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Antiviral, Antifungal and Antiparasitic Drugs Nursing 3703 Pharmacology By Linda Self.

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Presentation on theme: "Antiviral, Antifungal and Antiparasitic Drugs Nursing 3703 Pharmacology By Linda Self."— Presentation transcript:

1 Antiviral, Antifungal and Antiparasitic Drugs Nursing 3703 Pharmacology By Linda Self

2 Viruses Intracellular parasites Enter host, bind to receptors on cell membranes Use cellular metabolic activities for replication May be DNA or RNA viruses

3 Viruses DNA viruses incorporate into chromosomal DNA, produce new viruses RNA viruses must be converted to DNA by reverse transcriptase in order to replicate

4 Viruses Induce antibodies and immunity Protein coat allows host recognition as foreign vs. self Exception is influenza

5 Viral illnesses Herpes Simplex 1 and 2 Cytomegalovirus Influenza RSV Rotavirus HIV and AIDS

6 Antiviral Drugs Catalyst was AIDS Both for Tx of AIDS and for opportunistic infections

7 Viral Vaccines Poliomyelitis Measles Rubella Varicella RSV HPV Herpes Zoster Yellow Fever others

8 Viral Vaccines Attenuated vaccines generally safe Do not use in patients who are: pregnant, on steroids, receiving immunosuppressants or antineoplastiacs, undergoing radiation Tx or who are immunodeficient

9 Drugs for Herpes Virus Infections Zovirax (acyclovir) for herpes labialis, varicella, herpes zoster, genital herpes Famvir (famciclovir) for zoster and genital herpes Valtrex (valacyclovir) for herpes labialis, zoster, recurrent genital herpes Famvir and Valtrex need titration in renally impaired

10 Influenza H=hemagglutinin N=neuramidase April 2009 Quadruple reassortment Tx—Tamiflu (oseltamivir) or Relenza (zanamivir) or Flumadine (rimantadine) Tx for 5 days Relenza can cause bronchospasm

11 Influenza To short course of infection, must be started within 48h Thereafter, ? may decrease severity

12 RSV Virazole (ribavirin) Administered by inhalation Can cause bronchospasm

13 Viral hepatitis Hepatitis B—Hepsera (adefovir), Epivir (lamivudine) Hepatitis C—peginterferon alfa 2a and Virazole (ribavirin)

14 HIV Unique features 2 proteins on surface of virus bind with 2 sites on CD4+ cell Virus infiltrates into genetic material Reverse transcriptase enzyme enables virus to become double stranded DNA

15 HIV Once double-stranded DNA, like the host cell, HIV can infiltrate cell nucleus of target cell Gains entry into target cell nucleus with aid of Integrase Following integration and replication, long protein chain is cleaved. Pieces then form into new viral particle

16 HIV Cleavage is accomplished with aid of protease See page 568

17 Drugs for HIV Infection Nucleoside reverse transcriptase inhibitors Nucleotide reverse transcriptase inhibitors Non-nucleoside reverse transcriptase inhibitors Protease inhibitors Entry inhibitors

18 Antiretrovirals Always used in combination Target enzymes or receptor sites Specific guidelines for pregnancy

19 Nucleoside Reverse Transcriptase Inhibitors Prototype is AZT Similar structurally to DNA components (adenosine, guanosine, cytosine or thymidine) Affect thymidine, thus inhibit reverse transcriptase Slow progression but do not cure Didanosine, Ziagen (abacavir), AZT (zidovudine), Epivir (lamivudine)

20 Nucleotide Reverse Transcriptase Inhibitors Also inhibit reverse transcriptase Differ structurally from nucleoside RTI so circumvent resistance Viread (tenofovir) Used to Tx hep B as well

21 Non-nucleoside Reverse Transcriptase Inhibitors Directly bind with reverse transcriptase Used in combination with NRTIs Viramune (nevirapine) and Sustiva (efavirenz)

22 Protease Inhibitors Inhibit action of protease Most protease inhibitors metabolized by cytochrome p450 system Many drug interactions Liver toxicities Lipid abnormalities Hyperglycemia lipodystrophies

