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  1. 1. Antifungal Agents 1
  2. 2. Antifungal Agents• Drugs used to treat infections caused by fungi• Systemic and topical 2
  3. 3. Cellular Structure of Fungi• Similar to human cells• Different steroid present in plasma membranes• Human: cholesterol• Fungi: ergosterol What is the pharmacologic implication of this difference? Discuss the limitations of antifungal therapy. 3
  4. 4. Fungi• Also known as mycoses• Very large and diverse group of microbes• Broken down into yeast and molds 4
  5. 5. Yeast• Single-cell fungi• Reproduce by budding• Very useful organisms – Baking – Alcoholic beverages 5
  6. 6. Molds• Mulitcellular• Characterized by long, branching filaments called hyphae 6
  7. 7. Mycotic InfectionsFour General Types:1. Cutaneous2. Subcutaneous3. Superficial4. Systemic * can be life-threatening * usually occur in immunocompromised host 7
  8. 8. Mycotic InfectionsCandida albicans• Due to antibiotic therapy, antineoplastics or immunosuppressants• May result in overgrowth and systemic infections 8
  9. 9. Mycotic InfectionsIn the mouth:• Oral candidiasis or thrush• Newborn infants & immunocompromised pts 9
  10. 10. Vaginal candidiasis:• Yeast infection• Pregnancy, DM, OC 10
  11. 11. Antifungal AgentsSYSTEMIC• Examples: – Amphotericin B – Fluconazole – Ketoconazole – ItraconazoleTOPICAL• Examples: – Clotrimazole – Miconazole – Nystatin 11
  12. 12. Antifungal AgentsBroken down into 4 groups based on their chemical structure1. Polyenes: amphotericin B & nystatin2. Flucytosine3. Imidazole: ketoconazole, miconazole, clotrimazol e, fluconazole4. Griseofulvin 12
  13. 13. 13
  14. 14. Generalized fungal cell depicting the sites of action of the common antifungal agents. 14
  15. 15. Antifungal Agents: Mechanism of ActionPolyenes: amphotericin B and nystatin• Binds to sterols in cell membrane lining• Allow K+ & Mg++ to leak out, altering fungal cell metabolism• Result: fungal cell death 15
  16. 16. Antifungal Agents: Mechanism of ActionFlucytosine• Also known as 5-fluorocytosine (antimetabolite)• Taken up by fungal cells and interferes with DNA synthesis• Result: fungal cell death 16
  17. 17. Antifungal Agents: Mechanism of Action Imidazoles: Ketoconazole, miconazole, clotrimazole, fluconazole• Inhibit an enzyme, resulting in cell membrane leaking• Lead to altered cell membrane• Result: fungal cell death 17
  18. 18. Antifungal Agents: Mechanism of ActionGriseofulvin• Disrupt cell division• Result: inhibit fungal mitosis (reproduction) 18
  19. 19. Antifungal Agents: Side Effects Amphotericin BFever chills headacheAnorexia malaise nauseahypotension tachycardiamuscle and joint painLowered K+ and Mg++ levels*renal toxicity*neurotoxicity: seizure & paresthesia 19
  20. 20. Antifungal Agents: Side EffectsFluconazole• N&V, diarrhea, abd’l pain• Increased liver function studiesFlucytosine• N&V, anorexiaGriseofulvin• Rash, urticaria, headache, N&V, anorexia 20
  21. 21. Antifungal Agents: Nursing Implications• Before beginning therapy, assess for hypersensitivity, possible contraindications, and conditions that require cautious use.• Obtain baseline VS,CBC, liver function studies and ECG• Assess for other medications used (prescribed and OTC) in order to avoid drug interactions. 21
  22. 22. Antifungal Agents: Nursing Implications• Follow manufacturer’s directions carefully for reconstitution and administration.• Monitor VS of pt receiving IV infusions every 15-30 mins• During IV infusions, monitor I&O and urinalysis findings to identify adverse renal effects. 22
  23. 23. Antifungal Agents: Nursing ImplicationsAmphotericin B• To reduce the severity of infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines and antiemetics may be given.• A test dose of 1mg per 20 mL of 5% dextrose in water infused over 30 minutes should be given.• Use IV infusion and the most distal veins possible. 23
  24. 24. Antifungal Agents: Nursing Implications• Tissue extravasation of fluconazole at the IV site may lead to tissue necrosis – monitor IV site carefully.• Oral forms of griseofulvin should be given with meals to decrease GI upset.• Monitor carefully for side/adverse effects. 24
