KARAVEERA.pptx

Nerium plant. One among cardia poisons and upavisha according to Ayurvedic categorization.

1. KAR A VEERA Dr Anu Mariam Varghese II nd MD Scholar Dept of Agadatantra GAVC,TVM

2. C ONTEN T S O Cases O Prevalence O In Ayurveda O Introduction, synonymous, Types, Class of poison O Botanical description O Toxic principles, Toxicodynamics and Toxicokinetics O Toxic part, Fatal dose, Fatal period O Diagnosis,Treatment ,PM appearance O Medicolegal importance O Sodana, Parts used, medicinal dose O Therapeutic uses, folkfore uses, Antidote O Agada yogas and other yogas O Research works O References

3. Case 1 O A 14 years old boy presented with vomiting, loose stools and giddiness. O Had a history of consumption of 1 oleander.. O Examination revealed bradycardia with irregular rhythm O Electrocardiograph (ECG) showed sinus bradycardia with pauses. O Stomach wash was given with activated charcoal. Temporary pacemaker implantation was done. Pacemaker was removed at the end of 48hours as ECG showed normal pulse rhythm. O DIAGNOSIS : Yellow oleander poisoning

4. CASE 2 O . A 42-year-old woman with a known history of malignant mesenchymal cancer was admitted to the emergency department with vomiting, gastrointestinal distress and cardiac symptoms with digoxin- like toxicity of 4 hour duration. Her complaints began within an hour of ingesting a bowl of Nerium oleander blooms which she took to reduce the pain caused by the cancer O . Oleandrin was detected in the blood sample at a concentration of 14.7 ng/ml. O With the conservatie management the patient became stable O DIAGNOSIS : Oleander poisoning

5. PREVALENCE O In India, the overall percentage of plant poisoning ranges from 6% to 15%, and for rural population alone it can be high as 63% and the oleander contributes most. O Most imp cause of livestock poisoning reported in South Africa. O At present yellow oleander poisoning has a 10% mortality rate in Sree Lanka O Ranks equally with mushrooms as major cause of children’s admission to hospital after accidental plant ingestion worldwide.

6. IN AYURVEDA -KARAVEERA O Mentioned in Brhatrayis, Laghutrayi s and Nighantus. O One among upavisha in later texts like RT, RRS, YR etc..

7. Common Oleander Yellow Oleander O Nerium odorum Nerium indicum O Apocynaceace C o mmon n a mes O White oleander, Pink oleander, Rose laurel, Rose bay, Rosa francesca, Laurier rose, Adelfa O Cerbera thevetia, Thevetia peruviana, T.nereifolia O Apocynaceae O Bastard oleander, Exile oleander, Be-still tree, Lucky nut, Tiger apple

8. O Regional name O Sankrit name O Hindi O Tamil : Arali : Karaveera : Kaner, Kanail : Alari O Synonymous Hyamaraka or Asvamaraka Karaveera Chandata Sataprasaha Pratihasa A nguli p a t r a k a

9. - Systemic ; Cardiovascular C l a s s o f p o i so n O Modern O Ayurvedic Charaka, Susrutha ,AS – Moola visha among sthavara BP, RT, RRS, YR - Upavisha O Types – 3 varietes ; Kaiyadeva Nighantu, Bhavaprakasha Nighatu Sveta, Rakta, Peetha Raja Nighantu – 4 varities ; Sveta, Rakta, Peetha, Krishna

10. Karaveera mentioned as Upavisha a/c different texts R.R.S R.T Y.R B.P R.S.S R.C R.K.D RVM R.Ci A.P Karaveera + + + + + + + + + - R . S.S R.C Rasendra Sara Sangraha Rasendra Chudamani R.K.D –Rasa Kamadenu RVM – Rasarnavam R.Ci – Rasendra chintamani A.P – Ayurveda Prakasha

11. Classical categorization Charaka Kushtaghna, Tikta skandha, Moola visha varga, Tikta varga Susrutha Lakshadi gana, Siro virechana gana, Moola visha varga, Tikta varga Vagbhata Lakshadi gana Bhavaprakasha Nighantu Guloochyadi varga, Vishoparisha varga Raja Nighantu Karaveeradi varga Shodala Nighantu Karaveeradi varga, Paniya varga Saligrama Nighantu Guloochaydi varga Madhanapala Nighantu Hantakyadi varga Dhanwanthari Nighantu Upavishagam of Misrakadi sapthamovarga

