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International Journal of Research in Pharmaceutical Technology
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2016
International
Journal of Research
in Pharmaceutical
Technology
A REVIEW ON DRUG - DRUG INTERACTIONS AND ITS PREVENTION AND
MANAGEMENT
Rajesh Z. Mujoriya1*, Dharmendra R. Mundhada2, Ankit S. Kediya3
1
Agnihotri College of Pharmacy, Wardha, Maharashtra.
Agnihotri College of Pharmacy, Wardha, Maharashtra.
2,3
ARTICLE INFO
Keywords
Drug Interactions,
Pharmacokinetic,
Pharmacodynamic,
Physical Mechanisms,
Chemical Mechanisms,
Adverse Effects.
ABSTRACT
Drug interactions can occur through pharmacokinetic, pharmacodynamic, physical or
chemical mechanisms and may result in enhanced action, reduced drug efficacy, increased
incidence of adverse effects or misinterpretation of laboratory tests. In some clinical
situations the use of interacting drugs may be deliberate. Drug interactions can be complex,
especially if multiple interactions exist in an individual patient. The literature on drug
interactions is always changing as new information and new drugs become available. When
patients are prescribed drugs known to interact, they should be monitored appropriately and
counseled about signs and symptoms that should trigger a call to the health care provider.
Corresponding author
Rajesh Z. Mujoriya
Agnihotri College of Pharmacy,
Wardha, Maharashtra.
[email protected]
08275160840
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Copy right © 2016 This is an Open Access article distributed under the terms of the International Journal of Research in
Pharmaceutical Technology, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work
is properly cited.
1
Please cite this article in press as Rajesh Z. Mujoriya et al. A Review on Drug - Drug Interactions and its Prevention and
Management. International Journal of Research in Pharmaceutical Technology. 2016:01(02).
Rajesh Z. Mujoriya
Vol 1 (2)2016
INTRODUCTION
The action of one drug upon the effectiveness or toxicity of another (or others) is known as drug interactions. The
Pharmacological result, either desirable or undesirable, of drugs interacting with themselves or with other drugs, with endogenous
chemical agents, with components of the diet or with chemicals used in or resulting from diagnostic tests.
A chemical or physiological reaction that can occur when two different drugs are taken together cause drug interaction, drug
interaction is alteration of the effects of a drug by reaction with another drug or drugs, with foods or beverages, or with a pre-existing
medical condition.
The effect of drug has on a person may be different than expected because that drug interacts with another drug the person is
taking (drug-drug interaction), Food, beverages, or supplements the person is consuming (drug-nutrient interaction), Another disease
the person has (drug-disease interaction).
The effects of drug interactions are usually unwanted and sometimes harmful. Interactions may increase or decrease the
actions of one or more drugs, resulting in side effects or failed treatment.Drug interactions can occur through pharmacokinetic,
pharmacodynamic, physical or chemical mechanisms and may result in enhanced action, reduced drug efficacy, increased incidence of
adverse effects or misinterpretation of laboratory tests.Drug interactions can take various forms, occurring immediately or over several
weeks. Some drugs simply should not be used together, while others can be combined only if done with careful monitoring to detect
emergency problems. Interactions can also occur when one therapy alters the effect of another. This includes how the other is
absorbed in the body, broken down (metabolized), distributed or excreted.
TYPES OF DRUG INTERACTION
 Drug – Drug Interaction
 Drug – Nutrients Interaction
 Drug - Disease Interaction
DRUG-DRUG INTERACTIONS:
Drug-drug interactions can involve prescription or nonprescription (over-the-counter) drugs. Types of drug-drug interactions
include duplication, opposition (antagonism), and alteration of what the body does to one or both drugs.
●Duplication:
When two drugs with the same effect are taken, their side effects may be intensified. Duplication may occur when people
inadvertently take two drugs (often at least one is an over-the-counter drug) that have the same active ingredient. For example, people
may take a cold remedy and sleep aid, both of which contain diphenhydramine
●Opposition (Antagonism):
Two drugs with opposing actions can interact, thereby reducing the effectiveness of one or both. For example, nonsteroidal
anti-inflammatory drugs (NSAIDs), such as ibuprofen which are taken to relieve pain, may cause the body to retain salt and fluid.
