1. ANTIHELMINTHICS (are drugs used to eradicate parasitic worms from the human body.) Dr. yasodha krishna janapati Associate Professor Dept. of Pharmaceutical Chemistry, College of Health Sciences (CHS), Ayder Campus, Mekelle University, Mekelle, ETHIOPIA. Krishna.yasodha@gmail.com 1

2. Helminths  Helminths (from the Greek Helmins, meaning worm).  Parasitic worms or helminths are a division of euk aryotic parasites that, unlike external parasites such as lice and fleas, live inside their host.  They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient absorption, causing weakness and disease. 2

3.  It has been estimated that about Half of country’s population suffers from helminthiasis, and number is on increase.  It is not only limited to tropical & subtropical countries, but is also endemic in many regions because of poor sanitation, poor family hygiene, malnutrition, and crowded living condition.  They are also causes blood loss, nutritional deficiencies, urticaria, allergic manifestation and even intestinal obstruction. 3

4. There are 3 classes of Helminths:  Nematodes (roundworms) Ascaris lumbricoides (roundworm), Enterobius vermicularis (threadworm), Trichuris trichiura (whipworm), Necator americanus and Ankylostoma duodenale (hookworms ).  Trematodes (flukes) Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum.  Cestodes (tapeworms) Taenia saginata, Taenia solium, Hymenolepis nana and Diphyllobothrium latum.. 4

5. Intestinal Worms A) Round worms (Nematodes)  Ascaris lmubricods (common, Round worm )  Enterobius vermicularis (pin worm)  Trichris trichuria (whip worm)  Strongyloids stercoralis (thread worm)  Ankylostoma dudenale (hook worm) 5

6. B) Tape worms (cestodes) Taenia saginata ( Beef) Taenia solium ( pork) Fish tapeworm – Diphyllobothrium latum  Humans become infected by eating raw or unde cooked meat containing larvae of infected cattle or pig.  In some cases the larva gets encysted in muscles, viscera, brain, eye resulting in cysticercosis 6

7. Tissue worms Filariae ( bancrofti, loa loa ) Adult filariae live in the lymphatics, causing lymphadenitis, swelling of limb. Microfilariae goes to blood stream to be ingested by mosquitoes Trichnella spiralis : larva migrats from intestine to tissues of leg or foot producing ulcer 7

8. ANTHELMINTIC DRUGS  Public health fights to reduce helminth infections in the US may be traced as far back as 1910, when the Rockefeller Foundation began the fight against hookworm – the so-called “germ of laziness” – in the American South  Are drugs used to eradicate parasitic worms from the human body.  Most anthelmintics in use today are active against specific parasites, and some are toxic.  Hence, the worms must be identified before treatment is started,usualy by finding the ova, parasite or larvae in the faeces, urine, blood, sputum or tissue of the host. 8

9. DRUGS Classified into 1.Benzimidazoles : Albendazole, Thiabendazole, Mebendazole. 2.Prazinoisoquinolines: Praziquantel. 3.Organophosphates: Metrifonate. 4.Piperazines: Piperazine, Diethylcarbamazine. 5.Others: Pyrantel, Niclosamide, Levamisole, Ivermectin, Oxamniquine, 9

10. Piperazine  Piperazine is used as an anthelmintic for the treatment of pinworm (Enterobius vermicularis) and roundworm (Ascaris lumbricoides) infestations.  Only recommended for the treatment of ascariasis cure rate 90% for 2 days treatment.  Readily absorbed orally and excreted mostly unchanged in urine  It is available in various salt forms, including the citrate (official in the USP) in syrup and tablet forms.  Treatment is continued for 3-4 days or repeated after one week in case of heavy infections. 10

11. Derivatives of Piperazine  Only piperazine shown anthelmetic activity  All the derivatives like 1-methyl piperazine and 4- methylpiperazine carboxamide does not have anthelmetic activity.  But diethyl carbamazine shown action against filariasis, including Bancroft, onchocerciasis, and laviasis.  It is also active against ascariasis. 11

12.  Relatively few adverse reactions have been associated with diethyl carbamazine.  It is usually available as citrate salt so it called as diethyl carbamazine citrate (DCC).  Mechanism of action: Causes paralysis in worms by blocking acetylcholine at myoneural junction, the live worms expelled by normal peristalsis.  Synthesis of DCC 12

13. Benzimidazoles : Albendazole, Thiabendazole, Mebendazole. 13 Thiabendazole

14. ALBENDAZOLE Broad spectrum Drug of choice for treatment of hydatid disease and cysticercosis. Used for the treatment of (intestinal nematodes) e.g. ascariasis, tricurasis and strongyloidiasis, pinworm, hookworm. MOA Inhibits microtubule synthesis that irreversibly impairs glucose uptake, intestinal parasites are immobilized and die slowly. Adverse effects such as bone marrow depression, elevation of hepatic enzymes, and alopecia.

15. MEBENDAZOLE (Vermox) Synthetic benzimidazole Broad spectrum and safer than albendazole Mechanism of action: Mebendazole irreversibly blocks glucose uptake in susceptible helminths, thereby depleting glycogen stored in the parasite. It apparently does not affect glucose metabolism in the host. It also inhibits cell division in nematodes. It kills hookworm, pin worm, ascariasis and trichuris eggs.

16. Adverse Effects & Precautions Short term therapy.Mild GI disturbance. High dose : hypersensitivity reactions, agranulocytosis, alopecia,elevation of liver enzymes. Used with caution under 2ys of age may cause convulsion. Contraindicated in pregnancy.

17. Thiabendazole Mechanism as other benzimidazole Chelating agent and form stable complexes with metals including iron, but does not bind with calcium. Thiabendazole has broad-spectrum anthelmintic activity. It is used to treat enterobiasis, strongyloidiasis (threadworm infection), ascariasis, uncinariasis (hookworm infection), and trichuriasis (whipworm infection). It has also been used to relieve symptoms associated with cutaneous larva migrans (creeping eruption) and the invasive phase of trichinosis. In addition to its use in human medicine, thiabendazole is widely used in veterinary practice to control intestinal helminths in livestock.

18. Worms (helminths)Drug of choice Tapeworms (cestodes) Niclosamide or Praziquantel or Albendazole Roundworms (nematodes) Enterobius vermicularis (pinworm) Ascaris lumbricoides Trichuris trichiura (whipworm) Trichinella spiralis (trichinellosis) Strongyloides stercoralis Necator americanus (hookworm) Ancylostoma duodenale Onchocerca volvulus (Onchocercosis) Wuchereria bancrofti (Elephantiasis) Mebendazole or Pyrantel Mebendazole or Albendazole Mebendazole and Thiabendazole Thiabendazole Mebendazole or Pyrantel Mebendazole, Pyrantel, or Albendazole Ivermectin Diethylcarbamazine Flukes (trematodes) Schistzoma (Schistozomes) Praziquantel

19. Insecticides Chlorphenothane (DDT – Dichlor-Diphenyl-Trichlorethan)  Kills insects after absorption of a very small amount, e.g. via foot contact with sprayed surfaces (contact insecticide).  The cause of death is nervous system damage and seizures.  In humans DDT causes acute neurotoxicity only after absorption of very large amounts.

20. DDT is chemically stable and degraded in the environment and body at extremely slow rates. As a highly lipophilic substance, it accumulates in fat tissues. DDT Widespread use of DDT in pest control has led to its accumulation in food chains to alarming levels. For this has now been banned reason its use has now been banned in many countries.

21. Elephantiasis (Lymphatic filariasis) of the lower extremity associated with Wuchereria bancrofti infection

22. THANK YOU 22