|Year : 2015 | Volume
| Issue : 2 | Page : 130-137
Pharmacovigilance study of Ayurvedic medicine in Ayurvedic Teaching Hospital: A prospective survey study
Manjunath N Ajanal1, Shradda U Nayak2, Avinash P Kadam3, BS Prasad4
1 Department of Dravyaguna, RGES's Ayurvedic Medical College Hospital and PG Research Center, Ron, Gadag, Karnataka, India
2 Department of Dravyaguna, KLEU's Shri BMK Ayurved Mahavidyalaya, Belgaum, Karnataka, India
3 Department of Research and Development, Rasayani Biologics Pvt Ltd., Pune, Maharashtra, India
4 Department of Panchakarma, KLEU's Shri BMK Ayurved Mahavidyalaya, Belagavi, Karnataka, India
|Date of Web Publication||3-Feb-2016|
Manjunath N Ajanal
Research Officer cum Asst. Prof., Department of Dravyaguna, RGES's Ayurvedic Medical College Hospital and PG Research Center, Ron, Gadag - 582 209, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Though Ayurveda is practiced in the Indian subcontinent since centuries, there is a paucity of systematic documentation related to the occurrence of adverse drug reactions (ADR) and other issues regarding the safety of Ayurveda medicines. Aim: To monitor and analyze the pattern and frequency of ADR to Ayurvedic medicines in an Ayurvedic hospital setup. Materials and Methods: In this prospective study, ADR monitoring was done in KLE Ayurveda Secondary Care Hospital, Belgaum, Karnataka, India by spontaneous and intensive monitoring technique for a span of 1-year (June 2010 to May 2011). Data pertaining to patient demography, drug and reaction characteristics, organ system involved and reaction outcomes were collected and evaluated. The reaction severity and predisposing factors were also assessed. Results: In a span of one year, 84 adverse drug events were reported out of which 52 confirmed as ADR. The overall incidence of ADR in the patient population was 1.14%, out of which 23 (44.23%) were related to Panchakarma (detoxification process), 13 (25.00%) related to the herbal formulations and 06 (11.53%) were of Rasa Aushadhi (mineral or herbo-mineral formulations). The commonly affected organ systems were gastrointestinal system 24 (46.15%) and skin 15 (28.84%). The majority of the reactions were moderate 30 (57.69%) to mild 20 (38.46%) in severity. Most patients recovered from the incidence. Conclusion: The present work has documented the incidence and characteristic of ADR to Ayurvedic medicine in a typical Ayurveda hospital setup. This will help in developing various strategies for boosting pharmacovigilance in Ayurveda, thereby ensuring safer use of Ayurveda medicines.
Keywords: Adverse drug reactions, Ayurveda, herbal medicine, Panchakarma pharmacovigilance, Rasaushadi
|How to cite this article:|
Ajanal MN, Nayak SU, Kadam AP, Prasad B S. Pharmacovigilance study of Ayurvedic medicine in Ayurvedic Teaching Hospital: A prospective survey study. AYU 2015;36:130-7
|How to cite this URL:|
Ajanal MN, Nayak SU, Kadam AP, Prasad B S. Pharmacovigilance study of Ayurvedic medicine in Ayurvedic Teaching Hospital: A prospective survey study. AYU [serial online] 2015 [cited 2021 Apr 16];36:130-7. Available from: https://www.ayujournal.org/text.asp?2015/36/2/130/175539
| Introduction|| |
India is known to be rich in biodiversity and based on this it also has its own indigenous codified systems of healing. Ayurveda is one of such healthcare system and forms an important component of healthcare in India as it is practiced here for thousands of years. It is the most commonly practiced form of nonallopathic medicine in India, comprising a wide range of therapeutic approaches such as use of herbs, minerals, various detoxifying regimes, dietary advices, and their combinations with various nondrug modalities. It is estimated that about 80% of Indian population use Ayurveda medicines for their healthcare needs. Also, use of Ayurveda in the Western countries is increasing. This increasing use of Ayurvedic medicines worldwide has led to increasing concern regarding their safety. Recently there are various publications which raise concern about the safety of Ayurveda medicines.,, Today Ayurveda is gathering increasing global attention with regard to both; as a therapeutic option to treat various chronic and noninfectious diseases as well as due to the possibility of health hazards associated with it. Though Ayurveda is practiced for centuries, there is a paucity of systematic documentation related to the occurrence of adverse drug reactions (ADRs) and other issues regarding the safety of Ayurveda medicines. Moreover, as compared to the practice of Ayurveda in olden ages, today a major change is seen in various aspects related to its use. Hence, safety monitoring has became very essential in lights of change with respect to environmental factors, increasing use of insecticides, adulteration of herbs, concomitant use of herbs with drugs of other system of medicines, new manufacturing techniques, lack of proper regulations in pharmaceutical industry, and easy availability of combinations of herbs over the counter. With the increased concern related to safety of Ayurvedic medicines, a National Pharmacovigilance Program in Ayurveda, Siddha and Unani (ASU) drugs has been initiated by Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH); Ministry of Health and Family Welfare, Government of India.
