Antiparasitic Agents PDF

Pharmacology of Antiparasitic Agents and Parasite Diseases Kanin Rungsardthong Faculty of Pharmacy, Thammasat University Outline  Antiprotozoal Drugs  Antimalarial drugs  Drug for treatment of amebiasis  Anthelmintic drugs ...

Pharmacology of Antiparasitic Agents and Parasite Diseases Kanin Rungsardthong Faculty of Pharmacy, Thammasat University Outline  Antiprotozoal Drugs  Antimalarial drugs  Drug for treatment of amebiasis  Anthelmintic drugs  Introduction of Malaria ัน องง งก -> เ อ Plas  a protozoan disease transmitted by the bite of infect Anopheles mosquitoes  Transmitted in 106 countries containing 300-500 million cases/in each year  Causes approximately 2000 deaths each day;  Mortality rates  from highly effective control programs  Malaria has been eliminated from western world; in the late twentieth and early twenty-first centuries, however, its prevalence rose in many parts of the tropics  A threat to nonendemic countries, and a danger to travelers ยุ ชื้ ป้ มี  Epidemiology  The exact geographic distribution of the various species is not well documented  It is reported that Plasmodium vivax is more prevalent in India, Pakistan, Bangladesh, Sri Lanka, and Central America  P. falciparum is predominant in Africa, Haiti, Dominican Republic, the Amazon region of South America, and New Guinea.  Plasmodium ovale occur in Africa, and the distribution of Plasmodium malariae is considered worldwide  In the United States, most cases of malaria are reported in immigrants from endemic areas and in American travelers เ าป  Thailand => Plasmodium vivax 56.8% P. falciparum 42.5% กาญจน ร์, ภาคเหห อ ดเ ขอ ตั ข้ น้ ตั บุ  Life cycle ่ในเ นเ ลองคน พเ อ วน อย ู อด พ ุง มา อย งจ จะไ ด ก ันเล Gametocytes in the host blood Mosquito injects ถ ้อ จ เซ are ingested by female asexual form sporozoite Anopheles mosquito · าG (sporozoites) into human host Subpop of merozoites →” sexual form” → sporozoite male and female เ ้าต บก gametocyte เพ่ม ปร 8. แบ น sexu แ งต วแบ บ asexual @ ก กCeL1 Asexual multiplication Merozoites invade new in liver → ่ ม daught เร er c blood cells and exoerythrocytic erythrocyte cycle RBC แตก schizogony (daughter RBCs cells, merozoites) ② rubtured Develop to กลาย เ น schizo ④ another Merozoites → sexual stage characteristic ring or “erythrocytic Released in to RBCs กลาย เป ↳ trophozoite in RBCs schizogony” cring form / ้ำมื บุ ชื ทั ตั ผุ ตั ข่ ข้ ป็ บ่ มี ก่ รู ลื ตั 🔗  -อาการ รไ หนาวส เ ดจา ก างกายหล ง Cyto -อากา รกก. แบบ เ อด eg. โล ตจ กิ ลื ร่ ั่ ข้ หิ  อยู่ในตับ K WK อนออ กไป ู  P. falciparum and P. malariae remain in the primary exoerythrocytic stage in the liver for about 4 weeks before invading erythrocytes ่ ใน อย ู่ บ นาน ่น ธอกาาสเป ป ามา  P. vivax and P. ovale can exist in the liver in the latent exoerythrocytic form for extended periods, therefore, infected subjects can experience relapses  The merozoites that invade the erythrocytes develop sequentially into ring ringform forms, trophozoites -> erythrocytic schizonts Visit sexual stage ได  Merozoites which can invade other erythrocytes or can develop into gametocytes, =>undergo the sexual stage in the Anopheles vector เ ากระแ สเลอ ไ เ ว , งก า Sp ec  P. falciparum -> high level of parasitemia (ability to invade erythrocytes) ์ า นทารกในครรภ ผ าน เข็ม  Malaria can be transmitted congenitally and contaminated needles ก่ พิ ผ่ ผ่ ข้ ด้ สู ตั ซ้ ว่ ร็   Drugs that eliminate developing or dormant liver forms called tissue schizonticides  Drugs that act on erythrocytic parasites are blood schizonticides -ใน RB2 ก.