DRUG INTERACTIONS

1. DRUG INTERACTIONS
Prepared by:
KRISHNA PRASAD DAHAL
PHARM D. (PU)
RPh. (Pb); RPh. (NEPAL)
CLINICAL PHARMACIST at G.N.S. SAGARMATHA ZONAL HOSPITAL
FACULTY MEMBER OF PHARMACOLOGY AND TOXICOLOGY
SAPTARISHI HEALTH SCIENCE COLLEGE
RAJBIRAJ, NEPAL

2. DRUG INTERACTION
• An interaction is said to occur when the effects of one drug are altered by the co-
administration of another drug, herbal medicines, food, drink or other
environmental chemical agent.
• The modification of effect of one drug (object drug) by the prior or concomitant
administration of another drug (precipitant drug) is drug reaction.
• Object drug: For each drug – drug interaction the object is defined as the
medication that has its therapeutic effect modified by the drug interaction
process.
• Precipitant drug: The precipitant drug is defined as the medication responsible
for the affecting the pharmacological action of the other drug (object drug).

3. • For e.g. metoclopramide + digoxin
When these drug are administered together metoclopramide is the
precipitant drug and digoxin is the object drug because metoclopramide is
the gastric motility promoter and absorption of digoxin is not proper in
presence of metoclopramide resulting in decreased activity of digoxin.
• Generally in drug interaction process, the net effect of the combination may be
manifested as an additive/enhanced effect or antagonism effect.
• Harmful drug-drug interaction are important to detect because as they are
responsible for 10-20% of ADRs and require hospitalization of patient.
Risk factors that precipitate to drug interaction
• Multiple drug therapy
• Multiple prescribers
• Multiple pharmacological effects of drugs.

4. • Multiple disease or predisposing illness
• Poor patient compliances
• Patient factor
a) age
b) renal and hepatic impairment
c) gender
d) obesity/malnutrition
• Drug related factor (narrow therapeutic index)

5. Types of drug interactions
The most important types of drug interaction are:
A) Drug-drug interaction.
B) Drug food interaction.
C) Drug lab interaction.
D) Drug gene interaction.
E) Drug herbal interaction.
A) Drug – drug interaction
Drug – drug interaction occurs when a drug interacts or interfere with another
drug.
It is the most common type of interactions seen.
This can alter the way one or both of the drug act in body and may can result in
unexpected side effects.

6. B) Drug food interaction
• A drug food interaction happens when the food you eat affects the
ingredients in a medicine you are taking so the medicine cannot work the way
it should.
• Many food that we take are commonly interacted with both OTC/prescribed
drug.
• Presence of food in the stomach may enhance or decrease the absorption of
drugs that we take.
• Common example of drug food interaction is when tetracycline is
administered with milk or food. Ca++ present in milk makes complex with
tetracycline and affect in absorption also presence of any other food decrease
the absorption of tetracycline.
• Other example is interaction with alcohol, when centrally acting drugs
(benzodiazepines, opioids, antipsychotics) are concomitantly administered
with alcohol then many ADRS such as ataxia, somnolence and respiratory
depression occurs.
• Excessive use of acetaminophen with alcohol can cause cirrhosis and liver
failure.

7. C) Drug lab interaction
• The interaction that affects the lab values after the administration of drug is
known as drug lab interaction.
• Many drugs are known to alter the concentration of substances in the body
such as serum potassium, calcium and creatinine level which could lead to
many ADRs (morbidity and mortality).
• E.g. Potassium sparing diuretics (spironolactone) increases the level of K+ in
the body and its concentration should be monitored thorough out the time of
medication.
D) Drug herbal interaction
• These type of interaction occurs with herbal medicines and conventional
drugs.
• These reactions occurs because herbal medicines often contains multiple
pharmacologically active ingredients while conventional drugs contain
typically one drug.
• E.g. St. John’s wart (herbal medicine) affects the clearance of drugs such
as digoxin (conventional drug) resulting in digoxin poisoning.

8. E) Drug disease interaction.
• Drug disease interaction occurs when a drug worsens an existing medical
conditions.
• Elderly patient are more susceptible to these kind of interactions because
they of have comorbidities or have multiple chronic disease and take multiple
medications.
• E.g. β blockers used during the Heart failure can worsen asthma by
obstructing bronchial tract.
• Quinidine a potent antimalarial drug can cause arrhythmia to the elderly
patient which can be seriously harmful.