●Alteration:
One drug may alter how the body absorbs, distributes, metabolizes, or excretes another drug.Acid-blocking drugs, such as
histamine-2 (H2) blockers and proton pump inhibitors, raise the pH of the stomach and decrease absorption of some drugs, such as
ketoconazole a drug for fungal infections.Many drugs are broken down and inactivated (metabolized) by certain enzymes in the liver.
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2
DRUG-NUTRIENT INTERACTIONS:
Nutrients include food, beverages (including alcohol), and dietary supplements. Consumption of these substances may alter
the effects of drugs the person takes.Like food, drugs taken by mouth must be absorbed through the lining of the stomach or the small
intestine. Consequently, the presence of food in the digestive tract may reduce absorption of a drug. Often, such interactions can be
avoided by taking the drug 1 hour before or 2 hours after eating.
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Vol 1 (2)2016
Table No.1 Some Drug-Food Interactions.
Some Drug-Food Interactions
● Anticoagulants
Foods high in vitamin K (such asSuch
foods
may reduce
the
effectiveness
of
broccoli, brussels sprouts, spinach, andanticoagulants
(such
as
warfarin)
kale)
increasing the risk of clotting. Intake of such foods should be
limited, and the amount consumed daily should remain
constant.
●Certain
benzodiazepinesGrapefruit juice
Grapefruit juice inhibits enzymes involved in drug
(such as triazolam)
metabolism and thereby intensifies the effect of certain drugs.
●Calcium channel blockers
(such
as
felodipine,
nifedipine, and nisoldipine)
●Estrogen
and
oral
contraceptives
●Certain statins (such as
atorvastatin, lovastatin, and
simvastatin)
●Digoxin
Oatmeal
The fiber in oatmeal and other cereals. consumed in large
amounts, can interfere with the absorption of digoxin
●MAO inhibitors
Foods high in tyramine, including
Severe headache and a potentially fatal increase in blood
(such asphenelzine
many cheeses (such as American
pressure (hypertensive crisis) can occur if people taking an
●and
tranylcypromineprocessed, cheddar, blue, brie,
MAO inhibitor (used most often to treat depression) consume
mozzarella, and Parmesan), yogurt, sourthese foods. These foods must be avoided.
cream, cured meats (such as sausage and
salami), liver, dried fish, caviar,
avocados, bananas, yeast extracts,
●Tetracycline
Calcium or foods containing calcium,These foods can reduce the absorption of tetracycline, which
such as milk and other dairy products. should be taken 1 hour before or 2 hours after eating.
DRUG-DISEASE INTERACTIONS:
Sometimes drugs that are helpful in one disease are harmful in another disorder. For example, some beta-blockers taken for
heart disease or high blood pressure can worsen asthma and make it hard for people with diabetes to tell when their blood sugar is too
low. Some drugs taken to treat a cold may worsen glaucoma.
COMMON DRUG PATHWAYS AND INTERACTIONS
Common prescription drug interactions in the treatment of diabetes, dyslipidemia, hypertension, and erectile dysfunction.
DRUG INTERACTIONS IN DIABETES
Pharmacokinetic drug interactions among medications used to treat diabetes are not very common because antidiabetic agents
are generally not substrates, inducers, or inhibitors of the major CYP450 enzymes. Repaglinide (Prandin) is an exception because it is
metabolized by CYP3A4 and is therefore a substrate; however, clinically significant drug interactions with repagli-nide are not
common.2 ,3 The more common clinically relevant drug interactions in the treatment of diabetes are drug-disease interactions.
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DRUG INTERACTIONS IN DYSLIPIDEMIA
Compared to medications used to treat diabetes or hypertension, drugs used to treat dyslipidemia are associated with more
clinically significant pharmacokinetic drug interactions. Also, drug interactions may be common in clinical practice because
atorvastatin (Lipitor), simvastatin, and pravastatin (Pravachol).5
3
●Metformin –
Since its approval in 1995, metformin has been widely prescribed to treat type 2 diabetes. Although it has many beneficial
effects, it is not the drug of choice for all patients because of the risk of lactic acidosis, which can occur with inappropriate use.
Metformin is absolutely contraindicated in patients with renal dysfunction (defined as a serum creatinine >1.5 mg/dl for males and
>1.4 mg/dl for females) and in those with congestive heart failure requiring pharmacological treatment. 4
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●Statins –
Atorvastatin, lovastatin, simvastatin, pravastatin, and fluvastatin (Lescol) are the currently available statins. Cerivastatin was
removed from the market because of its association with unusually high rates of rhabdomyolyis and death.
