Anti-parasitics, and Antivirals

cell wall composed of chitin and glucans and ergosterol cell membrane

Common targets for drug therapy of Anti-fungals

Polyenes

An Anti-fungal that have macrocyclic lactones with amphoteric property.

Polyenes

Drugs that binds to ergosterol to form pores in the membrane leading to cellular leakage and death

Polyenes

Drugs that are used for mycoses (Histoplasma, Blastomyces, Coccidioides) molds (Aspergillus), yeast (Candida), filamentous (Fusarium).

Polyenes: Nystatin (topical) and Amphotericin B (IV)

Drugs with a structure of conjugated carbons (alkenes) with a linear hydroxyl alkyls.

Azoles

Anti fungals containing a triazole (systemic) or imidazole (topical except ketoconazole; both) pharmacophore. Azoles are potent CYP 450 inhibitor

Azoles

Anti-fungal drugs that inhibits ergosterol synthesis by blocking oxidative demethylation of lanosterol.

Allylamines

Drugs that are embedded within the antifungal structure

Allylamines

Drugs that inhibits ergosterol synthesis by blocking squalene epoxidation

Allylamines: terbinafine (both), naftifine and butenafine (topicals)

-fines (which is topical, which is systemic?)

Echinocandins

Drugs with cyclic peptides with large lipophilic groups. It is used for deep invasive candidiasis.

Echinocandins

Drugs that inhibits fungal cell wall synthesis by blocking 1,3-β-D-glucan synthesis resulting to decreased cell wall rigidity.

-Fungins/Echinocandins

Drugs with long aliphatic chain after a ketone/ether.

Flucytosine

prodrug deaminated into 5-Fluorouracil (5-FU). It blocks DNA synthesis by blocking thymidylate synthase. Used for cryptococcus meningitis in AIDS patients

Griseofulvin

disrupts mitotic spindle by binding to microtubule protein to block mitosis. It is used for Microsporum, Epidermophyton and Trichophyton infection

Ciclopirox

MOA is unclear but hypothesized to produce ROS. It is used for Candida, Epidermophyton and Trichophyton

Tolnaftate

topical agent for tine infection and works by inhibiting epoxidation of squalene (similar to allylamine)

Undecylenic acid

fungistatic agent. MOA is unclear but hypothesize to prevent morphogensis of fungi from yeast to hyphen form (active infection)

Tavaborole

inhibits leucyl-tRNA synthetase to prevents addition of leucine in the growing peptide

Anti-parasitic agents

Drugs used for used for treatment of the following: Protozoal, Helminth and Ectoparasite infection.

Protozoal infections

Type infection causing amebiasis, giardiasis, trichomoniasis, PCP infection, trypanosomiasis, leishmaniasis, and malaria

Helminth infections

Type infection causing roundworms, tapeworms, and filariasis

Ectoparasite infections

Type infection causing parasites on skin surface; scabies and pediculosis

Anti-protozoal

Nitroimidazoles and Aromatic Ester-Amides

Nitroimidazoles

Anti-protozoal: generate ROS (superoxide radicals) that damages key cellular components (e.g. DNA/RNA) leading to protozoal cellular death.

Aromatic ester-amide

Anti-protozoal: blocks pyruvate:ferredoxin oxidoreductase (PFOR)→no formation of dactyl thiamine pyrophosphate (TPP) complex → no lactic acid formation (lactic acid is essential to protozoa)

Nitroimidazoles

-nidazoles

Aromatic Ester-Amides

-xanides

Emetine

An Anti-protozoal used as alkaloidal antiprotozoal to induce vomiting

Iodoquinol

An Anti-protozoal used as luminal amebicide chelates ferrous ions

Paromomycin

An antiprotozoal aminoglycoside

Pneumocytsis carinii pneumonia (PCP)

A common life-threatening condition among immunocompromised patients (e.g HIV, organ transplant, cancer patients).

Trimethoprim-Sulfamethoxazole (TMP-SMX)

DOC of PCP-agents

Pentamidine

PCP agents: drug where amino groups binds DNA causing interference in DNA synthesis; inhibits topoisomerase II

Atovaquone

PCP agents: drug that has structural similarity with Co-Q10 hence activity on ETC complex; inhibits nucleic acid/ATP synthase

Tritryps Agents

Agents used to combat neglected parasitic tropical diseases (NTDs), uncommon in the Philippines: Leishmania spp., Trypanosoma cruzi (American sleeping/Chaga’s disease), Trypanosoma brucei gambiense/rhodisiense (West/East African sleeping disease

Suramin, Eflornithine, Melarsoprol

Tritryps Agents for African Trypanosomiasis (rhodisiense/gambiense)

Benznidazole and Nifurtimox

Tritryps Agents for American Trypanosomiasis (cruzi/Chaga’s)

Stibogluconate, Miltefosine, Antimony Potassium Tartrate

Tritryps Agents for Leishmaniasis

Quinolines

This drug, both natural and artificial, prevents conversion of hematin (toxic) to hemozoin (non-toxic)

Quinine

natural agent first extracted from Cinchona

Primaquine

artificial agent that is considered as a “radical cure”

Chloroquine

artificial agent C7-Cl gives higher activity than quinine

Anti-folate antimalarial

Anti-protozoal that targets dihydrofolate reductase (DHFR) similar to trimethoprim

Anti-folate antimalarial

Proguanil and Pyrimethamine is under?

