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Drug induced diseases

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International Journal of Pharmaceutical Research and Development

International Journal of Pharmaceutical Research and Development

www.pharmaceuticaljournal.net
Online ISSN: 2664-6870; Print ISSN: 2664-6862
Received: 02-07-2019; Accepted: 03-08-2019
Volume 1; Issue 2; July 2019; Page No. 06-09

Drug induced diseases

Mahewashsana A Pathan1*, Mahesh D Londhe2, Dayanand R Jadhav3
1-3
Department of Pharmaceutics, SSJP R.P. College of Pharmacy, Osmanabad, Maharashtra, India

Abstract
The Indian pharmaceutical industry is valued at Rs. 90000 crore and is growing at a rate of 12-14% annually. Exports are growing at a
rate of 25% compound annual growth rate. The total exports of Pharma products is to extent of Rs. 40000 crore. India has also
emerged as a hub for the clinical trials and drug discovery and development. Further more and more drug entities are being introduced
which includes new chemical entities, Pharma products, vaccines, dosage forms, and new routes of administration and new therapeutic
claims of existing drug moieties. The safe use of medicines is perhaps the single most important criteria that any regulatory authority
within a given country has to ensure in order to protect the public health and the integrity of its health care system. Drug induced
disease is defined as the unintended effect of a drug that results in mortality or morbidity with symptoms sufficient to prompt a patient
to seek medical attention and/or to require hospitalization and may persist even after the offending drug has been withdrawn. Drug
induced diseases also called as iatrogenic diseases, are well known but least studied entity. In this review, we have collected the
information from review and research articles related to the drug induced diseases. This review is intended to aid the understanding of
some basic concepts regarding the drug induced diseases. This tends to provide information about the some commonly occurring drug
induced disorders, the drugs responsible for inducing disorders, their prevention and some of the treatments.

Keywords: drug induced diseases, adverse effect, unintended drug reactions

Introduction
A drug-induced disease is an unintended effect of a drug, which prevent clotting of blood can cause bleeding as a side effect.
results in mortality or morbidity with symptoms sufficient to Several anti-diabetes medications like insulin and sulfonylureas
prompt a patient to seek medical attention and/or require can cause low blood glucose levels.
hospitalization. Drug-induced disease can result from Unpredictable: On the other hand, unpredictable effects are
unanticipated or anticipated drug effects [1]. Public and completely unrelated to the therapeutic effect of the drug. For
professional concern about drug induced diseases first arose in example, amiodarone, a drug used to treat abnormal heart
the late 19th. In 1922; there was an enquiry into the jaundice rhythms, can cause lung damage. Depending on their severity,
associated with the use of SALVARSAN, an organic arsenical drug-induced diseases may be classified as mild, moderate,
used in the treatment of Syphilis. In 1937 in the USA, 107 severe, or lethal if they cause death [2]. Drug-induced diseases
people died from taking an elixir of sulfanilamide that contained can affect various organ systems of the body. Several drugs
the solvent diethylene glycol. This led to the establishment of have been banned because of their ability to cause serious
the Food and Drug Administration (FDA), which was given the diseases. here are some examples listed below according to the
task of enquiring into the safety of new drugs before allowing organ system affected [2].
them to be marketed. The major modern catastrophe that Cardiovascular system: Cardio-toxicity is not restricted to
changed professional and public opinion towards medicines was anticancer agents, and almost all therapeutic drug classes have
the thalidomide tragedy. The thalidomide incident led to a unanticipated cardio-toxicities. However, cardiotoxicity induced
public outcry, to the institution all round the world of drug by chronically administered drugs, such as
regulatory authorities, to the development of a much more neurologic/psychiatric agents and anticancer chemotherapeutic
sophisticated approach to the preclinical testing and clinical agents, represents a major problem because toxicity may
evaluation of drugs before marketing, and to a greatly increased become evident only after long-term accumulation of the drug
awareness of adverse effect of drugs and methods of detecting or its metabolites. Drug-induced cardiotoxicity, commonly in
them. With the adverse reactions some drugs have been the form of cardiac muscle dysfunction that may progress to
withdrawn from use or for some the label has been changed. [1] heart failure, represents a major adverse effect of some common
traditional Antineoplastic agents, e.g., anthracyclines,
2. Types cyclophosphamide, 5 fluorouracil, taxanes, as well as newer
Diseases caused by drugs or drug induced diseases can be either agents such as biological monoclonal antibodies, e.g.,
predictable or unpredictable. trastuzumab, bevacizumab, and nivolumab; tyrosine kinase
Predictable: Predictable effects are an extension of the normal inhibitors, e.g., sunitinib and nilotinib; antiretroviral drugs, e.g.,
pharmacological effects of the drug. For example, blood zidovudine; antidiabetics, e.g., rosiglitazone; as well as some
thinners (anticoagulant and anti-platelet drugs) that are used to illicit drugs such as alcohol, cocaine, methamphetamine,

