Antifungal agents are used for superficial and deep (systemic) fungal infections презентация

Antibiotics
Polyenes: Amphotericin B (AMB), Nystatin, Hamycin
Echinocandins: Caspofungin, Micafungin
Heterocyclic benzofuran: Griseofulvin
Synthetic drugs:
Antimetabolite - Flucytosine (5-FC)
Azoles:
Imidazoles
1.Topical: Clotrimazole, Miconazole, Oxiconazole
2.Systemic: Ketoconazole
Triazoles: Fluconazole (systemic), Intraconazole
Allylamine - Terbinafine

Polyenes have double-bonded structure. Amphotericin B binds to ergosterol in the plasma membranes of sensitive fungal cells. It forms pores (channels). The pores disrupt membrane function, allowing electrolytes (potassium) and small molecules to leak from the cell, resulting in cell death.
It is either fungicidal or fungistatic. It is effective against: Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, many strains of Aspergillus and leishmania.

Amphotericin B is administered by slow, intravenous (IV) infusion, It is extensively bound to plasma proteins and is distributed throughout the body. But it does not pass BBB.
Adverse effects: fever and chills, renal impairment, hypotension, thrombophlebitis.
Hamycin is used to topical application for oral thrush, cutaneous candidiasis, monilial and trichomonas vaginitis and otomycosis by Aspergillus.

Nystatin is used only locally in superficial candidiasis.
It is not absorbed from GIT; it can be used for monilial diarrhoea.
Side effects: nausea and bad taste in mouth.

Caspofungin inhibits the synthesis of β-1, 3-glucan (a unique component of the fungal cell wall. It is active mainly against Candida and Aspergillus.
Uses: deep and invasive candidiasis, invasive aspergillosis.
It is infused i.v., distributed into tissues, but does not enter CSF.
Adverse effects: rash, vomiting, dyspnoea, hypokalemia and joint pain, acute febrile reaction.

Azoles are predominantly fungistatic, but may be fungicidal.
Mechanism of action: They inhibit C-14 α-demethylase, block the demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes.
The inhibition of ergosterol biosynthesis disrupts membrane structure and function, inhibits fungal cell growth.
They have broad-spectrum antifungal activity covering dermatophytes, Candida, other fungi involved in deep mycosis, Nocardia and Leishmania

Clotrimazole is effective in the topical treatment. Uses: tinea infections, ringworm, Athletes’ foot, otomycosis, oropharyngeal candidiasis, vaginal candidiasis.
Adverse effects: local irritation with stinging.
Ketoconazole is the broad-spectrum antifungal drug, useful in both dermatophytosis and deep mycosis.
Adverse effects: nausea and vomiting; loss of appetite, headache, paresthesia, rashes and hair loss.

Fluconazole is well absorbed after oral administration and distributes widely to body fluids and tissues. The majority of the drug is excreted unchanged via the urine. It is used orally, IV .
It is highly active against Cryptococcus neoformans and certain species of Candida, including C. albicans
Uses: deep fungal infections (including meningitis), ringworm, mucocutaneous candidiasis (the oral cavity, gastrointestinal tract, vagina).
Side effects: dyspepsia, liver dysfunction, skin rash.

Griseofulvin is fungistatic for most dermatophytes, including Epidermophyton, Trichophyton, Microsporum.
Griseofulvin interferes with microtubule function in dermatophytes and may also inhibit the synthesis and polymerization of nucleic acids.
Griseofulvin is fungistatic.
The oral formulation of the drug is indicated for dermatophytoses of the skin and hair.
Adverse effects: headaches, mental confusion, gastrointestinal irritation, photosensitivity and changes in liver function.

Terbinafine inhibits a fungal enzyme squalene epoxidase. It causes accumulation of toxic levels of squalene, which can interfere with ergosterol synthesis.
Terbinafine is fungicidal.
Terbinafine is available in both oral and topical forms. It accumulates in keratin, but it is much more effective than griseofulvin in onychomycosis.
Adverse effects include gastrointestinal upsets, rash, headache, and taste disturbances.

Antiviral Chemotherapy
Prophylaxis
As obligate intracellular parasites, the replication of viruses depends on synthetic processes of the host cell.
Antiviral drugs can exert their actions at several stages of viral replication including viral entry, nucleic acid synthesis, late protein synthesis and processing, and in the final stages of viral packaging and virion release.

Acyclovir is a guanosine analog active against herpes simplex virus, varicella-zoster virus and some Epstein-Barr virus.
Acyclovir is monophosphorylated in the cell by the herpes virus-encoded enzyme thymidine kinase .Virus-infected cells are most susceptible. The monophosphate analog is converted to the di- and triphosphate forms by the host cell kinases. Acyclovir triphosphate competes with deoxyguanosine triphosphate as a substrate for viral DNA polymerase and is itself incorporated into the viral DNA, causing premature DNA chain termination.

