Antiparasitic

Short description: Class of medications

Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths,[1] amoeba,[2] ectoparasites, parasitic fungi,[3] and protozoa,[1] among others. Antiparasitics target the parasitic agents of the infections by destroying them or inhibiting their growth;[4] they are usually effective against a limited number of parasites within a particular class. Antiparasitics are one of the antimicrobial drugs which include antibiotics that target bacteria, and antifungals that target fungi. They may be administered orally, intravenously or topically.[4] Overuse or misuse of antiparasitics can lead to the development of antimicrobial resistance.

Broad-Spectrum antiparasitics, analogous to broad-spectrum antibiotics for bacteria, are antiparasitic drugs with efficacy in treating a wide range of parasitic infections caused by parasites from different classes.

## Contents

* 1 Types
* 1.1 Broad-spectrum
* 1.2 Antiprotozoals
* 1.3 Antihelminthic
* 1.3.1 Antinematodes
* 1.3.2 Anticestodes
* 1.3.3 Antitrematodes
* 1.4 Antiamoebics
* 1.5 Antifungals
* 2 Medical uses
* 2.1 Administration
* 3 Drug development history
* 4 Research
* 5 See also
* 6 References

## Types

### Broad-spectrum

* Nitazoxanide[5][6][7][8]

### Antiprotozoals

Main page: Biology:Antiprotozoal

* Melarsoprol (for treatment of sleeping sickness caused by Trypanosoma brucei)
* Eflornithine (for sleeping sickness)
* Metronidazole (for vaginitis caused by Trichomonas)
* Tinidazole (for intestinal infections caused by Giardia lamblia)
* Miltefosine (for the treatment of visceral and cutaneous leishmaniasis, currently undergoing investigation for Chagas disease)

### Antihelminthic

#### Antinematodes

Ancylostoma caninum, a type of hookworm, attached to the intestinal mucosa.

* Mebendazole (for most nematode infections)
* Pyrantel pamoate (for most nematode infections)
* Thiabendazole (for roundworm infections)
* Diethylcarbamazine (for treatment of Lymphatic filariasis)
* Ivermectin (for prevention of river blindness)

#### Anticestodes

* Niclosamide (for tapeworm infections)
* Praziquantel (for tapeworm infections)
* Albendazole (broad spectrum)

#### Antitrematodes

* Praziquantel

### Antiamoebics

* Rifampin
* Amphotericin B

### Antifungals

Main page: Chemistry:Antifungal

* Fumagillin (for microsporidiosis)[3][9]

## Medical uses

Antiparasitics treat parasitic diseases, which impact an estimated 2 billion people.[1]

### Administration

Antiparastics may be given via a variety of routes depending on the specific medication, including oral, topical, and intravenous.[4]

Resistance to antiparasitics has been a growing concern, especially in veterinary medicine. The Egg hatch assay can be used to determine whether a parasite causing an infection has become resistant to standard drug treatments.[10]

## Drug development history

Early antiparasitics were ineffective, frequently toxic to patients, and difficult to administer due to the difficulty in distinguishing between the host and the parasite.[4]

Between 1975 and 1999 only 13 of 1,300 new drugs were antiparasitics, which raised concerns that insufficient incentives existed to drive development of new treatments for diseases that disproportionately target low-income countries. This led to new public sector and public-private partnerships (PPPs), including investment by the Bill and Melinda Gates Foundation. Between 2000 and 2005, twenty new antiparasitic agents were developed or in development.[11] Metal-containing compounds are the subject of another avenue of approach.[12]

## Research

In the last decades, triazolopyrimidines and their metal complexes have been looked at as an alternative drug to the existing commercial antimonials, searching for a decrease in side effects and the development of parasite drug resistance.[13]

## See also

* Balsam of Peru, which has antiparasitic attributes
* Naegleria fowleri
* Balamuthia mandrillaris