แ ง  Drugs that kill sexual stages and prevent transmission to mosquitoes => gametocides  No single agents are radical cure มั บ่  Pathology &32 แตก เบอะ  The erythrocytic phase causes “extensive *hemolysis” → in anemia and เ ือเ า splenomegaly า นโ ดระบ -เช  The most serious complications usually are associated with P. falciparum < - - - ด เ ด hemolysi s ม าก infections ธน แรง ⑥2. เ อ-แ พ เ ก & ไป &แ พร ่ งส า MBC มา >สมอง, บ,ไต, ปอด  Infants and children younger than 5 years of age and nonimmune pregnant ท ให ก C ไป หลอดเ อดแด women are => organ างา น อ at high risk for severe complications from falciparum malaria  The complications associated with falciparum malaria are primarily a result of the 1) high parasitemia and 2) ability of the parasites to sequester in capillaries and postcapillary vessels of organs such as the brain and the kidney ②2 M  Tissue hypoxia from anemia, together with P. falciparum –parasitized red blood cell adherence to endothelial cells in capillaries -> to extensive vascular disease and severe metabolic effects จะ ท ใ ห้ไตเ อย, ไ  P. malariae is implicated in immune-mediated glomerulonephritis and nephrotic syndrome ม้ สุ ข้ ตั ยั ข้ อุ ห้ กิ กิ ำ น้ ำ ร่ ฮื ลื ส้ ท่  Characteristics of Indicated Species อยด : :แพ เ า Cell อา ยุ ข้ น้  Clinical presentation of malaria หนาว Initial presentation: เห ่อ Nonspecific fever, chills, rigors, diaphoresis [production of fluids secreted by the sweat glands], malaise [feeling of general discomfort], vomiting, Orthostatic hypotension ↳ ่นเ Electrolyte abnormalities นแร งข Erythrocytic phase: เ ออาห Prodrome: headache, anorexia, malaise, fatigue, and myalgia Nonspecific complaints such as abdominal pain, diarrhea, chest pain, and arthralgia อ น เ บหน งเ Paroxysm: high fever, chills, and rigor รุ ห้ บื่ ส้ งื คั จ็ นื สั  Clinical presentation of malaria erythro ม.3 rivi ฝาก ด หนาวส ① Cold phase: severe pallor and cyanosis of the lips ไ ส ② Hot phase: fever between 40.5◦C(104.9◦F) and 41◦C(105.8◦F) ③ Sweating phase: Follows hot phase by 2-6 hours ่มก เร พบ าง ก.ระ Fever resolves ออ ไ ล ง, อนเพ ย เห ออกมาก , , Marked fatigue and drowsiness, warm, dry skin, tachycardia, cough, severe headache, nausea, vomiting, abdominal pain, diarrhea, and delirium Lactic acidosis and hypoglycemia (with falciparum malaria) < - Anemia Splenomegaly ็ดใ ส บพ น, เก ในเ ค P.Falciparum infections Hypoglycemia, acute renal failure, pulmonary edema, severe anemia, thrombocytopenia, high-output heart failure, cerebral congestion, seizures and coma, and adult respiratory syndrome ซั ลี ข้ ข้ ฉั งื รุ อ่ ร่ ลั  Classification of Antimalarial Drugs The spectrum of antimalarial drug activity ssexual ไม่ ผลต อ li ผ ลใน asexua blood stag Doxycycline เร่ม ผลใน li ออก กฤ หนอ อ บหม ก้ มี มี ต่ ม์  Treatment of Malaria อย่ ใน gen 1 + gen 3 ู่ Cou "ได้ แ ใ นGGP 8 ไ ่แน ุ่ ก & แบ บไม ่ นแร งใ บาก น (ไ , หนาว # ต นแ ร ง ต อย / ต่ กั ห้ ค่ ม่ ำ ลุ รุ ข้ ตั รุ  Antimalarial drugs x ไม่จ P R profi le xchose , V  Chloroquine  Piperaquine  Artemisinin & its derivatives  Quinine  Mefloquine  Primaquine ำ  1 gene 1. Chloroquine =- blood schizontiside  Drug of choice for treatment and chemoprophylaxis since the 1940s  MOA: inhibit polymerization of heme (free heme is toxic), but