Drug interactions can occur through pharmacokinetic or pharmacodynamic mechanisms. Pharmacokinetic interactions involve effects on absorption, distribution, metabolism or excretion of drugs and can increase or decrease a drug's effects. Pharmacodynamic interactions involve drug actions at receptor sites and can cause additive, antagonistic or synergistic effects. It is important for clinicians to understand how drugs may interact and to monitor patients carefully when multiple medications are prescribed to avoid adverse reactions.

1. DRUG INTERACTIONS
Presented by
SWASTIK JYOTI PAL
M.Pharm 2nd
sem(Pharmaceutics)
Roll no.-01
Bengal School of Technology
Hooghly
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2. Definition
 A drug interaction is defined as a measurable
( modification in magnitude or duration) of the action of
one drug by prior or concomitant administration of
another substance (including prescription and non
prescription drugs,food or alcohol)
 Interactions can occur by pharmacokinetic or
pharmacodynamic mechanisms
 The drug whose activity is affected by such interaction
is called the OBJECT DRUG.
 An agent which precipitates such interaction is referred
to as the PRECIPITANT.
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3. Effects of drug interactions
 These can be desirable, adverse or
inconsequential.
 Quantitative result- increased or decreased effect
 Seldom qualitative result- rapid or slower effect
 Precipitation of newer or increased adverse
effect.
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4. 4
Types and effects-

5. 5 Drug interactions include-
Drug drug interaction (eg-aspirin +warfarin
synergism i.e excessive bleeding)
Food drug interaction(eg-acetaminophen+alcohol
liver damage )
Chemical drug interaction
Drug laboratory interaction
Drug disease interaction(eg-nasal
decongestants+high blood pressure increased
heart rate)

6. Drug interaction mechanisms
 Mechanisms of drug interactions-
pharmacokinetic and pharmacodynamic.
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Pharmacokinetic interactions-
1.Chemical interactions
2.Interactions affecting oral availability
3.Protein binding interactions.
4.Interactions due to altered biotransformation
5.Interactions due to altered renal excretion.