23 Protease Inhibitors Prezista (darunavir), Crixivan (indinavir), Viracept (nelfinavir), Norvir (ritonavir), Invirase (saquinavir)

24 Combination Antiretrovirals Combovir (stavudine and zidovudine) Trizivir (abacavir, lamivudine and zidovudine) Decrease pill burden

25 Entry Inhibitors Fuzeon (enfuvirtide) Selzentry (maraviroc) Do not act on enzymes but rather affect glycoproteins that allow binding and fusion of the virus to the CD4+ cell

26 Integrase inhibitors Still in clinical trials

27 Fungi (mycoses) Mild or life threatening Widely present in environment Dermatophytes—tinea capitis, tinea pedis, tinea cruris, tinea corporis Examples: Candida, Aspergillosis, Cryptococcus, Histoplasmosis, B

28 Antifungal Drugs Development of antifungals difficult because fungal cells closely resemble human cells Polyenes—Amphotericin B, Nystatin Azoles—Sporonox (itraconazole), Nizoral (ketoconazole), Diflucan (fluconazole) Echinocandins—Eraxis (anidulafungin), Cancidas (caspofungin)

29 Fungizone (amphotericin B) Give in D5W Use separate line In line filter depending on formulation Adverse effects: Infusion reaction with chills, fever, tachypnea Treat with Benadryl, Tylenol or steroids Nephrotoxicity most serious SE

30 Amphotericin B Indicated for life-threatening fungal infections such as aspergillosis, blastomycosis, candidiasis, coccinioidomycosis, crytococcis and histoplasmosis Drug concentrations are highest in inflamed tissues

31 Miscellaneous Antifungals Lamisil (terbinafine) griseofulvin

32 Mycostatin (nystatin) Same mechanism of action as Amphotericin B Too toxic for systemic use

33 Azoles Largest group of commonly used antifungals Can be used topically or systemically Prototype is Nizoral (ketoconazole0 All azoles are contraindicated in pregnancy

34 Azoles Less toxic than ampho Many drug interactions Poor absorption if achlorhydric Some hepatotoxicity Can be given orally

35 Diflucan (fluconazole) Synthetic, broad spectrum against candidiasis, cryptococcis, coccidioidomycosis Not effective against aspergillosis PO or IV Fewer side effects than ketoconazole Does not require gastric acidity, does not cross blood-brain barrier Reduce dosage in renal failure

36 Sporanox (itraconazole) Similar to Diflucan Drug of choice for blastomycosis, histoplasmosis and sporotrichosis Good for suppressive Tx in AIDS patients w/histo Contraindicated for dermatophytic infections and onychomycoses in heart failure patients IV or PO Many drug interactions

37 Cancidas (caspofungin) First chicocandin antifungal Affects glucan in fungal cell wall leading to leakage of cellular contents Indicated for Tx of invasive aspergillosis who cannot take or do not respond to Fungizone or Sporanox

38 Cancidas Can cause thrombophlebitis Abnormalities in blood count Liver impairment Drug interactions Mix only with normal saline, infuse over at least one hour

39 Fulvicin (griseofulvin) For dermatophyte infections of the scalp and nails and for extensive skin eruptions Drug binds to keratin, over time the infected tissues are shed and replaced by uninfected tissues Need 3-8 weeks to Tx ringworm Up to one year for onychomycoses

40 Fulvicin Side effects: GI upset, skin rash, insomnia, fatigue, hepatotoxicity, blood dyscrasias and peripheral neuritis Take with fatty meal May affect efficacy of OCP Coumadin may warrant adjustment

41 Lamisil (terbinafine) Synthetic with broad spectrum of activity Inhibits an enzyme needed for synthesis of ergosterol, a structural component of fungal cell membranes Good for Tx of ringworm, nails hepatotoxic

42 Drug Treatment for Specific Infections Aspergillosis—Sporonox, Amphotericin B Blastomycosis—Sporonox, Amphotericin B Candidiasis—varies r/t area of infection Oral Cutaneous Vaginal Systemic

43 Drug Treatment for Fungal Infections Histoplasmosis—Sporanox PCP—Bactrim, pentamidine, dapsone, others Cryptococcis-Amphotericin B Coccidioidomycosis- azole to Amphotericin B

