interactions at the receptor site.
Pharmacodynamic Interactions may result into
synergism(Potentiation), antagonism, or additive effect.

4. 1. Pharmacokinetic Interactions:
• Absorption:
• E.g. Altered GIT absorption of drug Tetracycline due to
formation of drug chelates or complexes with divalent ions like
calcium/magnesium present in milk or antacid preparations.
• Distribution:
• E.g. Warfarin-Anticoagulant, displaced by salicylates, increases
risk of haemorrhage due to increased clotting time.

5. Pharmacokinetics Interactions:
• Metabolism: Due to enzyme induction/enzyme inhibition
• E.g. Enzyme inhibition: Metronidazole increases anticoagulant
activity of Warfarin. Grape fruit juice enhances absorption of
drugs-increases risk of toxicity.
• Excretion:
• E.g. Penicillin compete with Probenecid for active tubular
secretion, increases plasma level of Probenecid and vice a
versa, increases risk of toxicity. Combination can be
advantageous as it involves dose reduction of Penicillin for
antibiotic treatment.

6. Pharmacodynamics Interactions:
• Synergistic effect:
• Effect of combined drugs is greater than the sum of the effect
of single-drug active components.
• (Potentiation)Type of synergistic effect): Effect of one drug
increases in the presence of the another drug.
• E.g. Alcohol enhances the analgesic activity of aspirin.
1 + 1 = 3

7. Antagonistic effect:
• Antagonistic effect:
• Effect of one drug is opposed by the effect of another drug.
• E. g β-adrenoceptor antagonists (e.g. Atenolol) diminish the
effectiveness of β-receptor agonists, such as salbutamol or
terbutaline.
• Acetylcholine and noradrenaline have opposing effects on
heart rate.
-1 + 1 = 0

8. Additive effect:
• Additive effect:
• The interacting drugs have similar actions and the resultant
effect is the sum of individual drug responses.
• E.g. CNS depressants like sedatives, hypnotics etc. (Diazepam+
Alprazolam)
1 + 1 = 2

9. Reasons/errors responsible for
therapeutic incompatibility:
Prescription writing
errors by doctors /
Prescription reading
error by Pharmacist
Improper Storage of drug
product

10. • Prescription errors by doctors:
• Poor handwriting. Missing information.
• Prescribing improper dose/frequency of administration.
• Prescribing wrong drug and dosage form.
• Prescribing look alike, sound alike drugs. ( Prednisolone is the
active metabolite of prednisone.) (Digoxin-eliminated via kidney &
Digitoxin-eliminated via liver)
• Inappropriate use of abbreviations.
• Inappropriate use of zeros and decimal points.
• Prescribing synergistic or antagonistic drugs.
• Prescribing drugs with wrong direction.
• Prescribing contraindicated drugs. E.g. Corticosteroids are
contraindicated in patients suffering from gastric ulcer.
Reasons/errors responsible for
therapeutic incompatibility:

11. Reasons/errors responsible for
therapeutic incompatibility:
• Patient noncompliance:
• Patient’s non adherence to prescribed drug regimen (drug
dose and dosage frequency).
• Improper storage of drug which may lead to drug degradation.

12. References:
• Text book of PHARMACEUTICS-II by Dr. A. K. Seth, PV books
page no. 71-73.
• Biopharmaceutics and Pharmacokinetics- A TRESTISE by D M
Brahmankar, Sunil B. Jaiswal, Published by M. K. Jain for
VALLABH PRAKASHAN, DELHI. Page no. 226-235.