Artemisinin

Anti-proozoal that is a natural product of chinese medicine (qinghaosu) or from sweetworm wood (Artemissia annua) MOA is unknown but the endoperoxide in the structure is hypothesized to from oxy radicals with the hemozoin

Anti-helminthic

Drug class/agents are used for parasitic helminthic infection (e.g. round worms, tape worms, filariasis).

Anti-helminthic

Drugs that inhibits fumarate reductase (benzimidazoles) and induces muscular paralysis in the helminth parasite (other agents).

Benzimidazoles; inhibits fumarate reductase

Subclass and MOA of Mebendazole, Thiabendazole, and Albendazole

Other agents; muscular paralysis in the helminth parasite

Subclass and MOA of Ivermectin (for river blindness), Praziquantel (fluke infection), Pyrantel pamoate, Diethylcarbamazine, Piperazine

ectoparasites

Sarcoptes scabiei (scabies), Pediculus humanus (pediculosis), and Cimex reticularis are 3 common ________ that can live in human skin surface.

Ectoparasite-agents

Lindane, Pyrethroids (Pyrethrin, Permethrin, Piperonyl), Crotamiton, Spinosad, Benzyl alcohol

Spinosad

Ectoparasite agent that is a mixture of macrocyclic lactones that paralyzes parasite by hyper exciting nicotinic acetylcholine receptors.

Benzyl alcohol

Ectoparasite agent that is not insecticidal but it asphyxiate lices by inhibiting respiratory spiracles

Crotamiton

scabicical agent approved by FDA

Lindane

blocks GABA receptor leads to parasite paralysis

Antiretrovirals/Anti-HIV

targets Reverse transcription; Taken in combination called HAART

Nucleoside RT Inhibitors

Anti-HIV that mimics nucleoside structures and usually possess a 3-letter code for their names. These are prodrugs that competes with natural nucleosides.

Nucleoside RT Inhibitors

Under what subclass of anti-HIV are Zidovudine (AZT), Didanosine (ddI), Stavudine (D4T)

Non-Nucleoside RT Inhibitors

Anti-HIV that are direct inhibitors of RT by binding to it and disrupting catalytic site. Universally taken with other anti-retrovirals.

Non-Nucleoside RT Inhibitors

Under what subclass of anti-HIV are Efavirenz, Nevirapine, Delavirdine

Fusion Inhibitors

Anti-HIV drugs that prevent gp41 viral protein conformational change that inhibits entry of virus into the host

Fusion Inhibitors

Enfuvirtide (36-AA peptide), Maraviroc

Protease Inhibitors

Anti-HIV drugs that prevent HIV protein cleavage that is required for viral maturity and pathogenicity

Protease Inhibitors

Saquinavir, Nelfinavir, Indinavir, Ritonavir

HIV Integrase Inhibitors

Anti-HIV drugs that prevent incorporation of cDNA into the host DNA preventing viral replication.

HIV Integrase Inhibitors

Raltegravir, Elvitegravir, Dolutegravir

Integrase Inhibitors

Anti HIV that is primarily characterized by their hydoxyethylamine structures

Crofelemer

adjunct therapy agent for HIV-related diarrhea

Hepatitis

presented as inflamed liver caused by any of the Hepatitis viruses (A,B,C are most common)

agents for HBV

Under what subclass are NRTIs (Adefovir, Entecavir, Telvibudine)

agents for HBC

PEG-IFN Alfa, Ribavirin

Anti-Herpes

Drugs where all agents inhibits DNA polymerase activity (“-clovirs”)

Other agents of Anti-Herpes

Cidofovir, Idoxuridine, Trifluridine, Foscarnet

Hemaglutinnin (HA) and neuramindasae (NA)

Influenza or “flu” targets the respiratory system. They are covered by an envelope made of glycoprotein _________ and __________

Anti-Influenza

Drug that prevents viral uncoating → inhibits viral replication

Amantadine and Rimantadine

Dominant agents for inhibiting viral uncoating

NA Inhibitors (Oseltamivir, Zanamivir)

Anti-Influenza that blocks NA, viral accumulation on cell surface → no viral replication