●Bile Acid Sequestrants –
Bile acid sequestrants (e.g., colestipol [Colestid] and cholestyramine [Questran]) are generally not used in the treatment of
hypercholesterolemia in patients with diabetes because they can raise TGs that may already be above target levels.
DRUG INTERACTIONS IN HYPERTENSION
As with dyslipidemia, the treatment of hypertension in patients with diabetes needs to be aggressive. Recom-mendations
from both the ADA1 and the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
suggest a goal blood pressure of <130/80–85 mmHg for patients with diabetes. At least 40–55% of patients will require more than one
medication to reach this goal 6. In clinical practice, we take advantage of pharmacodynamic drug interactions in the treatment of
hypertension to prescribe medications that will have additive effects to lower blood pressure.
DRUG INTERACTIONS IN ERECTILE DYSFUNCTION
Approximately 50% of men with diabetes have erectile dysfunction (ED). Since sildenafil (Viagra) became available in 1998,
it has become the drug of choice for most men with ED.
When sildenafil is combined with nitrates (e.g., isosorbide dinitrate, isosorbide mononitrate, and nitroglycerin) severe
hypotension and possible death may result. Therefore, concomitant use of nitrates and sildenafil is absolutely contraindicated. The
American College of Cardiology in collaboration with the American Heart Association published guidelines for sildenafil use in 1999.
Those guidelines emphasize that all men must be warned of the danger of taking sildenafil 24 hours before or after taking a nitrate
preparation.
MECHANISM OF DRUG INTERACTIONS
The administration of one drug (A) can alter the action of another (B) by one of two general mechanisms:
I. Modification of the pharmacological effect of B without altering its concentration in the tissue fluid (pharmacodynamic
interaction)
II. Alteration of the concentration of B that reaches its site of action (pharmacokinetic interaction).
1) For such interactions to be important clinically it is necessary that the therapeutic range of drug B is narrow (i.e. that a small
reduction in effect will lead to loss of efficacy and/or a small increase in effect will lead to toxicity).
2) For pharmacokinetic interactions to be clinically important it is also necessary that the dose-response curve of drug B is steep (so
that a small change in plasma concentration leads to a substantial change in effect).
3) For many drugs these conditions are not met: even quite large changes in plasma concentrations of relatively non-toxic drugs like
penicillin are unlikely to give rise to clinical problems because there is usually a comfortable safety margin between plasma
concentrations produced by usual doses and those resulting in either loss of efficacy or toxicity.
PHARMACODYNAMIC INTERACTION
Pharmacodynamic interaction can occur in many different ways. There are many mechanisms, and some examples of
practical importance are probably more useful than attempts at classification. Consider the following:
Adrenoceptor
-receptor agonists, such as salbutamol or terbutaline.
Many diuretics lower plasma potassium concentration, and thereby enhance some actions of digoxin and predispose to glycoside
toxicity.
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I) Absorption
Gastrointestinal absorption is slowed by drugs that inhibit gastric emptying, such as atropine, or accelerated by drugs (e.g.
metoclopramide) which hasten gastric emptying.
Alternatively, drug A may interact with drug B in the gut in such a way as to inhibit absorption of B, e.g.
A) Calcium (and also iron) forms an insoluble complex with tetracycline and retards its
Absorption.
B) Cholestyramine, a bile acid binding resin used to treat hypercholesterolaemia, binds several drugs (e.g. warfarin, digoxin)
preventing their absorption if administered simultaneously.
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PHARMACOKINETIC INTERACTION
All of the four major processes that determine the pharmacokinetic behaviour of a drug—absorption, distribution,
metabolism and excretion—can be affected by co-administration of other drugs. Some of the important mechanisms are given here,
with examples.
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Vol 1 (2)2016
II) Distribution
 Displacement of a drug from binding sites in plasma or tissues transiently increases the concentration of free (unbound) drug, but
this is followed by increased elimination so a new steady state results, in which total drug concentration in plasma is reduced but the
free drug concentration is similar to that before introduction of the second 'displacing' drug.
 There are several direct consequences of potential clinical importance:
1) Toxicity from the transient increase in concentration of free drug, before the new steady state is reached.