8. Chemical Interactions
 Drugs can react physically or chemically with each other
before they are administered to the patient or in case of oral
preparations before they are absorbed.
 Mixing of drugs before parenteral administration may cause
interaction and thereby and significantly decrease the
activity of one or both drugs.
 Chemical interactions are very unlikely to occur once drugs
reach systmic circulation because the concentrations in
plasma are low.
 Example-oral tetracycline chelates the cations
calcium,magnesium,aluminium or iron resulting in a cation-
tetracycline complex that cannot be absorbed
 Also cholestyramine and colestipol bind some anionic drugs
and decrease their absorption.
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9. Interactions affecting oral
availability
This can be divided into interactions
affecting -
1.gastric emptying
2.drug absorption
3.presystemic elimination.
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10. a.Gastric emptying
 Gastric emptying-rate of gastric emptying is important
when a rapid onset of effect of the drug is desired. Eg in
rapid relief from pain or onset of sedation is needed and
parenteral drug administration is not possible.
 Slowed gastric emptying occurs in;
 Food, recumbency ,autonomic neuropathy,heavy exercise,
drugs eg antacids, anticholinergic drugs and narcotics
 Enhanced gastric emptying occurs in ;
 Drug administration eg metoclopramide,cisapride,
domperidone.
 This results in earlier and higher peak concentrations of
the index drug.
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11. b.Drug absorption
 Most drugs are absorbed in the small intestine by
passive diffusion
 Some drugs eg oral neomycin,antineoplastic
drugs can damage the intestinal absorptive
surface and potentially result in decreased
absorption of other drugs ( especially those in
which drug absorption is incomplete)
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12. c.Presytemic elimination
 Drugs have the capacity to be absorbed, metabolised or extracted
during transit across the intestinal epithelium into the portal
circulation and during the first pass through the liver.This is
phenomenon is called presystemic elimination or First pass effect
effect.
 Drugs subject to significant presystemic elimination and
consequently low bioavailability include propranolol,
metoprolol,
chlopromazine,labetalol,amitriptyline,imipramine,felodipine and
morphine.
 These drugs can compete with each hence increasing each others
bioavailability eg chlopromazine and propranolol.
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13. Protein binding interactions.
 Drugs that are highly bound in plasma are potentially subject to
displacement from their carrier proteins by another drug with
affinity for the same protein.
 When another highly bound drug is added,competitive
displacement may occur,resulting in a transient increase in free
concentration of the index drug.
 This is then followed by rapid redistribution of the index
drug,transient increase in the rate of elimination creating anew
equilibrium for both drugs
 This displacement is only likely to cause a clinically significant
effect if the index drug has a small volume of
distribution,narrow therapeutic index and rapid onset of action.
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14. Interactions due to altered
biotransformation
 Drug metabolism most often occurs in the liver and involves
the conversion of an active non polar drug to more polar
metabolites(- generally less active or inactive) that are cleared
by the kidneys.
 CYP450 family is the major metabolizing enzyme in phase I
(oxidation process).
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15. 1.Interactions involving enzyme
inhibition
 Many drugs have the potential to inhibit the metabolism of other drugs
 The magnitude of inhibition effect in an individual is variable because it
depends on the specific enzyme or enzymes inhibited and the
quantitative importance of that pathway in overall clearance of the index
drug.
 example;-isoniazid is a potent inhibitor of the microsomal oxidation of
both carbamazepine and acetaminophen.
 With acetaminophen,conjugative metabolic pathways (type 2)
predominate,resulting in a clinically insignificant 15% decrease in total
plasma clearance of acetaminophen.
 With carbamazepine,oxidative metabolic pathways (Type 1) predominate
and isoniazid inhibits total plasma clearance by 45%.This results in and
increase in steady state serum concentration of 85% and a significant risk
of toxic effects.
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16. 2.Interactions involving enzyme
induction
 The microsomal enzyme systems in the liver and
other tissues can be induced several fold by many
drugs and chemicals.
 Enzyme induction occurs by a number of different
mechanisms,but generally leads to increased amounts
of the enzyme and consequently, an increase in the
highest rate (Vmax) of the biotransformation reaction.
 Example;Administration of isoniazid may increase
the risk of acetaminophen induced hepatotoxicity by
increasing theformation of the toxic metabolite of
acetaminophen.
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17. Interactions due to altered renal
excretion
 Elimination interactions can occur when drugs interfere with
Blood flow to the kidney,active tubular secretion and kidney
tubular fluid Ph.
 In Active Renal tubular secretion,drugs that use the same active
transport system in the kidney can compete with one another for
excretion.
 Example; Probenecid given to increase plasma penicillin levels
by delaying excretion.
 Only the non ionized drug is lipid soluble and able to diffuse
back.At alkaline Ph, weak acids exist in the ionized state and
will be excreted.Renal clearance is increased if the urine is more
alkaline.Also at acidic Ph, weak bases will be excreted.
 Urine acidification causes increased amphetamine excretion in
amphetamine poisoning;
 Urine alkalinization causes increased salicylate excretion in
salicylate poisoning
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18. Pharmacodynamic Interactions
 In pharmacodynamic interactions, the effects of one drug are
changed by the 2nd
drug at its site of action.
 Can involve competition for specific sites but can also be
indirect and involve interferance with physiological systems.
 Example
1.Synergisticinteractions:1+1>2(Eg-
antidepresants,antiepileptics,antihistamines when given
together lead to excessive drowsiness)
2.Antagonistic interactions: 1-1=0(Eg- alpha adrenergic agonists
eg metaraminol may be used in management of priapism
induced by alpha adrenergic antagonists eg phentolamine.)
3.Additive interactions :1+1=2
4.Potentiation interactions :1+0=2
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Important drug drug interactions

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The consequences of drug interactions may be:
1.Major: Life threatening.
2.Moderate: Deteriotion of patients status.
3.Minor: Little effect.
Consequences of drug
interactions

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1.Identify the patients risk factors.
2.Take through drug history.
3.Be knowledge about the actions of the drugs
being used.
4.Consider therapeutic alternatives.
5Avoid complex therapeutic regiments when
possible.
6.Educate the patient.
7.Monitor therapy.
REDUSING THE RISK OF DRUG
INTERACTIONS:

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Conclusion
The nature of drug interaction is complex and not an
exact science due to interplay of multiple mechanisms
that require the prescribers care in choosing or changing
medication when necessary;adjusting the dose,time and
sequence of administration as required.It is desirable to
understand the basic pharmacology of drugs so as to
avoid any kind of possible drug interactions.Thus the
clinicians must understand the basic manner in which
these interactions occur and try their best to prevent
them.

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References
1. Biopharmaceutics and Pharmacokinetics –
Brahmankar D.M, Jaiswal S.B , 3rd
edition,vallabh prakashan, page-227-236
2. Essentials of medical pharmacology –Tripathi
K.D ,6th
edition,jaypee publication,page 889-895
3. Basic and clinical pharmacology- Katzung
B.G,Masters S.B, Trevor A.J,12th
edition,Mc
Graw Hill publication,Page 1149-1160