Define Drug Interaction – Mechanism-Treatment-Causes-Uses

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Define Drug Interaction is a wide topic to study so in this post you can define drug interaction, mechanism of drug interaction its causes, treatment, and some examples. Define drug interaction has two Definitions which is given below;

Define Drug Interaction

Drug interaction can be defined as the effects of drugs altered by another drug or food that is prior or concurrent administration with it, then it is called as Drug-Drug or Drug-Food Interactions.


Define Drug Interaction (definition)

Define Drug Interaction can be defined as effect of one drug is changed or transformed by interaction with other drug or food and the drug therapeutic effect is changed is called as Drug interaction.


Causes of Drug interaction (define drug interaction)

1. Use of non-prescription drugs: – e.g. OTC drugs like aspirin, antacid, nasal decongestant etc. with prescribed drug can result into drug drug interaction.

2. Multiple pharmacological effects:-when 2 drugs are administered simultaneously it will affect some of same system.

3. Multiple physicians:-Treatment from physicians for different illness. E.g. patient taking anticholinergic for GIT disorder, and Neostigmine and Physostigmine for ophthalmic purpose.

4. Patient Non-compliance:-Many Patients do not adhere to the instructions of prescriber or pharmacists advices on prescribed drugs e.g. A diabetic patient is strictly advised to prevent alcoholic drinks/liquor to avoid further hypoglycaemic crises.

5. Drug abuse: Thinking of more consumption of drug will produce quick relief, can result into drug interaction.

Mechanisms of Drug interaction

Mechanisms of Drug interaction are classified as;

1. Pharmacokinetic Drug interaction

2. Pharmacodynamics Drug interaction

3. Miscellaneous Drug interaction

1. Pharmacokinetic Drug interaction

(I) One drug affect the ADME of another drug with resultant change in the plasma cone of another drug.

a. pH

Non-ionisable Drug (the more lipid soluble) and acidic drug (low pH) is readily absorbed. If antacid id administered with acidic drug, it will raise the pH of GI content and inhibit the absorption.

The enteric coated Bisacodyl (oral dosage form of laxative) should not be given with antacid or milk because increase in pH and cause disintegration of drug in stomach, Causing vomiting and irritation.

b. Complexation

Avoid tetracycline like fluoroquinolones (ciprofloxacin, and norfloxaxin) with metal ions Ca, Mg, Al, iron. To avoid complexation which are poorly absorbed.

c. .Adsorption

Anti-diarrhoea mixtures contain the adsorbent like kaolin which adsorb the other medications, if administer decreases the absorption of these drugs.

d. Change in GI motility

Drugs like cathartics increases GI motility resulting in a decreased absorption of drugs, whereas,

Anticholinergic drug decrease GI motility, increased absorption of drug.

Barbiturates reduce the absorption of other drugs — e.g. the absorption of warfarin is inhibited by Hepatobarbitone, and Griseofulvin by Phenobarbitone.

e. Food

The presence of Food in stomach reduces the absorption of Drugs by binding with it, or by changing the PH of GI contents it reduces the dissolution rate of drug.

Absorption of antibiotics in presence of food. Hence penicillin and Tetracycline Derivatives should be given 1 hour before meal or 2 hours after meal.

Some drug like Diazepam achieve higher serum level following food. Cimetidine needs slower absorption, hence it is advantageous to take it with meal.

f. Inhibition of GI Enzyme

Folic acid – phenytoin Interaction

Phenytoin inhibits the enzyme intestinal conjugate which is responsible for poorly absorbed form of folic acid i.e. polyglutamate into readily absorbed form of folic acid i.e. monoglutamate. This results into deficiency of Folic acid known as Anemia.

Examples: Polyglutamate and Monoglutamate.

(II). Interaction affecting Distribution of Drug

The drug gets distributed by binding to plasma proteins. Hence if 2 drugs are capable of binding to protein are administered, the interaction affects the distribution. The better affinity for binding sites will displace the other. Displacement increases the level of that drug in free or unbound state. Competitive binding may result in drug interaction when the drug which is displaces is at least 90% protein bound.


1. Phenyl butazone replaces tolbutamide from protein binding and enhances hypoglycaemic effect.

2. Phenyl butazone displaces the warfarin from its binding sites resulting in increased amount of free form of warfarin causing haemorrhage.

a. Distribution alteration

Displacement from Receptor binding Sites:

Displacement from Receptor binding site

Sr.noBound DrugsDisplacing DrugResult
1TolbutamideSalicylates PhenylbutazoneHypoglycemia
2WarfarinSalicylates ClofibrateHaemorrhage
3ThiopentoneSulphonamidesProlong anaesthesia

 Interaction affecting Metabolism of Drug

(i) Inhibition of metabolism

Isoniazid inhibits the hydroxylation of Diphenyl hydantoin and may cause toxicity of Diphenylhydantoin.