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International Journal of Pharmaceutical Research and Development

ecstasy, and synthetic cannabinoids. Most of the affected eruptions; hypersensitivity syndrome; Stevens-Johnson
patients had no prior manifestation of the disease [3]. syndrome (SJS) and toxic epidermal necrolysis (TEN);
Skin: Drug-induced skin disorders are often classified as either warfarin-induced skin necrosis; vasculitis; serum sickness–like
acute or chronic. Acute diseases include erythematous reaction; acute generalized exanthematous pustulosis (AGEP);
eruptions; urticaria, angioedema, and anaphylaxis; fixed-drug and photosensitivity. Chronic disorders include drug-induced
lupus, drug-induced acne, and pigmentary changes [4].

Table 1: Types of drug induced skin disorders

Type Common causative agent
Acute
Erythomatous eruptions penicillins, cephalosporins, sulfonamides, anticonvulsants, and allopurinol
Urticaria, angioedema NSAIDs, antimicrobials, anticancer drugs, ACE inhibitors, corticosteroids.
Fixed-Drug Eruptions Tetracyclines, barbiturates, sulfonamides, codeine, Carbamazepine, acetaminophen, NSAIDs
Drug Hypersensitivity Syndrome Allopurinol, sulfonamides, anticonvulsants, Phenytoin
SJS and TEN Antibacterial sulfonamides, anticonvulsants, nevirapine
Warfarin-Induced Skin Necrosis Warfarin
Serum Sickness–Like Reactions Cefaclor, minocycline, penicillin
AGEP Aminopenicillin, macrolides, quinolones
Photosensitivity Quinolones, Amiodarone, psoralens, Antineoplastic agents
Chronic
Drug-Induced Lupus (DIL): Procainamide, hydralazine, quinidine, Isoniazid, chlorpromazine,
Drug-Induced Acne (Acneiform Eruption) TNF inhibitors. Corticosteroids, androgenic hormones, anticonvulsants
Drug-Induced Pigmentary Changes Minocycline, antimalarials, oral contraceptives, imipramine, anticancer drugs.

Neurological conditions: The term neurologic side effect is wide variety of symptoms, including loss of coordination and
commonly used to describe a new drug-induced neurologic muscle strength, numbness, loss of consciousness, seizures, and
syndrome and/or disorder. Changes in the central nervous paralysis (Table 2) [5].
system (brain, spinal cord) or peripheral nerves can cause a

Table 2: Drug induced neurological conditions

Lung: The manifestations of drug-induced pulmonary diseases serious reactions, often requiring intervention. Apnea may be
span the entire spectrum of pathophysiologic conditions of the induced by central nervous system depression or respiratory
respiratory tract. As with most drug-induced diseases, the neuromuscular blockade. Although the benzodiazepines are
pathological changes are nonspecific. Therefore, the diagnosis is touted as causing less respiratory depression than barbiturates,
often difficult and, in most cases, is based on exclusion of all they may produce a profound additive or synergistic effect when
other possible causes. Adverse pulmonary reactions are taken in combination with other respiratory depressants.
uncommon in the general population but are among the most Combining IV diazepam with phenobarbital to stop seizures in

