drug interactions

1. DRUG INTERACTIONS
Dr. K.Vinay Kumar
Assistant Professor
Department of Pharmacology
RVM Institute of Medical Sciences & Research
Center

2. DRUG INTERACTIONS:LEARNING
OBJECTIVES
1. Definition of Drug interactions
2. Types of Drug interactions
3. Pharmacokinetic Interactions with examples
4. Pharmacodynamic Interactions with examples
5. Food drug interaction with examples.
6. Drug disease interactions
7. Selection of drug to avoid drug interactions.
8. Management of drug interactions

3. DRUG INTERACTION DEFINITION
 When two drugs are administered simultaneously
or quick succession they causes the modification
of response of one drug is called drug
interactions.
DRUG
A
DRUGB
OBJECT
DRUG
PRECIPITANT
DRUG

4. DRUG
DRUG FOOD
LABORATORY
DISEASE
Quantitative Qualitative
Increase Decrease Abnormal Different type
of response
TYPES OF DRUG INTERACTION

5.  They are several mechanism that can involved to
cause drug interaction

6. Regular Medications During Likely To Be Involved
In Drug Interactions.
Antidiabetic drugs Oral contraceptives
Antihypertensive drugs Antiasthmatic drugs
Antianginal drugs Antipeptic ulcer drugs
Antiarthritic drugs Corticosteroids
Antiepileptic drugs Antitubercular drugs
Antiparkinsonian drugs Anti-HIV drugs.

7. DOES DRUG INTERACTIONS ARE SEEN IN
ALL THE PATIENTS TAKING SAME DRUG
Patients Factors Drug Specific Factors
Genetics Dose
Gender Route of administration
Concurrent disease Drug formulation
Diet Sequence of drug
administration.
YES NO

8. WHAT IS THE MAIN CAUSES OF DRUG
INTERACTIONS
1. Due multiple drug therapy
2. Due to multiple prescriptions
3. Due to multiple pharmacological effect of drugs
4. Due to Multiple diseases
5. Poor patients compliance
6. Advancing age of the patients

9. PHARMACOKINETIC DRUG-INTERACTION
Drug A (orally administered) + Drug B (orally
administered)  Drug A interfere with Absorption
of drug B  due to insolubility and poorly
absorbed complex in the gut lumen
Example: Tetracycline's, Calcium/Iron, Salts,
Antacids or Sucralfate. Such interactions can be
minimized by administering the two drugs with a
gap of 2-3 hrs.

10. DRUG INTERACTION AT ABSORPTION.
1. Complexation and absorption
2. Alternation in GIT pH.
3. Alternation in gut motility
4. Alternation of GI microflora

11. 1. ALTERNATION IN GIT PH.
Drugs are absorbed from stomach (acidic media),
so when this media become neutral or alkaline,
this will affect the absorption of drug
Example
Ketoconazole +H2 blockers + PPIs
 Ketoconazole absorption is reduced by H2
blockers and PPIs because they decreases gastric
acidity which promotes dissolution and
absorption of ketoconazole.

12. 2. ALTERNATION OF GI MICROFLORA
Antibiotics (Ampicillin + Tetracycline +
Clotrimazole) + Oral Contraceptive.
Were antibiotics reduces the gut flora, gut flora is
required to normalize the deconjugation of oral
contraceptive pills (in bile as glucuronides)
Contraceptive failure.

13. 3. ALTERNATION IN GUT MOTILITY
 Accelerated gastric emptying increases drug
absorption
 Atropine and Opiates delay gastric emptying
 Metaclopramide induces gastric emptying.
 Example: Digoxin and Riboflavin, increased
gastrointestinal motility is associated with a
decrease in the rate of absorption.

14. ..TOXICITY FROM TRANSIENT
INCREASE IN FREE DRUG
CONCENTRATION
DRUG INTERACTION AT DISTRIBUTION OF
DRUGS – Displacement interactions

15.  Significant displacement
interaction is seen with
tissue binding site
drugs such drugs will
not under goes
metabolism or excretion.

16. Quinidine + Digoxin
Quinidine Decreases
tissue plasma protein
binding of Digoxin
Quinidine competitively
inhibit P – glycoprotein
transport
Reduces distribution of
Digoxin
Reduces renal and biliary
excretion of Digoxin
Inc plasma conc. of Digoxin (2 folds)
Digoxin Toxicity

17. CYP450
Drug A
Increase
Drug
B effect
Inhibit
Drug B
effect
DRUG INTERACTION AT
METABOLISM OF
DRUGS

18. EXAMPLES OF MICROSOMAL INDUCERS
AND INHIBITORS

19. Examples : 01 – Enzyme Inhibitors
Statins + Fibrates, Niacin, Erythromycin, Azole and
HIV Protease.
Inhibits the metabolism of statins.
Induced myopathy of statins .

20. MICROSOMAL ENZYME INDUCTION
 Drug that increases the activity of microsomal
enzymes and increases the metabolism of several
drugs is called microsomal enzyme induction
(gene mediated increase synthesis of CYP450).
 1 – 2 weeks  produce maximal effects.
 1 – 3 weeks  regresses gradually after
discontinuation of inducer.