12. BOTANICAL DESCRIPTION Common Oleander O Habitat Many subtropical and tropical areas of the world. Large evergreen ornamental shrub, 2-6 meters height O Leaves Long, narrow, lanceolate, leathery, dark-green on upper surface, lighter beneath, 10-25 cm Yellow Oleander O evergreen tropical shrub or small tree, Ornamental (grows to about 30 feet height) O Pointed, lanceolate , dark green upper surface, lighter green undershades, edges- rolled

13. Common Oleander Yellow Oleander O Flowers Pink,or white fragnant flowers ( with terminal clusters O Fruit Long narrow capsule, 8 to 10 cm long, split open at maturity to release numerous downy seeds O Seeds Pod is slim, cylindrical, ribbed , turns brown, dries and splits, releasing small seeds tipped with coma of light brown hairs, light and dusky O large ,yellowish funnel shaped flowers O Globular, light green, contains single nut which is triangular with a deep groove along edge. O Each nut contains 5 pale yellow seeds. Seeds are vaguely heart shaped.

14. RASA P ANCH AKA Rasa Guna V e e r ya Vipaka : Katu, Tikta, Kashaya : Laghu, Rooksha, Teekshna : Ushna : Katu Doshakarma Prabhava Karma : kaphavatasamana : Hridya : Hrdhya, Raktasodhana, Svasagna, Kushtagna, Kandugna, Swedajanana, Jwaragna, Bandaka, Vrnasodhana, Ropana, Sothahara, Deepana, Vidahi, Pachana, Bhedana

15. TOXIC PRINCIPLES Yellow Oleander Common Oleander O Cardiac glycosides- Oleandrin (oleandroside) Nerin (nerioside) Folinerin Rosagenin Digitoxigenin Neriodorin, Neriodorein Karabin Oxalate crystals (leaves) Peruvoside Ruvoside Thevetin A Nerifolin Cerberin Thevetin B

16. TOXICOKINETICS Cardiac glycosides- Toxic to cardiac myocytes and autonomic system O Inhibit Sodium- Pottasium ATPase O Increasing Cardiac Contractibility O Decreasing AV conduction and heart rate. A cardiac glycoside has 2 parts 1- carbohydrate , 2- aglyconic portion Carbohydrate- imp for solubility ,absorption and bioavailability. Aglyconic portion – divided into steroid backbone and unsaturated lactone ring- role in primary interaction with receptor

17. Inhibit Na+-K+ -ATPase pump an extracellular portion of the pump Binding occurs within Decreases the active transport of Na+ with consequent excretion of pottasium Increased intracellular sodium levels leads to inhibition of NCX( Na+/ Ca 2+ exchanger) Increased level of Ca 2+ in intracellular space positive inotropic effect of cardenolides and toxicity Na, Ca cause partial membrane depolarisation which increases automaticity and ventricular ectopy

18. IN CARDINOMYOCYTES O Leads to increased contractibility ( + ve inotropic effect) O Reduce velocity of electrical conduction ( -ve dromotropic effect) via AV node depression. O Reduction of heart rate( -ve chronotropic effect) via SA node depression. O In neurons of vagal nerve leads to reduced velocity of elec t ric al co nd u cti on which ca u ses red u ced he a r t ra t e via a reflexive reduction of sympathetic transmission

19. OLEANDRIN O Due to prominent lipophilicity. O Results in slow urinary excretion. O Longer duration of action as cardio toxic agent. O Rapid and conspicuous GI absorption with bioavailability 3 % .

20. TOXICODYNAMICS INGESTION Frothy salivation Difficulty in swallowing & articulation Tingling and burning sensation in mouth and tongue. Dryness of throat GIT Vomiting, •Pain in the abdomen Nausea Di a r r hea CVS Pulse first slow , later rapid and weak Hypotension A V b l ock

21. Marked bradycardia –Acute overdose Ventricular tachycardia –severe toxicity Ventricular Fibrillation CNS Locally Skin contact dermatitis Delirium Lethargy Dizziness Drowsiness Occasionally seizures and coma Rarely xanthopsia Headache

22. O Tetanic spasm O Lock jaw O Hyperkalemia – severe poisoning common O Metabolic acidosis O Asphyxial symptoms -later O Respiratory paralysis , Death Inhalation Headache Respiratory difficulty Dizziness Nausea

