The document discusses drug interactions, highlighting both their beneficial and harmful effects, including that they account for a significant portion of adverse drug reactions (ADRs) and are the fourth leading cause of death. It outlines the various types of drug interactions—pharmaceutical, pharmacokinetic, and pharmacodynamic—and elaborates on their mechanisms and contributing factors, including multiple drug therapies and patient compliance. Examples are provided to illustrate how these interactions can impact drug effectiveness and safety.

1. THE GOOD AND BAD SIDES OF
DRUG INTERACTIONS
PRESENTED BY
BERNARD BAHAAH (PG 4575315)
MPHIL BIOCHEMISTRY

2. Drug Interactions Intro.
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• More than 30 drugs are introduced each year leading to
new DIs (Ament et al., 2000)
• Meta-analysis of 39 prospective clinical trials has proved
ADRs are 4th most frequent cause of death (Lazaron et al.,
1998)
• Analysis of USA National Drug Register has proved that 2/3
of ADRs are drug interactions (Philips et al., 2001)
• Harmful drug-drug interactions cause 10-20% of ADRs
(Doran et al., 2012)

3. Introduction Cont.
• Drug Interactions takes into account the ff.
Pharmacological activity of a drug
Activity altered by concomitant use of another drug
Or some other substance
Sometimes good, sometimes bad
• Not all drug interactions are clinically significant or undesired,
and some are actively sought in pharmacotherapeutics to
increase drug effectiveness, decrease toxicity, or both
(Flockart,2007)
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4. Contributing Factors
• Multiple drug therapy
• Multiple prescribers
• Multiple pharmacological activity of a drug
• Multiple diseases/predisposing illness
• Poor patient compliance
• Advancing age of patients (www.pharmainfo.net)
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5. Mechanisms of Drug Interactions
1. Pharmaceutical Interactions
2. Pharmacokinetic Interactions
3. Pharmacodynamic Interactions
(www.pharmainfo.net)
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6. Pharmacodynamic Interactions
• PIs are interactions in
which the activity of the
object drug is altered at
the site of action by the
precipitant drug
• There are two types of
PIs
• Direct and Indirect PIs
• With Direct PIs, drugs with
similar or opposing
pharmacological effects
are used together
• This leads to antagonism,
Summation, Potentiation
or Synergism
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Flockart,2007
6

7. Drug Interactions Cont.
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Flockart,2007

8. E.gs. of Direct Pharmacodynamic
Interactions
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TYPE EXAMPLE
Antagonism Acetylcholine and
Noradrenaline have opposing
effects on heart rate
Summation CNS depressants like
sedatives and hypnotics
Synergism Alcohol enhances the
analgesics activity of aspirin

9. Indirect Pharmacodynamic Int.
• In Indirect PIs the drug affects a precursor
which then leads to the pharmacodynamic
interaction
• E.g. is Salicylates decrease ability of platelets
to aggregate thus impairing the homeostasis if
warfarin induced bleeding occurs (Horn, 2009)
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10. Pharmaceutical Interactions
• Physicochemical interactions that occur when drugs
are mixed in intravenous injections
• Leads to precipitation or inactivation of active
principles
• Examples are Ampicillin,Chlorpromazine and
Barbiturates interact with dextrans in solution
• They get broken down and forms turbid
solution,particles or may change colour (Becker,2011).
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11. Pharmaceutical Interactions
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Bercker,2011

12. Pharmacokinetic Interactions
• This type of drug interactions affects ADME
properties of a drug.
• It may lead to faster or slower drug activity
• Affects oral medications only
• Four key reactions occur as a result. They are
1. Absorption reactions
2. Distribution reactions
3. Metabolism reactions
4. Elimination/Excretion reactions (Berker,2011).
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13. Drug
absorption
Drug
excretion
Drug metabolism
(biotransformation)
CYP3A4, CYP2D6, CYP2C9…
Pharmacokinetic drug interactions
Drug
displacement
(protein-binding)
Transport of
the drug inside the
body

