Antiparasitic Drugs

Malaria, one of the most widespread disease, is caused by a Plasmodium parasite. Its name is derived from mala aria (bad air), and it has been called ague, intermittent fever, marsh fever, and The Fever. The name is based on the early knowledge that malaria was associated with swamp and badly drained areas. The disease was spread by mosquito. Proof that the Anopheles mosquito is the carrier of the causative protozoa was obtained by Dr. Ronald Ross, who was recognized in 1902 with the Nobel Prize in Medicine.

Malaria
Malaria is caused by plasmodium whose sporozoites was inoculated to initiate human infection by anopheline mosquito. Four species of plasmodium cause human malaria:
Plasmodium falciparum responsible for nearly all serious complicationsand deaths. P vivax benign malaria P malariae P ovale seldom

Parasite Life Cycle

I.

Asexual stage in human:

Primary exoerythrocytic stage: sporozoites invade liver cells schizonts incubation period Asexual erythrocytic stage: merozoites invade erythrocytes, trophozoites schizonts, rupture host erythrocytes repeated cycles cause clinical illness Secondary exoerythrocytic stage: In P vivax and P ovale infections, a dormant hepatic stage, hypnozoite relapses

II.

Sexual stage in anopheline mosquito:

Sexual stage gametocytes also develop in erythrocytes before being taken up by mosquitoes, where they develop into infective sporozoites.

Malaria transmission life cycle: Sporozoites tissue schizonts (in liver) merozoites infect RBC (blood schizonts) rupture of RBC (clinical attack) new crops of merozoites Sexual form: some merozoites differentiate into male & female gametocytes ingested by a mosquito where they form Sporozoites human

 P. malariae & p. falciparum have one cycle of liver invasion and end by the 4th week i.e. no relapse occurs. P.ovale & p. vivax have dormant stages (hypnozoites) in the liver. These hypnozoites may rupture months or years later causing relapse of the attacks.

Treatment of malaria
P. vivax, P. ovale & P. malariae:

Chloroquine
NB: It is also allowed in pregnancy. P. Falciparum (most cases are chloroquine-resistant):

Quinine 600 mg salt/8h till patient become better and blood is free of parasites (usually in 3-5 days).
Followed by a single dose of fansidar (3 tablets). In pregnancy 7-day course of quinine alone should be given.

Alternative therapy Mefloquine 20 mg base/kg up to a maximum of 1.5 g in two divided doses 8 hours apart. Mefloquine is contraindicated in pregnancy. Cerebral malaria: Quinine 10 mg/kg i.v infusion over 4 h. could be repeated at intervals of 8-12 h. until patient can take drug orally. Or Halofantrine: orally only Or Qinghaosu (Artemisinin): oral & i.v

Antimalarial Agents
Quinoline group
quinine, quinidine, CQ, MQ, PQ, amodiaquine, halofantrine

Anti-folate
pyrimethamine, proguanil, chloroproguanil, trimethoprim

Artemisinin analog
artemisinin, artisunate, artemether, arteether, dihyroartemisinin

Some antibiotics like

tetracycline, Clindamycin, macrolides (azithromycin), atovaquone

Classification of Antimalarial Drugs

Antimalarial Drugs
Chemoprophylaxis Radical Cure Acute Attack Prevent Transmission

Drugs for Acute Attack

Known also as blood schizoniticidal agents Used for clinical cure (suppressive) Act on Erythrocytic form of plasmidium Can affect a cure for P. falciparum and P. malariae (no exoerythrocytic stage) Agents:
Quinine, quinidine, chloroquine, mefloquine, halofantrine, sulphones, pyrimethamine, atovaquone, doxycycline, Qinghaosu derivatives

Agents Used for Prophylaxis

Prevents malaria attack by blocking the link between Pre-erythrocytic and Erythrocytic stages Agents:
Chloroquine Mefloquine Doxycycline Atovaquone/Proguanil Dapsone

Agents for Radical Cure

Also known as tissue schizonticidal agents Cause a radical cure (eradication) of dormant stage in the liver of P vivax, P ovale Agents:
PRIMAQUINE