21. Rifampin induces CYP-2C-9 & CYP-2C-19 which
metabolizes phenytoin
Decrease plasma levels of phenytoin
Therapeutic failure
Poor control of Seizures
RIFAMPIN + PHENYTOIN

22. DRUG INTERACTION AT EXCRETION OF
DRUGS.
 Drug interaction takes place in excretion mostly
by inhibiting tubular transport mechanism.
 Weak acidic drugs like penicillin's,
phenobarbitone, Acetazolamide, nitrofurantoin,
will get eliminated in alkaline medium.
 Basic drugs like Chloroquine will get eliminated
with acidic urine.

23. EXAMPLE 01: PENICILLIN + PROBENECID
Probenecid and penicillin both excrete by renal
tubular secretion
Both competes with each other for excretion
Probenecid inhibits excretion of penicillin
Probenecid prolongs the half-life of penicillin,
allowing single dose therapy

24. Example 02 : -
 Aspirin + Probenecid  Aspirin blocks the
uricosuric action of probenecid.
Example 03 : -
 Aspirin + Methotrexate  Aspirin decreases
tubular secretion of Methotrexate.

25. PHARMACODYNAMIC DRUG-INTERACTION
 Modification of one drug at the target site by
another drug.
1. Pharmacological antagonism
2. Interfere with neuronal uptake or
neurotransmitter release.
3. Additive or summative action
4. Changes in ionic balance.

26. COMPETITIVE VS NON COMPETITVE
ANTAGONISM
Warfarin – Vitamin K Diazepam - Bicuulline

27. ALCOHOL & METRONIDAZOLE
Alcohol
Dehydrogenase
Aldehyde
Dehydrogenase
Metronidazole
X
Ethanol Acetaldehyde Acetate
Interaction of Metronidazole & alcohol it leads to
accumulation of Acetaldehyde which results in
“Disulfiram like reaction”— Abdominal distress,
nausea, vomiting, flushing, headache, tachycardia,
hyperventilation.

28. AMPICILLIN & TETRACYCLINE
 Ampicillin (Penicillin's) usually more effective
against rapidly multiplying bacteria as being a
cell-wall synthesis inhibitor.
 Tetracycline (protein
synthesis inhibitor) is
Bacteriostatic  inhibits
multiplication
Tetracycline Antagonize the effect of Ampicillin

29. SYNERGISM
DIAZEPAM
PROMETHAZINE
/ALCOHOL/
OPIOD
SEDATION;
RESPIRATORY
DEPRESSION
ANTIPLATEL
ETS
ANTICOAGUL
ANTS
EXCESSIVE
BLEEDING

30. LEVODOPA + CARBIDOPA
 Carbidopa is peripheral dopa-decarboxylase
inhibitor which inhibit peripheral conversion of
levodopa in Dopamine.
Levodopa
X
Increased levels of levodopa in brain 
increase efficacy Decrease peripheral side effects
Dopamine
Dopa-decarboxylase
Carbidopa

31. DRUG INTERACTION WITH DIAGNOSTIC
TESTS
Nalidixic acid, Salicylates and Vitamin C
Provides false positive test of urine sugar in
Benedicts solution

32. FOOD -DRUG INTERACTION
 Food effects the rate and extend of absorption of
drug from GIT
Herbal Metabolic ‘s Drugs
Avocado Enzymatic
inductor
Warfarin
Soya
Enzymatic
inhibition
Clozapine, haloperidol,
Olanzapine, caffeine,
NSAIDs, phenytoin, za
firlukast, warfarin

33. Example
Statins (treatment for high cholesterol) + Grape
juice.
.
decreases the
absorption of
statins
Increases the risk
of liver or kidney
damage
Rhabdomyolysis
(skeletal muscle breaks
down, releasing a protein
called myoglobin into the
blood)
Kidney damage

34. DRUG DISEASE INTERACTIONS
The use of a drug alters or worsens a condition or
disease.
Example : Metformin in kidney disease patients
In kidney disease patients use metformin in low
dose if not, not to continue.
Because metformin get accumulated in kidney
causing for other kidney damage

35. SELECTION OF DRUG TO AVOID DI
 The drug compound in combination should be
selected in such a way that it should not cause any
side effects and it should be complemented.
Example :- Antibiotics is used along with an
analgesic to treat an painful infectious condition.
 In some cases multiple drugs are used to treat a
patients suffering from two or more diseases at
same time. Examples :– Patients suffering from
hypertension and diabetes

36.  In such cases adverse drug interaction may seen
in later situation, because of some other drugs
may be administered to patients depending on
his/her disease/symptoms.

37. MANAGEMENT OF DRUG INTERACTIONS
1. Identify the patients risk factors.
2. Take history of the patients
3. Be knowledge about the action of the drug being
used.
4. Patient must be monitored if the drug is
prescribed for the first time
5. If the interaction is potentially serious , seek for
alternative drugs.

38. 4. High risk drugs must be checked for probable
drug interactions.
5. Drug interactions must be predicted while
prescribing the drugs.
6. Interaction can occur with OCT drugs which the
patients might not tell about.
7. Educate the patients.
8. Monitoring of drugs should be done.

39.  The elderly are at great risk of drug interaction
because of polypharmacy, age related impairment
of metabolism and excretion.
 Complementary and alternative medicine (
dietary supplements, herbal or homeopathic
medicines) as well as recreational drugs,
including alcohol, tobacco should be kept in mind
which considering drug interactions.