Anthelmintic drugs.pptx

SAR of Anthelmintic drugs

1. ANTHELMINTIC DRUGS DR. MANJOOR AHAMAD SYED ,                             M.Pharm,Ph.D Associate. Professor  Department of Medicinal Chemistry,  College of Public Health and Medical Sciences, Mettu University, Mettu Post Box No-318 Ethiopia.

2. ANTHELMINTHIC DRUGS Definition: Anthelmintic are the drugs or agents which are capable of eradicating worms and helminth parasite from the body are termed as Anthelmintics. INTRODUCTION: Helminthics infections are the major health problem in tropical countries. Helminths (worms) can cause various Gastrointestinal and general symptoms. They also cause blood loss, nutrition deficiency, urticaria, allergic manifestations and even intestinal obstruction. Humans are the primary hosts for many helminth infections. Most of the worms reproduce sexually in human host producing Eggs and Larvae which pass out of the body and infect secondary or intermediate host. Helminths mainly cause infection by living in hosts alimentary canal or in other tissues of the hosts’ body.

3. Classification of helminth parasites: Nemathelminths Platy helminths NEMATHELMINTHS They are subdivided into following seven species. Hook worms: They attach themselves to mucosa of duodenum and sucks blood from surrounding blood vessels for their nourishment. They are basically two types American variety: Nicator americanus European variety: Acyclostoma duodenal b. Round worms: They will acquire upper part of small intestine. E.g. Ascaris lumbricoides   c. Whip worm: These are whip like mostly present in the Cecum and also in appendix and lower parts of Ileum.

4. d. Whip worm: These are whip like mostly present in the Cecum and also in appendix and lower parts of Ileum.   e. Pinworm: These are also called thread worms resides mainly in small intestine, cecum and colon. E.g. Enterobias vermicularis.   e. Trichinella spiralis: It is also called Trichinosis; infections mainly result from ingestion of improper cooked pork which contain larvae of worm.   f. Wucheraria Bancrafti: It is a kind of filarial worm transmitted usually by mosquito bite, resulting in the blockage of lymphatic ducts. g. Strongyloidiasis stercoralis: Mainly resides in the duodenum.

5. 2 . PLATY HELMINTHS These are also called Flatworms, and they are devided into following two groups. Cestodes (Segmented cestodes) ii. Trematodes (Non-segmented trematodes)   Cestodes (Segmented cestodes): These include tape worms of following four categories. Beef tapeworm – Taenia saginata Pork tapeworm – Taenia solium Fish tapeworm – Diphyllobothrium latum Dwarf tapeworm – Hymenolepis nana Trematodes (Non-segmented trematodes) Flukes present mainly in the blood stream and are known to cause epigastric distress, abdominal pain, diarrhoea, blood and mucous in the stool etc. E.g. Schistosoma Haematobium, Schistosoma Mansoni, Schistosoma Mekongi

6. CLASSIFICATION OF ANTHEMINTIC DRUGS Based on their chemical structure they are classified in to following types 1 Piperazines Diethylcarbamazine citrate (DEC), Piperazine citrate 2 Benzimidazoles Albendazole, Mebendazole & Thiabendazole. 3 Heterocyclics Oxamniquine, Praziquantel 4 Amides Niclosamide 5 Nitro derivatives Niridazole 6 Imidazothiazole Levamisole. 7 Natural products Ivermectin, Avermectin 8 Vinyl pyrimidines Pyrantel, Oxantel.

7. PIPERAZINE Synthesis : Mechanism of Action: The drug exerts its effect mainly by blocking ASCARIS MUSCLE response towards Acetylcholine and thereby causes Neuromuscular blocking, which results muscle paralysis of the worms and consequently dislodged to expelled in the faeces. Adverse drug reactions: Abdominal pain, bronchospasm, muscular incoordination, confusion, blurred vision. Uses: Anthelmintics are used in the treatment of worm infections. Piperazine is used to treat: common roundworms (ascariasis) and. pinworms ( enterobiasis ; oxyuriasis ).