23. In Ayurveda, O Moola visha lakshana –Susrutha Udweshnam - Voluntary stretching of the body Pralapam - Delerium Moham – Delusion

24. Common Oleander Yellow Oleander O T o x i c p a rt All parts esp root, including nectar seeds = roots > fruits > leaves O F at a l d os e 15-20 g root 5-15 leaves O F at a l p e r i od 20-36 hours All parts esp seeds and root seeds = roots > fruits > leaves O 8-10 seeds 15-20g root 5-10 leaves O 2-3 hours

25. DI A GNOSIS O Radio-immunoassay O Fluroscence polarization immunoassay O Thin layer chromatography O Fluroscence spectrophotometry O Reverse –phase HPLC and HPLC/MS –more specific O Liquid chromatography(LC) with high resolution masspectrometer (HRMS) O LC-MS/MS - best of forensic interest

26. E C G Potentially severe cardiac arrhythmias Premature ventricular beats. T-wave inversion or flattening. Deformed ST segment( “scooped” or “sagging” ST segments) ↓ QT interval ↑PR interval Atrial tachycardia with AV block.

27. TREATMENT O Gastric lavage, activated charcoal O Measure urea, electrolytes, magnesium and creatinine. Serum potassium correlates cardiac toxicity. O Hyperkalemia life threatening – IV bicarbonate, glucose, insulin. O ECG monitoring O Cardiac arrhythmias with anti rhythmic drugs O Correction of fluid and electrolytic imbalances

28. O Atropine , Adrenaline, Noradrenaline for sinus bradycardia and A-V block O Digoxin-specific antibody fragments (Anti-digoxin fab fragments) O Correct hypotension by adequate fluid resuscitation with a crystalloid. O Correction of metabolic acidosis O Hemodialysis or hemo perfusion O Symptomatic treatment.

29. According to Ayurveda Buffalo curd mixed with sugar Buffalo milk with powder of arka twak.

30. O Same treatment mentioned in KriyaKoumudhi

31. POSTMORTEM APPERANCE Common Oleander O Not characteristic O Congestion of organs. O Fragments of root may be present in the stomach O Petechial hemorrhages seen on surface of heart O Can be detected long after death. O Resist heat ,therefore can be detected even from burnt dead body Yellow Oleander O Not specific O Stomach and deodenum may be congested O May show fragments of seeds O S ube n doca r di al ecchymoses O Resists putrefaction and can be detected long after death in exhumed putrefied bodies

32. MEDICOLEGAL IMPORTANCE O Accidental poisoning - from its use in traditional medicine Herbal tea Children and animals may be attracted by its flowers Smoke from burning plant. When plant material used as firewood poisonous sap transferred into food may be lethal Root is taken internally for treating venereal diseases. Root , used for treating cancers and ulcers as paste. Decoction of leaves externally to reduce swelling O Suicidal – decoction or paste prepared from leaves, fruit or root is common in rural areas.

33. O Homicidal rare – Powdered kernel of fruit mixed with alcohol. O Abortifacient , root either locally or taken internally O Cattle poison – juice of root is applied on piece of cloth and inserted into anus of animal. Also seeds are crushed and fed to animal with corn or bread.

34. SODHANA O Dolayantra swedana of Karaveera with cow’s milk for 3 hrs Then wash with hot water and get dried ( Yogaratnakara ) Cardenolide content less in post sodhana sample Preparative TLC and LC-MS showed reduction in oleandrin peak

35. Principles Pre Shoditha Post Shoditha Saponins Absent Present Alkaloids Present Absent Carbohydrates Present Present Proteins Present Present Steroids Present Present Triterpinoids Present Present And in the post sodhitha sample absolute absence of symptoms found in toxicity studies that when compared with pre sodhitha sample.

36. P A R T USED O Moolam, Moolatwak, Patrm MEDICINAL DOSAGE Choorna : 30-125 mg (API)

37. THERAPEUTIC USES Cardio tonic Antipyretic Anti helminthic Antiseptic Cardiac asthma Circulatory disorders Fever Leprosy Respiratory disorders Skin diseases Anti-inflammatory Antimicrobial Locomotor activity Anti-Leukemic Anticancer Immuno-modulating Diuretic

