INTRODUCTION:

Iatrogenic means "caused by a physician."¹Iatrogenic disease is the result of diagnostic and therapeutic procedures undertaken on a patient. In other term the iatrogenic disease can be define as the conditions induced by the physician or the care prescribed. Iatrogenic comes from a Greek word Iatros meaning the healer iatrogenic means brought by the healer, Iatrogenic problems have always occurred to some extent often unknown to the physician ranging from mild to the severe. With the multitude of drugs prescribed to a single patient adverse drug reactions are bound to occur². The Physician should take suitable steps to detect and manage them.“Iatrogenic (of a disease or symptoms) induced in a patient by the treatment or comments of a physician”.

There have been numerous studies on iatrogenic diseases (IDs) during the past 3 decades. Although the incidence of community-acquired ID is not precisely known, it seems to account for 2% to 10% of outpatient consultations. The elderly are most at risk, but the severity of the underlying diseases, the number of prescribed drugs and the pattern and location of care are also factors. Iatrogenic complications are life threatening in 10% to 26% of cases.³ Iatrogenesis can also result from complementary and alternative medicine treatment.Adverse drug reaction (ADR) has been implicated as a leading cause of considerable morbidity and mortality worldwide.⁴ Morbidity related to ADRs can be permanent sometimes to the extent of 20.4 per cent of admissions in ICU⁵the suspected ADRs in the form of DIDs were classified in term of causality using WHO-UMC (Uppsala Monitoring Centre) scale. Types of reaction were classified as Type A (augmented); Type-B (bizarre), Type C (continuous use); Type D (delayed); and Type E (end of use as per recommended standard operating procedure of PvPI⁶

Risk factors for iatrogenic diseases:

Patient’s age and normal age related changes, diet and nutritional status genetic variability preexisting pathology or high prevalence of the chronic disease and comorbid conditions (especially of the kidneys and the liver) presences of the impaired host mechanism and the drug sensitivity, atypical presentation of the disease, inadequate geriatric training of healthcare provider¹⁴.

DRUG INDUCED DISEASES:

A drug-induced disease is the unintended effect of a drug, which results in mortality or morbidity with symptoms sufficient to prompt a patient to seek medical attention and/or require hospitalization. Drug-induced disease can result from unanticipated or anticipated drug effects. Disease also can occur from product impurities, as was the case with deaths attributed to the use of contaminated heparin in 2008. Vigilance on the part of regulatory authorities, drug manufacturers, clinicians, and patients is necessary to minimize the potential harm that is inherent in drug use.⁷

There are certain drugs which on administration to the mother are capable of crossing the placenta and affecting the fetus e.g. alcohol, barbiturates, narcotic and non-narcotic analgesics etc. During lactation, the drugs like antihistamines, morphine, and tetracycline which are excreted in the milk should be avoided. Elderly patients are more sensitive to some drug affects e.g. hypnotics and tranquillizers. Which may produce confusion state in them? People have drug problems that may trigger the first symptoms of mental illness. Some drugs cause a condition called drug-induced Psychosis, which usually passes after a few days¹². Excessive use of drugs like cocaine, amphetamines, hallucinogens, nicotine, opioids, sedatives etc, may cause mental illness.

ANTIBIOTIC INDUCED DISEASES:

Antibiotic allergies or hypersensitivity reactions are some of the most common side effects of antibiotics leading to emergency room admission.⁸Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The use of probiotics for these two related diseases remains controversial.⁹ The most common antibiotics implicated in antibiotic-associated diarrhea are amoxicillin-clavulanate, ampicillin, and cefixime; however, other antibiotics may lead to this side effect, including cephalosporins, fluoroquinolones (e.g., side effects of Cipro antibiotic), azithromycin (e.g., Z Pak), clarithromycin (Biaxin), erythromycin, and tetracycline.¹⁰

Penicillin and other beta-lactum antibiotic and vaccines and sera and human insulin are the most common agents that cause anaphyllaxis. Aspirin and others Non-Steroidal Anti Inflammatory Agents (NSADs) cause non- IgE mediated anaphylacted reactions.¹¹ Cephalosporins can induce Ash, diarrhea, nausea/vomiting (rare), hypersensitivity (allergic) reactions, serum sickness, vaginal candidiasis Aminoglycosides can induce Renal (kidney) toxicity, ototoxicity (hearing loss), dizziness, nausea/vomiting, nystagmus. lincomycin derivatives can causes Pseudomembranous colitis (may be severe), diarrhea, nausea/vomiting, rash, hypersensitivity, jaundice (clindamycin)¹²

HYPERSENSITIVITY:

Hypersensitivity or drug allergy is an adverse reaction to particular chemical resulting from a previous exposure to the substance, occurring in only a small fraction of all people receiving the particular drug. Most common allergic effects are skin rashes, edema, anaphylactic shock, bronocho-spasm, serum sickness syndrome, etc and examples of drug which may produce it are penicillin, sulfonamide, phenacetin etc Salicylism may produce by chronic dosing of aspirin¹⁶. Drug administration by injections produces rapid drug action. The maximum drug is available to elicit pharmacological action.

