Antifungal and Antiviral Drugs Chapter 42 Antifungal and Antiviral Drugs

Fungal Infections Locations of fungal infections Fungi are found in soil, air, and contaminated food. Mycoses are infections or diseases caused by a fungus. Types of infections Systemic - Throughout the body Dermatophytic - Hair, skin, and nails Candida - Skin and mucous membranes Learning Outcome 42.1 Describe the location and types of some fungal infections in humans. There are three principal areas where fungi are encountered that require drug intervention: systemic infection, dermatophytic infection, and opportunistic Candida albicans causing infections localized in the mouth, vagina, and GI tract.

Fungal Infections Locations of fungal infections Systemic Infect blood, bones, and lungs Can be dangerous in chronically ill patients Common in hospitals Neutropenic patients Immunocompromised by HIV Patients in intensive care for extended periods Learning Outcome 42.1 Describe the location and types of some fungal infections in humans. Systemic or invasive infection is always a serious clinical problem because multiple organs may be involved. Systemic fungal infection is becoming more common in modern hospitals. Severe systemic fungal infection in hospitals is commonly seen in three major settings: neutropenic patients following chemotherapy or with immune suppression; persons immunocompromised by HIV infection; and patients in intensive care who are not necessarily neutropenic but are compromised due to the presence of long-term intravascular (IV) lines, severe systemic illness or burns, and prolonged broad-spectrum antibiotic therapy.

Fungal Infections Locations of fungal infections Dermatophytic Infect hair, nails, and skin Common type of fungal infection Symptoms - Itching, discolored and scaling skin, inflammation, blisters, and broken skin Caused by Tinea species Tinea capitis- scalp Tinea unguium- nail Tinea pedis- foot Learning Outcome 42.1 Describe the location and types of some fungal infections in humans. Dermatophytic fungal infections usually inhabit a specific location: skin, hair, and nails. These organisms obtain nutrients from keratinized material and are usually restricted to the nonliving cornified layer of the epidermis because the immune system blocks penetration to other tissues. These infections are caused by a variety of Tinea species such as ringworm (Tinea capitis) in the hair or skin. Toenail and fingernail infection (Tinea unguium), referred to as onychomycosis, occurs in about 8 percent of the population.

Fungal Infections Locations of fungal infections Candida infections Vaginal yeast infections Thrives in Mouth Pharynx Esophagus GI tract Urinary bladder Thrush - Candida infection of the mouth or pharynx Learning Outcome 42.1 Describe the location and types of some fungal infections in humans. Superficial infections of skin and mucosal membranes by Candida albicans causing local inflammation and discomfort are very common. Candidiasis is a very common cause of vaginal irritation referred to as a yeast infection or moniliasis, but it also occurs in men.

Antifungal Drugs Classes of antifungal drugs Large class of drugs Discovered in nature but are also synthetically made Used in the treatment of systemic fungal infections and candidiasis Antifungal drugs have no antibacterial or antiviral activity Learning Outcome 42.2 Describe the mechanism of action of antifungal drugs. Some of the antifungal drugs some were discovered in nature, but most are synthetically made. The largest and most frequently used synthetic drugs are the imidazoles and triazoles. This group includes any drug name ending in azole: econazole, itraconazole, ketoconazole, and voriconazole. Drugs useful in the treatment of systemic mycotic infections and candidiasis are usually fungicidal (capable of killing fungi).

Systemic Antifungal Drugs Amphotericin B Drugs used in treatment of systemic fungal infections are usually fungicidal First-line therapy for systemic fungal infections Associated with transfusion reaction Chills, fever, muscle spasm, headache, vomiting, and hypotension Associated with serious renal damage Learning Outcome 42.3 Identify systemic antifungal drugs. Drugs used in the treatment of systemic infections are always administered intravenously, although often they are combined with an oral medication. For years, amphotericin B was the only drug available to treat serious systemic fungal infections. It has a broad spectrum of fungicidal activity, which makes it clinically valuable, especially against Aspergillus. Drugs used to treat systemic infections are associated with serious side effects. The side effects include chills, fever, muscle spasm, headache, vomiting, and hypotension. The effects may be reduced by pretreatment with an NSAID, hydrocortisone, or diphenhydramine; reducing the dose and infusion time of amphotericin B; or using alternate-day drug administration. There is an increased potential for hypokalemia and cardio and renal toxicity with coadministration of any amphotericin B and antineoplastic drugs, steroids, and digitalis glycosides. Combination therapy with azole antifungal drugs may induce fungal resistance to amphotericin B, especially in immunocompromised patients.

Antifungal Drugs Azoles Wide spectrum of activity against common fungal pathogens Adverse effects Fever Rash GI- nausea, vomiting, diarrhea Headache and hallucinations Skin peeling All azoles prolong the anticoagulant action of warfarin Learning Outcome 42.3 Identify systemic antifungal drugs. The availability of the azole antifungal drugs represents a major advance in the management of systemic fungal infections. The azoles have a wide spectrum of activity against common fungal pathogens, although it varies with each member of this group. Fluconazole is a water-soluble drug absorbed almost completely after an oral dose. It is excreted largely unchanged in urine, allowing for single daily dosing. It has high penetration into CSF and has been especially useful in treating cryptococcal and coccidioidal meningitis.

