Jul-Sep, 2012 - Indian Journal of Pharmacy Practice

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Indian Journal of Pharmacy PracticeAssociation of Pharmaceutical Teachers of IndiaDrug Induced Syndromes: An Overview1 2 3 4Mahendra Kumar BJ , Soumya M , Jyothi K and Jagadish B. D*1Director PG Studies, Prof. & Head, Department of Pharmacy Practice, JDT Islam College of Pharmacy, Jamiath Hill, Kozhikode, Kerala.2Lecturer, Department of Clinical Pharmacy, SAC College of Pharmacy, BG Nagara, Karnataka3,4Pharm D Students, Department of Clinical pharmacy, SAC College of pharmacy, KarnatakaA B S T R A C TSubmitted: 04/07/2012Accepted: 12/08/ 2012Many drugs have come into the market in recent years and its usage is increased for multiple disorders which in turn leads to poly pharmacy andincreased drug related problems. One such drug related problem is Drug-induced syndrome. These syndromes are one of the major problems inthe health care sector. Drug related problems are found to be a reason for hospital admission and also for an increased patients stay in thehospital. The syndromes can be associated with any pathological conditions or may be drug related. This overview article provides theinformation regarding the different drug induced syndromes with its causative agents, clinical manifestation and therapy.Keywords: Drug induced syndrome, drug related problem,INTRODUCTIONThe word "Syndrome" derived from the Greek wordsundrom, which means concurrence of symptoms, or fromword sundromos, which means running together. Syndromeis a set of symptoms occurring together. In medical contextsyndromes are classified as syndromes caused due toenvironmental causes, cardiovascular, iatrogenic, neoplastic,congenital, endocrine, pulmonary, infectious, renal,neurological, gastrointestinal, reticulo-endothelial,1hematologic, others.Drug-induced syndromes or iatrogenic (physician induced)syndromes are produced by drugs themselves and leads tocertain pathological changes. These are temporally relatedwith starting a drug, and the symptoms and signs generally2, 3regress with its discontinuation. The increasing number andcomplexity of diagnostic procedures and therapeutic agents,monitoring of untoward events is essential, and attentionshould be paid to educational efforts to reduce the risks of4iatrogenic illness. Important risk factors for adverse drugevents or reactions included polypharmacy, drugs withnarrow therapeutic range, renal elimination of drugs, age >65years and use of anticoagulants or diuretics. Since medicationerrors are strong risk factors for preventable adverse drugevents or reactions, strategies have to be put in place for theirreduction. Such strategies include ensuring that all personsinvolved in the medication process (nurses, pharmacists andAddress for Correspondence:Dr. BJ Mahendra Kumar, Director PG Studies, Prof. & Head, Department ofPharmacy Practice, JDT Islam College of Pharmacy, Jamiath Hill, Kozhikode,Kerala.Email address:bjmahendra2003@yahoo.co.inphysicians) have good pharmacological knowledge,computerization of the entire medication process, and theengagement of a sufficient number of clinical pharmacists on5the wards.The drugs with single or combination can leads to iatrogenicsyndromes with severity ranging from mild to severe.Awareness should bring towards health care professionals forthe management of drug induced syndromes. This articlebrings brief description of drug induced syndromes includingcausative agents, symptoms and management.Drug Rash with Eosinophilia and Systemic symptomsSyndrome (DRESS): DRESS syndrome reflects a serioushypersensitivity reaction to drugs and has been classifiedunder a delayed type IVb hypersensitivity reaction, where T6helper type II cells play a significant role. (Fig 1)Causative drugs: Anticonvulsants, Sulfonamides, Dapsone,Allopurinol, Minocycline, Gold, Hydroxychloroquine(HXQ) Sulfate, Isoniazid, Rifampicin, Ethambutol and6, 7Pyrazinamide.Symptoms: Fever is usually present. Skin eruption may varyfrom a diffuse maculopapular inflammatory rash toerythroderma, Stevens–Johnson syndrome or erythemamultiform. Concerning organ involvement, lymph nodes,liver and kidney are frequently affected; lung and heart are6involved in a minority of the cases.Treatment: Causative drugs should be withdrawn as a part ofthe treatment and steroids are useful for patients with lifethreateningvisceral manifestations such as interstitialPneumonitis or nephritis. In milder cases, topical steroidsimprove the skin manifestations. Interferon-α is also useful6, 7for long-lasting DRESS.Indian Journal of Pharmacy Practice Volume 5 Issue 3 Jul - Sep, 2012 13