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International Journal of Pharmaceutical Research and Development

an emergency department frequently results in admissions to an blockers [ARBs], NSAID, cyclo- sporine, and tacrolimus).
intensive care unit for a short period of assisted mechanical Certain drugs such as ampicillin, ciprofloxacin, sulfon- amides,
ventilation, regardless of the drug administration rate. Too rapid acyclovir, ganciclovir, methotrexate and triam- terene are
IV administration of any of the benzodiazepines, even without associated with crystal nephropathy. Statins and alcohol may
coadministration of other respiratory depressants, will result in induce rhabdomyolysis because of a toxic effect on myocyte
apnea. Epidemiologic studies demonstrate an increase in the function. Drugs associated with tubular cell toxicity and acute
prevalence of asthma and COPD with increased use in- terstitial nephropathy include aminoglycosides, ampho-
of acetaminophen. The use of aspirin or ibuprofen is not tericin B, cisplatin, beta lactams, quinolones, rifampin,
associated with asthma or COPD. Administration sulfonamides, vancomycin, acyclovir, and contrast agents.
of acetaminophen in the first year of life was associated with a Chronic use of acetaminophen, aspirin, di- uretics and lithium is
46% increase in risk of asthma symptoms at the age of 6 to 7 associated with chronic interstitial nephritis leading to fibrosis
years. Bronchoconstriction is the most common drug-induced and renal scarring [8].
respiratory problem. Bronchospasm can be induced by a wide Blood: The incidence of idiosyncratic drug-induced
variety of drugs through a number of disparate pathophysiologic hematologic disorders varies depending on the condition and the
mechanisms. The frequency of aspirin-induced bronchospasm associated drug. Few epidemiologic studies have evaluated the
increases with age, on average at 30 years of age. Both actual incidence of these adverse reactions, but these reactions
ethylenediamine tetraacetic acid (EDTA) and benzalkonium appear to be rare. Drugs can produce anaemia by reducing the
chloride, used as stabilizing and bacteriostatic agents, production of red blood cells by the bone marrow (e.g.
respectively, can produce bronchoconstriction. Cough has chloramphenicol, sulfonamides and carbamazepine), or
become a well-recognized side effect of angiotensin-converting destroying the formed red blood cells by a process called
enzyme (ACE) inhibitor therapy. According to spontaneous hemolysis (e.g. primaquine, penicillin and sulfonamides).
reporting by patients, cough occurs in 1% to 10% of patients Hemolysis is particularly a problem in patients with the
receiving ACE inhibitors, with a preponderance of females. [6] deficiency of an enzyme called glucose-6-phosphatase. Some
Gastro-intestinal tract: Medication-induced gastrointestinal drugs reduce white blood cell counts and increase the chances of
(GI) symptoms and endoscopic pathology are commonly suffering from infections. These include methimazole,
encountered in clinical practice. Medication-induced GI phenylbutazone and clozapine. Heparin has been associated