precise mechanism is unknown. ไม่ active e ใ o live  Highly effective blood schizonticide (not reliably active against other stage parasites) ่ม เร  Resistance is very common for P falciparum and uncommon but increasing for P vivax ด้ 1. Chloroquine *  PK  Absorption: rapidly and almost complete  Tmax: 1-2 hr  Distribution: eyes, heart, kidneys, liver, leukocytes, and lung  Vd: 100–1000 L/kg  Protein binding: 55%  Excretion: Urine (~70%, 35% as unchanged drug) Urine acidification  elimination  T1/2: healthy 74.7±30.1 hr, CKD 191.4±69.1 hr (range: 103.5 to 30.9.9 hr)  1. Chloroquine o highlight  ADR ผ น  Usually very well tolerated, even with prolonged use.  Pruritus is common, primarily in Africans. std น ทา นพ อมอาห  Other side effects are uncommon and dosing after meal may  some ADRs  IM & IV chloroquine hydrochloride can result in severe hypotension and respiratory and cardiac arrest -> should be avoided  Contraindications เ นพต่อ retin a (กก.ก. มองเ  Retinal or visual field abnormalities (retinal toxicity)  Warnings/precautions จะเ ดเ น : ด ปก ต ในก. ป porp  May exacerbate symptoms of psoriasis or porphyria  Could be used in pregnancy and young children  Drug interaction ีพ์ c 3 ลด ก. /ท  kaolin and calcium- and magnesium-containing antacids interfere with the absorption ผั ดู ซั ป็ ำ ั่ งิ กิ ร้ ถ้ 2. Piperaquine ไทย Men. Pocoartem  Widely used to treat chloroquine-resistant falciparum malaria in China in the 1970s–1980s  Resistance became widespread  Combination with dihydroartemisinin showed excellent efficacy and safety for the treatment of falciparum malaria  First-line therapy for the treatment of uncomplicated falciparum malaria in Thailand   efficacy has been seen recently in Southeast Asia  T1/2 ~28 days  3. Artemisinin & its derivatives * borghinic asexual stage & gametocyte *  Artemisinin (qinghaosu) is a sesquiterpene lactone endoperoxide  An herbal antipyretic that has been used in China for more than 2000 years  MOA: heme iron cleave the artemisinin endoperoxide bridge -> free radical inhibit protein and nucleic synthesis ->  parasite growth and survival บ ้ง grow th ข อง plasmodi um ในเ  Activity  Very rapidly acting blood schizonticides  Active against young, but not mature gametocytes  No effect on hepatic stages gen  Effective in the treatment of severe malaria ยั ยั  3. Artemisinin & its derivatives  Artemisinin is insoluble and can only be used orally  Analogs have been synthesized to increase solubility and improve antimalarial efficacy  Artesunate (water-soluble; oral, IV, IM, and rectal administration) /ใชใน uncomplicate infectio  Artemether (lipid-soluble; oral, IM, and rectal administration)  Dihydroartemisinin or DHA (water-soluble; oral administration) "ไ ่อย ม่ ค่ 3. Artemisinin & its derivatives  PK  Absorption: artemether rapid,  with food particularly high fat meal  Tmax: artemether ~2 hr  Protein binding: artemeter 95%, DHA 47% - 76%  T1/2: artemether 2–3 hr, artesunate and DHA 30-60 min  Metabolism:artemether: CYP3A4/5 -> DHA (active metabolite) artesunate: hydrolysis by plasma esterase -> DHA DHA: glucuronidation  3. Artemisinin & its derivatives  ADR  generally, very well tolerated  N/V, diarrhea, and dizziness are most reported (may often be due to underlying malaria)  delayed hemolysis for severe malaria (~13%)  Onset 2–3 weeks after therapy  73% of identified cases requiring transfusion  Artemisinin-based