8. Synthesis : Uses: Diethylcarbamazine is used to treat certain parasitic diseases caused by  infection  with roundworms of the Filarioidea type, including lymphatic filariasis caused by  infection  with Wuchereria bancrofti, Brugia malayi, or Brugia timori; tropical pulmonary eosinophilia; and loiasis. DIETHYLCARBAMAZINE CITRATE (DEC)

9. Adverse drug reactions: Common side effects include itching, facial swelling, headaches, and feeling tired. Other side effects include vision loss and dizziness. It is a recommended treatment in pregnancy and appears to be safe for the baby. Mechanism of Action: The exact mechanism is not known but it believed to alter microfilarial membrane surface rendering it more susceptible to destruction by the host defence mechanism.

10. ALBENDAZOLE Adverse drug reactions: Bone marrow suppression, headache, abnormal liver function, abdominal pain, nausea, vomiting, dizziness, vertigo, temporary hair loss and fever. Uses: Albendazole is an anthelmintic or anti-worm medication. It prevents newly hatched insect larvae (worms) from growing or multiplying in your body.  Albendazole is used to treat certain infections caused by worms such as pork tapeworm and dog tapeworm.

11. Mechanism of Action: It causes degenerative alteration in the intestinal cells of the worm by binding to the colchicine-sensitive site of β-tubulin, thus inhibiting its polymerization or assembly into microtubules (it binds much better to the β-tubulin of parasites than that of mammals). It also prevents the formation of spindle fibres which needed for cell division. At higher concentration it disrupts helminthic metabolic pathway by inhibiting metabolic enzymes such as Malate dehydrogenase and fumarate reductase which decreases energy production and the parasite immobilized and dies.

12. MEBENDAZOLE Adverse drug reactions: Transient diarrhoea, headache, abdominal pain, nausea, vomiting, dizziness, fever, dizziness, hypersensitivity. Uses: Mebendazole (MBZ) is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm disease, hookworm infections, guinea worm infections, hydatid disease, and giardia, among others.

13. Mechanism of Action: Acts by destroying the cytoplasmic microtubules in the worm intestinal cells by interfering with the uptake of glucose by helminth parasites and simultaneously glycogen store in parasite get depleted. Which thereby results in decreases the generation of energy in the form of ATP and eventually death of parasites.

14. THIABENDAZOLE Adverse drug reactions: dizziness, drowsiness, or headache, numbness, nausea, vomiting, diarrhea, upset stomach, or decreased appetite, unusual urine odor, fever or chills, ringing in the ears, blurred vision or dryness of the eyes or appearance of live worms in the mouth or nose. Uses: This medication is used to treat roundworm infections such as threadworm, hookworm/creeping eruption (cutaneous larva migrans ), and visceral larva migrans (toxocariasis).

15. Mechanism of Action: It is a potent inhibitor of enzyme fumarate reductase and brings about supress assembly of microtubules, leading to inhibition of secretion of parasites acetylcholinesterase and causes cessation of parasitic activity.

16. Synthesis : Uses: Niclosamide is used to treat broad or fish tapeworm, dwarf tapeworm, and beef tapeworm infections. Niclosamide may also be used for other tapeworm infections as determined by your doctor. It will not work for other types of worm infections (for example, pinworms or roundworms). NICLOSAMIDE

17. Adverse drug reactions: Dizziness or light headedness, drowsiness, itching of the rectal area, skin rash, unpleasant taste. Adverse drug reactions increase with consumption of alcohol, GIT disturbance and pruritis. Mechanism of Action: It is acts by inhibiting the anaerobic phosphorylation in the mitochondria of parasite, an energy producing process which is dependent on CO 2 fixation and thereby inhibiting respiration and glucose absorption by the intestinal adult worms. Or It inhibits oxidative phosphorylation in the mitochondria of the worms, results in energy depletion.