Drug Used to Prevent Transmission

These agents destroy gametocytes and prevent transmission by the mosquito, thus preventing spread of disease Not used alone for this action, usually combined with other agents Agents:
Primaquine Pyrimethamine Proguanil

Chemoprophylaxis of malaria
Chloroquine-sensitive area: Chloroquine 150 mg base ( 2 tab/week) Chloroquine-resistant area: Chloroquine ( 2 tab/week) plus proguanil 100 mg (one or two tab/ day) or Mefloquine 250 mg (one tab./ week)

Control symptoms

Chloroquine

A synthetic 4-aminoquinoline formulated as the phosphate salt for oral use. Pharmacokinetics
Rapidly and almost completely absorbed from the gastrointestinal tract. Very large apparent volume of distribution of 100-1000 L/kg. Necessitate the use of a loading dose to rapidly achieve effective serum concentrations. Slowly released from tissues and metabolized. Principally excreted in the urine.

Chloroquine (4- aminoquinoline derivative) Mechanism of action: Inhibits synthesis of DNA and RNA in the plasmodium. Increases pH of the vacules in the parasite, so prevent its utilization of erythrocyte hemoglobin. Uses: Acute attack 600 mg base (4 tab.) then 300 mg after 6 h. then 150 mg bid for two more days. Add 100 mg proguanil/ day (2 tab.) in chloroquine-resistant area.

Mechanism of action:

The organism digest HB of the host releases heme which is toxic to the
organism polymerizes heme to hemozoin (non toxic to the parasite).Chloroquine inhibits heme polymerization to hemozoin oxidative damage lysis of parasite and RBC.

Pharmacological Effects
1. Antimalarial action: highly effective blood schizonticide. Moderately effective against gametocytes of P vivax, P ovale, and P malariae but not against those of P falciparum. not active against liver stage parasites. Mechanism: plasmodium aggregates chloroquine. chloroquine incorporated into DNA chain of plasmodium inhibit proliferation. chloroquine prevents the polymerization of the hemoglobin breakdown product, heme, into hemozoin and thus eliciting parasite toxicity due to the buildup of free heme. pH plasmodium protease activity Resistance: very common among strains of P falciparum and uncommon but increasing for P vivax. The mechanism of resisitance to chloroquine is resistant strains excretes drug more rapidly. 2. Killing Amibic trophozoites : chloroquine reaches high liver concentrations. 3. Immunosuppression action:

Clinical Uses
1. Treatment: non falciparum and sensitive falciparum malaria. Primaquine must be added for the radical cure of P vivax and P ovale, because chloroquine does not eliminate dormant liver forms of these species. 2. Chemoprophylaxis: for without resistant falciparum malaria in malarious regions. 3. Amebic liver abscess: not effective in the treatment of intestinal or other extrahepatic amebiasis.

 Adverse Effects and Cautions

Usually very well tolerated, even with prolonged use. Pruritus is common. Nausea, vomiting, abdominal pain, headache, anorexia, malaise, blurring of vision, and urticaria are uncommon. Dosing after meals may reduce some adverse effects. Rare reactions include hemolysis in G6PD-deficient persons, impaired hearing, confusion, psychosis, seizures, hypotension, ECG changes. teratogenesis

Control symptoms

Quinine

Quinine and quinidine remain first-line therapies for falciparum malariaespecially severe disease. Quinine is an alkaloid derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. Quinine is the levorotatory stereoisomer of quinidine. Rapidly absorbed after oral administration. Metabolized in the liver and excreted in the urine.

 MOA:
acts primarily as a blood schizonticide. May be by intercalation of the quinoline moiety into the DNA of the parasite, thereby reducing the effectiveness of DNA Also by pH elevation in intracellular organelles of the parasites

 Pharmacological Effects
Highly effective blood schizonticide against the four species of human malaria paresites. Gametocidal against P vivax and P ovale but not P falciparum. Not active against liver stage parasites. Depressing cardiac contractility and conduction, lengthening refractory period, exciting uterine smooth muscle, depressing central nervous system, little antipyretic-analgesic effect.