combination is safe in second and third trimesters of pregnancy ใ ไ ้ใ นคน ง ด  IV artesunate is safe for the treatment of severe malaria during all stages of pregnancy ช้ ตั้  Artemisinin-based combination therapy ่คน + 1 ใช้ใ นไ แน ค' ไม ้ า กซ ม่ ฝ่  4. Quinine - าานเร รา อน าง resistant-ใ เ น alterna tiv  Derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America  Exact MOA is unknown, may inhibit nucleic acid and protein synthesis, glycolysis in P falciparum  Resistance is common in border areas of Thailand  Quinine remains an important therapy for falciparum malaria, especially severe disease, although toxicity may complicate therapy ป็ บ้ ช่ ค่ ข้ 4. Quinine PK  Absorption: rapid (F: 76% - 88%)  Tmax: healthy subject: adult 2.8 hr, pediatric 2 hr malaria-infected patients: adult 5.9 hr, pediatric 4 hr  Vd: healthy subject: adult 2.5 – 7.1 L/kg, pediatric 1.43 L/kg malaria-infected patients: adult , pediatric 0.87 L/kg severe hepatic impairment: Vd is increased  Protein binding: healthy subject: 69% - 92% malaria-infected patients: 78% - 95%  Metabolism: extensively by liver (CYP3A4) -> 3-hydroxyquinine (less active)  C 4. Quinine ADR มองเห่นปป. ไไ น  Cinchonism is common (tinnitus, headache, nausea, dizziness, flushing, and visual disturbances) น , โรค ว  Hypersensitivity: skin rashes, urticaria, angioedema, and bronchospasm x VINPOX  Hematologic abnormalities: hemolysis (especially with G6PD deficiency), leukopenia, agranulocytosis, and thrombocytopenia ↳0. hemolysis -ท ไ มท ใ โร คแต  Hypoglycemia through stimulation of insulin release (problematic in severe infections and in pregnant patients, who may have increased sensitivity to insulin)  Thrombophlebitis from IV infusions ผื่ บิ ด้ ห้ ำ ำ ผิ  4. Quinine Contraindications & Cautions  Discontinue if signs of severe cinchonism, hemolysis, or hypersensitivity occur  Avoid in patients with underlying visual or auditory problems  Not be given concurrently with mefloquine  Reduce dose in renal insufficiency Drug interaction บต กผล  Aluminum-containing antacids:  absorption of quinine  Quinine can raise plasma levels of warfarin and digoxin จั  ยา น ใ ไ เ ก , ค นก 5. Mefloquine gen 1 Alternative dru  A synthetic 4-quinoline methanol  Exact MOA is unknown จะ ม า  Strong blood schizonticidal activity against P falciparum and P vivax  Not active against hepatic stages or gametocytes  A recommended chemoprophylactic drugs for use in most malaria-endemic - มาล าเ บร ้อพ ท. อC regions with chloroquine-resistant strains น เ าไปใ ค น ar ea ะบา ด ห ร แนะน  Mefloquine resistance may not associate with resistance to chloroquine  Only be given orally because severe local irritation occurs with IV route Use for uncomplicated falciparum malaria (esp. artesunate+mefloquine => combination therapies) ที่ ำ ด้ รั ช้ ที่ ข้ กิ ดื้ ด็ 5. Mefloquine PK  Absorption: well absorbed (increased by food)  Tmax: 18 hr  Protein binding: ~98%  Distribution: tissues, erythrocytes, blood, urine, CSF  Vd: 20 L/kg  T1/2: 3 weeks (2-4 weeks) -> weekly dosing for chemoprophylaxis  Metabolism: extensively by CYP3A4  Excretion primarily bile and feces  5. Mefloquine Contraindications า มก  Recent history of depression, psychosis, and schizophrenia  History of convulsions, arrhythmia, or cardiac conduction defects ADR  CNS: dizziness, sleep and behavioral disturbances, headache  GI: N/V, epigastric pain, diarrhea, abdominal pain  More common in treatment dose  Administer two divided doses 6-8 hr apart to minimize toxicity  Safe in children and pregnant women ห้  6. Primaquine  Mechanisms of antimalarial action are unknown อย่ ใน บ Drug of choice for liver forms of P vivax and P ovale ู่  Standard therapy for these infections includes chloroquine to eradicate erythrocytic forms and primaquine or tafenoquine to eradicate liver hypnozoites and prevent a subsequent relapse.  