  25. 25. Antifungal Agents: Nursing ImplicationsMonitor for therapeutic effects:• Easing of the symptoms of infection• Improved energy levels• Normal vital signs, including temperature 25
  26. 26. Antiviral Agents 26
  27. 27. Understanding VirusesViral Replication• A virus cannot replicate on its own.• It must attach to and enter a host cell.• It then uses the host cell’s energy to synthesize protein, DNA and RNA. 27
  28. 28. Understanding VirusesViruses are difficult to kill because they live inside our cells.• Any drug that kills a virus may also kill our cells. 28
  29. 29. Viral InfectionsCompetent immune system:• Best response to viral infections• A well-functioning immune system will eliminate or effectively destroy virus replicationImmunocompromised patients have frequent viral infections• Cancer pts, esp leukemia/lymphoma• Transplant pts, due to pharmacological therapy• AIDS pts, disease attacks immune system 29
  30. 30. Antiviral DrugsKey characteristics:• Able to enter the cells infected with virus• Interfere with viral nucleic acid synthesis and/or regulation.• Some agents interfere with ability of virus to bind to cells.• Some agents stimulate the body’s immune system. 30
  31. 31. Antiviral DrugsViruses killed by current antiviral therapy:• Cytomegalovirus (CMV)• Herpes simplex virus (HSV)• Human immunodeficiency virus (HIV)• Influenza A (flu)• Respiratory syncytial virus (RSV) 31
  32. 32. Antivirals: Mechanism of Action• Inhibit viral replication• Inhibit viral attachment• Prevent genetic copying of virus• Prevent viral protein production 32
  33. 33. Antivirals Synthetic Purine Nucleoside Analogues2 types of nucleosides:Purine nucleosides• Guanine• AdenosinePyrimidine nucleosides• Thymine• cytosine 33
  34. 34. Antivirals: Purine NucleosidesAgent Antiviral ActivityGuanines HSV 1&2 1.acyclovir CMV retinitis & systemic infection 2.ganciclovir Influenza type A&B, RSV 3.ribavirinAdenosines HIV HSV, herpes zoster 1.didanosine 2.vidarabine 34
  35. 35. Antivirals:Pyrimidine NucleosidesAgent Antiviral ActivityCytosine 1. lamivudine HIV 2. zalcitabine HIVThymine 1. Idoxuridine HSV 2. Stavudine HIV 3. Trifluridine HSV 4. Zidovudine HIV 35
  36. 36. Other Antiviral Drugs1. Amantadine (Symmetrel)2. Rimantadine (Flumadine) – Influenza A3. Foscarnet (Foscavir) – CMV (retinitis & systemic)4. Neuraminidase Inhibitors: oseltamivir (Tamiflu) – Influenza A&B 36
  37. 37. Antivirals: Side EffectsAcyclovir• Burning when topically applied, N&V, diarrhea, headacheAmantadine & rimantadine• Anticholinergic effects, insomnia, lightheadedness, anorexia, nauseaDidanosine• Pancreatitis, peripheral neuropathies, seizures 37
  38. 38. Antivirals: Side EffectsZidovudine (AZT) – Bone marrow suppression, nausea, headacheFoscarnet (Foscavir) – HA, seizures, acute renal failure, N&V, diarrheaGanciclovir (Cytovene) – Bone marrow toxicity, N&V, anorexia 38
  39. 39. Antivirals: Nursing Implications• Before beginning therapy, thoroughly assess underlying disease and medical hx, including allergies.• Assess baseline VS and nutritional status• Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions. 39
  40. 40. Antivirals: Nursing Implications• Teach proper application technique for ointment, aerosol powders, etc• Emphasize handwashing before and after administration of medications to prevent site contamination and spread of infection.• Patient should wear glove when applying ointments or solutions to affected areas. 40
  41. 41. Antivirals: Nursing Implications• Instruct to consult their physician before taking any other medication, including OTC medications• Emphasize the importance of good hygiene.• Inform patient that antiviral agents are not cures, but do help to manage symptoms. 41
  42. 42. Antivirals: Nursing Implications• Instruct on the importance of taking these medications exactly as prescribed and for the full course of tx• With zidovudine: – Inform pt that HAIR LOSS MAY occur so they are prepared for this rare AE. – Should be taken on an empty stomach. 42
