CLINICAL PHARMACIST INTERVENTIONS ON MILIARY KOCH’S PATIENT WITH ANTITUBERCULAR THERAPY-INDUCED HEPATOTOXICITY AND PSYCHOSIS: A RARE CASE REPORT

Psychosis and hepatotoxicity are the dangerous side effects of the antitubercular drugs directly observed treatment short course (DOTS) therapy. Hematological spreading of tubercular bacteria in the lungs is also known as miliary tuberculosis. In this case study, 45-year-old man, weighing 55 kg was brought to the hospital with the chief complaints of vomiting (multiple episodes), fever, pain in abdomen, difficulty in breathing, mucoid cough, and disturbed sleep for the past 1 week. He had a known case of smear-positive pulmonary tuberculosis (in the past 1 month), but at that time, patient was not taking regular antitubercular treatment (ATT) medications (DOTS therapy). After 3 th week of irregular antitubercular drug treatment, patient developed with the problems such as vomiting (multiple episodes), fever, pain in abdomen, difficulty in breathing, cough with expectorations, disturbed in sleep, and delirium. Pulmonologists had found the provisional and final diagnosis on the bases of subjective and objective observations miliary KOCH’S with antitubercular drugs induced hepatotoxicity and psychosis. Patients recovered from psychosis and hepatotoxicity withdrawn the first line ATT medication and tablet pyridoxine, antipsychotic medicines, and modified ATT were added in the therapy. Psychotic in a patient on ATT can be one of the complications of tablet isoniazid. As a clinical pharmacologist, we prevent and minimize drugs-induced complications and adverse drug reactions. Proper patients counseling and patients’ education are important for the better management of patients.


INTRODUCTION
Tuberculosis is also known as KOCH'S.It is a granulomatous disease.Hematological spreading of tuberculosis bacteria in the lungs is also known as miliary tuberculosis.Antitubercular drug therapy is generally used in the tuberculosis, this therapy is also known as directly observed treatment short course (DOTS) therapy [1][2][3].Antitubercular treatment (ATT) drugs therapy is mainly responsible for the irreversible/ reversible hepatotoxicity, hepatitis, ototoxicity, neuromuscular blockage, neuropathy, ophthalmopathy, thrombocytopenia, and nephrotoxicity.Several antitubercular medications are known to cause neuropsychiatric adverse reactions such as delirium, depression, mania, psychosis, seizure disorder, and hepatotoxic adverse drug reactions (ADRs) such as nausea, vomiting, gastritis, and abdomen pain.[4,5].Psychosis and hepatotoxicity are the known complication of the isoniazid (INH) and other antitubercular drug therapy.Neuropsychiatric ADRs usually appear during the initiation of the treatment or while changing from a previously prescribed regimen [6,7].Isoniazid is the first-line antitubercular agent for the treatment of tuberculosis.Tuberculosis is the life-threading public health problem [8].Although there are many case reports already done previously, INH induced psychosis and hepatotoxicity particularly in tuberculosis (TB) patients, in this case, patient's condition was resolved only after discontinuation of the DOTS therapy and started the modified ATT therapy [9,10].

CASE STUDY
• A case of 45-years-old male, weighing 55 kg was brought to the hospital with chief complaints of vomiting (multiple episodes), fever, pain in abdomen, difficulty in breathing, mucoid cough, disturbed sleep, delirium for the past 1 week with no past and family history of hypertension, diabetes mellitus, thyroid disease, mental disorder, and pulmonary tuberculosis (PTB).• Patient was an ex-smoker, ex-alcoholic, and prefentially nonvegetarian.
• At the time of general vital study pulse rate (PR)-93 bpm, blood pressure (BP)-120/90 mmHg, oxygen saturation (SPO 2 ) 94% at the atmospheric air, abdomen examination was soft and non-tender and cardiac sounds S1, S2 positive were noted.• He had a known case of smear-positive PTB (in the past 1 months), but at that time, patient was not taking regular ATT medications (DOTS therapy).
• Pulmonologist monitored the laboratory investigations in the reports LFTs, KFTs, CBCs, CXR, MRI brain, and HRCT shown abnormalities.• On 2 nd day, fresh complains of patient were vertigo, insomnia, psychosis, and headache pulmonologist referred the patient to neurology department for the psychosis-related problem (Table 2).• On the 3 rd and 4 th day, BP was normal, that is, 120/70 mmHg and PR was 86 beats/min with SPO 2 concentration 96%.Patient no fresh complaints on day 4. • On 5 th day, patient complains loss of appetite, on brief discussion of pulmonologist with a clinical pharmacologist, counseling, along with diet assessment was done of patient.• Patient was advised to take proper fluid, high protein, and diet rich in fibers.Pomegranate juice was advised to be avoided.