The drugs are also gametocidal  Modest activity against asexual erythrocytic stage  Chemoprophylaxis against all malarial species ตั 6. Primaquine PK  Absorption: well absorbed  Tmax: 1-2 hr  Metabolism: CYP1A2 -> carboxyprimaquine (active)  T1/2 3-8 hr  Excretion: urine (small amount as unchanged drug)  6. Primaquine ADR (generally well tolerated)  nausea, epigastric pain, abdominal cramps, and headache are infrequent these symptoms are more common with higher dosages and when the drug is taken on an empty stomach  hemolysis, especially in G6PD deficiency นแร  Serious ADR (rare): leukopenia, agranulocytosis, leukocytosis, and cardiac arrhythmias Contraindications & Cautions  history of granulocytopenia or methemoglobinemia, receiving myelosuppressive drugs  Pregnancy, G6PD deficiency รุ 7. Atovaquone gen2 ์ ฤทธ Atovaquone, a hydroxynaphthoquinone is a component of Malarone  recommended for the treatment and prevention of malaria  has also been approved by the FDA for the treatment of mild to moderate P jirovecii pneumonia. Initial use of atovaquone to treat malaria led to disappointing results, with frequent failures due to the selection of resistant parasites during therapy.  7. Atovaquone ADR (generally well tolerated)  abdominal pain, nausea, vomiting, diarrhea, headache, insomnia, and rash, and these are more common with the higher dosage required for treatment  It is considered safe for use in children with body weight above 5 kg  Plasma concentrations of atovaquone are decreased about 50% by coadministration of -> tetracycline or rifampin คค ใใ วม ก conc.ยา อะ ลดลง 50% ห้ ำ ร่  Amebiasis  Amebiasis is infection with Entamoeba histolytica สศ. กร ส  This organism can cause asymptomatic intestinal infection, mild to moderate colitis, severe น ออร ร intestinal infection (dysentery), ameboma, liver abscess, and other extraintestinal infections รรค อ งเ น จอ ร ม กเลอด , ป วด อ Treatment of Specific form of Ambiasis ,  1. Asymptomatic intestinal infection  2. Amebic colitis  3. Extra-intestinal infections รุ อั ท่ มี ลู ส้ ต้ ย์ Paronomycin  Metronidazole  Clinical Uses 1. Amebiasis Metronidazole or tinidazole is the drug of choice in the treatment of all tissue infections with E histolytica Neither drug is reliably effective against luminal parasites and so must be used with a luminal amebicide to ensure eradication of the infection ดเ อร า (Teara ia lambi 2. Giardiasis Treatment of choice for giardiasis. The dosage for giardiasis is much lower than that for amebiasis, and the drug is thus better tolerated. Efficacy after a single treatment is about 90%. Tinidazole is at least equally effective, and can be used as a single dose 3. Trichomoniasis ตกขาว ก นค Metronidazole is the treatment of choice A single dose of 2 g is effective. Metronidazole-resistant organisms can lead to treatment failures. Tinidazole may be effective against some of these resistant organisms ตั ลิ่ ชื้  Metronidazole Adverse Effects & Cautions  Nausea, headache, dry mouth, and a metallic taste in the mouth occur commonly  Infrequent adverse effects include vomiting, diarrhea, insomnia, weakness, dizziness, thrush, rash, dysuria, dark urine, vertigo, paresthesia, encephalopathy, and neutropenia. Taking the drug with meals lessens gastrointestinal irritation. Pancreatitis and severe central nervous system toxicity (ataxia, encephalopathy, seizures) are rare  Metronidazole has a disulfiram-like effect, so that nausea and vomiting can occur if alcohol is ingested during therapy &ต ททาน วม น / นไ a ตอ. คล Caution in patients with central nervous system disease. Intravenous infusions have rarely caused seizures or peripheral neuropathy. The dosage should be adjusted for patients with severe liver or renal disease ADR อยก า , tolerat e ก Tinidazole has a similar adverse effect profile, although it appears to be somewhat better tolerated than metronidazole  Metronidazole has been reported to potentiate the anticoagulant effect of coumarin type anticoagulants =inducer enc. Cytochrome  Phenytoin and phenobarbital may accelerate elimination of the drug, whereas cimetidine may decrease plasma clearance &เพ ม ออก metronida กะท ลาย บ  Lithium toxicity may occur when the drug is used with metronidazole ้ำ กั ขั ิ่ ั่ ำ ร่ ส้ น้ ว่ Anthelminthic drugs  Albendazole  Mebendazole broad spectrum ใช่เบอ  Diethylcarbamazine citrate (DEC)  Ivermectin  Niclosamide  Praziquantel  Pyrantel pamoate Anthelminthic drugs  Helminths (worms) are multicellular organisms that infect very large numbers of humans and cause a broad range of diseases  More than 1 billion people are infected with intestinal nematodes, and many millions are infected with filarial nematodes, flukes, and tapeworms.  Many drugs, directed against a number of different targets, are available to treat helminthic infections  Drugs for the treatment of helminthic infection Albendazole / mebendazole พ บา ธ์แ พยา เ นด ยิ ต้ ส้  Drugs for the treatment of helminthic infection เ มหม ัวม หั ช่ Drugs for the treatment of helminthic infection Praziquantel  Drugs for the treatment of helmintics Prazignantel ติ  1. Albendazole  A broad-spectrum oral antihelminthic  Effective in the treatment of pinworm and hookworm infections, ascariasis, trichuriasis, and strongyloidiasis ์ไ ่ส์พลง. > พ ยา ธ ม  MOA: inhibit microtubule synthesis,  ATP production causing energy depletion, immobilization, and worm death  Clinical Uses ไ เ ัวม  Ascariasis, Trichuriasis,  Hookworm and Pinworm Infections  Hydatid disease ↳ อต หั ส้ ต้ ดื 1. Albendazole PK  Absorption: poor; high fat meal may  absorption up to 5 times  Tmax: 3 hr  Distribution: urine, bile, liver, cyst wall, cyst fluid, and CSF  Protein binding: 70%  Metabolism: extensive first-pass effect -> albendazole sulfoxide (active metabolite)  T1/2: 8-12 hr  Excretion: fecal in small amounts, renal as albendazole sulfoxide monitor CBC and LFT Warnings/precautions  Cross hypersensitivity with other benzimidazole may occur  dexamethasone, praziquantel, and cimetidine increase exposure of albendazole  phenytoin, phenobarbital, carbamazepine, and ritonavir decrease exposure of albendazole ใช้ อมก- จ -ลดปรม ต้ ปี ม่ ช้ ฮ่ ท้  2. Mebendazole เพ น า 500  Wide spectrum of antihelminthic activity  MOA: inhibiting microtubule synthesis  Clinical uses: ascariasis, trichuriasis, hookworm and pinworm infections  PK  Absorption: 