disorders may closely mimic other GI conditions (eg, irritable with thrombocytopenia, a condition that lowers the platelet
bowel syndrome (IBS) and inflammatory bowel disease (IBD)), counts in the blood and increases the chances of bleeding [9].
and failure to recognise drug-related symptoms may lead to Bone: Drugs can cause accelerated bone loss as well as
unnecessary investigations and treatment. Medications produce disturbances in serum calcium levels. Long-term use of
symptoms by altering GI physiology (eg, constipation induced glucocorticoids can weaken bones causing osteoporosis and
by anticholinergic medication), by causing tissue toxicity and increasing the risk of fractures. The anti-tubercular drugs
damage (eg, ulcers from non-steroidal anti-inflammatory drugs ethambutol and pyrazinamide can increase the blood uric acid,
(NSAIDs)), by changing the intestinal microbiota (eg, causing a gout-like disease [10].
antibiotics causing Clostridium difficile infection), or by
unknown mechanisms, such as with metformin. The 3. Diagnosis of DIDs
pharmacologically active compound, as well as the excipient (or Drug-induced diseases are primarily diagnosed based on the
packaging) of the tablet or capsule can cause problems. Nausea history of drug intake obtained from the patient or the family.
and vomiting may be caused by mechanisms remote from the GI The symptoms should appear at a reasonable time frame after
tract [7, 2]. taking the medication. By default, physicians should enquire
about drug intake to any patient coming to the clinic with a
Table 3: Drugs which causes GIT adverse effects problem so as not to miss out on a drug-induced disease. If the
Conditions Drug responsible drug is re-administered the symptoms may reappear. This is
Dyspepsia Taxanes, NSAIDs referred to as re-challenge. Re-challenge confirms a drug-
Acute esophagitis Tetracyclines, bisphosphates. induced disease, but is usually not done due to ethical reasons
[2]
Reactive gastropathy NSAIDs .
Peptic ulcer NSAIDs, corticosteroids
Granulomatous (in stomach) Lanthanum carbonate 4. Treatment of DIDs: The first step in the treatment of drug-
Acute gastritis Resins induced diseases is to report the adverse effect to the physician
IBD Rituximab, TNF inhibitors, NSAIDs who may stop the intake of the medication or at times, reduce
Sodium phosphate, PPI’s, statins, the dose gradually, and replace with an appropriate alternative.
Colitis
colchicines Many times, this simple step can relieve the patient of the
Digitalis, ergotamine, cocaine, oxygen symptoms. Those who do not recover require additional
Ischemia
peroxide.
treatments depending on the adverse event [2].
Kidney: Drug-induced nephrotoxicity is a common problem in 5. Prevention of DIDs
clinical medicine and the incidence of drug-related acute kidney Steps that could help to prevent a drug-induced disease include
injury (AKI) may be as high as 60 percent. Drugs can cause the following:
nephrotoxicity by altering intraglomeu- lar hemodynamics and
decreasing GFR (ACEI, angiotensin-converting enzyme