38. O In Indralupta after Gada prachana ,lepana with juice of Karaveera and honey is mentioned (AH.U.24.29) O In Sannipata Udara along with madya moolakalka of Kakadani, gunja and Karaveera mentioned (visha prayoga) – (AH.Chi. 15.78) O In Arsas , for lepana leaves of Karaveera along with other drugs like sigru, nimba etc.. macreated with snuhi ksheera mixed with hingu mentioned – (AH.Chi.8.23). O In Kikkisa , Karaveera patra sidha Taila abhyanga for mardana mentioned –(AH.Sa.1.61)

39. O Kaphaja Visarpa – Lepana of karaveera with other drugs like triphala, ushira ….- (Ca.Chi 18.14) O Visha Chikitsa – If any visual impairement, Anjana by devadru, trikatu,karaveera etc by triturating with ajamootra.(Ca.Chi .23.69) O Apachi – karaveera taila is used as nasya (Su.Chi.18/22)

40. FOLKLORE USES O Administration of choorna of root bark of Nerium oleander cures Bronchitis, Bronchietasis, Emphysema. O The seed oil is applied externally to treat skin infections. O Toxic bites- External application of Nerium oleander. O Dermatitis – Macerated leaved of oleander may be applied. O Macerated leaves of oleander also used in superficial tumor, syphilis, loss of hair. O Gingivitis –Decotion of oleander leaves have been used.

41. ANTI D O TE O Antidote for Karaveera is Haritaki

42. A GA D A Y OGAS O Sarvakarmika Agada – friuts and flowers of Karaveera –AH.Utt.36.70 O Yapana Agada – AS.Utt 40.68.

43. OTHER YOGAS O Malathyadi Tailam O Kanakaksheeri taila O Vajraka Tailam O Brhat kaseesadi Tailam O Karaveera Tailam O Karaveeradya Tailam – AH.U.24/24 – Ca.Chi 7/114 – Su.Chi 9/54, AH.Chi 19/79 – BP.5/60-62 - Chakradhatta 50/49 – Rasa Tarangini 24.493

44. RESEARCH WORKS O Studies available regarding yellow oleander as a weight loss supplement, antibacterial, antifungal, anti inflammatory effects etc... O Anti cancer agent – Leaf extract of Nerium oleander L. inhibits cell proliferation, migration and arrest of cell cycle at G2 /M phase in HeLa Cervical Cancer Cell. O Oleandrin : A bioative phytochemical and potential cancer killer via multiple cellular signaling pathways. O Phytoremediation for urban landscaping and air pollution control- a case study in Trivandrum city, Kerala, India. (pubmed)

45. O Analytical study of effect of sodhana on peetha karaveera moola (Thevetia nerifolia juss ex Steud)- Praseethamol.K, K.V.G Ayurveda medical college, Sullia. O A comparative analytical study of moola of sweta karaveera (Nerium indicum Mill) and peeta karaveera (Thevetia nerifolia juss)w.r.s to its purification –Dr Pavithra. P, K.V.G Ayurveda medical college, Sullia. O Safety and efficacy of karaveeradi taila as Lomashaatana on healthy volunteers – Dr Anjana Mohan , K.V.G Ayurveda medical college, Sullia. O Pharmacological and phytochemical evaluation of karaveera beeja (Thevetia nerifolia Juss ex Steud) w.s.r to its purificaion- Dr.U.Santhosh Nayak, Alva’s Ayurvedic medical college & hospital.

46. REFERENCES O https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723884/ (assessed on 11 may 2021 10.32 am) O https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996654/ (assessed on 11 may 2021 11.52 am) O Comprehensive Medical Toxicology,3 rd Edition ;V V Pillay,page no 963 O The essentials of forensic medicine &Toxicology; 34 th edition Dr K.S N Reddy ; Dr O P Murthy, page no 573 O International Journal of Applied Ayurved Research ISSN: 2347-6362 ; A review of Karaveeraand its therapeutic utlitity

47. O Rasa Tarangini of Sri Sadananda Sarma; Dr Ravindra Angadi, 1 st edition, page no 484-485. O Pharmacological and phytochemical evaluation of karaveera beeja (Thevetia nerifolia Juss ex Steud) w.s.r to its purificaion- Dr.U.Santhosh Nayak. O Kriyakoumudhi-V.M .Kuttikrishna Menon page no 751 O A textbook of Agadatantra – Dr .U.R.Sekhar Namburi, page no 110-114. O A textbook of Agadatantra- Dr Sobha Bhat.K, page no 138- 142

48. YOU ARE ONLY CONFINED BY THE WALLS YOU BUILD YOURSELF