Mahendra Kumar BJ - Drug Induced Syndromes: An OverviewSerotonin Syndrome: Serotonin Syndrome is a toxic statelargely attributable to the changes in the sensitivity ofserotonin receptor system, resulting from increasedserotonergic activity in central neurologic system, due to8serotonergic agents either in overdose or in combination.Causative drugs: L-tryptophan, Amphetamine, Lithium,Dextromethorphan, Merperidine, Fluoxetine, Trazodone,9Venlafaxine, Buspirone.Symptoms: Neuromuscular (clonus, myoclonus, tremor,hyperreflexia) and autonomic (fever, mydriasis, tachycardia,tachypnea) symptoms, mental status changes (confusion,9agitation) and may result in death in severe cases.Treatment: The main and foremost therapy is the cessation ofthe medication and the syndrome usually resolves within 24hours after the withdrawal of the causative drug. If serotoninsyndrome has occurred as a result of an acute overdose,activated charcoal may be beneficial soon after the ingestion.Supportive care is the mainstay of treatment. Hyperthermiashould be treated with aggressive external cooling measuressuch as ice, mist, fans and a cooling blanket. Rigidity,seizures, and agitation are treated with Benzodiazepines. Onestudy revealed that the severe symptoms can be successfullytreated with Cyproheptadine (5-hydroxytryptamine9antagonist).Red Man Syndrome (Red-Neck Syndrome /RMS): Red-Neck syndrome is characterized by pruritus; erythema of theface, neck, and upper torso; and in severe cases, angioedema10, 11and cardiovascular collapse.Causative drugs: Vancomycin, Ciprofloxacin, Amphotericin11B, Rifampicin and Teicoplanin.Symptoms: Sensation of burning and itching, agitation,11dizziness, headache, chill, fever and perioral paresthesia.Treatment: The effects of red man syndrome can be relievedby antihistamines. Pretreatment with hydroxyzine cans i g n i f i c a n t l y r e d u c e e r y t h e m a a n d p r u r i t u s .Diphenhydramine hydrochloride intravenously or orally can11abort most of the reactions.Blue-Gray Syndrome: Blue gray syndrome is anamiodarone related hyperpigmentation considered as a skin12storage disease secondary to drug deposition.12, 13, 14Causative drug: Amiodarone.Symptoms: Blue-gray skin pigmentation, dyspnea, cough and12, 13, 14fever. (Fig 2)Treatment: Discontinuation of the causative agent withoutintroducing other medication is considered as the mostpracticed therapy in clinical setup. Careful and regular long13, 14term follow-up is mandatory.Severe Dapsone Hypersensitivity Syndrome: Adversereactions to Dapsone, a potent anti-inflammatory, antiparasiticcompound, first line drug for leprosy includedramatic, generalized hypersensitivity syndrome termed asDapsone syndrome which has a frequency of 0.2% - 0.5% inpatients on Dapsone therapy typically begins with several15weeks of starting the drug.15, 16, 17Causative drug: Dapsone.Symptoms: High fever lasting for about 4-5 days associatedwith malaise, sore throat, dysphagia, productive cough, and a16pruritic rash, methamoglobinemia and hemolytic anemia.(Fig 3) .Treatment: Patients can be treated with corticosteroids bothorally (Prednisolone 40 mg/d) and topically (Beclomethasonedipropionate ointment 0.025%, 2 times a day). Cetirizine andHydroxyzine are also given for the management of Dapsone16syndrome.Neuroleptic Malignant Syndrome (NMS): NMS is a rare,but sometimes fatal, adverse reaction of neuroleptics18characterized principally by fever and rigor.Causative drugs: Butyrophenones, Phenothiazines,Thioxanthenes, Hydroxyzine, Reserpine;, Amitriptyline,Amoxapine, Desipramine, Maprotiline, Phenelzine,Tranylcypromine, Diazepam, Lorazepam, Carbamazepine,Phenytoin, Amantadine, Bromocriptine, Levodopa,18Lithium.Symptoms: Dopaminergic blockade cardinal featuresincluding autonomic dysfunction, altered mental status,muscular rigidity, hyperthermia, cogwheel rigidity,dyskinesia, dysphagia, festinating gait, lead pipe musclerigidity, oculogyric crisis and opisthotonos are seen in19patients.Treatment: Strong suspension of NMS neuroleptics should bedone immediately. Supportive measures are of greatimportance especially rehydration and cooling.Bromocryptine and Dantrolene given in divided doses orally20or parenterally up to 60mg per day.Nicolau Syndrome (Livedoid Dermatitis/NS): NicolauSyndrome is a rare adverse drug reaction with unknown21pathogenesis at the site of intramuscular drug injection.Causative drugs: Non-steroidal Anti-Inflammatory Drugs,21Corticosteroids, and Penicillin.Symptoms: Pain around the injection site soon after injection,followed by erythema, livedoid patch, haemorrhagic patch,finally resulting into the necrosis of skin, subcutaneous fat,22and muscle tissue. (Fig 4)Treatment: Treatment ranges from local care to surgicalintervention. Antibiotic use is restricted to cases with signsIndian Journal of Pharmacy Practice Volume 5 Issue 3 Jul - Sep, 2012 14
Page 7: Chang J - India's Progress towards
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