 Clinical Uses: mainly for chloroquine-resistant falciparum malaria, especially for cerebral malaria.
Parenteral treatment of severe falciparum malaria Oral treatment of falciparum malaria Malarial chemoprophylaxis Babesiosis

Adverse Effects and Cautions

1. Cinchonism: tinnitus, headache, nausea, dizziness, flushing, visual disturbances 2. Cardiovascular effects: severe hypotension and arrhythmia can follow too-rapid intravenous infusion. 3. Idiosyncrasy: hemolysis with G6PD deficiency. 4. Others: hypoglycemia through stimulation of insulin release, stimulate uterine contractions

Control symptoms

Mefloquine

A synthetic 4-quinoline methanol that is chemically related to quinine. Pharmacokinetics

Only be given orally because severe local irritation occurs with parenteral use. Well absorbed. Highly protein-bound, extensively distributed in tissues, and eliminated slowly. t1/2 is 20 days.

Pharmacological Effects:
Strong blood schizonticidal activity against P falciparum and P vivax, but not active against hepatic stages or gametocytes.

 MOA: causes destruction of asexual blood forms of malaria Clinical Uses

Chemoprophylaxis: Treatment: mainly for chloroquine-resistant falciparum malaria.

Adverse Effects and Cautions

Nausea, vomiting, diarrhea, abdominal pain dose-dependent Neuropsychiatric toxicities: dizziness, headache, behavioral disturbances, psychosis, seizures.

Control symptoms

Malaridine

Developed by China. blood schizonticidal activity. Treatment for all types malaria, including chloroquine-resistant falciparum malaria. Mechanism: destroy parasite compound membrane and food vacuoles.

Control symptoms

Artemisinin

Extracted from yellow flower mugwort. Kill trophozoites of erythrocytes. quick and effective. maybe kill earlier period trophozoites. Through blood-brain barrie, treatment for cerebral malaria. recurrence rate is high. Resistence. Interaction with others antimalarial drugs:

Control symptoms

It is a blood schizonticide against all types of malaria including chloroquine-resistant p. falciparum. Artemether and Artesunate Dihydroartemisinin

Control relapse and transmission

Primaquine

Synthetic 8-aminoquinoline. Pharmacological Effects

Against hepatic stages of malaria parasites. The only available agent active against the dormant hypnozoite stages of P vivax and P ovale. Also gametocidal against the four human malaria species.

MOA:
Unknown ? disrupts mitochondria and binds to DNA

 Clinical Uses
Therapy (Radical Cure) of Acute Vivax and Ovale Malaria: chloroquine + primaquine Terminal Prophylaxis of Vivax and Ovale Malaria: prevent a relapse Chemoprophylaxis of Malaria: protection against falciparum and vivax malaria. But potential toxicities of long-term use limited its routinely administration. Gametocidal Action: A single dose of primaquine (45 mg base) can be used as a control measure to render P falciparum gametocytes noninfective to mosquitoes. This therapy is of no clinical benefit to the patient but will disrupt transmission Pneumocystis carinii infection: clindamycin+primaquine mild to moderate pneumocystosis

 Adverse Effects and Cautions Nausea, epigastric pain, abdominal cramps, headache. Hemolysis or methemoglobinemia, especially in persons with G6PD deficiency or other hereditary metabolic defects.

Etiological factor prophylaxis

Pyrimethamine

Pharmacokinetics
Slowly but adequately absorbed from the gastrointestinal tract. Slowly eliminated and excreted from urine.

Pharmacological Effects
Kill schizonts of primary exoerythrocytic stage. Act slowly against premature schizonts of erythrocytic stage. No action against gametocytes, but can inhibit development of plasmodium in mosquito. Inhibit plasmodial dihydrofolate reductase inhibiting breeding of plasmodium.