44 Aspergillosis Found in soil, decaying plant matter, cellars May be found in cereals, powdered milk, peanuts, cashews, coffee beans Characterized by granulomatous lesions of lungs,skin, eyes, nose, urethra and may infiltrate to vital organs Occurs in debilitated and immunocompromised Tx w/ Amphotericin or Sporonox

45 Histoplasmosis Found in soil, organic debris around chicken houses, bird roosts and caves inhabited by bats Develops when spores are inhaled Tx with Sporanox, possibly Ampho

46 Candidiasis Yeast infection commonly affects those on abx therapy, inhaled steroids, diabetics, those on antineoplastic Tx or on steroids or who have AIDS Presents as: vaginal candidiasis, skin candidiasis, oral candidiasis or systemic disease

47 Tx for Candidiasis Systemically—Amphotericin B Vaginally-Lotrimin (clotrimazole), Diflucan Oropharyngeal, esophageal, vaginal and systemic—Diflucan PO or IV

48 Parasites Organisms that live within, upon or at expense of another organism to survive Include protozoa, helminths, scabies and pediculi

49 Protozoa Include amebiasis, giardiasis, malaria, toxoplasmosis and trichomoniasis Single celled, may be saprophytes. Usually contracted by oral-fecal route, by contaminated water or by bite of an insect.

50 Amebiasis Common in Africa, Asia and Latin America In US, more likely in homosexuals and bisexual men and in those who travel to areas with poor sanitation

51 Amebiasis Drugs used are classified according to site of action Extraintestinal e.g. liver—use Aralen (chloroquine) For Intestinal use Yodoxin (lodoquinol) Flagyl is effective for intestinal and extraintestinal amebiasis May also use tetracycline or doxycycline as they alter bacterial flora

52 Giardiasis Caused by Giardia lamblia Spread by food or water contaminated with feces with encysted forms of organism Also can contract by person to person transmission in day cares, institutions and in homosexual or bisexual men

53 Giardiasis Seen in campers who drink water Causes diarrhea Can progress to chronic condition with malabsorption, wt. loss, anorexia Can result in B12 deficiency Tx is Flagyl

54 Malaria Seen in tropics Rare in US Caused by four species of protozoa of genus Plasmodium-vivax, malariae, ovale and falciparum Transmitted by the Anopholes mosquito Antimalarials act at different stages in life cycle

55 Malaria Chloroquine with primaquine is used for prophylaxis Lariam (mefloquine) for prevention and Tx, better in more resistant forms Plaquenil (hydroxychloroquine) used to Tx erythrocytic malaria Daraprim (pyrimethamine) folic acid antagonist also used in prevention

56 Malaria Quinamm (quinine) prototype Derived from bark of cinchona tree Sometimes still used for leg cramps Replaced by agents with fewer SE

57 Trichomoniasis Vaginal infection caused by Trichomonas vaginalis Contracted sexually Treat both partners Flagyl is Tx

58 Helminthiasis Infestation with parasitic worms Some types of worms penetrate body tissues or produce larvae that migrate to blood, lymph, lungs, liver or other sites Some anthelminthics act locally, some systemically

59 Vermox (mebendazole) Effective for hookworms, pinworms, roundworms, whipworms May be useful with tapeworms Prevents uptake of glucose necessary for parasitic metabolism Only 10% is absorbed systemically

60 Stromectrol (vermectin) Used for various parasitic infections, most useful in stronguloidiasis Also used for resistant lice

61 Scabies and Pediculosis Parasitic infestations of the skin Scabies by the itch mite called the Sarcoptes scabeii Scabies caused by one of three types of lice: pediculosis capitis, pediculosis corporis and pediculosis pubis

62 Scabicides and Pediculocides Permethrins drug of choice for both Two applications recommended Pediculosis is a 1% preparation (Nix) Scabies used a 5% cream (Elimite) Permethrins safest Second line use Lindane (gamma benzene hexachloride)

63 Scabicides and Pediculosis Ovide (malathion) is a pediculicide for head lice Rid (pyrethrin) for pediculosis


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