1. Antiviral Agents

2. Understanding Viruses Viral Replication A virus cannot replicate on its own. A virus cannot replicate on its own. It must attach to and enter a host cell. It must attach to and enter a host cell. It then uses the host cell’s energy to synthesize protein, DNA, and RNA. It then uses the host cell’s energy to synthesize protein, DNA, and RNA.

3. Understanding Viruses Viruses are difficult to kill because they live inside our cells. Any drug that kills a virus may also kill our cells. Any drug that kills a virus may also kill our cells.

4. Viral Infections Competent immune system: Best response to viral infections Best response to viral infections A well-functioning immune system will eliminate or effectively destroy virus replication A well-functioning immune system will eliminate or effectively destroy virus replication Immunocompromised patients have frequent viral infections Cancer patients, especially leukemia or lymphoma Cancer patients, especially leukemia or lymphoma Transplant patients, due to pharmacological therapy Transplant patients, due to pharmacological therapy AIDS patients, disease attacks immune system AIDS patients, disease attacks immune system

5. Antivirals Key characteristics of antiviral drugs: Able to enter the cells infected with virus. Able to enter the cells infected with virus. Interfere with viral nucleic acid synthesis and/or regulation. Interfere with viral nucleic acid synthesis and/or regulation. Some agents interfere with ability of virus to bind to cells. Some agents interfere with ability of virus to bind to cells. Some agents stimulate the body’s immune system. Some agents stimulate the body’s immune system.

6. Antivirals Viruses killed by current antiviral therapy: cytomegalovirus (CMV) cytomegalovirus (CMV) herpes simplex virus (HSV) herpes simplex virus (HSV) human immunodeficiency virus (HIV) human immunodeficiency virus (HIV) influenza A (the “flu”) influenza A (the “flu”) respiratory syncytial virus (RSV) respiratory syncytial virus (RSV)

7. Antivirals: Mechanism of Action Inhibit viral replication Inhibit viral attachment Inhibit viral attachment Prevent genetic copying of virus Prevent genetic copying of virus Prevent viral protein production Prevent viral protein production

8. Sites of Drug Action

10. Antiviral Agents Block viral entry into the cell or must work inside the cell Block viral entry into the cell or must work inside the cell Most agents are pyrimidine or purine nucleoside analogs Most agents are pyrimidine or purine nucleoside analogs

11. Antivirals Synthetic Purine Nucleoside Analogues Two types of nucleosides: Purine nucleosides guanine guanine adenosine adenosine Pyrimidine nucleosides thymine thymine cytosine cytosine

12. Antivirals: Purine Nucleosides AgentAntiviral Activity guanines acyclovirHSV 1 & 2, VZV ganciclovir (DHPG)CMV retinitis and systemicCMV infection ribavirin (RTCD)Influenza types A and B,RSV, LV, HV adenosines didanosine (ddl)HIV vidarabine (Ara-A)HSV, herpes zoster

13. Antivirals: Pyrimidine Nucleosides AgentAntiviral Activity cytosines lamivudine (3TC)HIV zalcitabine (ddC)HIV thymine idoxuridine (IDU)HSV stavudine (d4T)HIV trifluridineHSV zidovudine (AZT)HIV

14. Other Antivirals amantadine (Symmetrel) and rimantadine (Flumadine) influenza A influenza A foscarnet (Foscavir) CMV (retinitis and systemic) CMV (retinitis and systemic) Neuraminidase Inhibitors: oseltamivir (Tamiflu) and zanamivir (Relenza) influenza types A and B influenza types A and B

15. Antivirals: Side Effects acyclovir Burning when topically applied, nausea, vomiting, diarrhea, headache Burning when topically applied, nausea, vomiting, diarrhea, headache amantadine and rimantadine Anticholinergic effects, insomnia, lightheadedness, anorexia, nausea Anticholinergic effects, insomnia, lightheadedness, anorexia, nausea didanosine (ddl) Pancreatitis, peripheral neuropathies, seizures Pancreatitis, peripheral neuropathies, seizures

16. Antivirals: Side Effects zidovudine (AZT) Bone marrow suppression, nausea, headache Bone marrow suppression, nausea, headache foscarnet (Foscavir) Headache, seizures, acute renal failure, nausea, vomiting, diarrhea Headache, seizures, acute renal failure, nausea, vomiting, diarrhea ganciclovir (Cytovene) Bone marrow toxicity, nausea, anorexia, vomiting Bone marrow toxicity, nausea, anorexia, vomiting