RESPIRATORY DISEASES:

Iatrogenic respiratory disease is an important cause of patient morbidity and mortality. Drug agents that cause respiratory disease can be divided into cytotoxic agents, specifically chemotherapeutic agents, and noncytotoxic agents, such as antibiotics, anti-inflammatory agents and anti arrhythmics. Several drugs can cause NSIP. It is the most commonly encountered drug-induced lung disease caused by amiodarone, methotrexate, and carmustine.¹³the relationship between the use of various drugs and pulmonary disease is being recognized with greater frequency. The means whereby drugs can cause pulmonary disease vary widely and are not well understood. Drugs such as nitrofurantoin, busulfan, methysergide, the ganglionic blockers, pituitary snuff, and sulfonamides and drugs producing the systemic lupus erythematosus syndrome probably incite a hypersensitivity pulmonary reaction.¹⁴

CARDIOVASCULAR DISEASES:

People with heart failure take an average of 6.8 prescriptions medicines a day that are likely to have drug-drug interaction. Heart failure is often caused by other health problems, like heart disease or diabetes. But common medications can also bring it on. Nonsteroidal anti-inflammatory drugs (NSAIDs). Prescription NSAIDs include diclofenac, ibuprofen, indomethacin, and ketorolac. NSAIDs can boost heart failure odds because they make you retain water and salt, make it harder for your blood to flow, Thiazolidinediones (pioglitazone, rosiglitazone) cause fluid retention and weight gain in people with heart failure dipeptidyl peptidase-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin).¹⁵ Drug induced cardiovascular disease may lead to exacerbation of angina, arrhythmias, cardiomyopathy, hypo or hypertension pericardial disease and torsade de pointes.

HEPATIC DISEASES:

Liver damage is due to intrinsic toxicity of the drug (paracetamol) and/or immunoallergic mechanisms (halothane). Drug-induced liver diseases are usually reversible, but prolonged treatment leads to progression and liver cirrhosis.¹⁶Drug-induced hepatic disease is a multifaceted phenomenon. It may occur as an unexpected idiosyncratic reaction to a normally nontoxic drug or may be an expected consequence of the intrinsic toxicity of an agent taken in sufficiently large dose to cause liver injury. Drug-induced injury encompasses virtually all known hepatic lesions, both acute and chronic. Acute injury may be cytotoxic (hepatocellular) or cholestatic. Chronic injury includes a variety of hepatocellular, cholestatic, vaascular, or neoplastic. The liver injury may be the only clinical manifestation of an adverse drug effect or may be accompanied by evident injury to other organs or systemic manifestations.¹⁷

Some drugs, such as statins (used to treat high cholesterol levels), can increase the levels of liver enzymes and cause liver damage (usually minor) but no symptoms. A very few drugs damage the liver enough to cause symptoms, such as jaundice, abdominal pain, itching, and a tendency to bruise and bleed.¹⁸ Because of pathological conditions like renal impairment or liver disease many drugs remain in body for longer period of time.

Some of the Drugs and their Induced Diseases:

