HELMINTHIC INFECTIONS

HELMINTHS Macroscopic, multiceullar organism Having their own digestive system, excretory, reproductive and nervous systems

INTRODUCTION Humans are the primary hosts. Most worms produce in 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 with characterstic tissue distribution. GENERAL FEATURES Worm-like parasites Outer protective covering- cuticle/integument Locomotion-muscular contraction & relaxation. Eggs or larvae produced in enormous numbers. 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, subcutaneous tissues. 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 WORMS (CESTODES) Taenia saginata(Beaf) , Taenia solium(Pork), Hymenolepis nana(Dwarf) , Diphylobothrium latum(Fish)

Wuchereria bancrofti 2. TISSUE WORMS 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 PLATYHELMINTHS 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 Lung flukes: Cough Haemoptysis Chest pain

CESTODES: Ribbon shaped Intestinal parasites 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 Hookworm filariasis 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.

Pinworm Trichuriasis Hookworm Ascaris infections. Whipworm Enterobius 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 PHARMACOKINETICS SPECTRUM OF ACTION Congener of Mebendazole Broad-spectrum activity Excellent tolerability Single dose administration SPECTRUM OF ACTION Comparable efficacy with mebendazole 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 MECHANISM OF ACTION 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

USES 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: 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. A broad specturm SPECTRUM: Threadworm, roundworm, hookworm, Ascaris, Enterobius and Ancylostoma, Necator infestation. Less active against Strongyloides Inactive against Trichuris and other worms.

Very effective against luminal organisms. 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 Causes hyperpolarization of Ascaris muscle 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.

For Ascaris infestation 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 MECHANISM OF ACTION A macrocyclic lactone Extremely potent semisynthetic derivative Obtained from streptomyces avermitilis 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. MECHANISM OF ACTION Acts on the parasites by binding to a novel allosteric site on the acetylcholine nicotinic receptor to cause an increase in transmission By opening glutamate-gated chloride 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

Giddiness Constipation Lethargy Transient ECG changes 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, bnezodiazepines, valproaic acid. Pregnancy Imparied blood brain barrier Children under 5 years of age. USES Filariasis Strongyloidosis Other intestinal nematodes Scabies Pediculosis

NICLOSAMIDE Inhibition of oxidative phosphorylation in mitochondria Highly effective Useful drug for treatment of tape worm (cestodes) infestation Safe during pregnancy. SPECTRUM Against cestodes infesting man – Taenia saginata, T. solium, Diphyllobothrium latum and Hymenolepis nana, as well as threadworm. MECHANISM OF ACTION Inhibition of oxidative phosphorylation in mitochondria Interference of anaerobic generation of ATP by tapeworm. Injured worms are digested or expelled (purgation)

Minor abdominal symptoms Malaise Pruritis Diarrhea Light headedness 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 is effective against adult parasite

PRAZIQUANTEL MECHANISM OF ACTION PHARMACOKINETICS 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