This document discusses drug interactions, including definitions, types, mechanisms, high risk patients, and how to handle interactions. It notes the main types are drug-drug, herbal-drug, food-drug, and drink-drug interactions. Mechanisms include effects on absorption, distribution, metabolism, and excretion. Absorption can be affected by changes in pH, bacteria, insoluble complexes, or motility. Metabolism interactions involve enzyme induction or inhibition. The document provides examples of interactions and notes some drugs are more prone to interactions. It outlines approaches to preventing or managing interactions.

1. Drug Interactions
(Ph.Warda Al –Salmi - 22/4/2017)

2. Review
Definitions
Types
Mechanisms
High risk patients
How to handle an interaction?
Resources

3. Only one answer is possible per question.
Please select the answer that is most
appropriate

4. Question 1
• Which drug can increase the platelet inhibiting
effect of NSAIDs?
A. Erythromycin
B. Mirtazapine
C. Citalopram
D. Rifampicin
E. Fluconazole

5. Question 1
• Which drug can increase the platelet inhibiting
effect of NSAIDs?
A. Erythromycin
B. Mirtazapine
C. Citalopram
D. Rifampicin
E. Fluconazole

6. Question 2
• The antihypertensive effect of ACE inhibitors can be
specifically reduced by inhibition of renal
prostaglandin synthesis. Which of the following
drugs interacts in this process?
A. Low-dose ASA
B. Hydrochlorothiazide
C. Verapamil
D. Diclofenac
E. Morphine

7. Question 2
• The antihypertensive effect of ACE inhibitors can be
specifically reduced by inhibition of renal
prostaglandin synthesis. Which of the following
drugs interacts in this process?
A. Low-dose ASA
B. Hydrochlorothiazide
C. Verapamil
D. Diclofenac
E. Morphine

8. Question 3
• A patient who has been taken beta-blocker
metoprolol is treated with fluoxetine for
depression. What unwanted effect should be
expected?
A. Bradycardia
B. Skin bleedings
C. Increase in blood pressure
D. Anemia
E. Hyperglycemia

9. Question 3
• A patient who has been taken beta-blocker
metoprolol is treated with fluoxetine for
depression. What unwanted effect should be
expected?
A. Bradycardia
B. Skin bleedings
C. Increase in blood pressure
D. Anemia
E. Hyperglycemia

10. Question 4
• What effect should be expected in a patient taking
clopidogrel and omeprazole?
A. Omeprazole increases the side effects of clopidogrel
B. Increased risk of thrombotic-thrombocytopenic purpura
C. Omeprazole raises the plasma concentration of the active
clopidogrel metabolite
D. Reduction of the clopidogrel-mediated inhibition of
platelet aggregation
E. Clopidogrel inhibits the breakdown of omeprazole

11. Question 4
• What effect should be expected in a patient taking
clopidogrel and omeprazole simultaneously?
A. Omeprazole increases the side effects of clopidogrel
B. Increased risk of thrombotic-thrombocytopenic purpura
C. Omeprazole raises the plasma concentration of the active
clopidogrel metabolite
D. Reduction of the clopidogrel-mediated inhibition of
platelet aggregation
E. Clopidogrel inhibits the breakdown of omeprazole

12. Question 5
• The term “synergy” is used in pharmacodynamics to
describe mutual influencing of the effects of two
drugs. What does synergy mean?
A. Strengthening of effect
B. The effect can only be achieved by giving the drugs at
the same time
C. An effect that is at least more than the additive effect
of both drugs
D. Reduction of the side effects
E. (neutralization) of effects

13. Question 5
• The term “synergy” is used in pharmacodynamics to
describe mutual influencing of the effects of two
drugs. What does synergy mean?
A. strengthening of effect
B. The effect can only be achieved by giving the drugs
at the same time
C. An effect that is at least more than the additive effect
of both drugs
D. Reduction of the side effects
E. (neutralization) of effects

14. What is Drug interaction ?

15. How to define drug interaction?
• An interaction occur when pharmacokinetics
or pharmacodynamic of drug are changed.

16. What are the types of interaction?
• Drug-drug interaction
• Herbal-drug interaction
• Food-drug interaction
• Drink-drug interaction
• Pharmacogenetic interaction

