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HELMINTHIC INFECTIONS HELMINTHS • Macroscopic, multiceullar organism • Having their own digestive system, excretory, reproductive and nervous systems INTRODUCTION GENERAL FEATURES • Humans are the primary hosts. • Most worms produce in • Worm-like parasites human sexually • By producing eggs and larvae. • These pass out of body and infect the secondary host. • Imature forms invade humans via skin or GIT. • Mature to adult worms characterstic tissue distribution. with • Outer protective cuticle/integument covering- • Locomotion-muscular contraction & relaxation. • Eggs or larvae produced enormous numbers. in • Inability to multiply in the body of the host. CLASSIFICATION • Based on external and internal morphology of egg, larval, and adult stages & the host organ they inhabit 1)NEMATHELMINTHES -Cylindrical round worms a) NEMATODES Eg: ascaris, ancylostoma, trichuris, strongyloides, enterobius, filariasis, dracunculus. 2) PLATYHELMINTHES -Flat worms a) TREMATODES or Flukes :• Leaf-like. Eg.Blood flukes(schistosomiasis), fasciola, clonorchis, paragonimus, b) CESTODES or Tape worms:• Tape-like Eg.Taenia,echinococcus,diphyllobothrium NEMATELMINTHS(ROUND) • ROUND WORMS • ASCARIS.L • HOOK WORMS • NECATOR A • WHIP WORMS • TRICHURIS T • THREAD WORMS • STRONGYLOIDES.S • PIN WORMS • ENTEROBIUS V • FILARIASIS WORMS • BANCROFTI • ONCHOCERCIASIS • O.VOLVULUS • GUINEA WORMS • DRACANCULUS M PLATYHELMINTHS A) TREMATODES-FLUKES • BLOOD FLUKES • SCISTOSOMIASIS • LIVER FLUKES • CLONORCHIASIS • INTESTINAL FLUKES • FASCIOLOPSIASIS • LUNG FLUKES • PARAGONIMIASIS B) CESTODES • BEEF TW • T.SAGINAT • PORK TW • T.SOLIUM • FISH TW • DIPHYLLOBO THRIUM • DWARF TW • HYMENOLEPIS.NANA TYPES (CLINICAL) 1. Worms live in hosts alimentary canal. 2. Worms or larvae live in other tissues of host body like muscles , viscera , menninges , lungs, tissues. subcutaneous 1)INTESTINAL A) ROUND WORMS (NEMATODES) • Ascaris lmubricods (common round worm) • Enterobius vermicularis (pin worm) • Trichuris trichuria ( whip worm) • Strongyloids stercoralis (thread worm) • Ankylostoma dudenale (hook worm) B) TAPE (CESTODES) • • • • WORMS Taenia saginata(Beaf) , Taenia solium(Pork), Hymenolepis nana(Dwarf) , Diphylobothrium latum(Fish) 2. TISSUE WORMS A) TREMATODES (Schisotomes) OR FLUKES(leaf like) • Schistosoma haematobium • Schistosoma Japonicum • Schistosoma mansoni (These cause SCHISTASOMIASIS ) also called (BILHARZIA) means disease of blood vessels. • Clonorchis sinensis (liver fluke) • Paragonimus westermani (lung fluke) B) TISSUE ROUND WORMS • Trichnella spiralis. • Dracunulus medinensis (guinea worm) larva • FILARIAE includes • Wuchereria bancrofti • Loa loa • Onchocerera volvulus • Brugia malayi C) HYDATID TAPE WORM NEMATHELMINTHS • Long, round bodies, unsegmented worms, tapered at both ends. • Most found primarily in intestine. • Attached to the mucosa and feed host blood and tissue fluid. Symptoms:Abdomianl pain Diarrhoea Pruritis In severe condition cause anaemia PLATYHELMINTHS A)Trematodes (Flukes) • Non segmented • Acquired - ingestion of food • Mature in intestinal track • Migrate and mature in liver- Liver flukes • Lung – Lung flukes Causes: • Diarrhoea • Abdominal pain • Anorexia Liver flukes: • • • • Bile duct obstruction Liver enlargement Cirrhosis of liver Diarrhoea Lung flukes: • Cough • Haemoptysis Blood flukes: Skin Lung Liver Mature Blood • Haematuria • Frequent & painful micturation • Abdominal pain •CESTODES: • Ribbon shaped • Intestinal parasites • Head, neck followed by segments • Head hold- intestinal walls • No digestive system host nutrients ROUND WORM filariasis Hookworm Pin worm male, female LIFE CYCLE OF HELMINTHS • Adult worms live in the lumen of