Acyclovir can be administered by the topical, and oral routes for the treatment of mucocutaneous and genital herpes lesions.
The oral drug is well tolerated but may cause gastrointestinal distress and headache.
Intravenous administration is used for severe herpes disease, including encephalitis, and for neonatal HSV infection.
Toxic effects with parenteral administration include delirium, tremor, seizures, hypotension and nephrotoxicity

Ribavirin is an analogue of guanosine. It is phosphorylated in monophosphate, reduces the synthesis of nucleotides.
It turns into triphosphate, inhibits viral dehydrogenase, disrupts the formation of RNA, proteins and virus replication.
It is used for influenza, herpes.
It can cause allergic reactions.
It is contraindicated in pregnancy.

Idoxuridine is a synthetic analog of thymidine.
It is embedded in the DNA molecule, suppresses the replication of some DNA viruses.
It is used locally for herpetic skin lesions

Zidovudine is a nucleoside derivative. It is phosphorylated in the cells and is converted to thymidine triphosphate. It inhibits the reverse transcriptase of virion, prevents the formation of DNA from viral RNA.
This DNA can be stored in human cells and become a source of RNA virus synthesis.
Zidovudine inhibits the synthesis of mRNA and viral proteins.
HIV reverse transcriptase is 20-30 times more sensitive to the inhibitory effect of the drug than DNA polymerase of macroorganism cells.

It is used for the treatment of HIV infection.
It is effective during the first 6 to 8 months from the start of disease and it delays the development of the disease.
It is used orally and IV, passes well into the tissue, through the BBB. It is excreted by the kidneys in the active form and in the form of metabolites.
Side effects: anemia, neutropenia, thrombocytopenia, headache, insomnia, myalgia, renal dysfunction, dyspepsia.

Saquinavir selectively inhibits the HIV protease. It disrupts the formation of structural proteins and enzymes of HIV virions, which are necessary for reproduction.
Immature virion precursors are formed. The development of infection is delayed.
Saquinavir is used orally for HIV-1 infection (causes HIV infection and AIDS) and HIV-2.
Side effects: dyspepsia, increased activity of liver enzymes, lipid metabolism disorders, hyperglycemia.

Remantadin and midantan reduce the penetration of the virus into the cell. They block the membrane protein M2, violate the deproteinization of virus of influenza A, suppress the replication of this virus.
They are used to prevent influenza according to the scheme.
Side effects: irritability, anxiety, drowsiness, tremor, hypotension, dyspepsia, allergy, development of resistance.

Oseltamivir inhibits neuraminidase on the surface of virus of influenza A and B. It reduces the release of viruses, the spread of infection to healthy cells.
It violates the replication of the viruses.
It reduces the production of cytokines and prevents the development of local and systemic inflammatory response.
It is used inside.
Side effects: nausea, vomiting

Neuraminidase promotes the release of virions from infected cells.

Arbidol and oxoline reduce the penetration of the virus into the cells.
Arbidol is active in influenza A and B, adenovirus infection. It increases humoral and cellular immunity, resistance to infections.
It is used orally.
Oxoline is used in drops or ointments for prevention of influenza, herpetic, adenovirus infection.
It can cause irritating effect.

Interferons-glycopeptides, which are produced by leukocytes (α), fibroblasts (β), lymphocytes (γ).
They bind to specific receptors on the surface of cells infected with the virus, activate protein kinases. They increase the synthesis of endonucleases that destroy RNA of viruses.
They reduce virus replication.
Interferons increase immunity, macrophage activity, cytotoxicity of T-killers.
They are used in viral diseases: hepatitis, encephalitis, rabies, herpes, influenza, adenovirus infections, etc. They reduce the risk of cancer.

Drugs are obtained from cells and by genetic engineering.
Preparations of α-interferon: Reaferon, Viferon
β-interferon: Betaferon
γ-interferon: Gammaferon.
They are used locally for the treatment and prevention of influenza, adenovirus infection, herpes.
They are administered IV, IM, SC in severe forms of influenza, viral hepatitis, measles, herpes, multiple sclerosis.
They penetrate into the tissues poorly, they quickly collapse.

Side effects of interferon: fever, chills, headache, soreness, hyperemia at the injection site, tachycardia, hypotension, dyspepsia, muscle pain.
In very high doses, they cause violation of hematopoiesis, paresis, paralysis, hepatotoxicity

Amixin has an immunostimulatory effect, it increases the production of α, β, γ interferons.
It is used for influenza, acute respiratory viral infections, hepatitis, neuroinfection, herpes, cytomegalovirus infection.
It can cause dyspepsia, chills, intermittent fever, allergic reactions.