 Adverse Effects and Cautions

Gastrointestinal symptoms, skin rashes. Interfering folic acid metabolism in human megalocyte anemia, granulocytopenia. Acute intoxication Teratogenesis

Etiological factor prophylaxis

Sulfonamides and Sulfone

Competing dihydropteroatesye synthase with PABA inhibiting to form dihydrofolic acid inhibiting production of purines and synthesis of nucleic acids. Only inhibiting plasmodial of exoerythrocytic stage Not used as single agents for the treatment. Combination with other agents.

Halofantrine: Old agent reemerging for treatment of MDRM MOA:

Similar to mefloquine, destruction of asexual blood forms, possible inhibition of proton pump Effective against erythrocytic stages of all human malaria species, not hepatic stages or gametoytes

 Used only by oral route in P. falciparum cerebral malaria. No parenteral preparation. Not used for prophylaxis. Not used during pregnancy unless benefit outweighs the risk.

Proguanil
MOA: similar to pyrimehamine (antifolate) Proguanil is a prodrug; needs to be metabolized to cycloguanil to be active Need to be given daily in prophylaxis; unlike pyrimethamine which is given weekly

Fansidar:
It is a combination of sulfadoxin and pyrimethamine. It is used in chloroquine-resistant p. falciparum. Not used for prophylaxis as it causes agranulocytosis & StevensJohnson syndrome. A.E: Sulfonamide: rashes, kidney damage, hemolysis & GIT upset. Pyrimethamine: folic acid deficiency, agranulocytosis & StevensJohnson syndrome. Disadvantages: slow blood schizonticide activity, drug resistance & numerous & serious adverse effects. C/I: pregnancy & nursing women, G-6-PD, renal impairment & children under 2 months of age.

Atovaquone: Unknown mechanism of action. Used alone for treatment of pneumocytosis and toxoplasmosis in patients with AIDS. Atovaquone + proguanil (malarone) for treatment & prophylaxis of chloroquine-resistant P. falciparum. A/E: fever, rashes, cough, nausea, vomiting, diarrhea, headache & insomnia.

Rational Use of Antimalarial Drugs

1.

Choice of Antimalarial Drugs:

Control symptoms: chloroquine Cerebral malaria: chloroquine phosphate, quinine bimuriate, artemisinin injection Chloroquine-resistant falciparum malaria: quinine, mefloquine, artemisinin Dormant hypnozoite stages : pyrimethamine + primaquine Prophylaxis: pyrimethamine, chloroquine

2.

Combination therapy:
chloroquine + primaquine: symptom stages pyrimethamine + primaquine: dormant hypnozoite stages Combination of drugs with different mechanisms: therapeutic effect, resistance

Anti-amebiasis Drugs
Amebiasis is infection with Entamoeba histolytic. Amebiasis is transmitted through gastrointestinal tract. Ameba has two stages of development: cyst and trophozoite.
Cysts small intestine little trophozoites (ileocecum)

cysts (colon) asymptomatic intestinal infection, source of infection big trophozoites (tissues of intestine) intestinal amebiasis

Treatment of amebiasis:
Infection with E.histolytica produced by ingestion of cysts (non invasive form). - In the intestine trophozoites (active invasive form) invade submucosa of the host cells resulting in: A-Luminal amebiasis: cysts are passed into faeces (carriers or cyst passers).

Treatment is directed at eradicating cysts luminal amebicides

diloxanide, iodoquinol, paromomycin &tetracycline.

B- Tissue invading amebiasis: dysentery (acute intestinal

amebiasis), amebic granuloma (ameboa in the intestinal wall,) hepatic abscess & extra-intestinal disease. A systemic tissue amebicides against trophozoites should be used e.g.nitroimidazole (metronidazole or tinidazole), dihydroemetine, and chloroquine. N.B.: treatment with tissue amebicide should be followed by

a course of luminal amebicide to eradicate the source of

infection

Metronidazole
A nitroimidazole.The nitro group of metronidazole is chemically reduced in anaerobic bacteria and sensitive protozoans. Reactive reduction products appear to be responsible for antimicrobial activity. Pharmacokinetics
Oral metronidazole is readily absorbed and permeates all tissues by simple diffusion. Protein binding is low (<20%) Through blood brain barrier Metabolizing in liver. Excreted mainly in the urine.