the small intestine. • A female may produce approximately 200,000 eggs per day, which are passed with the feces . • Fertile eggs embryonate and become infective , depending on the environmental conditions (optimum: moist, warm, shaded soil). • After infective eggs are swallowed • The larvae hatch • Invade the intestinal mucosa portal, systemic circulation lungs penetrate the alveolar walls ascend the bronchial tree to the throat, and are swallowed . • Upon reaching the small intestine, they develop into adult worms. • Between 2 and 3 months are required from ingestion of the infective eggs to oviposition by the adult female. • Adult worms can live 1 to 2 years. ANTHELMINTICS OR ANTIHELMINTHICS • Drugs that expel parasitic worms (helminths) from the body by either stunning or killing them. • They may also be called vermifuges (stunning) or vermicides (killing). CLASSIFICATION • AGAINST NEMATODES • ALBENDAZOLE, MEBENDAZOLE, PYRANTEL PAMOATE, LEVIMASOLE, PIPERAZINE, IVERMECTIN, DIETHYLCARBAMAZINE, THIABENDAZOLE, DOXYCYCLINE • AGAINST TREMATODES • METRIFONATE, OXAMNIQUINE, BITHIONOL, TRICLABENDAZOLE • AGAINST CESTODES • NICLOSAMIDE • AGAINST TREMATODES AND CESTODES • PRAZIQUANTEL MEBENDAZOLE • A synthetic benzimidazole • Introduced in 1972 • Broad-spectrum SPECTRUM: • 100% cure rate • For round worm, hook worm, enterobius (less for Strongyloides) and trichuris (not for tissue Trichinella spiralis) • 75% effective • For tape worms but not for H. nana • Hadatid cyst: prolonged treatment • Hatching of nematode eggs and larva inhibited and Ascaris eggs are killed MECHANISM OF ACTION • Action is slow: takes 2-3 days to develop. • Inhibits microtubule synthesis • That irreversibly impairs glucose uptake • Inhibition of glucose uptake • Disruption of metabolic pathway • Resulting in the gradual immobilization and die slowly. CLINICAL USES •Pinworm •Trichuriasis •Hookworm •Ascaris infections. •Whipworm •Enterobius •Trichinella spiralis •Hydatid disease ADVERSE EFFECT In heavy infestation cases:• Diarrhoea • Nausea • Abdominal pain In high dose:• Granulocytopenia • Allergic reaction • Alopecia ALBENDAZOLE MECHANISM OF ACTION • Congener of Mebendazole • Broad-spectrum activity • Excellent tolerability • Single dose administration SPECTRUM OF ACTION • Comparable efficacy mebendazole with • Same for round worm, hook worm and enterobius • Less effective against trichuris • More effective against strongyloides • Trichinella effectiveness is almost same • More effective in tape worm (including H. nana) and hydatid larvae and ova of ascaris and hook worm • Weak microfilarial action and cutaneous larva migrans • Binds with β-tubulin and inhibits microtubules polymerization. • Blocks glucose and other nutrients uptake. • Intestinal parasites are immobilized and die slowly. PHARMACOKINETICS • Benzimidazole carbamate • Moderate and inconsistent oral absorption • Fatty meals enhance absorption • For intesinal worm given in empty stomach and for tissue action – with fatty meals ADVERSE EFFECT • Well tolerated • GI side effects • Dizziness • Prolonged used in hydatid and cysticercosis - Headache, fever, alopecia, neutropenia, jaundice. USES • Used on empty stomach when used against intestinal worms • With a fatty meal when used against cysticercosis, hydatid and cutaneous larva migrans . • Ascaris, hookworm, Enterobius and Trichuris • Tapeworms and strongyloidosis • Trichinosis • Neurocysticercosis • Cutaneous larva migrans • Hydatid disease • Filariasis THIABENDAZOLE • First benzimidazole polyanthelmintic • Introduced in 1961 SPECTRUM • All species of nematodes infesting the g.i.t.