Pharmacovigilance program aims to collect data pertaining to the occurrence of ADR and to identify and quantify the risk associated with the use of drugs. Such data is used to reach at inferences to recommend informed regulatory interventions and communicating risks to health care professionals and the public. The aim of present study to undertake ADR monitoring in a Peripheral Pharmacovigilance Center of National Pharmacovigilance Program. The primary objective of the study was to analyze the pattern and frequency of ADR to Ayurvedic medicines in an Ayurvedic hospital setup. The secondary objective to evaluate and understand various aspects related to the safety of Ayurvedic medicines.
| Materials and Methods|| |
This prospective and observational study was conducted over a period of 1-year from June 2010 to May 2011 at KLE Ayurveda hospital, Belgaum, Karnataka, India after obtaining the approval of the Ethics Committee for Research on Human Subjects', KLE University's Shri BMK Ayurved Mahavidyalaya, Belgaum, with IEC number “IEC/09/PG/ADR/MA.” The study was registered with the Clinical Trial Registry of India (CTRI) ref. no. CTRI/2010/091/001164.
Detection of adverse drug reactions
Spontaneous and intensive reporting techniques were followed to detect the ADRs according to the World Health Organization (WHO) definition of ADR as “A noxious and unintended response at doses normally used for prophylaxis, diagnosis, or therapy of diseases, or for the modification of physiological function.”
All outpatient department (OPD) and inpatient department (IPD) patients presenting with the ADR were included in the study. The patients with intentional or accidental poisoning and under allopathic treatment were excluded from the study.
Under spontaneous reporting technique, the physicians of the hospital were provided with reporting cards on which they will record the suspected ADRs. The ward incharge, ward nurse, and internee were also provided with similar reporting forms. After the initial notification of the suspected ADR by the physician, additional details were collected by interviews and review of case record forms. Awareness of ADR monitoring was created through the clinical meeting with health and clinicians and nurses of the hospital.
In intensive monitoring technique, all the admitted patients (IPD) were screened for ADRs during the study period. Patients were interviewed, monitored daily throughout their hospital stay by doing rounds. The patients with suspected ADRs were followed up till resolution or till 45 days, whichever is earlier via telephone. Their medical records were also reviewed.
In the suspected cases, past medical/medication history with their respective dosage form, route of administration, frequency, date of onset of reaction, and the patients allergy status (drug or food) along with constitution (Prakriti), area of residence (Desha), age (Vayah), time (Kala), strength (Bala), exercise capacity (Vyayamashakti), digestive capacity (Agnibala) and disease strength (Rogabala), etc., were collected. The suspected adverse events (AE) were carefully analyzed and documented in the standard ADR monitoring for ASU drugs forms provided from National Pharmacovigilance Program for ASU drugs Jamnagar, India.
The causality analysis was done as per approved group suggested in National Seminar cum Workshop on “Pharmacovigilance of Ayurvedic Medicine – 2006” and National Pharmacovigilance Programme for ASU medicine. Accordingly each suspected case was thus defined under the WHO definition ADR and further case analyzed by presentation followed by intensive discussion with heads of Dravyaguna, Rasashastra, Kayachikitsa, Panchakarma, Prasuti Tantra, and modern pharmacology before coming to conclusion of suspected cause of occurrence of event. Subsequent analysis was done by following causality categories recommended by Uppsala Monitoring Center - WHO probability scale  and Naranjo's ADR probability scale  to assess the probability of ADRs.