Cimetidine (histamine H2-antagonists) inhibits the metabolism Benzodiazepine and enhances sedative effect.

Erythromycin inhibits the hepatic metabolism of carbamazepine increasing its toxicity

(ii) Induction of metabolism /Stimulation of metabolism

Barbiturates stimulate the microsomal enzyme in liver and thus increases metabolic degradation of other drugs such as alcohol, coumarin, anticoagulants, phenytoin etc.

Drug and Inducing Agents

Sr.noDrugInducing agentsResult
Decreased hypoglycemia
Decreased anticoagulant effect
3Oral contraceptivesRifampicinPregnancy
Reduced Quinidine level

(iii) Interaction affecting Excretion of Drug:

One drug may block the renal excretion of another by competing for the same tubular transport system or may increase the excretion of drug by increase its ionization.

    1. Inhibition of excretion:-

Competition for tubular transport between concurrently administered drugs commonly interferes with urinary excretion this can block or lower the excretion of the competing drugs.

Probenecid Competes with penicillin in renal secretion and thus inhibit the excretion

Of penicillin.

Probenecid (uricosuric drug) also decreases the renal excretion of methotrexate (Anti-Rheumatic)

Quinine and verapamil both will increase the serum Digoxin level by inhibition of renal excretion and non-renal clearance of digoxin.

1IndomethacinProbenecidIndomethacin toxicity
2SalicylateProbenecidSalicylate toxicity
3PASProbenecidPAS toxicity
4DigoxinSpironolactoneIncreased plasma digoxin level

2. Increase in renal excretion:

Change in urinary pH: Non ionised drugs diffuse from urine, back into the blood. Whereas ionised form of drug is excreted easily. Thus any drug that will change urinary pH will alter the excretion of weak acid and weak base.

Thus acidic drug will be excreted in basic urine, when urine is acidic a large portion of drug will diffuse back into blood and produce prolonged action.

Drug Acidifier Excretion

Sr.noUrinary AcidifiersDrugs whose excretion is enhanced in acidic urine
1Ascorbic acid, PAS, Ammonium chloride, calcium chloride, Phenyl butazone.Amphetamine, Quinidine, Pethidine, Procainamide.

Drug Alkalinisers Excretion

Sr.noUrinary AlkalinisersDrugs whose excretion is enhanced in Alkaline urine
1Acetazolamide, Potassium citrate, sodium citrate, sodium bicarbonate..Salicylate, barbitone, phenobarbitone, streptomycin

 Pharmacodynamics drug interaction

This involves interaction between the drug or drug effects or interaction at receptor level, This may enhance or inhibit the total effect.

1. Interaction enhancing effect

In this type of interaction, excessive response to one drug is observed. e.g., Synergistic effect of Trimethoprim and sulphamethoxazole.

Alcohol and CNS depressants: Excessive CNS depression is observed in such interactions.

Interaction between anticholinergic drugs: If phenylpropanolamine and diphenhydramine is administered concomitantly (alongside, it results in excessive CNS depression and may produce dizziness.

2. Interaction inhibiting the effect

E.g. In this type of interaction, the drugs having opposing pharmacological effects interact and Produce suppression of effects of one drug.

Diuretics-antidiuretic agent interactions: Thiazide diuretics elevate blood sugar level. If such diuretics are combined with insulin or oral hypoglycaemic agents, the effects of ant diabetic agents is suppressed and dose adjustment is required.

Diuretics-allopurinol interaction: Diuretics produce hyper uremic effects (increased Serum level of uric acid. Allopurinol is a gout and it acts by inhibiting uric acid formation .if taken together allopurinol become ineffective and require dose adjustment.

Miscellaneous Drug interaction

Alteration of electrolyte levels: Drugs which causes alteration in fluid and electrolyte balance like captopril and enalapril cause elevated serum potassium. Potassium-sparing diuretics also causes elevated serum potassium. If both administer concomitantly serve hyperkalaemia may occur.


Thiazide cause excessive potassium loss (hypokalaemia). In such concomitant state the concomitant administration of digoxin results in increased sensitivity of heart and may lead to digoxin toxicity,

Interaction with additives: Additives like CMC, gelatine increases the viscosity around the drug particle hence decreasesdrug dissolution.

Drug interactions at receptor sites:

Drug interactions at same receptors, Drugs that act at the same receptor site if prescribed together, may produce additive effect or antagonize one anothere.g. respiratory depression and other central effects of morphine are antagonized by nalorphine.