2) If dose is being adjusted according to measurements of total plasma concentration, it must be appreciated that the target therapeutic
concentration range will be altered by coadministration of a displacing drug.
3) When the displacing drug additionally reduces elimination of the first, so that not only is the free concentration increased acutely,
but also chronically at the new steady state, severe toxicity may ensue.
III) Metabolism
1) Enzyme induction
Over 200 drugs cause enzyme induction and thereby decrease the pharmacological activity of a range of other drugs.
Induction (stimulation) of cytochrome isozymes in the liver and small intestine can be caused by drugs such as barbiturates,
carbamazepine, glutethimide, phenytoin, primidone, rifampin, and troglitazone.
Enzyme inhibition
Drugs that may inhibit hepatic microsomal metabolism of other drugs include allopurinol, amiodarone, androgens, chloramphenicol,
cimetidine, ciprofloxacin, clarithromycin, cyclosporine, diltiazem, disulfiram, erythromycin, fluconazole, fluoxetine, fluvoxamine.
IV) Excretion
The main mechanisms by which one drug can affect the rate of renal excretion of another are: by inhibiting tubular secretion; by
altering urine flow and/or urine pH;
1) Inhibition of tubular secretion:
Probenecid inhibits penicillin secretion and thus prolongs its action. It also inhibits the excretion of other drugs, including
azidothymidine (AZT)
2) Alteration of urine flow and pH:
DYANAMICS OF DRUG INTERACTION
ALIMENTARY SYSTEM:A. HYPERACIDITY, REFLUX, ULCER.
(A) CIMETIDINE
CATEGORY:-H2 Receptor Antagonist Antiulcer.
ACTION: - Cimetidine competitively inhibits histamine at H2 receptors of the gastric parietal cells resulting in decreased gastric acid
secretion.
INTERACTION: - 1. Absorption reduced by antacids (avoid antacids) with in 1 hr. may potentiate anticoagulants, phenytoin,
theophylline benzodiazepines β blockers, lidocaine
1. Procainamide clearance is reduced.
2. Reduced absorption of ketoconozole and itraconazole.
(B) ESOMEPRAZOLE
CATEGORY: - Proton pump inhibitor.
ACTION: - Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+ ATPase
in the gastric parietal cells.
INTERACTION: - May interfere with the elimination of other drugs metabolized by cyp2c19. Changes in gastric pH can affect the
bio-availability of ketoconazole and iron salts. Clarithromycin and amozicillin may increase plasma level.
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(D) OMEPRAZOLE
CATEGORY: - Proton pump inhibitor.
ACTION:-Omeprazole suppresses gastric acid secretion by specific inhibition of enzyme H+/K+ ATPase this blocks the final and
common step in gastric acid secretion. Peptic activity is reduced and also suppresses H.Pylori.
INTERACTION:-Reduces absorption of atazanavir, indinavir, ketoconazole and itraconazole.
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(C) FEMOTIDINE
CATEGORY: - H2 receptor antagonist.
ACTION: - Femotidine competitively blocks histamine H2 receptors thus reducing basal, nocturnal and stimulated gastric acid
secretion.
INTERACTION: - Reduced absorption of femotidine with antacids hence antacids can be given separately after 2 hrs.
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(E) PANTOPRAZOLE
CATEGORY: - Proton pump inhibitor.
ACTION: - Pentoprazole inhibits H+/K+ ATPase pump function there by reducing gastric acid secretion.It also has a role in the
evadication of H.Pylori.
INTERACTION:-Decreased effect with cyp2c19 inducers.Decreased absorption of ketoconazole and itraconazole.
(F) RANITIDINE
CATEGORY: - H2 receptor antagonist.
ACTION: - Ranitidine blocks histamine H2 – receptors in the stomach and prevents histamine–mediated gastric acid secretion. It does
not affect pepsin secretion, pentagastrin- stimulated factor secretion or serum gastrin.
INTERACTION:-Antacids may interfere with absorption. Decreased effect of non depolarising muscle relaxants.
(G) SUCRALFATE
CATEGORY: - Cytoprotectant – Antiulcer.
ACTION: - Sucralfate protects GI lining against peptic acid, pepsin and bile salts by binding with positively- charged proteins in
exudated forming a viscous paste like adhesive substance thus forming a protective coating.
INTERACTION: - Reduced absorption of warfarin, flouroquinolones and sulpiride.