The ADRs thus confirmed were classified according to demographic, system involved, medicine involved, organ system involved and symptom wise. Outcome and severity of suspected ADRs were determined by referring previous published study.
Data analysis was performed using Predictive Analytics SoftWare statistics ® version 18. Descriptive statistics including frequency distribution of key items and bivariate analysis was carried out to describe the relationship between reported ADRs and variables as age, gender, type of reaction and therapeutic modalities. Chi-square statistic was used to test the association between reported ADRs and patient's age, gender, and the seasonal occurrence of ADR. The association between reported ADRs and specific variables was assessed by an odd ratio (OR) at 95% confidence interval. The reported P < 0.05 were used to determine the statistical significance except where otherwise indicated.
| Observations and Results|| |
During the study period, a total of 60,000 patients visited OPD and 4196 patients to visits to IPD. Of these 2260 were female, 1936 were male. A total 84 AE reported from both IPD and OPDs. Out of which 52 were confirmed as ADRs. Of this, 04 ADR reported in OPD while 48 ADRs developed during the hospital stay (IPD). The overall incidence was 1.143%. Females experienced a slightly higher incidence of ADRs 28 (1.3%) than males 20 (1.03%) with OR being 1.2 and P = 0.52 which is insignificant (P < 0.05) [Table 1].
Age wise classification on the occurrence of incidents of ADR shows that old age (age of >41) group experienced more numbers of ADRs 25 (1.27%) compare to other groups [Table 2].
Season wise classification suggested that 25 (1.18%) patients suffered with ADRs in period between 16th January and 15th July (the Northern solstice, “Adanakala”) which is high when compared period between 16th July and 15th January (the Southern solstice, “Visargakala”) 23 (1.10%) with OR of 0.93. Statistical insignificant difference was seen in the incidence rate of ADR with respect to factors such as sex, age, and season.
Wills and Brown classification of ADR showed that most of the reactions 20 (38.46%) were of Type A followed by Type U 11 (21.15%) and there were no ADRs of Type B, E, and G. According to the Naranjo algorithm scale, 38 (73.07%) reactions were assessed to be probable, 12 (23.07%) as possible and, 01 (01.92%) as definite. As per WHO probability scale 19 (36.58%) were classified as possible and only 01 (01.92%) as certain. Severity assessment of the ADRs showed that the majority of the reactions reported were moderate 30 (57.69%) and severe were 02 (03.84%). There were no fatal reactions. In 46 (88.46%) ADRs complete recovery was achieved, 2 (03.84%) were still recovering till reporting period (followed 6-month) and 4 (07.69%) ADRs were classified as “unknown outcomes” in which the outcomes could not be assessed as the patients sought voluntary discharge from the hospital, and some were not followed by phone also [Table 3].
In relation to different routes of administration, maximum ADRs were from oral route 28 (53.84%) followed by topical application 14 (26.92%) and rectal 07 (13.46%) [Table 4].
|Table 4: Occurrence of ADR relation in relation to route of administration of drugs|
Click here to view
In most common treatment modality causing the ADRs and their reaction, Panchakarma produced the highest number of reactions 23 (44.23%), and least numbers were associated restricted diet (Pathya) and material/environmental of 02 (03.84%) [Table 5].
Skin rashes 12 (23.07%) were the most common ADR reported followed by diarrhea 09 (17.30%), vomiting 07 (13.46%) [Table 6]. The organ systems affected due to ADRs are accordingly, gastrointestinal (GI) system was found to be the most commonly affected organ system 24 (46.15%) followed by the skin 15 (28.84%) [Table 7].
|Table 6: Individual reactions reported for each therapeutic modality is presented|
Click here to view
Out of 52 ADRs reported Vatapittaprakriti (constitution) patients were the most vulnerable and experiencing the highest numbers of ADRs 15 (28.84%), followed by Pitta kapha 14 (26.92%), Kaphapittaja 08 (15.38%). There were no Ekaprakriti patients detected during the study period [Table 8].