  43. 43. Antivirals: Nursing Implications• Monitor for side effects: – Effects are varied and specific to each agent• Monitor for therapeutic effects: – Vary depending on the type of viral infection – Effect range from delayed progression of AIDS and ARC(AIDS- related complex) to decrease in flu-like symptomes, decrease frequency of herpes-like flare-ups or crusting over of herpetic lesions 43
  44. 44. Antimalarial AntiprotozoalAntihelmintic Agents 44
  45. 45. Protozoal InfectionsParasitic protozoa: live in or on humans• Malaria• Leishmaniasis• Amebiasis• Giardiasis• Trichomoniasis 45
  46. 46. Malaria• Caused by plasmodium protozoa• 4 different species• Causes: – Bite of infected adult mosquito – blood transfusion, – Congenitally – infected needles by drug abusers 46
  47. 47. Malarial Parasite2 Interdependent Life Cycles• Sexual cycle: in mosquito• Asexual cycle: in human – Knowledge of the life cycle is essential in understanding antimalarial drug tx – Drugs are only effective during asexual cycle. 47
  48. 48. Plasmodium Life CycleAsexual cycle: 2 phases• Exoerythrocytic phase Occurs “outside” the RBC• Erythrocytic phase Occurs “inside” the RBC 48
  49. 49. Antimalarial Agents Attack the parasite during asexual phase when it is vulnerable• Erythrocytic phase drugs: – chloroquinine – hydroxychloroquine – quinine – mefloquine• Exoerythrocytic phase drugs: – primaquineMay be used together for synergistic or additive killing power. 49
  50. 50. Antimalarials: Mechanism of Action4-aminoquinoline derivatives chloroquine and hydroxychloroquine• Bind to parasite nucleoproteins and interfere with protein synthesis• Prevent vital parasite-sustaining substances from being formed• Alter pH within the parasite• Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin• Effective only during the erythrocytic phase 50
  51. 51. Antimalarials: Mechanism of Action4-aminoquinoline derivatives quinine and mefloquine• Alter pH within the parasite• Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin• Effective only during erythrocytic phase. 51
  52. 52. Antimalarials: Mechanism of ActionDiaminophyrimidines pyrimethamine and trimethoprim• Inhibit dihydrofolate reductase in parasite• This enzyme is needed by parasite to make essential substances• Also blocks synthesis of tetrahydrofolate.These agents may be used with sulfadoxine or dapsone for synergistic effects. 52
  53. 53. Antimalarials: Mechanism of Actionprimaquine• Only exoerythrocytic drug• Binds and alter DNAsulfonamides,tetracycline, clindamycin – Used in combination with antimalarials to increase protozoacidal effects 53
  54. 54. Antimalarials: Drug Effects• Kills parasitic organisms• Chloroquine and hydroxychloroquine also have antiinflammatory effects. 54
  55. 55. Antimalarials: Therapeutic Uses• Used to kill plasmodium organisms• Drugs have varying effectiveness on different malaria organisms• Some agents are used for prophylaxis against malaria• Chloroquine is also used for rheumatois arthritis and lupus. 55
  56. 56. Antimalarials: Side Effects• Primarily GI: – N&V – Diarrhea – Anorexia – Abd’l pain 56
  57. 57. Antiprotozoals• atovaquone(Mepron)• metronidazole (Flagyl)• pentamidine (Pentam)• iodoquinol (Yodoxin, Di-Quinol)• paromomycin (Humatin) 57
  58. 58. Protozoal Infections• Amebiasis• Giardiasis• Pneumocystosis• Toxoplasmosis• Trichomoniasis 58
  59. 59. Protozoal InfectionsTransmission• Person-to-person• Ingestion of contaminated water/food• Direct contact with parasite• Insect bite (mosquito/tick) 59
  60. 60. Antiprotozoals: Mechanism of Actionatovaquone (Mepron)• Protozoal energy comes from the mitochondria• Atovaquone: selective inhibition of mitochondrial electron transport• Result: no energy, leading to cell death Used to tx mild to moderate P. carinii 60
  61. 61. Antiprotozoals: Mechanism of ActionMetronidazole• Disruption of DNA synthesis as well as nucleic acid synthesis• Bactericidal, amebicidal, trichomonocidal 61
  62. 62. Antiprotozoals: Mechanism of ActionPentamidine• Inhibit DNA & RNA• Binds to and aggregate ribosomes• Directly lethal to P. carinii• Inhibit: – glucose metabolism – CHON & RNA synthesis – intracellular amino acid transport Mainly used to tx P. carinii 62