CARDIOVASCULAR SYSTEM
A. ANTIHYPERTENSIVE
(A) ATENOLOL
CATEGORY: Selective β1 receptor blockers, Antihypertensive
ACTION: Atenolol selectively blocks the β1 receptors and significantly reduces both maximal and submaximal exercise heart rates in
the dose related manner.
INTERACTION: Concomitant administration of indomethacin may reduce antihypertensive effect of atenolol disopyramide when
given in combination with atenolol depresses myocardial contractility and may precipitate cardiac failure.
(B) AMLODIPINE
CATEGORY: Calcium channel blockers, Antihypertensive.
ACTION: Amlodipine relaxes coronary vascular smooth mucle, produce coronary vasodilation.
INTERACTION: Increased metabolism with rifampin, potentiate effects of thiazide diuretic and ACE inhibitor.
(C) DILTIAZEM
CATEGORY: Calcium channel blockers, Antihypertensive
ACTION: Diltiazem relexes coronary vascular smooth muscle by inhibiting calcium ion from entering the slow channel.
INTERACTION: Increased serum theophylline level.Cimetidine may increase plasma concentration levels of diltiazem.
(D) ENALAPRIL
CATEGORY: - ACE inhibitor, Antihypertensive.
ACTION: - After de-esterification into the active enalaprilat, there is potent inhibition of ACE, reduced level of angeotensin-II and
reduced aldosterone levels.
INTERACTION: Diuretic potentiate hypotensive action, may increased lithium levels.other antihypertensive potentiate enalapril
action.
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B. ANTIARRHYTHMICS
(A) DISOPYRAMIDE
CATEGORY: - Antiarrthytmic
ACTION: It acts by decreasing myocardial excitability and conduction velocity.it lengthens the effective repractory period of the
atrium.
INTERACTION: Avoid other antiarrhythmics and other cardiac depressants including β blockers except in life threatening
arrhythmias.
6
(E) LOSARTAN
CATEGROY: Angiotensin II receptor antagonist, Antihypertensive
ACTION: It acts as antihypertensive by blocking the action of angiotensin II of renin angiotensin – aldosterone system.
INTRACTION: - NSAIDS decrease efficiency.cimetidine may increase the AUC of losartan by about 18%. Phenobarbital and other
enzyme inducers may decrease level of losartan; ketoconazole inhibits the conversion of losartan to its active metabolite.
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(B) VERAPAMIL
CATEGORY: Calcium channel blockers antiarrhythmic
ACTION: Verapamil inhibits entry of calcium ions into arterial smooth muscle cell as well as the mycocytes and conducting tissue.
INTERACTION: Phenobarbitone, rifampicin and phenytoin increase metabolism of verapamil.
C. DIURETICS
(A) CHLORTALIDONE
CATEGORY: Diuretic
ACTION: Chlortalidone is an oral long acting antihypertensive diuretic. It acts by enhancing the excretion of sodium and chloride
ions and water by interfering with the transport of sodium across the renal tubular epithelium.
ONSET: 2 hrs.
DURATION: 48-72 hrs.
INTERACTION: NSAIDS antagonize hypotensive effect.Suppresses action of oral anticoagulant due to reduced prothrombin
activity.
(B) HYDROCHLORTHIAZIDE
CATEGORY: Diuretic
ACTION: Hydrochlorthiazide inhibits the reabsorbtion of Na and Cl at the beginning of the distal convoluted tubule.
INTERACTION: Symptomatic hyponutraemia when combined with carbamazepine.potentiates hypotensive effect of α-blockers and
ACE inhibitors these also reduce diuretic induced hypokalaemia.
CENTRAL NERVOUS SYSTEM
A HYPNOTICS
(A) NITRAZEPAM
CATEGORY: Benzodiazepines, hypnotic.
ACTION: Nitrazepam is a benzodiazepine with a pronounced sleep inducing activity when taken at bed time
ONSET- 30-60 min
DURATION - 6-8 hrs.
INTERACTION: Antacid delay absorption.
(B) ZOPICLONE
CATEGORY: Non benzodiazepines, hypnotic
ACTION: Zopiclone is a cyclopyrrolone derivative with hypnotic and sedative action, it increases duration of sleep, reduces sleep
latency and decreases the number of nocturnal awakenings.