17. What are the Mechanisms of drug
interaction?
• Absorption interaction Synergistic interaction
• Distribution interaction Antagonistic interaction
• Metabolism interaction
• Excretion interaction
Pharmacokinetics: Pharmacodynamic:

19. What's the important in Absorption
interaction?
Rate Amount

20. What are the Mechanisms of
Absorption interaction?
• Altered PH
• Altered bacteria flora
• Formation of insoluble complexes
• Altered GIT motility

21. Altered PH
• Some drugs are
absorbed from stomach
(acidic media),so when
this media became
neutral or alkaline ,this
will affect the
absorption of drug
• Antacid and ciprofloxacin

22. Altered bacteria flora
• Bacterial flora has marked role in
metabolization of some drugs
• Long term antibiotics may kill normal flora and
affect drug absorption
• Erythromycin and Digoxin

23. Formation of
insoluble
complexes
• Tetracycline and
quinoloes with
divalent and trivalent
e,q Ca, Al…….etc

24. Altered GIT motility
• Some drugs increase peristalsis and descrease
time of absorption and absorbed amount
prokinetic

25. What's the important factor in
Distribution?
Only drugs with low Vd will be affected
Volume
Distribution

26. 99% 90%

27. What's important in Metabolism interaction ?
(biotransformation)
Most drugs are chemically altered within liver to:
less toxic and less lipid soluble metabolites
Hepatic metabolism has two pathways:
• Phase 1 (modification)
• Phase 11 (conjugation)

29. Question?
• Why some drugs are aggressively interact with
most all types of interaction e.q: warfarin or
ciclosporine?
• Some drugs can be metabolized by more than
one CPY450 isoenzymes,

30. Metabolism cont
• Types of drug metabolism interaction
Enzyme induction
Enzyme inhibition

31. Types of drug metabolism interaction
• .
Enzyme inhibitionEnzyme induction
takes 2-3 daysslow (days -2 weeks)Onset
Fast to solveslow to solvesolve
Reduce the doseincrease the dose.overcome
Most commonLess commonFrequancy
decease drug metaboilsmIncrease drug metaboilsmEffect
increase its concentration in serumDecrease its concentration in serum
Ritonavir inhibit metabolism of
slidenafil by inhibiting CYP3A4
Grapefruit will enhance the
metabolism of Ciclosporine
Example

32. Execration
• Where dose most drug are execrated?
• Why some drugs are still in circulation for
longe time?
• Is the changing in urine PH will affect drug
serum level and execration?
• How frequent is execrations interaction
happen?

33. Excreation

34. Pharmacodynamics interaction
Synergistic interactions
Antagonist interactions

35. Synergistic interaction
• When two drugs have the same effect are
given together ,so the total effect will increase
It may be desired:
sulphamethoxazole and Trimethoprim (Septrin)
May be not desired
K-sparing drugs & (ACEIs)and K-supliment cause
(hyperkalaemia)

36. Antagonistic Interaction
When the effects of two drugs are opposite
Warfarin x Vitamin K

37. Herbal –drug interaction

38. Patients in high risk of drug
interactions
• Polypharmacy people (elder)
• Hepatic disorders
• Renal disorders
• Genetics factors

39. How to prevent all interaction?
Is the interaction
clinically
important
No
Yes
Using the dose space
will solve the
interaction
Yes
No
Using alternative will
solve the interaction?
Yes
No

40. If the previous solution doesn’t work?

41. If the previous solution doesn’t work?
Adjust drug dosage
Monitoring of drug level
Monitoring physiological
functions

42. Drug interaction Classification-
checker?
2000-2017 Multum Information Services, Inc
Highly clinically significant. Avoid combination: risk of the interaction
outweighs the benefit
Major
Moderately clinically significant, Usually avoid combinations: use it only
under special circumstances.
Moderate
Minimally clinically significant, minimize risk: assess risk and consider an
alternative drug, take steps to circumvent the interaction risk and or
institute a monitoring plan
Minor

43. Books for further reading

44. Resources
• Stockelys Drug interaction (9th edition)
• Online Drug interaction:
• http:/referance medscape.com/drug
interaction checker
• https://online .epocreates.com/u/1300M ulti
Checker ?CID=search-DDI
• http://www.drug.com/drug interactions html
• https://www.uptodate.com/contents