  63. 63. Antiprotozoals: Mechanism of ActionIodoquinol• “luminal” or “contact” amedicide• Acts primarily in the intestinal lumen of the infected host• Directly kills protozoa Used to tx intestinal amebiasis 63
  64. 64. Antiprotozoals: Mechanism of ActionParomomycin• “luminal” or “contact” amebicide• kills by inhibiting protein synthesis Tx of amebiasis & intestinal protozoal infections Adjunct therapy in hepatic coma 64
  65. 65. Antiprotozoals: Side EffectsAtovaquone – N&V, diarrhea, anorexiaMetronidazole – METALLIC TASTE,N&V, diarrhea, abd’l crampsIodoquinol – N&V, diarrhea, anorexia, agranulocytosis 65
  66. 66. Antiprotozoals: Side EffectsPentamidine – Bronchospasm – Leukemia – Thrombocytopenia – Acute pancreatitis – ARF – Inc liver function studiesParomomycin – GI s/sx 66
  67. 67. Antihelmintics• diethylcarbamazine (Hetrazan)• mebendazole (Vermox)• niclosamide (Niclocide)• oxamniquine (Vansil)• piperazine (Vermizine)• praziquantel (Biltricide)• pyrantel (Antiminth) thiabendazole (Mintezol) 67
  68. 68. Antihelmintics• Drugs used to tx parasitic worm infections: helmintic infection• Unlike protozoa, helminths are large and have complex cellular structures• Drug tx is very specific 68
  69. 69. Antihelmintics• It is VERY IMPORTANT to identify the causative worm• Done by finding the parasite ova or larvae in feces, urine, blood, sputum or tissue – Cestodes (tapeworms) – Nematodes (roundworms) – Trematodes (flukes) 69
  70. 70. Antihelmintics: Mechanism of Actiondiethylcarbamazine (Hetrazan) – Inhibit rate of embryogenesisthiabendazole (Mintezol) – Inhibits helminth-specific enzyme, fumarate reductase Both used for nematodes 70
  71. 71. Antihelmintics: Mechanism of Actionpiperazine (Vermizine) and pyrantel (Antiminth)• Blocks acetylcholine at neuromuscular junction, resulting in paralysis of worms, which are then expelled through the GI tractUsed to tx nematodes (giant worms & pinworms) 71
  72. 72. Antihelmintics: Mechanism of Actionmebendazole (Vermox)• Inhibits uptake of glucose and other nutrients, leading to autolysis and death of parasitic worm Used to tx cestodes & nematodes 72
  73. 73. Antihelmintics: Mechanism of Actionniclosamide (Niclocide)• Causes the worm to become dislodged from the GI wall• They are then digested in the intestines and expelled. Used to tx cestodes 73
  74. 74. Antihelmintics: Mechanism of Actionoxamniquine (Vansil) and praziquantel (Biltricide)• Cause paralysis of worms’ musculature and immobilization of their suckers• Cause worms to dislodge from mesenteric veins to the liver, then killed by host tissue reactions Used to tx trematodes, cestodes 74
  75. 75. Antihelmintics: Side Effectsniclosamide, oxamniquine, praziquantel, thiabendaz ole, piperazine, pyrantel – N&V, diarrhea, dizziness, HAmebendazole – Diarrhea, abd’l pain, TISSUE NECROSIS 75
  76. 76. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications• Before beginning therapy, perform a thorough health hx & medication hx, and assess for allergies• Check baseline VS• Check for conditions that may contraindicate use, and for potential drug interactions. 76
  77. 77. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications• Warn the pt ahead of time on some agents may cause urine to have an asparagus-like odor, or cause an unusual skin odor, or a metallic taste• Administer ALL agents as ordered and for the prescribed length of time• Most agents should be TAKEN WITH FOOD to reduce GI upset. 77
  78. 78. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications• Assess for + of malarial sx• When used for prophylaxis, agents should be started 2 WEEKS BEFORE potential exposure to malaria, and for 8 WEEKS AFTER leaving the area.• Medications are taken weekly, with 8 ounces of water. 78
  79. 79. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications• Instruct to notify HCP immediately id ringing in the ears, hearing decreases, visual difficulties, N&V, profuse diarrhea, or abd’l pain occur.• Alert pt to possible recurrence of symptoms of malaria so they will know to seek immediate tx. 79
  80. 80. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing ImplicationsMonitor for side effects:• Ensure pt knows the SE that should be reported.• Monitor for therapeutic effects and AE with long- term therapy. 80