14. 5/2/2016 Bahaah Bernard 14
OBJECT DRUG PRECIPITANT DRUG INFLUENCE ON OBJECT DRUG
1. Complexation and
adsorption e.g.
Penicillamine
Antacids,foods and mineral
supplement containing
Al,Mg,Fe,Zn and Ca ions
Formation of poorly and
unabsorbable complexes with
these heavy metals
2. Alteration of GIT pH e.g.
Sulphonamides,Aspirin,Fe
-rroussulphate
Antacids Decreased dissolution and
hence decrease absorption.
Moves pH of drug to basic
zone.
3. Alteration of GIT motility
e.g. Levodopa,Lithium
Carbonate,Mexiletine
Anticholinergics Delayed gastric emptying,
Decreased rate of absorption
4. Alteration of GIT motility
e.g. Diazepam, Levodopa
Metoclopramide Rapid gastric emptying,
Increased rate of absorption
5. Alteration of GI microflora
e.g. Digoxin
Broad spectrum antibiotic Increased bioavailability due
to destruction of bacterial
flora that inactivates digoxin
in lower intestine
6. Malabsorption syndrome
e.g. Vit A,B12, Digoxin
Neomycin Inhibition of absorption due
to malabsorption
Table 3: Examples of Absorption reactions
Horn,2009

15. Distribution Reactions
• Distribution pattern of the object drug is altered.
• Major mechanism is alteration in protein binding
of the object drug.
• More protein binding drug displaces less protein-
binding drugs
• Also known as competitive displacement
interactions (Horn,2009).
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16. Table 4: Examples of Distribution Reactions
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DISPLACED DRUG DISPLACER EEFECT
1. Anti coagulant Phenylbutazone,Chloral
hydrate
Increased clotting
time,Increased risk of
hemorrhage
2. Tolbutamide Sulphonamides Increased hypoglycemic
effect
Horn,2009

17. Metabolism Reactions
• Metabolism of object drug is altered
• Leads to either enzyme induction or enzyme
inhibition
• Enzyme induction will increase rate of
metabolism whilst enzyme inhibition will
decrease rate of metabolism
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18. Table 5: Examples of Metabolism Reactions
OBJECT DRUG PRECIPITANT DRUG EFFECT
ENZYME INDUCTION
1. Corticosteroids,Oral
Contraceptives,
Coumarins, Phenytoin
2. Oral Contraceptives and
oral hypoglycaemics
Barbiturates
Rifamicin
Decrease plasma levels,
Decrease efficacy of object
drug.
Decrease efficacy of plasma
levels
ENZYME INHIBITION
1. Coumarins
2. Alcohol
Phenylbutazone,
Metronidazole
Disulphiram
Metronidazole
Increase anticoagulant
activity
Increase in plasma
acetaldehyde levels
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Horn,2009

19. Elimination/Excretion Reactions
• Normal elimination pattern of the drug in question is altered
• The key mechanisms are;
 Alteration in renal blood flow
 Alteration of urine pH(Ionisation of drugs and reabsorption)
 Competition for active secretion ( particularly in the kidney)
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20. Examples of Other Forms of Drug
Interactions
SUBSTANCE DRUG EFFECT/INFLUENCE
CAUSED
Smoking Diazepam,Olanzapine etc. Activity of drug
metabolizing enzymes
increased in the liver
leading to rapid
metabolism and
decreased effect
Alcohol Warfarin Effect and influence same
as smoking
Alcoholic beverages Sedative/Depressant Excessive depressant
response
Milk containing foods Tetracycline Absorption decreased
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21. REFERENCES• http://www.aafp.org/afp/2000/0315/p1745.html 1/29/2016 11:43 PM
• Flockhart DA. Drug interactions: cytochrome P450 drug interaction table Indiana University School
of Medicine, 2007. Available at: http://medicine.iupui.edu/clinpharm/ ddis/table.asp. Accessed
April 15, 2010.
• Horn JR. Important drug interactions and their mechanisms. In: Katzung BG, Masters SB, Trevor AJ,
eds. Basic and Clinical Pharmacology.11th ed. City, State: McGraw-Hill Companies Inc, 2009.
• Burke A, Smyth E, FitzGerald GA. Analgesic-antipyretic agents; pharmacotherapy of gout. In:
Brunton LL, Lazo
• JS, Parker KL, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New
York, NY: McGraw-Hill, 2006.
• Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects
of aspirin. N EnglJMed. 2001;345:1809^1817.
• MacDonald TM,Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet.
2003;361:573^574.
• Patrono C. Aspirin as an antiplatelet drug. N EnglJ Med. 1994;330:1287^1294.
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22. THANK YOU FOR
LISTENING
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