INTRACTION: Reduced effect with phenytoin and carbamazepine
B. ANTYPSYCHOTICS
(A) CHLORPROMAZINE
CATEGORY: Phenothiazine, Antipsychotic
ACTION: Chlorpromazine is a neuroleptic that acts by blocking the postsynaptic dopamine receptor in the meso limbic dopaminergic
system and inhibit the release of hypothalamic and hypophyseal hormones;
ONSET: 15 min. IM, 30-60 min.oral
INTERACTION: Potentiation of anticholinergic effect of antiparkinson agents and tricyclic antidepressants may lead to an
anticholinergic crisis. Reverses antihypertensive effect of guanethidine, methyldopa and clonidine.
(B) CLOZAPINE
CATEGORY: Dibenzodiazepin, antipsychotic.
ACTION: Clozapine has relatively weak dopamine receptor blocking activity at D1, D2, D3 and D5 but has high affinity for the D4
receptor.
INTERACTION: Reduced plasma concentrations with concomitant use of phenytoin may enhance the central effects of MAOIS.
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(C) HALOPERIDOL
CATEGORY: Butyrophenone, Antipsychotic.
ACTION: Haloperidol blocks postsynaptic dopamine D1 and D2 receptors in the mesolimbic system.
INTERACTION: Carbamazepine and rifampicin reduce plasma concentration.
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(D) OLANZAPINE
CATEGORY: Antipsychotic
ACTION: Olanzapine is a selective monoaminergic antagonist with high affinity binding to serotonin 5-HT, dopamine, muscarinic.
INTERACTION: Olanzapine may antagonize the effect of levodopa and dopamine agonists.carbamazepine may increase the
clearance of olanzapine.
C. ANXIOLYTICS, SEDATIVES
(A) ALPRAZOLAM
CATEGORY: Benzodizepine, Anxiolytic.
ACTION: Alprazolam has anxiolytic, muscle relaxant anti convulsant, anti depressant and sleep modifing effects.
INTERACTION: Potentiates action of alcohal and CNS depressants.Reduced concentration with cigarette smoking by 50%.
(B) BUSPIRONE
CATEGORY: Anxiolytic
ACTION: Buspirone exerts anxiolytic activity through high affinity for serotonin 5-HT1 and 5-HT2 receptor.
INTERACTION: Enhanced sedative effects with alcohoal or CNS depressants increases serum haloperidol.
(C) DIAZEPAM
CATEGORY: Benzodiazepine, Anxiolytic.
ACTION: Diazepam is a long acting benzodiazepine with anti convulsant anxiolytic, sedative, muscle relaxant and amnestic
properties. Enhancing the GABA inhibitory effects resulting in hyperpolarisation and stabilization.
INTERACTION: Altered clearance of phenytoin and levodopa.Cimetidine reduces clearance combination with Li may produce
hypothermia.
7.3. D. ANTIDEPRESSANTS:
(A) IMIPRAMINE
CATEGORY: Tricyclic anti depressant.
ACTION: Imipramine inhibits NA reuptake and to a lesser extent that of, serotonin.Reduces REM sleep with increase in stage 4
sleeps.
INTERACTION: Barbiturates reduce plasma levels therapy reducing antidepressant effect.
(B) AMITRIPTYLINE
CATEGORY: Tricyclic antidepressant
ACTION: Amitriptyline exerts its antidepressant action by blocking the neuronal reuptake of nor adrenaline and serotonine.
INTERACTION: Potentiates sedative effect of alcohol, antiparkinson agent and antipsychotic drug increase risk of anticholinergic
effects.
7.3.E. ANTICONVULSANTS
(A) CARBAMAZEPINE
CATEGORY: Anticonvulsant.
ACTION: Carbamazepine reduces polysynaptic responses and block post tetanic potentiation.
INTERACTION: Reduces tolerance to alcohol, shortens half-life of doxycycline antibiotic. Failure of oral contraceptives leading to
pregnancy when given along with carabamazepine.
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PREVENTION, ASSESSMENT AND MANAGEMENT OF DRUG INTERACTION
A drug interaction occurs “when administration of, or exposure to a substance modifies a patients response to a drug”. The
substance may be a drug or another factor such as blood products, enteral feeds, foodstuffs, chemicals, therapeutic devices or the
environment. Disease states may also interact with drug therapy, and drugs may influence the accuracy of some laboratory tests.
As a component of drug therapy monitoring and clinical review pharmacists seek to:
 Identify patients at risk of drug interactions and suggest suitable methods of management.