9. Mechanism of drug interaction
• Drug interaction often involve more than one mechanisms and most common
type of mechanisms are given below:
A) Pharmacokinetics Interaction
B) Pharmacodynamics Interaction
A) Pharmacokinetics interaction
• Pharmacokinetic interactions are those that affect the process by which drugs
are absorbed, distributed, metabolized or excreted.
• Such interaction may result in a change in the drug concentration (either high
or low) at the site of action with subsequent toxicity or decreased efficacy.

10. • Pharmacokinetic interactions further divided into:
i) Drug absorption interaction
ii) Drug distribution interaction
iii) Drug metabolism interaction
iv) Drug excretion interaction
I) Drug absorption interaction
Following oral absorption, drugs are absorbed through the mucous membrane if
the GIT.
A reduction in absorption where a rapidly achieved high concentration is needed (e.g.
hypnotics or analgesics) may result in failure to achieve adequate effect.
A numerous factors can affect the rate and extent of absorption.
Some important factor are:
a) Effect of change in gastric pH.
b) Adsorption chelation and other complexing mechanisms.
c) Effects on gastro-intestinal motility.

11. II) Drug distribution interaction
After absorption drugs are rapidly distributed around the body by
circulation.
During the process of distribution drug interaction may occur principally as a result
of displacement from protein binding sites (albumin and globulin).
A drug displacement interaction is defined as the reduction in the extent of plasma
protein binding of one drug in presence of another drug, resulting in extent of
unbound fraction of the displaced drug.
Once displacement from plasma protein occurs, the concentration of the free drug
rises temporarily , but falls rapidly back to its previous steady state concentration
due to metabolism and distribution.
The short term rise in free drug concentration is generally of little clinical
significance but may need to be taken into account in Therapeutic Drug Monitoring
(TDM).

12. III) Drug metabolism interaction
It is the most clinically important interactions involving in the effect of one
drug in the metabolism of other drug.
Liver is the principle site for drug metabolism and kidney, lungs are partly involved.
Liver is the major site of CYP450 (microsomal enzymes) mediated metabolism and
partly enterocytes are also potentially important.
Some drugs has capacity to induce the enzyme activity and some has capacity to
inhibit the enzyme activity resulting in increasing and decrease in metabolism of
object drug respectively.
Enzyme induction usually results in a decreased pharmacological effect of the
object drug (exception is increased activity if the object drug has active metabolite)
whereas enzyme inhibition results in increased toxicity of the object drug.
Enzyme inhibition activity results in severe Adverse Drug Events (ADEs) resulting in
morbidities which is most challenging for the health care professionals.

13. IV) Drug excretion interactions
With exception of the Inhalers, most drugs are excreted either in the bile
juice or in the urine.
Blood entering in kidney is filtered through the glomerulus and pass through the
tubule where the metabolites are removed, secreted or reabsorbed.
Interaction occurs when the drug interfere with the kidney tubule fluid pH, active
transport system or blood flow to the kidney altering the excretion of the other
drugs.
For e.g. drugs that use same active transport system in the kidney tubules can
compete with one another for excretion. This competition between the drugs can
be used for therapeutic advantages.
The drugs which are excreted through bile are metabolized by the gut flora (gut
microbes) and are reabsorbed to the blood and prolong the stay of the drug within
the body.
If the gut flora are diminished by the presence of antibiotics, the drug are not
recycled and probable therapeutic activity is minimized.

14. B) Pharmacodynamics interactions
pharmacodynamics interaction are those where the effect of one drug are
changed by presence of another drug ate the site of action.
Pharmacodynamic interaction may be either Antagonistic interaction (warfarin and
vitamin K) of additive/synergistic interaction (warfarin and NSAIDs).
These interaction may result in both advantages and disadvantages.
Management of drug interactions
• By not combining two drugs which are resulting in potential interactions.
• If needed reducing the dose of one of the drug by half or one third as needed.
• Close monitoring of the patient while in medication periods.
• Avoiding of food which may interact with the administered drug.

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