 Mechanism of action:

Anaerobic

protozoa

like

Entamebia

have

ferrodoxin-like, electron transport proteins

that share in the electron removal reactions. The nitro group of the drug acts as an electron

acceptor cytotoxic compounds that bind to

DNA causing their damage cell death.

Pharmacological Effects and Clinical Uses

1. Anti-amebiasis: kills E histolytic trophozoites but not cysts. Treatment of all tissue infections with E histolytic. No effection against luminal parasites and so must be used with a luminal amebicide to ensure eradication of the infection. 2. Anti-trichomoniasis: 3. Anti-anaerobic bacteria: 4. Anti-giardiasis:

 Adverse Effects and Cautions

Nausea, headache, dry mouth, a metallic taste in the mouth. Infrequent: vomiting, diarrhea, rash, insomnia, neutropenia, Rare: severe central nervous system toxicity ( ataxia, encephalopathy, seizures)drug withdrawal Has a disulfiram-like effect, so that nausea and vomiting can occur if alcohol is ingested during therapy.

Adverse effects:
1.GIT disturbances; the most common, with metallic taste.

2.CNS:

headache,

insomnia,

sensory

neuropathies. 3. Rash, moniliasis & neutropenia. 4.Disulfuram- like action with alcohol 5.Mutagenic& carcinogenic in mice(CI in pregnancy). 6.Dysuria & dark urine. Tinidazole: similar to metronidazole with same activity and adverse effects but longer t (14 h) shorter courses.

Emetine and Dehydroemetine

Emetine, an alkaloid derived from ipecac, and dehydroemetine, a synthetic analog, are effective against tissue trophozoites of E histolytic . Because of major toxicity concerns they have been almost completely replaced by metronidazole. Administered subcutaneously (preferred) or i.m. (but never i.v.) because oral preparations are absorbed erratically.

 Pharmacological Effects and Clinical Uses kills E histolytic trophozoites of histolytic tissues but no effection against luminal trophozoites. a luminal amebicide should also be given. Rapidly alleviate severe intestinal symptoms, used to treat amebic dysentery for the minimum period because of toxicity. Occasionally as alternative therapies for amebic liver abscess.

 Mechanisms
Inhibiting peptidyl-tRNA transposition inhibiting elongation of peptide chain inhibiting protein synthesis interfering cleavage and breeding of trophozoites

Adverse Effects and Cautions

low selection also inhibiting protein synthesis of eukaryocyte. Toxicity increase with length of therapy. 1. Cardiac toxicity: arrhythmias, congestive heart failure, hypotention, ECG changes 2. Neuromuscular blockade: muscle weakness and discomfort 3. Local stimulation: pain and tenderness in the area of injection. 4. Gastrointestinal tract discomfort: nausea, vomiting Not be used in patients with cardiac or renal disease, in young children, or in pregnancy.

Diloxanide
Diloxanide furoate is a dichoroacetamide derivative. Effective luminal amebicide but is not active against tissue trophozoites. The unabsorbed diloxanide in the gut is the active antiamebic substance. Effective for asymptomatic luminal infections. It is used with a tissue amebicide, usually metronidazole. Adverse Effects: flatulence, nausea, abdominal cramps, rashes, abortion.

2- Iodoquinol: -Effective luminal amebicide, not effective against tissue trophozoites. Adverse effects: peripheral neuropathy (optic neuritis), thyroid enlargement.

3-Paromomycin:
effective only against luminal amebicide as it is not significantly absorbed. Affect also intestinal flora GIT adverse effects.

-Has direct amebicidal action through affection of

4- Tetracycline:

cell

membranes, causing leakage and also by reducing intestinal flora. in sever cases of amebic dysentery decrease the risk of perforation and peritonitis.