Drug interactions at different receptors:

Drugs may interact on the same target organ but at different receptor sites. E.g. Adrenaline activates adenylcyclase system and cause an increase in cyclic 3-5 AMP (Adenosine Monophosphate which then acts as the mediator in a number of beta effects of adrenaline for relaxation of bronchial smooth muscles.

Theophylline produces the same effect, an increase in cyclic 3-5 AMP by inhibiting phosphor-di-esterase and also cause bronchial smooth muscles relaxation. Thus drugs that inhibit different enzymes may show synergistic effects.

Drug Food Interaction


Food affects the absorption of the drug. It may be attributed to

1) Dilution of the drug

2) Adsorption or complexation of drug

3) The alteration of gastric emptying.


1) Food reduces the absorption of aspirin, isoniazid, tetracycline, benzyl penicillin, amoxicillin, Ampicillin, levodopa and Rifampicin

2) Food increases the absorption of hydralazine, nitrofurantoin, lithium citrate, riboflavin, carbamazepine, metoprolol, propranolol, and spironolactone.

3) Iron absorption is reduced if food has been taken with in the previous two hours. On other hand, nausea is more likely if iron is taken on empty stomach so iron tablets are often given with food.

4) Nitro-furantoin is given with food to avoid GIT irritation

5) Metals containing high fat increases the absorption of fat soluble drug Griseofilvin. Fat containing drug increases degree of ionization of griseofulvin, so increases its absorption.

6) The diuretic effect of tea takes place rapidly if given before meals but diuresis is delayed if it is given after food.

7) The absorption of nitrazepam, glibenclamide, metronidazole, oxazepam, and theophylline is unchanged by food.

8) Monoamine oxidase MAO is an enzyme which breaks down catecholamines such as or epinephrine. When the enzyme is inhibited, there are increased levels of norepinephrine in adrenergic neuron. Thus MAO inhibitors are used as antihypertensive. Certain food like cheese, chocolate, alcoholic beverages, liver, yeast extract contain tyramine. Tyramine is metabolised by MAO. When the patient being treated with MAO inhibitors also take tyramine containing food, tyramine reaches the food systemic circulation causing severe hypertension.

9) Milk reduces absorption of tetracycline by forming an insoluble complex.

In vitro drug-drug interaction (Outside the body)

These types of interaction occurs when two or more drugs are mixed during I.V infusion. one drug may be inactivated before it enters the body.

E.g. Concurrent administration of heparin and tetracycline in infusion results in inactivation of tetracycline.

Alcohol with Disulfiram: Disulfiram inhibits the metabolism of alcohol which produces non-toxic end products with unpleasant reactions. (Flushing, fast heart beats, nausea, thirst, chest pain, vertigo, decreased blood pressure).

Drug dependence and drug abuse:

Repeat administration of drug causes habit and dependence. If habit forming drug is not made available to the patient then withdrawal symptoms occur. These symptoms are psychic disturbances like headache, restlessness, emotional upset, convulsions and vasomotor collapse.

1. Drug dependence

A state of psychic and also sometimes physical resulting in which the user has a compelling desire to continue taking the drug either to experience its effect or to avoid the discomfort of its absence.

2. Drug abuse

It is defined as the consumption of a drug apart from medical needs or in excess quantity or not for purpose of any drug to experience its pleasurable effects.

3. Drug Addiction

It is a state of chronic or periodic intoxication resulting from repeated consumption of drug.

The addicts continues taking drug for following reasons;

a. At first for its medicinal use.

b. To satisfy curiosity about the drug effect.

c. To have new thrilling or dangerous experience.

d. To relax from stress and strain.

 e. To escape from reality and have a dreamy state.

4. Drug Habituation

It is a state resulting from the repeated use of drug

5. Drug Tolerance

It is a condition in which a decreased therapeutic response of a drug related drug effect show by an individual.

Drug abuse

It is defined as the consumption of a drug apart from medical need or in excess quantity or not for medical purpose of any drug to experience its pleasurable effect.