Oral and Topical Antifungal Drugs Topical administration Application to the surface of the skin or mucous membrane Useful in superficial, less-serious fungal infections Less than 10% of drug is absorbed with topical administration Safe during pregnancy Patients must complete the entire course of therapy even when symptoms have improved Drug hypersensitivity is the only absolute contraindication for antifungals Learning Outcome 42.4 Identify commonly used oral and topical antifungal drugs. The various types of topical administration include creams, lotions, ointments, tinctures, sprays, and powders that can be applied to the surface of the skin and mucous membranes. Topical applications are useful in superficial fungal infections of the scalp, skin, nails, and mucous membranes, with special application devices for intravaginal infections.

Viral Diseases Virus exposure Virus - Small infectious agent that must invade a living cell to reproduce Viral diseases Influenza, chickenpox, cold sores, rabies, mononucleosis, pneumonia, and AIDS Viral immunity Acquired- antibody formation from having the disease, usually in childhood Passive acquired immunity- vaccination with live or inactivated virus Learning Outcome 42.5 Describe the clinical profile of specific antiviral diseases like influenza, herpes, and HIV. Diseases caused by viruses include influenza, chicken pox, cold sores, mononucleosis, pneumonia, rabies, poliomyelitis, and AIDS. A virus is a small infectious agent, much smaller than a fungus or bacterium, that must invade a living cell to reproduce. Viruses are unique organisms because they cannot reproduce without a host cell. They do not contain the enzymes needed to carry out the chemical reactions for life. Instead, viruses carry only one or two enzymes that decode their genetic instructions. After contact with a host cell, a virus gets its genetic material into the cell and commandeers the cell’s activity. Instead of its usual proteins, the infected host cell produces viral proteins and genetic material (more viruses). Many viral diseases such as chickenpox, measles, and mumps occur during childhood. Usually, these diseases occur only once because antibodies are produced that protect individuals from reinfection. This protection is referred to as active acquired immunity. Immunity also can be achieved without experiencing the disease through vaccination. For example, with viruses such as smallpox, polio (Sabin), chickenpox, and H1N1 (swine influenza nasal spray), vaccination exposes individuals to a weakened (attenuated) live virus, which stimulates antibody production without producing the disease.

Viral Diseases Viruses are dependent upon the host. Use the host’s cells to replicate Inject their own DNA or RNA into cells, which then produce viral proteins and genetic material Cells are programmed to rupture and release new viruses into the host to infect more tissue Drug therapy is aimed at killing the virus without killing the host cells Difficult to accomplish Learning Outcome 42.7 Describe the mechanisms and sites of action of antiviral drugs. Unlike other microorganisms, viruses are totally dependent upon the metabolic system of the host’s cells. In order to multiply, viruses must enter the cell nucleus. The cells become efficient factories that produce new viruses using host DNA, amino acids, enzymes, bases, and ions. Periodically, the new viruses are expelled into the circulation and more host cells become infected. Drugs have been developed that arrest the infection after symptoms appear. The goal of drug therapy is to destroy the viruses and reduce the severity and length of infection.

Viral Diseases Influenza Flu viruses- there are many Exposure results in immunity to only the particular subtype that a person is exposed to Vaccine is formulated each year containing strains of the virus expected to produce flu Grown in highly purified chicken eggs Adverse reactions include soreness at injection site. Mild fever and myalgia may occur Recommended for high-risk persons or those who could transport the virus to them, such as health care providers Contraindicated in persons allergic to eggs Learning Outcome 42.5 Describe the clinical profile of specific antiviral diseases like influenza, herpes, and HIV. Flu viruses (e.g., Asian influenza) primarily affect the upper (nasal passages and pharynx) and lower (lungs) respiratory tracts. The virus is spread in the aerosolized droplets from the sneeze or cough of an infected person. Influenza is a family of RNA viruses categorized as types A, B, and C. Influenza A and B infect humans, although the alternate host for type A is often birds, such as chickens, or pigs prior to human inoculation.

Antiviral Drugs Influenza Amantadine, rimantadine, Tamiflu Used prophylactically to reduce severity Given to patients who have been symptomatic for less than 3 days Should be given to patients in the high-risk categories- elderly, immunocompromised, and patients with chronic diseases Antiviral drugs are effective because they block virus attachment to human cells or interfere with viral proteins needed for replication All antivirals may be associated with nausea, gastritis, GI pain, vomiting, diarrhea, headache, confusion, dizziness, insomnia,, arthralgia, myalgia, allergic reactions, hypertension, edema, and rash Should not be given during pregnancy Learning Outcome 42.6 Identify specific antiviral drugs that are used to treat influenza, herpes, and HIV. Amantadine (Symadine, Symmetrel) and rimantadine (Flumadine) are used prophylactically to reduce the severity of influenza attacks, specifically the influenza A virus, in susceptible groups.