-roundworm, hookworm, Enterobius, Trichuris, Strongyloides and Trichinella spiralis. • Inhibits the eggs of worms and kills larvae. • Symptomatic relief in cutaneous larva migrans, Trichinella spiralis larvae, guinea worm disease. • MECHANISM OF ACTION • The precise mode of action of thiabendazole on the parasite is unknown, but it most likely inhibits the helminth-specific enzyme fumarate reductase. • Thereby inhibiting the citric acid cycle, mitochondrial respiration and subsequent production of ATP, ultimately leading to helminth's death. PHARMACOKINETICS • It is chelating agent and form stable complexes with metals including iron, but does not bind with calcium. • It can also get absorbed through skin ADVERSE EFFECTS • Frequent • Often interfere with normal activity. • Nausea, vomiting, loss of appetite, headache, giddiness are most common. • It can impair alertness-driving and operation of machinery should be prohibited. • Itching, abdominal pain, diarrhoea. CLINICAL USES • Because of frequent side effects and poor patient acceptability used only when other better tolerated drugs are ineffective. • strongyloidosis • Cutaneous larva migrans • Trichinosis-intestinal infestation and larvae in muscles PYRANTEL PAMOATE •A broad specturm SPECTRUM: •Threadworm, roundworm, hookworm, Ascaris, Enterobius and Ancylostoma, Necator infestation. •Less active against • Strongyloides •Inactive against • Trichuris worms. and other MECHANISM OF ACTION • Acts as a depolarizing neuromuscular blocker • Causes the release of acetylcholine and inhibits cholinesterase • Activation of nicotinic cholinergic receptors in the worms • Resulting in persistent depolarization • Slowly developing contracture and spastic paralysis. • Paralyzing the helminthes • Result of causing the worm to "lose its grip" on the intestinal wall and be passed out of the system by natural process. • Worms are then expelled. ADVERSE EFFECTS • Infrequent mild transient GI disturbance • Drowsiness,headache, insomnia. • Rash ,fever CONTRAINDICATIONS • Should not be used in liver diseases. • Pregnancy • Child under 2 years of age CLINICAL USE • Very effective against luminal organisms. • Entrobius vermicularis (pin worm) • Ascariasis lumbricoids (common round worm) • Ancylostoma dudenale (hook worm) PIPERAZINE • Introduced in 1950 • Highly active drug against Ascaris and Enterobius MECHANISM OF ACTION • Causes hyperpolarization of Ascaris muscle • By a GABA agonistic action • Opening Cl- channels • That causes relaxation and depresses responsiveness to contractile action of ACh. • Flaccid paralysis • Worms are expelled alive • It does not affect neuromuscular transmission in man CLINICAL USES • Only recommended for the treatment of ascariasis cure rate 90%. ADVERSE EFFECTS • Safe and well tolerated. • Nausea, vomiting, abdominal discomfort and urticaria • Dizziness and excitement occur at high doses • Toxic doses produce convulsions; death is due to respiratory failure. CONTRAINDICATIONS • • • • In epileptics Impaired liver or kidney functions Pregnancy Malnutrition LEVAMISOLE, TETRAMISOLE • Tetramisole :- in the late 1960s. • Recemic; levo isomer (levamisole):more active and is preferred. SPECTRUM • Both are active against many nematodes • But use is restricted to ascariasis and ancylostomiasis. • Strongyloides larvae are killed, but adult worms are not sensitive. • MECHANISM OF ACTION • Two mechanisms: • The ganglia in worms are stimulated causing tonic paralysis and expulsion of live worms. • Interference with carbohydrate metabolism (inhibition of fumarate reductase) may also be contributing. PHAMACOKINETICS • • • • Given orally Rapidly absorbed Widely distributed. Crosses the blood-brain barrier. ADVERSE EFFECTS • • • • • • Nausea, Abdominal pain, Giddiness, Fatigue, Drowsiness Insomnia USES • For Ascaris infestation • Levamisole is a second line drug for