natural antimalarial drugs

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A SEMINAR ON “ANTIMALARIAL DRUGS” (FROM NATURAL ORIGIN) 1 SHRAVAN KUMAR M.PHARM (PHARMACOGNOSY)

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CONTENTS 1)INTRODUCTION. 2)HISTORY. 3)SYMPTOMS. 4)INCUBATION PERIOD. 5)THE AIM OF USING ANTIMALARIAL DRUGS. 6)LIFE CYCLE OF MALARIA PARASITE. 7)TRADITIONAL ANTIMALARIAL DRUGS. 8)RECENT ANTIMALARIAL DRUGS. 9)REFERENCES. 2

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INTRODUCTION ANTIMALARIAL DRUGS ARE USED FOR PROPHYLAXIS ,TREATMENT, & PREVENTION OF RELAPSES OF MALARIA . Malaria caused by four species of protozoal parasite Plasmodium (P.falciparum, P.ovale , P.vivex , P.malariae ) & is endemic in most part of India & other tropical countries. It is one of the major health problem. As per WHO estimates there are 300-500 million cases globally 1.5-2.7 million deaths occur due to malaria each year, 90% of which are in Africa. 3

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HISTORY : In India the National Malaria Eradication Programme (NMEP) , started in 1958. There was a target for complete disappearance of this disease upto 1960s. However to the development of insecticidal resistance among mosquitoes and other factors, it was concedeing that eradication of malaria is not possible. Therefore NMEP has been renamed National Antimalarial Programme. In 2001 NAMP has reported > 2 million malaria cases, out of which approx. 48% were due to Plasmodium falciparum with 1003 confirmed deaths. WHO estimates that actual number of malaria cases in India is 6 times more, i.e. 12-15 million. 4

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SYMPTOMS There are 3 stages of distinctive symptoms :- STAGE 1:- It is characterised by uncontrolable shivering for 1-2 hours . STAGE 2:- The patients temperature rises quitly up to 1060 F. STAGE 3:- The patient begins to sweat and his/ her temperature drops rapidly. After the third stage the patient often falls asleep from exhaustion. 5

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INCUBATION PERIOD An incubation period is the time between the mosquite bite and appearance of malarial symptoms. The incubation period differs depending upon the kind of parasite involved. For most serious form of malaria the incubation period may be 8- 12 days. In some rare form of malaria the incubation period can be as long as 10 months. 6

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THE AIMS OF USING DRUGS IN RELATION TO MALARIA INFECTION ARE :- 1 ) To prevent and treat clinical attack of malaria . 2) To completely eradicate the parasite from the patients body . 3) To reduce the human reservoir of infection and cut down transmission to mosquito. 7

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LIFE CYCLE OF MALARIA PARASITE:- VECTOR- Female Anopheles mosquito . SPECIES- Anophlese gambiae. ASEXUAL CYCLE (INSIDE HUMAN….) A person infected with Plasmodium is biten by a (female) Anophlese mosquito. Biting insects often injects a small amount of saliva before sucking out blood . The saliva contains an anticoagulents which prevents blood clotting , simultaneously entry of Plasmodium (sporozoits) occurs . These sporozoits passes into the blood stream , & quickly into the liver & invade the liver tissue & other body organs including the brain. Over 5-16 days , the sporozoites grows , divide , & produce thousands of haploids(cells containing half sets of chromosomes) called merozoites . The merozoites exit the liver cells & re-enter the blood stream, & invade the RBC ,asexual replication , & release newly formed merozoites from RBC repeatedly over 1-3 days . 9

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6) When infected RBC burst it releases immature male & female gamatocytes that circulates in blood stream. SEXUAL CYCLE (INSIDE MOSQUITO….) When a mosquito bites to infected human ,it ingests the gamatocytes & forms mature gametes in mosquito gut wall linings. Male & female gamets fuse to form diploid zygotes which developed into actively moving ookinetes that burrow into the mosquito mid gut wall & forms oocysts. Growth & division of each oocysts produces thousands of active haploids form called sporozoites . After 8-25 days the oocysts burst & releasing sporozoites into the body cavity of mosquito, from which they travel to & invade the mosquito salivary glands . The cycle of human infection re-starts when the mosquito takes blood meal & injecting the sporozoites from its salivary glands into the human blood stream. 10