DISCUSSION WITH CLINICAL PHARMACOLOGIST INTERVENTIONS ADR analysis
On the basis of ADRs analysis on the Naranjo Scale, possible hepatotoxicity and psychosis induced by ATT has found probable and found to be the major ATT-induced ADRs.The case history analysis found the "B" Type of ADRs with H, R, and Z and found to be preventable at a very early stage, and acute phases (Table 4).

ADR management
ADRs were known as diagnosed at a very early stage of ATT therapy.In general, B Type ADRs are bizarre and need hospitalization if became  Ensure protein powder, 2TSP-BD with water/milk after meals.

CONCLUTION
• Thus, pulmonologist and clinical pharmacologist should be aware about the drug toxicity profiles of antitubercular drugs like H, R, Z, and E. • ATT Drug-induced adverse effects seen in most of the TB patients; Although many case reports have been published on ATT-induced hepatotoxicity, psychosis, etc., but we encountered this first case in pulmonary isolation ward.
• The patient's conditions were gradually improvised and the druginduced psychosis and hepatotoxicity were controlled and patient was discharged with proper counseling and advised to visit everyone in months with all reports.• Patients undergoing treatment for tuberculosis need health education in detail concerning not only adherence and the benefits of ATT but also the side effects.• As a health-care team member clinical pharmacologists are need to be made aware of these potentially fatal adverse effects associated with antitubercular therapy through conduction of quality-based seminars, published medical literature, learning programs, conferences, and health-care awareness camps.
The study was done after getting clearance from Hospital Ethical Committee.Informed consent was obtained from all the patients.

LFT:Fig. 1 .
Fig. 1.Chest X-ray and high-resolution computed tomography of chest On the 2 nd day, BP was recorded as 130/80 mmHg and PR was 92 beats/min.According to the laboratory reports, patient laboratory investigations in the report LFTs, CBCs, CXR, HRCT, and viral marker are show many abnormalities.Chest X-ray was seen the miliary KOCHS.Viral markers for hepatitis, including hepatitis A, B, and C viruses, and human immunodeficiency virus all were negative (Table1and Fig.1).•Pulmonologist was on hold of previous antitubercular drug therapy.Although it was started with modified antitubercular drugs © 2023 The Authors.Published by Innovare Academic Sciences Pvt Ltd.This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/)DOI: http://dx.doi.org/10.22159/ajpcr.2023v16i12.48098.Journal homepage: https://innovareacademics.in/journals/index.php/ajpcr

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Pulmonologist stopped the tab lorazepam and haloperidol on the consult of neurology doctors.He started Tab Quetiapine 50 mg/day, Tab Risperidone 4 mg/day and find the diagnosis INH-induced psychosis.• On 6 th , 7 th , 8 th , and 9 th days, no fresh complaints were seen, and all vitals and laboratory's reports were normal.• On the basis of subjective and objective observation, pulmonologist had made a final diagnosis of Miliary KOCH'S with ATT Induced Hepatotoxicity and Psychosis.• After staying 10 days in hospital, the patient condition was improved and then Tab Quetiapine and Risperidone were stopped.• On normalization of patient's conditions, pulmonologist started firstline antitubercular drug therapy containing Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol with continued liver tonics.• Patient discharged with appropriate medication (Table 3) and patient counseling after advising review once in a month with LFTs reports.

Table 1 : Clinically investigational findings Parameter Test value Test value Reference value
Chest X-ray s/o Miliary KOCH'S HRCT Finding a case of suggestive of acute infective airway disease pulmonary KOCH'S.Clinicopathological correlations.MRI brainAcute impact and cerebral atrophy.

Table 5 )
. • As a clinical Pharmacologist and Pharmacotherapist has a crucial role in early detection, management, prevention, and control of the drugs-related adverse effects.• As a clinical pharmacologist, the possible diagnosis and prevention of ADRs are the first and priority.It helps in maintaining the QOL of patient and increase life expectancy of patients.• The ADR detection and treatment are necessary to maintain the proper drug therapy and proper medication adherence.• As a clinical pharmacologist should be aware of this adverse effect of INH and other ATT medications, that it may present with a broad clinical picture.• Hepatotoxicity, gastritis, optic neuritis, thrombocytopenia, psychosis, etc. is the most important serious adverse effects of the ATT therapy.