Paromomycin
Aminoglycoside antibiotic. Not significantly absorbed from the gastrointestinal tract. Only as a luminal amebicide and has no effect against extraintestinal amebic infections. inhibiting protein synthesis kill trophozoites; inhibiting symbiosis flora indirectly inhibiting ameba protozoa.

Chloroquine
Chloroquine reaches high liver concentrations treatment of amebic liver abscess. Not effective in the treatment of intestinal or other extrahepatic amebiasis.

Drugs to treat Giardiasis

Giardiasis is flagellate protozoon which mostly lives as an commensal in the intestine. It sometimes invades mucosa and causes diarrhoea requiring treatment. Metronidazole Quinidochlor Furazolidine Nitazoxanide: this is prodrug or PFOR enzyme inhibitor tizoxanide has recently become available for treatment of diarrhoea and dysentry caused by E.Hystolytica&Giardiasis

Anti-filariasis Drugs
Epidemic in China:
Wuchereria bancrofti Brugia malayi

Parasitize in lymphatic system.

Diethylcarbamazine
A synthetic piperazine derivative. Rapidly absorbed from the gastrointestinal tract; excreted rapidly in the presence of acidic urine. Pharmacologic Effects and Mechanisms
Immobilizes microfilariae (which results in their displacement in tissues) and alters their surface structure, making them more susceptible to destruction by host defense mechanisms. Adult parasites are killed more slowly. Against adult worms is unknown.

Clinical Uses
1. 2. The drug should be taken after meals. Wuchereria bancrofti, Brugia malayi, Brugia timori, and Loa loa Tropical Eosinophilia Drug-induced Reactions: mild and transient, headache, malaise, anorexia, nausea, Reactions induced by Dying Parasites: release of foreign proteins. Eosinophilia and leukocytosis. Papular rash, muscle or joint pains.

Adverse Reactions

Anthelmintic Drugs
Classification of Helminth
Roundworms (nematodes) epidemic in China Tapeworms Flukes (trematodes)

ANTHELMINTIC DRUGS
Helminth Infections 1-Tapeworms ( cestodes) Beef tapeworm / fish tapeworm 2- Intestinal round worms ( nematodes) Ascaris, pinworm ,whipworm, strongyloides, ancylostoma ( hookworm ). A skin infection is termed cutaneous larva migrans

Visceral larva migrans .

Anthelminthic Drugs
May act by causing : 1- paralysis of the worm. 2- damaging the worm leading to partial digestion or rejection by immune mechanisms. 3- interfere with the metabolism of the worm.

*Worms or larvae live in tissues of host body like muscles , viscera , menninges , subcutaneous tissues.

 Adult filariae live in the lymphatics, connective tissue or mesentery of host and produce live embryos or microfilariae, which goes to blood stream. They are ingested by mosquitoes or similar insects, they develop to larvae in 2ndry host and pass to mouth parts of insect and re-injected to humans

Ascaris lumbricoids ( common round worm)

filariasis

Hookworm

Pinworm male ,female

Tapeworm

whipworm

Dircrocoelium dendriticum

Fasiola hepatica

Tricuris tricura

Trichinela spiralis

elephantiasis

Hydateid cyct

cysticercosis

Mebendazole
A synthetic benzimidazole that has a wide spectrum of anthelmintic activity and a low incidence of adverse effects. Pharmacokinetics
Oral absorption 10 First pass elimination is high. Protein-binding 90 Excreted mostly in the urine, a portion of absored drug and its derivatives are excreted in the bile. Absorption is increased if the drug is ingested with a fatty meal.

 Pharmacologic Effects
Inhibits microtubule synthesis in nematodes, thus irreversibly impairing glucose uptake. Intestinal parasites are immobilized or die slowly. Kills hookworm, ascaris, and trichuris eggs.

Clinical Uses
Pinworm infection Ascaris lumbricoides, Trichuris trichiura , Hookworm, and Trichostrongylus Other infections: intestinal capillariasis, trichinosis, taeniasis(, strongyloidiasis, dracontiasis, et al.