## References

1. ↑ 1.0 1.1 1.2 Kappagoda, Shanthi; Singh, Upinder; Blackburn, Brian G. (2011). "Antiparasitic Therapy". Mayo Clin. Proc. 86 (6): 561–583. doi:10.4065/mcp.2011.0203. PMID 21628620.
2. ↑ "A novel antiamoebic agent against Acanthamoeba sp. – A causative agent for eye keratitis infection". Spectrochimica Acta Part A: Molecular Spectroscopy 153: 714–21. 2016. doi:10.1016/j.saa.2015.09.021. PMID 26474244. Bibcode: 2016AcSpA.153..714K.
3. ↑ 3.0 3.1 "Fumagillin treatment of intestinal microsporidiosis". N. Engl. J. Med. 346 (25): 1963–9. June 2002. doi:10.1056/NEJMoa012924. PMID 12075057.
4. ↑ 4.0 4.1 4.2 4.3 "ANTIPARASITICS". Purdue Research Foundation. http://www.cyto.purdue.edu/cdroms/cyto2/17/chmrx/anthelmi.htm.
5. ↑ "Research perspective: potential role of nitazoxanide in ovarian cancer treatment. Old drug, new purpose?". Cancers (Basel) 5 (3): 1163–1176. 2013. doi:10.3390/cancers5031163. PMID 24202339. "Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths.  ... Nitazoxanide (NTZ) is a main compound of a class of broad-spectrum anti-parasitic compounds named thiazolides. It is composed of a nitrothiazole-ring and a salicylic acid moiety which are linked together by an amide bond ... NTZ is generally well tolerated, and no significant adverse events have been noted in human trials [13]. ... In vitro, NTZ and tizoxanide function against a wide range of organisms, including the protozoal species Blastocystis hominis, C. parvum, Entamoeba histolytica, G. lamblia and Trichomonas vaginalis [13]".
6. ↑ "Nitazoxanide: a new broad spectrum antiparasitic agent". Expert Rev Anti Infect Ther 2 (1): 43–9. 2004. doi:10.1586/14787210.2.1.43. PMID 15482170.
7. ↑ "Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections". Expert Opin Pharmacother 7 (7): 953–64. 2006. doi:10.1517/14656566.7.7.953. PMID 16634717.
8. ↑ Anderson, V. R.; Curran, M. P. (2007). "Nitazoxanide: A review of its use in the treatment of gastrointestinal infections". Drugs 67 (13): 1947–1967. doi:10.2165/00003495-200767130-00015. PMID 17722965.
9. ↑ "Microsporidiosis in solid organ transplant recipients: two Enterocytozoon bieneusi cases and review". Transpl Infect Dis 11 (1): 83–8. February 2009. doi:10.1111/j.1399-3062.2008.00347.x. PMID 18803616.
10. ↑ Sargison, Neil (2009-01-26) (in en). Sheep Flock Health: A Planned Approach. John Wiley & Sons. ISBN 9781444302608. https://books.google.com/books?id=-nS2JylUCCEC&q="Egg+hatch+assay"+definition&pg=PA174.
11. ↑ Pink, Richard; Hudson, Alan; Mouries, Marie-Annick; Bendig, Mary (September 2005). "Opportunities and Challenges in Antiparasitic Drug Discovery". Nature 4 (9): 727–740. doi:10.1038/nrd1824. PMID 16138106.
12. ↑ Gambino, Dinorah; Otero, Lucia (2019). "Chapter 13. Metal Compounds in the Development of Antiparasitic Agents: Rational Design from Basic Chemistry to the Clinic". in Sigel, Astrid; Freisinger, Eva; Sigel, Roland K. O. et al.. Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic. 19. Berlin: de Gruyter GmbH. 331–357. doi:10.1515/9783110527872-019. ISBN 978-3-11-052691-2.
13. ↑ "Leishmanicidal and Trypanocidal Activity of Metal Complexes with 1,2,4-Triazolo[1,5-a]pyrimidines: Insights on their Therapeutic Potential against Leishmaniasis and Chagas Disease". Curr. Med. Chem. 24 (25): 2796–2806. 2017. doi:10.2174/0929867324666170516122024. PMID 28521698.