A. duodenale • It is less efficacious against Necator. DIETHYL CARBAMAZINE CITRATE (DEC) • Developed in 1948 • It is the first drug for filariasis. • Piperazine derivative SPECTRUM • Highly selective effect on Microfilariae (Mf). • Active against Mf of W. bancrofti and B. malayi, Loa loa, onchocerca volvulus . MECHANISM OF ACTION • • • • Immobilizes microfilariae Alters their surface structure Displacing them from tissues Making them susceptible to destruction by host defense mechanism. ADVERSE EFFECTS • Nausea, loss of appetite, headache, weakness and dizziness • A febrile reaction with rash, pruritus, enlargement of lymph nodes and fall in BP • Leukocytosis and mild albuminuria USES • Filariasis • Tropical eosinophilia • For Loa loa and 0. volvulus infections IVERMECTIN • A macrocyclic lactone MECHANISM OF ACTION • Extremely potent semisynthetic derivative • Acts on the parasites by binding to a novel allosteric site on the • Obtained from streptomyces acetylcholine nicotinic receptor to avermitilis cause an increase in transmission • By opening glutamate-gated chloride SPECTRUM • Choice for single dose treatment of • Onchocerciasis and strongyloidosis. • Highly effective in • Bancroftian, brugian filaria,cutaneous larva migrans and ascariasis, • Moderate Efficacy against • Enterobius and Trichuris • Certain insects, notably scabies and head lice are killed by ivermectin. channels • Chloride influx increased • Hyper polarization occurs • Resulting in paralysis of the worm. MECHANISM OF ACTION Ivermectin Targets GABA receptors of parasite Chloride ion influx enhanced Hyper polarization occurs Paralysis of the worm ADVERSE EFFECT • Fatigue, dizziness, GI disturbance • Nausea • Abdominal pain • Pruritis • Giddiness • Constipation • Lethargy • Transient ECG changes CONTRAINDICATION • Other drugs that enhance GABA • e.g Barbiturates, valproaic acid. bnezodiazepines, • Pregnancy • Imparied blood brain barrier • Children under 5 years of age. USES • • • • • Filariasis Strongyloidosis Other intestinal nematodes Scabies Pediculosis NICLOSAMIDE • Highly effective MECHANISM OF ACTION • Inhibition of oxidative • Useful drug for treatment of tape phosphorylation in worm (cestodes) infestation mitochondria • Safe during pregnancy. • Interference of anaerobic SPECTRUM generation of ATP by • Against cestodes infesting man – tapeworm. Taenia saginata, T. solium, • Injured worms are digested Diphyllobothrium latum and or expelled (purgation) Hymenolepis nana, as well as threadworm. ADVERSE EFFECT • Well tolerated • No systemic toxicity • Minor abdominal symptoms • Malaise • Pruritis • Diarrhea • Light headedness • Safe during pregnancy and in patients with poor health. CLINICAL USES • T.Saginata (Beef tape worm) • T.solium (pork tape worm), • Diphyllobothrium latum (fish tape worm) • Hymenolepis nana: It effective against adult parasite is PRAZIQUANTEL • Novel anthelmintic • Wide ranging activity against Schistosomes, other trematodes, cestodes and their larval forms but not nematodes. • Effective against wide variety of cestodes and tremetodes. • SCHISTOSOMIASIS - LIVER FLUKES - LUNG FLUKES. • Taeniasis • Neuro Cysticercosis MECHANISM OF ACTION • Rapidly taken up by worms. • Leakage of intracellular Ca++ causing paralysis. • Worms lose grip on intestinal wall including tissues and veins. • Acts against all stages of worm including larvae. PHARMACOKINETICS • Absorption is enhanced with food. • Crosses blood-brain barrier ADVERSE EFFECT • Bitter in taste • Nausea • Abdominal pain • Headache • Dizziness and sedation • Rashes, fever, itching and body pain CLINICAL USES • • • • • • Tapeworms T. saginata, T. solium H. nana, O. latum Neurocysticercosis Schistosomes Other flukes THANK YOU -PHARMA STREET