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TRADITIONAL ANTIMALARIAL DRUGS 11

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MECHANISM OF ACTION:-- Quinine is an alkaloid that acts as a blood schizonticidal and weak gametocide against Plasmodium vivax and Plasmodium malariae,like chloroquine , it is weak base gets concentrated in vacuoles of the plasmodium species, specially P. falciparum. It acts by inhibiting polymerization of heme to hemozoin, free heme or heme-quinine complex damages parasite membranes and kills it. However, the exact MOA is not known. 12

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OTHER PHARMACOLOGICAL ACTION : LOCAL IRRITANT AND ANAESTHETIC GASTRIC SECRETION CNS STIMULANT HYPOTENTION (Rapid i.v.) HYPOGLYCAEMIA DECREASES SKELETAL MUSCLE CONTRACTION PHARMACOKINETICS : Quinine is rapidly & completely absorb orally. It is 70% bound to the plasma proteins, specially α1 acid glycoprotein. A large fraction of the doses metabolised in liver & excreted in urine with a t1/2 of 10-12 hrs. 13

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ADVERSE EFFECTS : Cinchonism – ringing in ears, nausea, vomiting, headache, mental confusion, vertigo . Tinnitus- a hearing impairment . Neurotoxicity- Quinine causing a decrease in the excitability of the motor neuron end plates resulting confusion, & coma. Quinine can cause hypoglycemia through its action stimulating insulin secretion. Repeated or over-dosage can result in renal failure & death through depression of the respiratory system. Quinine occasionally causes haemolysis, specially in pregnant women & in patients of falciparum malaria, resulting in haemoglobinuria (black water fever) and kidney damage. 14

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DOSE : It can be given by oral, i.v., i.m. routes. “The WHO recommendation for quinine is 8mg / kg TDS for three days & for 7 days ( where parasites are sensitive to quinine)”. USES : Quinine is used orally for uncomplicated chloroquine resistant malaria, & i.v. for complicated / cerebral malaria (chloroquine sensitive or resistant). 15

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3) Cerebral malaria- quinine (i.v.) is the drug of choice for cerebral malaria (falciparum malaria) : 600mg(10mg/kg)of quinine dihydrochloride is diluted with 200-500ml 5% glucose solution & infused i.v. over 4 hrs. This is repeated every 8 hrs till the patient is conscious . 4) Quinine (300mg) a single tablet used for Nocturnal muscle cramp. 5) Spermecidal: in vaginal creams etc . 16

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RECENT ANTIMALARIAL DRUGS :- #Anti-malarial activities of Andrographis paniculata & Hedyotis corymbosa extracts & their combination with curcumin. “The present study assessed the anti malarial property of 2 Indian traditional plants, A. paniculata & H.corymbosa, individually & in combinations & compared their activity with curcumin.” RESULTS :- The 50% inhibitory concentration(IC50) of A. paniculata (7.2μg/ml) was found better than H. corymbosa (10.8μg/ml). Combination of these two herbal drug showed substantial enhancement in their anti-malarial activity . 23

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Combnatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP+HC) and their individual synergism with curcumin (AP+ CUR, HC+ CUR) were evident from this study . Increased in-vivo potency was also obsered with the combination of plant extracts over the individual extracts & curcumine. Both the plant extracts were found to inhibit the ring stage of the parasite & did not show any in-vivo toxicity, whether used in isolation or in combination. 24

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OTHER RECENT ANTIMALARIAL DRUGS :- 1) Acorus calamus Linn {Bach} Family:- Araceae Chemical constituents:- calamen ,calameon , calamenol , asarone. USES:- a) Dried rhizome contain aromatic volatile essentile oil having above C.C. & used as carminative, stomachic , febrifuge, antibacterial, insecticidal, agent. b) The rhizome extract (2 TSF BD for 5 days) bringing down temperature of malaria fever by perspiration. 25

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2) Andrographis paniculata (Kalmegh) Family- Acanthaceae Chemical constituents- andrographin, andrographolide, kalmeghin Uses- febrifuge, anthelmintic, stomachic, “Decoction of the whole plant (10ml BD for 5 days) shows antimalarial activity.” 26

