Antimicrobials; antibacterials, antifungals, antiprotozoans, antivirals,

and antihelminthics 7

Antihelminthic Drugs Niclosamide Praziquantel Mebendazole Ivermectin Pyantel pamoate

Figure 12.26

Antihelminthic Drugs Niclosamide;

usual 1st choice, so the request for niclosamide is used by CDC to estimate the incidence of tapeworm infections.

Against tapeworms. Tapeworm infection increases with the sushi Prevents ATP generation under aerobic condition.

Praziquantel equally effective to tapeworms to Niclosamide. Alters membrane permeability. Broad spectrum, Flatworms (flukes) &

schistosomiasis. Causes muscular spasm of helminth & exposes surface antigens. well absorbed (approximately 80%) from the gastrointestinal tract, but due

to extensive first-pass metabolism, only a relatively small amount enters systemic circulation (serum half-life: 0.8 to 1.5 hours in adults with normal renal and liver function).

Niclosamide Praziquantel

Febantel (Drontal Plus and Rintal) - an anthelmintic manufactured by Bayer. - Effective against flatworms. - Veterinary anthelmintic compound belonging to the chemical class of

the benzimidazoles (so-called pro-benzimidazole, i.e. it is transformed into a benzimidazole once it gets into the host's organism).

- Transformed into fenbendazole in the stomach and the intestine of the host, shortly after ingestion.

- For dogs, cats, other pets, and livestocks. Available mainly in the form of drenches, tablets, pills, etc, all for oral administration.

- For pets it is very often used in combinations that broaden the spectrum of activity. Typical mixtures for dogs and cats include another broad-spectrum nematicide (often pyrantel) and/or another taenicide (e.g. praziquantel).

Mebendazole & albendazole broad spectrum, few side effects. Becoming drugs of choice for treating

many intestinal helminthic infections including Intestinal roundworms Inhibit microtubule formation interfering with absorption of nutrients. Widely used for veterinary applications. Relatively more effective in

ruminant animal.

Mebendazole albendazole

Ivermectin (Nobel prize in 2015) drug with wide range of applications. Effective against nematodes

(roundworms), mites (Scabies), ticks, insects (head lice). Known to be produced by only one species, Streptomyces avermectinius Primary use in livestock industry. Unknown mechanism but final result is paralysis & death without

affecting mammalian host

Pyrantel pamoate (in US) Pyrantel Embonate (in Europe), used in the treatment of hookworms (all

species) and roundworms (Ascaris lumbricoides, aka ascarids in humans) in domesticated animals, and also used for pinworm treatment for humans.

a combination of pyrantel and pamoic acid. Sometimes, combined with with praziquantel for tapeworms, or febantel for whipworms to provide more complete treatment for intestinal parasites in one dose.

Pyrantel pamoate is also commonly included in monthly administered chewable heartworm preventative tablets for dogs.

acts as a depolarizing neuromuscular blocking agent, causing sudden contraction, followed by paralysis of the helminths. This causes the worm to "lose its grip" on the intestinal wall and be passed out of intestine.

poorly absorbed by the host's intestine, the host is unaffected by the small dosage of medication used.

In developed countries, viruses cause >60% of infections Relatively few antiviral drugs have been approved in US Effective against only limited diseases Recent development of antivirals has biased to anti-HIV agents for AIDS It is very difficulties to target viruses since they;

Replicate within host cells Very often use host genetic & metabolic machinery Little of their own specific metabolisms

Many antivirals in use today are Analogs of components of viral DNA or RNA Reverse transcriptase inhibitors or Protease inhibitors Inhibitors of attachment & uncoating Interferons

Antiviral Drugs

"항생물질학" 2판 (수정판), p274, 이강만 저, 라이프 사이언스

Antiviral Drugs

Nucleoside and nucleotide analogs

"Microbiology-An introduction" 11th edition, p576, G. J. Tortora, B. R. Funke, and C. L. Case, Pearson

Acyclovir − Widely used for herpes, especially in immunosuppressed individuals − Acylclovir derivatives; famciclovir (oral), ganciclovir, similar mode of action

Ribavirin − Resemble guanine and accelerates the already high mutation rate of RNA

viruses until the accumulation of errors reaches a crisis point, killing the virus.

Lamivudine − Used for hepatitis B

Adevovir dipivoxil (Hepsera) − For lamivudine resistant patient

Cidofovir − Cytomegalovirus treatment of eyes − Promising for possible treatment of small pox

Nucleoside and Nucleotide Analogs

"Microbiology-An introduction" 10th edition, p564, G. J. Tortora, B. R. Funke, and C. L. Case, Pearson

Antiviral Drugs: Anti-influenza

Zanamivir and Oseltamivir − inhibitor of neuraminidase, which virus use to separate itself from

the host cell after it replicates, against Influenza, − Zanamivir (Relenza): can be administrated by inhalation − Oseltamivir (Tamiflu) : orally administrated. If taken within 30 hours

of onset of influenza, these drugs slow replication

Figure 13.2b

Influenza

Hemagglutinin (H) spikes used for attachment to host cells.

Neuraminidase (N) spikes used to release virus from cell.

"Microbiology-An introduction" 8th edition, p692, G. J. Tortora, B. R. Funke, and C. L. Case, Pearson

Oseltamivir (Tamiflu) Zanamivir (Relenza)

Amantadine (Symmetrel) & Rimantadine: Inhibit uncoating − approved for use both as an antiviral and an anti-parkinsonian drug.

It is the organic compound consisting of adamantane backbone that has an amino group substituted at one of the four methyne positions.

− According to the US Centers for Disease Control and Prevention, 100% of seasonal H3N2 and 2009 pandemic flu samples tested have shown resistance to adamantanes, and amantadine is no longer recommended for treatment of influenza in US. Additionally, its effectiveness as an antiparkinsonian drug is undetermined, concluding that there was insufficient evidence in support or against its efficacy and safety (a 2003 Cochrane Review).

Antiviral Drugs: Anti-influenza

Antiviral Drugs: Anti-influenza