Anti-fungals And Anti-virals - Table

Pharma Antivirals and Antifungals Tabulated

1 week of 4th Shift Antifungals MYCOTIC INFECTIONS Four General Types Cutaneous Subcutaneous Can be superficial but may not be in the skin Superficial Systemic* *Can be life threatening *usually occur in immunocompromised Candida Albicans Due to antibiotic therapy, antineoplastics, or immunosuppresants (steroids) May result in overgrowth & systemic infections Opportunistic organism, may multiply in number because of the decline in the normal flora Drug Polyenes: Amphotericin B & Nystatin

MOA

Binds to sterols in cell membrane lining Allowing K+ & Mg2+ to leak out, altering fungal cell metabolism Result: fungal cell death

In the mouth: Oral candidiasis or thrush New born infants & immunocompromised patients have increased frequency of oral thrush Vaginal Cadidiasis “yeast infections” Pregnancy, DM, OCP May occur to both male and females (urethritis and balanitis) Antiviral Agents Broken Down into 4 major grps based on their chem’l structures (1) Polyenes: amphoterincin B , nystatin (2) Flucytosine (3) Imidazoles: ketoconazole, miconazole, clotrimazole, fluconazole (4) Griseofulvin Indication

IV: fatal systemic mycotic infections Aspergillosis Blastomycosis Coccidiomycosis, Paracoccidiodomycosi Histoplasmosis Sporotrichosis

Flucytosine

aka 5-fluorocytosine Taken up by fungal cells & interferes with DNA synthesis Result: fungal cell death

Alone or in combination with amphotericin B for serious systemic infections caused by susceptible strains of Cryptococcus & candida species

ADR Fever Malaise Ms and jt pain Chills Nausea Headache Hypertension Anaphylaxis Anorexia Tachycardia Renal Toxicity Neurotoxicity Nausea, vomiting, anorexia Confusion, hallucination, headache, sedation Agranulocytosis (dec WBC) Elevated BUN & creatinine Elevated transaminases

Imidazoles

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Ketoconazole Fluconazole

Interferes with synthesis of ergosterol Increase in cell permeability & ultimately inhibition of fungal cell growth

Miconazole

Rash (if topical), anaphylaxis N & V, liver cirrhosis Gynecomastia, uterine bleeding, loss of libido, impotence, oligospermia, hair loss Acute hypoaldosteronism, renal hypofunction Headache Nausea and vomiting Abdominal pain Diarrhea Increase AST in Px w/ cryptococcal meningitis & AIDS Rash

Disrupts cell division Result: inhibited fungal mitosis (reproduction) Deposits in keratin precursor cells & has special affinity for diseased tissue. It is tightly bound to new keratin of skin, hair, & nails, w/c becomes highly resistant to fungal invasion

Vulvovaginal burning when used as ointment, cream and vaginal suppository Itching Irritation Maceration Allergic contact dermatitis Abnormal liver function tests Stinging, erythema, edema Cystitis, urethritis Vaginal soreness during intercourse Rash, urticaria Headache Nausea/Vomiting & anorexia Leukopenia Nephrotoxicity Hepatotoxicity Overgrowth of nonsusceptible organisms (Candida)

Understanding Viruses: • Viral replication: A virus cannot replicate on its own It must attach to and enter a host cell It then uses the host’s cell energy to synthesize protein, DNA and RNA (genetic parasites) Spread is fast • Viruses are difficult to kill because they live inside our cells • Any drug that kills a virus may also kill ourselves

Viral Infections Competent immune system • Best response to viral infection • A well functioning immune system will eliminate or effectively destroy virus replication • Immunocompromised patients have frequent viral infections Cancer patients Transplant patients AIDS patients

inhibit uptake of components essential for cell reproduction & growth as well as cell wall structures, thus promoting cell death of fungi