90%  Vd: 1 – 2 L/kg  Metabolism: liver (extensive)  Excretion: fecal 98%, renal hyperpolarization ->  Metabolism: hepatic via พยาธ paralyzing and killing the CYP3A4 (major), CYP2D6 (minor), invertebrate CYP  T1/2: 16 hr  Excretion:feces ตั ด้ ต่  4. Ivermectin Clinical uses  Strongyloidiasis 200 mcg/kg OD x2 days  Onchocerciasis (พยาธิ ตาบอด) มา พยา >- เ อ, ้น นพ ย ว ห ด น างกา ย -> ท วใ ADR  Fatigue, dizziness, nausea, vomiting, abdominal pain, and rashes are infrequent  In onchocerciasis treatment, adverse effects are principally from the killing of microfilariae (fever, headache, dizziness, somnolence, weakness, rash, increased pruritus, diarrhea, joint and muscle pains, hypotension, tachycardia, lymphadenitis, lymphangitis, and peripheral edema)  Shouldn’t be used in patients weight less than 15 kg ชั ธิ วั ร่ นื้ ส้ ลุ ธิ วิ 5. Niclosamide  Second-line drug for the treatment of most tapeworm infections  MOA: inhibition of oxidative phosphorylation or stimulation of ATPase activity  Adult worms are rapidly killed  Clinical uses: esecond line  Taenia saginata (beef tapeworm), taenia solium (pork tapeworm), and diphyllobothrium latum (fish tapeworm)  Intestinal fluke infections  Absorption:minimal  The tablets must be chewed thoroughly and then swallowed with water  5. Niclosamide Adverse Reactions, Contraindications, & Cautions  Infrequent, mild, and transient  N/V, diarrhea, and abdominal discomfort เ ่ยงท าน วม บ  Alcohol should not be consumed during or for 1 day after treatment  Safety has not been established in pregnancy or for children younger than 2 years กั ล่ ร่  6. Praziquantel ่าใ ใ ก าม เ ้อพ ยา ย  / MOA: Increases the cell permeability to calcium in schistosomes, causing strong contractions and paralysis of worm musculature leading to detachment of suckers from the blood vessel walls and to dislodgment  Clinical Uses  Schistosomiasis (drug of choice for all forms of schistosomiasis)  Clonorchiasis, opisthorchiasis, and paragonimiasis  Taeniasis  Praziquantel tablets should be swallowed without chewing because their bitter taste can induce retching and vomiting ธิ น้ ห้ บั ท่ ล้ 6. Praziquantel PK  Absorption: rapid (increased with high-carbohydrate meal)  F:80% (markedly reduced by phenytoin, carbamazepine, or corticosteroids)  Tmax: 1-2 hr  Distribution: CSF 14–20% of plasma concentration  Protein binding: 80%  T1/2: 0.8-1.5 hr  Excretion: urine 60%-80%, feces 15%-35% 6. Praziquantel Adverse Reactions, Contraindications, & Cautions  Mild and transient adverse effects are common  Headache, dizziness, drowsiness, and lassitude (avoid driving or activity requiring alertness)  The intensity and frequency of adverse effects increase with dosage such that they occur in up to 50% of patients who receive 25 mg/kg three times daily  Safe and well tolerated in children  Contraindicated in ocular cysticercosis because parasite destruction in the eye may cause irreparable damage  7. Pyrantel pamoate  A broad-spectrum antihelminthic  MOA: causes release of acetylcholine and inhibition of cholinesterase -> paralysis of worms  Effective against mature and immature forms of susceptible helminths within the intestinal tract เ น  Not effective in trichuriasis or strongyloidiasis  Not against migratory stages in the tissues or against ova  Poorly absorbed ADR ไ ่อ  Adverse effects are infrequent, mild, and transient  Data in pregnant women and children