S.No	Drug	Diseases
1.	Cocaine	Heart, respiratory, nervous, digestive disorders
2.	Inhalants	Heart failure, kidney, lung, brain disease
3.	Opioid, anti-anxiety, sedatives	Misuse of the drug can lead to death
4.	Heroin	Serious infectious diseases
5.	Amphetamines	It can cause high body temperature, serious heart problems, and seizures.
6.	MDMA	Increase body temperature, heart rate, and blood pressure, toxic to nerve cells.
7.	Nicotine	Cancer, emphysema, bronchial disorders, cardiovascular disease.
8.	Steroids	Heart and liver disease, depression, stroke and suicide.
9.	LSD	Traumic experience.
10.	Marijuna	Tachycardia, psychosis.
11.	Penicillin (Penicillin, amoxicillin, amoxicillin-clavulanate, ampicillin, piperacillin-tazobactam, nafcillin, oxacillin	Rash, diarrhea, hypersensitivity (allergic) reactions.
12.	Cephalosporins (Cephalexin, cefaclor, cefuroxime, ceftibuten, cefdinir, cefixime, ceftriaxone	Hypersensitivity (allergic) serum sickness, vaginal candidiasis.
13.	Aminoglycosides (Gentamicin, tobramycin, amikacin)	Renal toxicity, ototoxicity, nausea/vomiting dizziness, nystagmus.
14.	Carbapenems (Meropenem, ertapenem, doripenem, imipenem-cilastatin	Diarrhea, headache, liver toxicity eosinophilia.
15.	Antituberculosis agents (Rifampin, isoniazid, pyrazinamide, ethambutol)	Diarrhea, anorexia, hemolytic anemia, liver toxicity, peripheral neuropathy.
16.	Glycopeptides (Vancomycin, telavancin)	Red man syndrome, phlebitis, tastes alteration.
17.	Macrolides (Erythromycin, azithromycin, clarithromycin)	Abdominal pain, diarrhea, anorexia, nausea/vomiting, taste alteration
18.	Sulfonamides (Trimethoprin, sulfamethoxazole, sulfisoxazole, sulfadiazine).	Nausea/vomiting, diarrhea, anorexia, abdominal pain, headache, dizziness, rash.
19.	Tetracyclines (Tetracycline, doxycycline, minocycline).	Nausea/vomiting, diarrhea, abdominal pain, liver toxicity, photosensitivity reactions.
20.	Quinolones (Ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin)	Lethargy, insomnia, diarrhea, photosensitivity.
21.	Lincomycin derivatives(Clindamycin, lincomycin)	Pseudomembranous colitis, hypersensitivity, jaundice.
22.	Miscellaneous (Metronidazole)	Nausea/vomiting, dizziness, headache, vaginal candidiasis.
23.	Cyclophosphamide	Cystitis
24.	Methotrexate	Anemia.
25.	Enoxaparin, tirofiban, paclixel, quinine.	Thrombocytopenia.
26.	Anticancer drugs	Bone marrow suppression
27.	Acetylsalicylic acid	Hemolysis.
28.	Steroids	Osteoporosis.
29.	Paclixel, Atorvastatin	Myalgia
30.	Methylprednisolone	Septic arthritis
31.	Paclixel	Athralgia
32.	Carbimazole	Hypothyroidism
33.	Prednisolone, torsemide, pyrazinamide, ethophylline, theophylline	Hyperuricemia leading to attack of gout.
34.	Prednisolone	Cushing syndrome.
35.	Risperidone	Obesity
36.	Olanzapine, steriods	Dyslipidemia.
37.	Thyroid hormone	Hyperthyroidism
38.	Deflazacort, methyl prednissolone, prednisolone	Diabetes.
39.	Hydroxychloroquine	Ocular toxicity.
40.	Digitoxin	Arrhythmia.
41.	Misoprostol	Menorrhagia
42.	Deflazacort	Menstrual dysfunction
43.	Levofloxacin, co-trimoxazole	Vasculitis
44.	Loperamide	Paralytic ileus
45.	Carbamazepine	DRESS Syndrome
46.	Acyclovir	Oligospermia
47.	Steroids, ceftriaxone	Secondary infections
48.	acetylsalicylic acid, diclofenac	Gastritis
49.	Ibuprofen	Alllergic rhinitis
50.	ceftriaxone, azithromycin	Diarrhoea.
51.	Metaprolol, diltiazem, digitoxin	Bradicardia.
52.	Diclofenac, ibuprofen	Upper GI bleed
53.	methylprednisolone, Levodopa	Pyschosis
54.	Phenobarbitone, prednisolone	Congnitive dysfunction
55.	Metocloperamide, escitalopram	Extrapyramidal symptoms
56.	Steroids	Acne
57.	Sulfonanide	Sickness syndrome.
58.	Ergot alkaloids	Unconsciousness, vision problem, convulsions

CONCLUSION:

Iatrogenic disease can occur by certain drug reactions or the treatment given to a patient with unintentional medical errors by the physician, surgeon, pharmacists or nurses that might be due to negligence or improper care. Many people died due to these adverse effects of medical treatment. The health care professionals should take suitable steps to avoid the errors.

REFFERENCES:

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4. Vishal R. Tandon, Vijay Khajuria, Vivek Mahajan, Aman Sharma, Zahid Gillani & Annil Mahajan*, Drug-induced diseases (DIDs): An experience of a tertiary care teaching hospital from India, Indian J Med Res 142, July 2015, pp 33-39 DOI:10.4103/0971-5916.162093

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Farm Hosp 2011 Sep-Oct; 35(5):236-43.

Received on 03.01.2018 Accepted on 14.03.2018

Asian J. Pharm. Res. 2018; 8(2): 113-116.

DOI: 10.5958/2231-5691.2018.00020.5