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metabolism (A)|

* stomach acid
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system (G)|

* Hormonal contraception
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Endocrine
system (H)|

* Hypothalamic–pituitary hormones
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* Glucocorticoids
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Infections and
infestations (J, P, QI)|

* Antimicrobials: Antibacterials (Antimycobacterials)
* Antifungals
* Antivirals
* Antiparasitics
* Antiprotozoals
* Anthelmintics
* Ectoparasiticides
* IVIG
* Vaccines

Malignant disease
(L01–L02)|

* Anticancer agents
* Antimetabolites
* Alkylating
* Spindle poisons
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(L03–L04)|

* Immunomodulators
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and joints (M)|

* Anabolic steroids
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nervous system (N)|

* Analgesics
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Respiratory
system (R)|

* Decongestants
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Sensory organs (S)|

* Ophthalmologicals
* Otologicals

Other ATC (V)|

* Antidotes
* Contrast media
* Radiopharmaceuticals
* Dressings
* Senotherapeutics

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* t
* e

Antiparasitics – antiprotozoal agents – Excavata antiparasitics (P01)

Discicristata|

| Trypanosomiasis|

* African trypanosomiasis: ornithine]] (Eflornithine#)
* arsenical (Melarsoprol#)
* benzamidine (Pentamidine#)
* naphthalenesulfonate (Suramin#)

* nitroimidazole (Fexinidazole†)

Chagas disease: nitroimidazole]] (Benznidazole#)

* nitrofuran (Nifurtimox#)

|

Leishmaniasis|

* macrolide (Amphotericin B#)

Pentavalent antimonials (Meglumine antimoniate#, Sodium stibogluconate)

* benzamidine (Pentamidine#)
* phosphorylcholine (Miltefosine)
* neomycin (Paromomycin)

PAM|

* macrolide (Amphotericin B)

Trichozoa|

| Giardiasis|

* nitroimidazole (Metronidazole#, Tinidazole)
* benzimidazole (Albendazole)

* thiazolide (Nitazoxanide)
* nitrofuran (Furazolidone)

* aminoacridine (Quinacrine)

|

Trichomoniasis|

* nitroimidazole (Carnidazole, Metronidazole#, Tinidazole)

Dientamoebiasis|

* nitroimidazole (Metronidazole
* Secnidazole)

* oxyquinoline (Iodoquinol)
* tetracycline (Doxycycline)
* neomycin (Paromomycin)

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

* v
* t
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Antiparasitics – antiprotozoal agents – Chromalveolate antiparasitics (P01)

Alveo-
late|

| Apicom-
plexa|

| Conoidasida/
(Coccidiostats)|

| Cryptosporidiosis|

* thiazolides (nitazoxanide)

|

Isosporiasis|

* trimethoprim/sulfamethoxazole#

Toxoplasmosis|

* pyrimethamine
* sulfadiazine
* clindamycin
* atovaquone

Aconoidasida|

| Malaria|

| Individual
agents|

| Hemozoin
inhibitors|

| Aminoquinolines|

* (4-): amodiaquine#
* chloroquine#
* hydroxychloroquine#

* (8-): primaquine#
* pamaquine‡
* tafenoquine†

|

4-Methanolquinolines|

* mefloquine#
* quinine#
* quinidine

Other|

* lumefantrine
* \+ artemether#

* halofantrine

Antifolates|

| DHFR inhibitors|

* pyrimethamine

* biguanides
* chlorproguanil
* proguanil#

|

Sulfonamides|

* sulfadoxine
* sulfalene

Co-formulation|

* sulfadoxine/pyrimethamine (SP)#

Sesquiterpene
lactones|

* artemether#
* artemisinin
* artemotil
* artesunate#
* dihydroartemisinin

Other|

* atovaquone (\+ proguanil)
* tetracycline
* doxycycline#
* clindamycin
* mepacrine
* pyronaridine
* piperaquine