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3) Azadirachta indica (Neem) Family- Meliaceae Chemical constituents- nimbin, nimbinin, nimbidine. Uses- antipyretic, antifertility, antidiabetic, spermicidal, wound healing. “ A decoction of leaves & bark is a bitter tonic & alternative in chronic malarial fever as a dose of 5ml TDS for 7 days .” 27

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4) Bacopa monnieri ( Brahmi) Family- Scrophulariaceae Chemical constituents- The two steroidal saponins (bacoside A & B), bacosaponins, alkaloids, flavonoids, glycosides,betulic acids,Phytosterols, Uses- Plant extract has anxiolytic, memory enhancing, relaxing, antioxident, & immune modulating activities. 28

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5) Calotropis procera (Aak) Family- Asclepidiaceae Chemical constituents- calotropin, calotoxin, uscharin . Uses- Antimicrobial (cures several ailments) “The powder of root bark (10gm BD for 5 days) is recommended for malarial fever. 29

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6) Eclepta prostata (Bhringraj) Family- Asteraceae Chemical constituents- Ecleptin, lactones,resins etc. Uses- Emetic , purgative, antiseptic, antiulcer, antiviral, hepatoprotective . “The juice of whole plant (5ml TDS for days) is useful to cure malaria.” 30

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7)Momordica charantia (Karela) Family-Cucurbitaceae . Chemical constituents- Charantin,momoridicine,carotine,glucoside,& highly aromatic essential oil. Uses- Hypoglycemic, astringent, purgative, anthelmintic, emetic . “Bitter leaf juice (2 TSF TDS for 5 days) shows antimalarial activity.” 31

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8)Ocimum sanctum Linn ( Tulsi ) Family- Lamiaceae . Chemical constituents- Eugenol, methyl eugenol, Carvacrol, Saponin, Tannins. Uses- Analgesic, anti-inflammatory, antiallergic antiulcer . “The extract of fresh leaves is a native medicine for malarial fever.” 32

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9) Rauwolfia serpentina (Sarpgandha) Family- Apocyanaceae . Chemical constituent- Reserpine, serpentine, Uses- Cardiotonic(hypotensive), antidote to snakebite. “Root extract is used as febrifuge to reduce the temperature in all kind of fever including malaria”. 33

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10) Tinospora cardifolia (Giloya) Family- Menispermaceae . Chemical constituents- The active glycoside is giloin . Uses- It is used in jaundice,diabetes, gynacological & joint disorders . Also having antiviral,antibacterial, & hypoglycemic activity. “The fine powder of dried stem prescribed (10gm BD for 5 days) for the treatment of malarial fever”. 34

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REFERENCES:- Tripathi K.D., “Essentials of Medical Pharmacology”, fifth edition-2003, Jaypee Brothers Medical publishers (P) LTD. ,New Delhi , pp.no. 735- 736 . Kokate C.K., Purohit A. P., & Gokhale S.B., “Pharmacognosy”, thirty- seven edition- 2007 , Nirali Prakashan, pp no. 499 – 501, 369 – 370. Dwivedi S., “Medicinal Plants used to Cure Malaria”, Farmavita. Net. Journal, Nov. 2007, pp. no. 1-2. Mishra K., Dash A. P., Swain B. K. and Dey N., “Antimalarial activities of Andrographis peniculata and H edyotis corymbosa extracts and their combination with curcumin”, Pubmed Central jurnal, vol. 8, 2009, pp. no. 1-10. html:fle://c:\Documents/maliria/feed back. http//Life cycle of malaria paracite. Html., “Nation Institute of allergy and Infectious Diseases- Leading research to understand, treat and prevent infectious, immunologic, and allergic diseases”, pp no. 1-2. 35

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7) “The History of Traditional chinese medicine”, http://www. beijingmuseum.gov.cn/culturehistory/html., Retrived 2007, pp no. 12-19. 8) White N. J., “Antimalarial Drug Resistance”, J. Clin. Invest., vol. 113 (8), pp no. 1084- 1092. 9) Ridley R. G., “ Medical need, Scientific opportunity and the drive for antimalarial drugs”, Insight Review Articl, Fab. 2002, vol. 415, pp no. 686- 693. 36

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THANK YOU 37