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International Journal of Pharmaceutical Research and Development

 Always inform your doctor if you suffer from any illness or The WHO -UMC (Uppsala Monitoring Centre) Global drug
take any other medication including a nutritional safety database for the year 2013 has 8.5 million ADR reports.
supplement before you are prescribed a medication. In this, India’s contribution accounts for nearly 0.7 per cent of
 Inform your doctor if you have suffered from any previous the global data base. In the last 30 years, India has witnessed
allergic reaction to a drug or any other substances like food banning or withdrawal of nearly 90 drugs for manufacture and
ingredients. sale by CDSCO (Central Drugs Standard Control Organization).
 Take the medication only as prescribed by the doctor. Stick This forecasts the urgent need to expand the countrywide PvPI
to the dose, duration of treatment as well as other activities so as to implement safety decisions and policy at the
instructions like taking it after meals [2]. regulatory levels in the interest of patient safety. Policy
decisions regarding patient safety and medication errors can be
6. Conclusion achieved through promotion of population based surveillance of
Iatrogenic disease or drug induced disease (DID) is an ever DIDs by PvPI in association with CDSCO. In addition,
enduring concern for patients, healthcare professionals and continuing medical educational programmes and training need
health administrators. In spite of being a major concern in to be imparted on the healthcare professionals to keep them
clinical practice, DID has not been given the due attention it updated about DIDs as well as on the measures taken to prevent
deserves. One of the reasons for this may be that DID causes them. The importance of spontaneous reporting of adverse drug
apprehension among health care professionals making them reaction needs to be included in the curriculum of all healthcare
uncomfortable as well as unwilling to be part of studies professionals and the habit needs to be cultivated right from the
undertaken to reduce DID. In India, several individual case undergraduate level. While doing so care should be taken to
reports have been published related to specific iatrogenic maintain confidentiality of the patients as well as reporting
disease but a comprehensive study on this problem is not yet personals so as to encourage further reporting. Likewise during
published. The true incidence or prevalence of DID in our diagnosis as well as while teaching medical graduates, emphasis
country is not known. needs to be given on deliberation of DID as one of the causes of
The magnitude of adverse drug reactions which includes DID is the disease. Basic and epidemiological researchers interested in
huge. Considering its importance, the Central Drugs Standard evidence based medicine and personalized medicine can be
Control Organization (CDSCO), New Delhi, Government of motivated to contribute towards the detection, quantification and
India, had initiated a nation-wide pharmacovigilance reduction of DIDs of the marketed drugs. In addition, carrying
programme of India (PvPI) in July 2010. The total number of out systematic reviews as well as meta-analysis to generate
Individual Case Safety Reports (ICSR) in PvPI database is evidence towards the occurrence of DID can add required
84,470. In the US, it was reported that ADRs accounts for more information to the armamentarium of pharmacovigilance.
than one lakh death each year and it is between the fourth and
sixth leading cause of death. In our country, we do not have 7. References
statistics on DID but the total ADRs in PvPI database for the 1. Suma TK. drug induced diseases. API 2017; 79:435-438.
last few years are less than one lakh. This indicates the scenario 2. Dr. Simi Paknikar, Drug Induced Diseases. Med India
of under reporting of ADRs in our country compared to United medical review. 2017.
States of America. 3. Kelleni MT, Mahrous AB, Drug Induced Cardiotoxicity:
The various factors contributing to DID can be related to Mechanism, Prevention and Management, Cardiotoxicity,
pharmacokinetic and pharmacodynamic of drugs, non- Intech Open, 2018.
adherence to prescribed drug therapy as well as medication 4. Clinard V, Jennifer DS. US Pharm. 2012; 37(4):HS11-
errors. Concurrent diseases (e.g. liver and renal impairments), HS18
genetic polymorphisms in drug metabolizing enzymes and 5. Demler TL, Drug-Induced Neurologic Conditions. US
transporters, nutritional factors (hypo-albuminaemia may result Pharm. 2014; 39(1):47-51.
in more free drug of highly protein bound drugs) and 6. Raissy, Hengameh H., Michelle Harkins. "eChapter 15.
concomitantly administered drugs may also contribute to Drug-Induced Pulmonary Diseases." Pharmacotherapy: A
alteration in drug metabolism as well as target receptor activities Pathophysiologic Approach, 9e Eds. Joseph T. DiPiro, et
of drugs. Hence in this era of personalized medicine, prescribers al. New York, NY: McGraw-Hill, 2014.
need to understand and update their knowledge on the rapidly 7. Philpott, HL, Nandurkar S, Lubel J, Gibson PR. Drug-
transforming drug information. The acquaintance of induced gastrointestinal disorders. Frontline
pharmacokinetic and pharmacodynamic knowledge of a drug gastroenterology. 2014 5(1):49–57.
can help to prevent the DID. Moreover, a good understanding of 8. Ghane SF, Assadi F. Drug-induced renal disorders. Journal
pharmaceutical formulations and their applications can help in of renal injury prevention. 2015; 4(3):57-60.
reducing DID. 9. Rao KV, Chapter 24. Drug-Induced Hematologic
Being on the front lines of patient care as well as Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR,
pharmacotherapy, healthcare professionals need to be Wells BG, Posey L. eds. Pharmacotherapy: A
knowledgeable regarding the risk of drug-induced diseases, Pathophysiologic Approach, 9e New York, NY: McGraw-
including methods of detection, prevention, and management. Hill, 2014.
To be more efficient, health care practitioners need to be skillful 10. Bohannon AD, Lyles KW. Drug-induced bone disease. Clin
in patient consultation and education in addition to possessing Geriatr Med. 1994; 10(4):611-23.
knowledge on complex biomedical science.

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