Classification of Drug Abuse

The drugs are classified as under:

1. CNS depressants: Alcohol, Barbiturate, non-Barbiturates, sedatives and tranquilizers.

2. CNS stimulants: Amphetamine, Cocaine, Tobacco.

3. Narcotics: Heroin, morphine, opium, codeine, methadone.

4. Hallucinogens: Marihuana (cannabis), LSD, Mescaline, Phencyclidine.

5. Volatile inhalants: Benzene, Acetone, Petrol, Trichloroethyline.

Drug addiction vs Drug Habituation

Sr.noDrug AddictionDrug Habituation
1It is a state of chronic or periodic intoxication due to repeated consumption of drug.It is a state resulting from the repeated use of drug.
2A compulsion to continue taking the drug or overpowering desireA desire but not compulsion to continue taking the drug to improve a sense of well being.
3A tendency to increase a dose of druglittle or no tendency to increase a dose of drug.
4A psychic, particularly physical dependency shown by the individual on the effects of the drug Some degree of psychic dependence but absence of physical dependence.
5Withdrawal symptoms are observedwithdrawal symptoms are not observed.
E.g.Morphine, Heroin, Alcohol etc.Tea, coffee. etc.

Treatment to drug abuse

1. Detoxification: It refers the body from the adverse effects of the drug. It is done by stopping the drug and taking medical treatment for the various withdrawal symptoms. It usually takes 10-21 days and can be done on outpatient basis or by admitting the patient, depending upon the severity of the problem. Detoxification is followed by long term treatment as otherwise relapses are very common.

Psychological Drug Dependence Drug DependencePhysical Drug Dependence
1It is a state characterised by an emotional or mental desire to continue taking a drug.It is a state which shows itself by intense physical disturbance in case the drug is not administered.
2No compulsion to take the drugThere is compulsion to take the drug
3Withdrawal symptoms is not observedWithdrawal Symptom is observed
4No need of specific drug to treat withdrawal symptoms in case of any.Specific antagonist with supportive therapy is needed.
5E.g. Nicotine, caffeine.E.g. Opiate, Alcohol.

Substitution therapy

Substituted drug (pharmacologically equivalent) for the original drug is replaced in the treatment.

Specific antagonist is used for treatment e.g. for morphine abuse naloxone is used as antidote.

After the use of antidote vitamins are used.

Rehabilitation of the patient is a part of long treatment. Depending upon the patient need, after detoxification, psychotherapy, family therapy, and group therapy are used.

The public should be educated regarding adverse effect of the drugs. Certain high risk groups (students, unemployed youth, industrial labour, and migrant workers) need constant monitoring. Legal measures should support the medical aspects.


1. Alcohol:

A) Acute alcoholism: The enzyme alcohol dehydrogenase is responsible metabolism of alcohol. It metabolizes about 10mg pure ethanol per hour. The features of acute alcoholism depends on the blood level.

Blood level-Features

Sr.noBlood level mg/100mlFeatures
120Feeling of warmth and relaxation
230relief from anxiety
350Incordination, Euphoria, Speech mistakes
4100Ataxia (breathing problem)
5100-200Vomiting, Imbalance vertigo.
6300Stupor (impaired consciousness)
7400Respiratory depression, Coma.


The treatment is supportive to maintain the respiration, blood pressure and body temperature.

If intracranial pressure is increased, administer hypertonic mannitol solution I.V.

Phenothiazine is used to control psychotic behaviour.

Give artificial respiration and electrolytes for balance.

Chronic alcoholism: It results in development of tolerance and then physical dependence. The Withdrawal of alcohol results in tremor fits anxiety, insomnia, and confusion, G.I disturbance like chronic gastritis, peptic ulcers, hepatitis, cirrhosis, and pancreatitis.

The termination of alcohol can lead to fever, tremors, tachycardia, agitation, sweating, hallucination, and convulsions. It also results in myopathy, bone marrow suppression and gout.



Counselling and attention to social and behavioural factors, supportive social interaction.

Pharmacotherapy with antianxiety agent

Give Diazepam I.V 40 mg daily for 4 days, 30mg daily for 3 days. 20 mg daily for 2 days, 10 mg daily for 1 day.

Supplemented with haloperidol 2-4 mg every 4-6 hours

High dose of vitamin B complex, Chlormethiazole (sedative), anxiolytic and anticonvulsant, lorazepam, if there is hepatic dysfunction.


1. Alcoholism

Medical complications: Acute Hepatitis, Cirrhosis of liver, pancreatitis Gastritis, fatty liver chronic diarrhoea ,beri-beri ulcers, delirium, convulsive disorders ,hypoglycaemia.

Withdrawal symptoms– Hangover, delirium, anxiety, course termers, weakness, sweating, insomnia, headache, muscle twitching, tachycardia, hallucination, disorientation and seizures. G.I disturbances like chronic gastritis, pancreatitis. The termination of alcohol can lead to fever, tremors, tachycardia, and agitation. It is also results in myopathy, bone marrow suppression and gout.