18. PYRANTEL PAMOATE  Mechanism of Action: Pyrantel pamoate acts as a depolarizing neuromuscular blocking agent, thereby causing sudden contraction, followed by paralysis, of the helminths. This has the result of causing the worm to "lose its grip" on the intestinal wall and be passed out of the system by natural process. Uses: Pyrantel pamoate is an anthelmintic, or dewormer . It is used to treat intestinal roundworm, hookworm, and stomach worm parasites in dogs. The use of pyrantel pamoate to treat intestinal parasites in cats is off label or extra-label. Adverse drug reactions: Nausea, vomiting, diarrhea, stomach/abdominal cramps, headache, drowsiness, dizziness, trouble sleeping, or loss of appetite may occur. If any of these effects persist or worsen

19. HETEROCYCLICS OXAMNIQUINE Uses: Oxamniquine is an antihelmintic , or anti-worm,  medication . It prevents  worms  from growing or multiplying in your body. Oxamniquine is used only to treat  infections  caused by the worm Schistosoma mansoni . This is an uncommon  infection  usually acquired through contact with freshwater in Africa.

20. Adverse drug reactions: the most common  adverse effects  were headache, dizziness, drowsiness, and abdominal pain. Patients who took the placebo also had drowsiness and abdominal pain. Mechanism of Action: Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release egg. Oxamniquine may associate with an irreversible inhibition of the nucleic acid metabolism of the parasites.

21. PRAZIQUANTEL Adverse drug reactions: Headache, dizziness,  stomach pain , nausea, tiredness, weakness, joint/muscle pain, loss of appetite, vomiting, and sweating may occur. Mechanism of Action: Praziquantel effects the permeability of the cell membrane resulting in the contraction of schistosomes. The drug further causes vacuolization and disintegration of the schistosome tegument. The effect is more marked on adult worms compared to young worms. An increased calcium influx may play an important role. Uses: Praziquantel is used to treat schistosoma (infection with a type of worm that lives in the bloodstream) and liver fluke (infection with a type of worm that lives in or near the liver). Praziquantel is in a class of medications called anthelmintics. It works by killing the worms.

22. NITRODERIVATIVES NIRIDAZOLE Adverse drug reactions: The side effects of the drug are nausea, vomiting, diarrhea, anorexia, abdominal pain and headache, which depend largely on the dose and duration of the treatment. Mechanism of Action: Niridazole is rapidly concentrated in the parasite and inhibits oogenesis and spermatogenesis. The compound also inhibits the phosphofructokinase enzyme, leading to glycogen depletion and hepatic shift. Uses: Niridazole is a schistosomicide . It is used to treat schistosomiasis, the helmintic disease caused by certain flatworms (trematodes) from the genus Schistosoma (formerly Bilharzia).

23. IMIDAZOTHIAZOLE LEVAMISOLE Adverse drug reactions: It causes nausea, vomiting, diarrhea, mouth sores, loss of appetite, stomach  pain , change in taste and smell, muscle aches, fatigue, dizziness, headache and skin rash.  Mechanism of Action: It is an antiparasitic agent appears to be tied to its agnositic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles. This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate. Uses: It is used to treat parasitic worm infections. Specifically, it is used for ascariasis and hookworm infections. 

24. NATURAL PRODUCTS IVERMECTIN Mechanism of Action: Ivermectin and its related drugs act by interfering with  nerve  and muscle function of helminths and insects. The drug binds to glutamate-gated  chloride channels  that are common to invertebrate nerve and muscle cells. Ivermectin binding pushes these channels open, increasing the flow of chloride ions and hyper-polarizing the cell membranes. This hyperpolarization paralyzes the affected tissue, eventually killing the invertebrate.

25. Adverse drug reactions: It include skin rash, nausea, vomiting, diarrhea, stomach pain, facial or limb swelling, neurologic adverse events (dizziness, seizures, confusion), sudden drop in blood pressure, severe skin rash. Uses: Ivermectin is a broad spectrum anti-parasitic agent, included in WHO essential medicines list for several parasitic diseases. It is used in the treatment of onchocerciasis (river blindness), strongyloidiasis and other diseases caused by soil transmitted helminthiasis. It is also used to treat scabies.