Time period of ADR after their admission shows that number of ADRs were seen in <3 days 36 (75.00%), between >3 days and <6 days it was 07 (14.58%) and very few ADRs were seen in >7 days 05 (10.41%) [Table 9].
| Discussion|| |
Observational studies help in understanding the tolerability profile of marketed medicines in a heterogeneous population and thus are an important source of evidence to know treatment outcomes. Pharmacovigilance is one such observational study which deals with evaluating and monitoring the safety of medicines and thus helps in identifying risk factors. Large numbers of such studies are carried in modern hospitals. But very little information is available for the ADR profile of Ayurvedic drugs.
In the present study, out of all admissions, 1.143% of patients experienced ADRs. This is minimal in comparison to a study carried in an Allopathic Hospital that is, 3.17–3.4%.,, Although this study used both spontaneous reporting and intensive reporting system for ADR monitoring, along with conducting regular seminars and guest lecturers among the Ayurvedic health workers and pharmacist to convey the importance in reporting ADRs in Ayurveda, there were more reports from intensive reporting method 48 (92.30%) with very few through spontaneous reporting 04 (07.69%) suggesting the lack of interest and subject ignorance among clinicians.
The ADRs were found more in female patients 28 (1.3%) than males 20 (1.03%) which are similar as reported by studies from Allopathic system.,, There were more number of ADRs from old age group (>40 years) patients 25 (1.27%) than other group (between 1–40 and <1 year) [Table 1] and [Table 2] this could be as females, children and old age group are believed to have low immunity (Alpabalayukta) and more susceptible for drug sensitivity.,
Season (Kala) one of the very important factor to considered during Ayurvedic treatment. It was observed that more numbers of ADR were seen in the Northern solstice period (Adanakala) 25 (1.18%) than the Southern solstice (Visargakala) 23 (1.10%). As Ayurveda believed, the Southern solstice is best for preventing the occurrence of diseases. In our study, it was observed that in Northern solstice occurrences of ADRs are more. Therefore, Ayurveda suggests the assessment of season before administering therapy plays a vital role in preventing drug events.
Wills and Brown ADR classification suggested that Type A reactions, 20 (38.46%) were more followed by Type U, which is unexplainable with Ayurvedic pharmacology (Rasapancaka). The study also observed Type D reactions, which might be due to a fault in drug delivery, which include the organoleptic character. One event was immaterialist wherein, suspected drug/therapy has no role in the occurrence of event hence, termed under pseudo allergic reaction.,
7 (13.36%) hypersensitive reactions observed in the present study and these are less than other reported studies. The cause would be selective drug allergy, idiosyncrasy, or pseudo allergic reactions to drugs. Familial (Type F) reactions were observed in 4 (07.69%). These types of reactions were seen in susceptible individuals by administration of drugs that are opposite to genetic constitution (Prakriti). There were no Type B, E, and G reactions, as the study was of short period the Type G (genetic toxicity) reactions, and Type B reactions (ADRs are related to microbial growth) could not be observed.
The causality assessment by WHO scale and Naranjo's ADR probability suggested possible and probable were more since, reactions were observed because of not only the drug, but also other factors like method of preparation of medicines, or improper diagnosis of disease.
Severity wise classification shows that moderate 20 (38.46%) to mild 30 (57.69%) reactions were more compare to severe 02 (03.84%). Wherein, other medical system results showed more severe (10.9%) reaction than other types. In observed ADRs, complete recovery was achieved in most and no permanent disability was seen and can be manageable over a period.
Therapy wise classification of occurrence of ADR suggested that more number were related to Panchakarma (detoxification process) treatment and most of them predominantly by an iatrogenic factor, of these very few were severe. Hence, Ayurveda has laid special precautions while practicing Panchakarma. Second main cause was found to be classical medications, and the reason could be irrational prescription, improper preparation or over dose of medication. There is misbelief that Rasaushadi are toxic and not safe in the community, but the current study shows ADRs pertaining to Rasaushadi were less in comparison to others.
GI system was most affected organ system by ADRs which could be due to the fact that oral is major route of drug administration in Ayurveda and site of digestion (Agni) is stomach and Ayurveda believe that most of the diseases occurring in human body is because of impaired digestion (Agnimandya). Skin related ADRs were second highest among the organ system affected; this could be because after the oral administration, skin is the second largest route of drug administration in Ayurveda and primary organ where, first sensitive reactions exhibits. Most of the hypersensitive reactions irrespective of drugs are seen on the skin. There were no cardio vascular, central nervous system and kidney related symptoms suggesting that Ayurvedic ADRs are mostly mild, self-limiting and do not affect the major systems.