1. Antidote treatment- use of disulfiram in a dose of 500mg daily.

2. For nutritional deficiencies- Vitamin B complex or thiamine injections are given.

3. Use of sedatives: Like chlordiazepoxide, diazepam and chloremethiozole.

Effective Medical Supportive therapy, like alcoholic anonymous and phychological counselling is effective.

4. Emetine or Apo morphine is given together with alcoholic drink to make the patient vomit.

5. Phenobarbitone is given to prevent tremors.

6. Behaviour therapy- It gives relaxation training, assertiveness training and self-control skills

   Lorazepam, if there is hepatic dysfunction.

2. BARBITURATES Taken Orally I.V or S.C

The chronic abuse of it results in drowsiness, ataxia (breathing problem), nystagmus (involuntary eye movement), reduce quality and quantity of work, increased appetite, impaired motor coordination, confusion, emotional instability and poor judgment

Withdrawal symptoms: anxiety, confusion, insomnia, anorexia, panic attack, hallucination and fits tremors to delirium (A temporary state of mental confusion and fluctuating consciousness).


1. Gradual withdrawal of the drug by decreasing the dose over a period of 3 weeks.

2. Psychotherapy

3. CNS stimulants Amphetamine I.V, orally or sniffed)

This drug is widely abused for their CNS stimulant by students, athletes, truck drives, executives. the dose of amphetamine is 5-1 5mg/day. It induces physical dependence. The acute administration of it results in excitement, euphoria, and little need for sleep, anorexia, psychotic schizophrenia like tachycardia arrhythmias, hypertension and fits.

Withdrawal symptoms:

Depression, fatigue, muscle pain hyperphagia hypersomnia, lethargy.

4. Cocaine

Cocaine The chronic use of it results in systemic effect.

1. CVS: Myocardial infarction arrhythmias

CNS: irritability, anxiety hallucinations, insomnia and visual disturbances

GIT: Nausea, weight loss, gangrene.

Urogenital – Difficulty in erection and delay in orgasm in both sexes.

Respiratory: perforation of nasal septum pulmonary oedema, rhinitis.


 Regular supportive therapy with tricyclic antidepressant and tranquilizers drugs. The vital function of cardiovascular and respiratory system should be monitored.


5. Narcotics

 Morphine, opium heroine, codeine and pethidine.

The abuse of it results in drowsy and relaxed feeling, restlessness and excitements pinpoint pupils malnutrition, vitamins deficiency thromboembolic complications constipation, hepatitis. Pulmonary oedema, cardiovascular respiratory collapse and coma.

Withdrawal symptoms

After 8 hours: Yawning, sweating, Anxiety, tearing, rhinorrhoea.

20hrs: chills sweating, panic

24-48 hours: Nausea and vomiting, diarrhoea, fever, hypertension

Up to 1 week: severe muscle cramps.

Up to several months: insomnia.

Treatment: The symptoms can be suppressed by substitution of another narcotic for opiate e.g. Methadone 30mg in divided doses for first 3days and then 10mg for 3 days

New Levo alpha acetylmethadol and narcotic antagonist Naltrexone (Texans) can also be used. Moral and social counselling is desirable in such condition.

6. Hallucinogens

Hallucinogens are a group of naturally occurring and synthetic compounds capable of

Producing distortion of reality, resulting in confusion, delirium, amnesia is a deficit in brain damage and loss of sense of direction space and time.

It is a state in which perception of matters with no reality or feeling with no external causes.

Cannabis: taken orally or smoked.

Product of cannabis sativa are available in 2 forms.

1. Hashish: Resin obtained from flowering top.

 2. Marihuana: Chopped leaves and stalks, the other products are charas, ganja, bhang.

The effects after one min are feeling of floating and increased sensitivity to external stimuli resulting perception of time, colour, music, and distance, social relaxation memory impairment for short term, Hallucination, in coordination, panic and delirium may recur after toxification. There may be confusion, disorientation and acute psychotic reactions. The major psychoactive ingredient in cannabis is delta-9- tetrahydrocannabinol (THC).

Treatment: – Manage the overdoses, the extreme agitation is best controlled by Antianxiety and tranquilizer diazepam.

LSD: – (Lysergic acid diethylamide): Most potent hallucinogens available in the form of tablet thin square of gelatine or impregnated paper Oral; dose is 25- 50 milligrams.

7. Volatile inhalants

Volatile liquids placed on a handkerchief and inhaled. The effects produced are CNS excitation, dizziness, auditory, or visual hallucination, tinnitus, blurred vision, slurred speech and staggering agit may develop. The larger the dose may result in unconsciousness, delirium, coma, cardiac arrest and death.

Treatment: Same like Barbiturates, Oxygen and other supportive treatment is required.

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