 Adverse Effects and Cautions

Low-dose: nearly free adverse effects. Diarrhea, abdominal pain is infrequent. High-dose: pruritus,rash, eosinophilia), reversible neutropenia, musculoskeletal pain, fever, transient liver function abnormalities, alopecia, glomerulonephritis, agranulocytosis

Albendazole
A benzimidazole carbamate A broad-spectrum oral anthelmintic for treatment of hydatid disease and cysticercosis, pinworm infection, ascariasis, trichuriasis, strongyloidiasis, and infections with both hookworm species. Effect better than Mebendazole.

 Clinical Uses
Administered on an empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites. 1. Ascariasis, Trichuriasis, and Hookworm and Pinworm infections. 2. Strongyloidiasis 3. Hydatid Disease 4. Neurocysticercosis 5. Other infections: cutaneous larva migrans, gnathostomiasis

Piperazine
Treatment of ascariasis No longer recommended for treatment of pinworm infection, because a 7-day couse of treatment is required. Not useful in hookworm infection, trichuriasis, or strongyloidiasis. Causes flaccid paralysis of ascaris by blocking acetylcholine at the myoneuraljunction. Neurotoxic adverse effects.

Levamizole
A synthetic imidazothiazole derivative and the L isomer of D,L-tetramisole. Highly effective in eradicating ascaris and trichostrongylus and moderately effective against both species of hookworm. Inhibiting succinic dehydrogenase energy flaccid paralysis Immunomodulating effect.

Pyrantel
A tetrahydropyrimidine derivative. A broad-spectrum anthelmintic Highly effective for the treatment of pinworm, ascaris, and Trichostrongylus orientalis infections. Moderately effective against both species of hookworm but less so against N americanus. Not effective in trichuriasis or strongyloidiasis. Oxantel, an analog of pyrantel, is effective against in trichuriasis; the two drugs have been combined for their broad-spectrum anthelmintic activity.

 Effective against mature and immature forms of helminths within the intestinal tract but not against migratory stages in the tissues or against ova. Inhibition of cholinesterase a depolarizing neuromuscular blocking agent spastic paralysis Used with caution in patients with liver dysfunction. No combination with piperazine because of antagonistic action.

Pyrvinium Embonate
A dye. Not absorb orally. treatment of pinworm Selectively interfering energy metabolism enzymatic system Inhibiting glucose-transporting enzymatic system Red feces

Niclosamide
A salicylamide derivative Treatment of most tapeworm infection. Pharmacologic Effects
Scoleces and segments of cestodesbut not ova are rapidly killed on contact with nicolsamide due to the drugs inhibition of oxidative phosphorylation or to its ATPase-stimulating property. With the death of the parasite, digestion of scoleces and segments begins.

 Clinical Uses
Given in the morning on an empty stomach. The tablets must be chewed thoroughly and are then swallowed with water. Niclosamide can be used as an alternative drug for the treatment of intestinal fluke infections.

Adverse Effects and Cautions

Infrequent, mild and transitory. Nausea, vomiting, diarrhea, and abdominal discomfort.

Praziquantel
A synthetic isoquinoline-pyrazine derivative. Pharmacological Effects
Effective in the treatment of schistosome infections of all species and most other trematode and cestode infections, including cysticercosis.Against adult worms and immature stages.

Mechanisms
Increases cell membrane permeability to calcium vacuolization, marked contraction, spastic paralysis, dislodgement, death.

 Clinical Uses
Schistosomiasis Clonorchiasis and Opisthorchiasis Paragonimiasis Taeniasis and Diphyllobothriasis Neurocysticercosis Hydatid disease Other parasites: fasciolopsiasis, metagonimiasis, heterophyiasis

 Adverse Reactions
Mild and trainsient. Headache, dizziness, drowsiness, lassitude low-grade fever, pruritus), and skin rashes (macular and urticarial)due to the release of foreign protein from dying worms.

Praziquantel
Effective in the treatment of schistosome infections of all species and most other trematode and cestode infections, including cysticercosis. A first choice in the treatment cestodiasis.