Vata-Pitta Prakriti patients were maximum sufferers of ADRs rather than other Prakriti signifies that, among the Dwandvaja Prakriti (two-fold of constitution), Vata-Pitta Prakriti is most vulnerable  and Vata predominant  persons are more prone for drug events probably as Vata Prakriti is said to be nastiest among other Prakriti. No Ekadoshaja Prakriti (single constitution) patients were reported in our study as it is difficult to find Ekadoshaja Prakriti persons.
Skin rash was the most common symptom among reported ADRs which indicates that most of reaction of Ayurveda are mostly by the hypersensitive or skin allergy and it is thus easy to suspect the event. Diarrhea was the second commonest symptom of Ayurvedic ADRs, and this is similar as that of other studies., The commonest used route of drug administration is oral or rectal route hence the primary symptom would be probably diarrhea. Also, many of the reported cases were self-limiting and doesn't pose a much financial burden on the patient hence they are safe when compared with the other systems of medicines.
It is observed that most of the ADRs occurred within 3 days of admission to IPD most of them were from Panchakarma therapy. The drug intended events which occur in a short period are termed as Badhana (immediate effect) type of drug events. In fact, there were few ADRs developed after 3-day of admission but these cannot be considered under the chronic effect of the drug, as the patients were followed only for 7-day.
Each reported case was discussed with the intention of identifying the underlying drug cause. It revealed that faulty technique, Bizarre, and drug interaction were common causes in ADRs of Ayurvedic drugs [Table 10].
Conducted study was short termed hence, the chronic ADR related to Ayurvedic medicine could not be observed. Considering the patient discomfort, de-challenge and re-challenge were not followed. Low incidence of ADR could be due to loss of subjects during follow-up, owing to low awareness among patients, underreporting and unintentional ignorance of adverse effects by treating physician. There could be ambiguity in assessing ADR as it is difficult to trace the actual cause because a single formulation has many drugs, and mostly combinations of these are prescribed. So only a presumption can be made which is subjective.
All the detected ADRs were reported to National Pharmacovigilance program for ASU drugs Jamnagar, India.
| Conclusion|| |
Pharmacovigilance study is the need of the hour as they help in understanding the safety profile of medicines. The present work is first of its kind with respect to Ayurvedic medicine.
As observed in the present study, ADRs in Ayurveda are very less 1.143% of total admissions compared to modern systems of medicine. Female to male ratio was 1.28; most are mild to moderate and are not fatal but recoverable and preventable. GI and skin are the most frequent system affected. Skin rash and diarrhea were common symptoms. Panchakarma related drug events were found to be more frequent. Causality of ADRs of Ayurveda was probable to possible as per standard scales.
It has shows that maximum numbers of ADR in Ayurveda are iatrogenic in origin rather than medicine. The other causes include irrational prescription, drug interaction, good manufacturing practice concerns, etc.
Most of these ADRs can be prevented with a thorough knowledge of the texts. Pharmacovigilance is a certain challenge with Ayurvedic medicines as Ayurveda gives ample scope for the logical use of medicines based on various factors like Prakruti, Desha, Kala, etc., So the combination becomes multifold and varies from patient to patient and physician to physician. Also, proprietary medicines are also combined with the classical preparations making it further more complicated. Thereby causality analysis is difficult. The standard scales also need modification to suit ADRs of Ayurveda.
This epidemiological study was conducted not to test any hypothesis or to reach any conclusion; it was to generate the hypothesis. There is a need to test these issues associated with the Ayurvedic medicines which are responsible for causing adverse reactions and need attention, policies, training, and further experimental studies to prevent them.
The study which was a maiden in its nature to the Ayurvedic system, has provided base line information about the incidence of ADRs with their distribution and the data thus generated will help for more extensive studies.
Authors are very much grateful to Dr. Amit Kamte, JRF, Department of MRC, KLE Ayurveda Hospital, Belgaum and Dr. I.B. Kotturshetti, Principal and CMO Rajiv Gandhi Education Society's Ayurvedic Medical College, Hospital and PG Research Center, Ron, for valuable encouragement and support in generating data and publishing this manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]