Clotrimazole

Griseofulvin

Altering fungal cell membrane permeability Permeating loss of P cmpds, K & other essential intracellular constituents w/ consequent loss of ability to replicate

Antivirals

Antivirals and Antifungals

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Viruses Affected by Current Antiviral Therapy • Cytomegalovirus (CMV) retinitis •

• •

Herpes Simplex Virus (HSV) o HSV 1: oral aphthous ulcers o HSV 2: genital ulcers Varicella Zoster Virus (VZV) Chickenpox, shingles Human Immunodeficiency Virus (HIV)

Drug MOA Purine Nucleoside Analogs: Guanines Acyclovir (Prototype) Acyclovir monoPO4

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Influenza A Virus (Flu)

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Respiratory Synctial Virus (RSV) Hepatitis B Virus (HBV)

Antivirals • Synthetic purine nucleoside analogs • Two types of nucleosides a. Purine – Guanine, Adenosine b. Pyrimidine – Thymidine, Cytosine Antiviral Activity Acyclovir

Cellular enzymes Acyclovir triPO4 Competes with DGTP thereby inhibiting DNA synthesis and consequently viral replication Ganciclovir

HSV1, HSV2, VZV

CMV retinitis, systemic CMV infection Influenza A & B, RSV

Ribavirin Purine Nucleoside Analogs: Adenosine Prototype: zidavudine Didanosine (ddI) Interferes with the HIV RNAdependent DNA polymerase (reverse transcriptase), thus preventing replication of the virus Vidaribine (Ara-A) inhibits DNA polymerase Pyrimidine Nucleoside Analogs: Cytosine Prototype: zidavudine Lamovidine Inhibition of HIV reverse transcriptase The monophosphate is incorporated into the viral DNA by HBV polymerase resulting in DNA chain termination Zalcitabine Pyrimidine Nucleoside Analogs: Thymidine Zidovudine (AZT) Converted to a triPO4 (the active form) by thymidine kinase and other cellular enzymes Incorporated into growing DNA chain by viral reverse transcriptase, thereby terminating viral replication Other Antivirals Amantadine (Symmetrel)

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ADR

As antiviral blocks uncoating of Influenza A virus preventing

HIV

HSV, VZV, CMV, EBV

HIV, HBV

rash, nausea & vomiting, headache, lethargy, dizziness, seizures, confusion, agitation, impaired renal function

bone marrow toxicity, fever, nausea, anorexia, vomiting

pancreatitis (9%), peripheral neuropathies (35%), seizures, retinal depigmentation burning, itching, lacrimation, photophobia

Headache Insomnia Malaise Pain Nausea & Vomiting Peripheral neuropathy

HIV

HIV

Influenza A Other Uses: Idiopathic Parkinson’s

Bone marrow suppression Nausea Anorexia Headache Fever Cough Rash Orthostatic hypotension Peripheral edema

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viral replication Antiparkinsonism activity: blocks reuptake of dopa into presynaptic neurons increased dopa release from presynaptic fibers

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Disease Postencephalitic Parkinsonism Drug induced extrapyramidal reactions and symptomatic Parkinsonism associated with _______

Foscarnet (Foscavir) Inhibits the replication of known herpes virus in vitro Indinavir

Oseltamivir (Tamiflu)

all

Protease inhibitor HIV protease is required for cleaving viral polyprotein precursors into individual final proteins found in infectious HIV. Inhibition prevents cleavage of these polyproteins resulting in the formation of immature non-infectious viral particles Neuraminidase inhibitor Preventing the release of nearly formed virus form the surface of the infected cells

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Insomnia Anorexia Nausea Xerostomia

CMV (retinitis and systemic)

Headache (26%), seizures (10%), acute renal failure (27%), nausea (47%), diarrhea (35%), anemia (33%)

HIV-1

Nausea, dyslipedemia, mild discoloration of indirect bilirubin

Influenza A & B

Fatigue Dizziness Headache Nausea & Vomiting