Combi-
nations|

| Fixed-dose (co-formulated) ACTs|

* artemether/lumefantrine#
* arterolane/piperaquine
* artesunate/amodiaquine (ASAQ)
* artesunate/mefloquine (ASMQ)
* artesunate/pyronaridine
* dihydroartemisinin/piperaquine

|

Other combinations
(not co-formulated)|

* artesunate/mefloquine
* artesunate/SP
* quinine/clindamycin
* quinine/doxycycline
* quinine/tetracycline

Babesiosis|

* clindamycin

Cilio-
phora|

* Balantidiasis: tetracycline

Hetero-
kont|

* Blastocystosis: metronidazole

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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Antiparasitics – antiprotozoal agents – agents against amoebozoa/amebicide (P01)

Entamoeba|

| Tissue amebicides|

| Nitroimidazole derivatives|

* Metronidazole#
* Tinidazole
* Ornidazole
* Nimorazole
* Secnidazole
* Azanidazole
* Propenidazole

|

Other|

* isoquinoline (Emetine/Dehydroemetine|Dehydroemetine)]]

Luminal amebicides|

| Hydroxyquinoline derivatives|

* Cl (Chlorquinaldol)
* Br (Tilbroquinol
* Broxyquinoline)
* I (Diiodohydroxyquinoline)
* I, Cl (Clioquinol)

* related: Chiniofon

|

Dichloroacetamide derivatives|

* Diloxanide#
* Clefamide
* Etofamide
* Teclozan

Aminoglycoside|

* Paromomycin

Other/ungrouped|

* arsenic (Arsthinol
* Difetarsone
* Glycobiarsol)
* phenanthroline (Phanquinone)
* aminoacridine (Mepacrine)
* quinazoline (Trimetrexate)
* thiazole (Tenonitrozole)
* sesquiterpene (Fumagillin)

Acanthamoeba|

* Propamidine
* Chlorhexidine

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

* v
* t
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Antiparasitics – Anthelmintics (P02) and Endectocides (QP54)

Antiplatyhelmintic agents|

| Antitrematodals
(schistosomicides)|

| Binds tubulin|

* benzimidazole
* Triclabendazole#

|

AI|

* phosphonic acid
* Metrifonate‡

Other/unknown|

* quinoline
* Praziquantel#
* Oxamniquine#
* phenol
* Bithionol
* thiazole
* Niridazole
* arylsulfonate
* Stibophen

Anticestodals
(taeniacides)|

| Binds tubulin|

* benzimidazole
* Albendazole#

|

Other/unknown|

* quinoline
* Praziquantel#
* salicylanilide
* Niclosamide#
* aminoacridine
* Quinacrine
* butyrophenone
* Desaspidin
* chlorophenol
* Dichlorophen

Antinematodal agents
(including
macrofilaricides)|

| Binds tubulin|

* benzimidazole
* Mebendazole#
* Albendazole#
* Tiabendazole
* Fenbendazole
* Ciclobendazole
* Flubendazole

|

Glutamate-gated chloride channel, GABA receptor|

* avermectins
* Abamectin
* Doramectin
* Emamectin
* Ivermectin#
* Selamectin
* milbemycins
* Moxidectin
* Milbemycin oxime

NMDA|

* tetrahydropyrimidine
* Pyrantel#
* pyrantel pamoate
* Oxantel
* Morantel
* Carbantel
* Febantel (aka felsantel)

Other/unknown|

* piperazine
* Piperazine
* Diethylcarbamazine#
* thiazole
* Levamisole#
* quinolinium
* Pyrvinium
* benzylammonium
* Bephenium
* naphthalenesulfonate
* Suramin#
* Tribendimidine

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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