Ensure early recognition of drug interactions to prevent or minimize adverse sequel
8
(B) CLONAZEPAM
CATEGORY: Anticonvulsant.
ACTION: Clonazepam raises the threshold for propagation of seizure activity and prevents generalization of focal of local activity.
INTERACTION: Carbamazepine, Phenobabitone or Phenytoin may accelerate clonazepam metabolism.
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This is particularly important during:
A patient medication history interview
The first review of a new therapy or dosage form
The cessation of a drug/agent or dosage form
The pharmacist maintains an up-to-date knowledge of common and clinically significant drug interactions and to have
prompt access to up-to-date sources of information dealing with drug interactions e.g.; specialized texts, literature search facilities.
Factors to consider in the management of actual or potential drug interactions include:
Details of interacting agents
 Therapeutic monitoring details
 Possible other causes e.g.; disease state, renal impairment
The clinical significance of the drug interaction and the risk/benefit ratio associated with combination therapy is considered
when making recommendations regarding the management of an interaction.
Recommendations may include one or more of the following:
 Consideration of an alternative agent.
 Carefully monitoring the patient without therapy alteration.
 Adjustment of dose of interacting agent.
Once management strategy has been implemented, the outcome is closely monitored and plans recessed as necessary. In
instances where adverse consequences do occur, the pharmacist should advice regarding further managements.All suspected drug
interactions with adverse sequlaeare discussed with the medical staff and appropriately documented. This will include documentation
in the patient’s medical record as well as the following where appropriate;
 A report to ADRAC.
 Publication of details in pharmacy department/hospital publications.
 A report in the medical literature.
Where an interaction associated with adverse sequlae has been identified, the pharmacist informs the patient or patient’s
party, and the healthcare provider, so that a recurrence of the same interaction in the future can be prevented. These individuals should
be informed of situations where deliberate interactions are instituted.
The counseling role of the pharmacist is essential in the prevention of drug interactions, as it provides the opportunity to warn
the patient or patient’s party concerning the concurrent use of various drugs/agents that might adversely interact with drugs the patient
has already been prescribed.
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2. Tatro Ds: Drug Interaction Facts. St. Louis, Mo., Facts And Comparisons, 2000
3. Hansten Pd, Horn Jr: Drug Interactions Analysis And Management: A Clinical Perspective And Analysis Of Current
Developments. St. Louis, Mo., Facts And Comparisons, 2002
4. Horlen C, Malone R, Dennis B, Carey T: Frequency Of Inappropriate Metformin Prescriptions (Research Letter). Jama
287:2504–2505, 2002
5. Nissen D: Mosby’s Drug Consult. St. Louis, Mo., Elsevier Science, 2002
6. Grossman E, Messerli Fh, Goldbourt U: High Blood Pressure And Diabetes Mellitus: Are All Antihypertensive Drugs Created
Equal? Arch Intern Med 160:2447–2452, 2000
7. Drug Drug Interactions By Professor Ghada Hashem Department Of Pharmacology Faculty Of Medicine Cairo University 2005
8. Cmp Medica Private Limited “Cims Updated Prescribers Hand- Book “3rd Edition, Page No. 69-87.
9. Cmp Medica Private Limited “Cims Updated Prescribers Hand- Book “3rd Edition, Page No.98-107.
10. Cmp Medica Private Limited “Cims Updated Prescribers Hand- Book “3rd Edition, Page No.114-134.
11. Cmp Medica Private Limited “Cims Updated Prescribers Hand- Book “3rd Edition, Page No.157-159.
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13. Cmp Medica Private Limited “Cims Updated Prescribers Hand- Book “3rd Edition, Page No.250-270.
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CONCLUSION
Drug interactions are ubiquitous but only rarely result in major adverse repercussions for the patient. The most of drugs,
which were analyses to identify DDIs, do not produce clinical significant potential DDIs in patients with mild to moderate illness. The
most common prevalence of interactions involved Anti-hypertensive drugs 18.50%.
Hereby I had concluded interaction of all well known drugs of various bodily systems. My review may be helpful in
understanding the Drug-Drug interactions, Drug-nutrient interactions, Drug-Disease interactions and most fruitful is to understand the
management and prevention of all types of Drug-Interaction at one place as: - “A review on Drug interactions and its prevention and
management.”