17. Antiherpes Agents Acyclovir- prototype Acyclovir- prototype Valacyclovir Valacyclovir Famciclovir Famciclovir Penciclovir Penciclovir Trifluridine Trifluridine Vidarabine Vidarabine

18. Mechanism of Action Acyclovir an acyclic guanosine derivative an acyclic guanosine derivative Phosphorylated by viral thymidine kinase Phosphorylated by viral thymidine kinase Di-and tri-phosphorylated by host cellular enzymes Di-and tri-phosphorylated by host cellular enzymes Inhibits viral DNA synthesis by: Inhibits viral DNA synthesis by: 1) competing with dGTP for viral DNA polymerase1) competing with dGTP for viral DNA polymerase 2) chain termination2) chain termination

20. Clinical Uses Acyclovir Oral, IV, and Topical formulations Oral, IV, and Topical formulations Cleared by glomerular filtration and tubular secretion Cleared by glomerular filtration and tubular secretion Uses: Uses: Herpes Simplex Virus 1 and 2 (HSV)Herpes Simplex Virus 1 and 2 (HSV) Varicella-zoster virus (VZV)Varicella-zoster virus (VZV) Side Effects: nausea, diarrhea, headache, tremors, and delirium Side Effects: nausea, diarrhea, headache, tremors, and delirium

21. Valacyclovir L-valyl ester of acyclovir L-valyl ester of acyclovir Converted to acyclovir when ingested Converted to acyclovir when ingested M.O.A.: same as acyclovir M.O.A.: same as acyclovir Uses: Uses: 1) recurrent genital herpes1) recurrent genital herpes 2) herpes zoster infections2) herpes zoster infections Side Effects: nausea, diarrhea, and headache Side Effects: nausea, diarrhea, and headache

22. Famciclovir Prodrug of penciclovir (a guanosine analog) Prodrug of penciclovir (a guanosine analog) M.O.A.: same as acyclovir M.O.A.: same as acyclovir does not cause chain termination does not cause chain termination Uses: HSV-1, HSV-2, VZV, EBV, and hepatitis B Uses: HSV-1, HSV-2, VZV, EBV, and hepatitis B Side Effects: nausea, diarrhea, and headache Side Effects: nausea, diarrhea, and headache

23. Trifluridine Trifluridine- fluorinated pyrimidine Trifluridine- fluorinated pyrimidine inhibits viral DNA synthesis same as acyclovirinhibits viral DNA synthesis same as acyclovir incorporates into viral and cellular DNAincorporates into viral and cellular DNA Uses: HSV-1 and HSV-2 (topically)Uses: HSV-1 and HSV-2 (topically)

24. Vidarabine An adenosine analog An adenosine analog inhibits viral DNA polymerase inhibits viral DNA polymerase incorporated into viral and cellular DNA incorporated into viral and cellular DNA metabolized to hypoxanthine arabinoside metabolized to hypoxanthine arabinoside Side Effects: GI intolerance and myelosuppression Side Effects: GI intolerance and myelosuppression

25. Anti-Cytomegalovirus Agents Gancyclovir Gancyclovir Valgancyclovir Valgancyclovir Cidofovir Cidofovir Foscarnet Foscarnet Fomivirsen Fomivirsen

26. Ganciclovir An acyclic guanosine analog An acyclic guanosine analog requires triphosphorylation for activation requires triphosphorylation for activation monophosphorylation is catalyzed by a phosphotransferase in CMV and by thymidine kinase in HSV cells monophosphorylation is catalyzed by a phosphotransferase in CMV and by thymidine kinase in HSV cells M.O.A.: same as acyclovir M.O.A.: same as acyclovir Uses: CMV*, HSV, VZV,and EBV Uses: CMV*, HSV, VZV,and EBV Side Effect: myelosuppression Side Effect: myelosuppression

27. Valgancyclovir Monovalyl ester prodrug of gancyclovir Monovalyl ester prodrug of gancyclovir Metabolized by intestinal and hepatic esterases when administered orally Metabolized by intestinal and hepatic esterases when administered orally M.O.A.: same as gancyclovir M.O.A.: same as gancyclovir Uses: CMV* Uses: CMV* Side Effect: myelosuppression Side Effect: myelosuppression

28. Foscarnet An inorganic pyrophosphate An inorganic pyrophosphate inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase does not have to be phosphorylated does not have to be phosphorylated Uses: HSV, VZV, CMV, EBV, HHV-6, HBV, and HIV Uses: HSV, VZV, CMV, EBV, HHV-6, HBV, and HIV Resistance due to mutations in DNA polymerase gene Resistance due to mutations in DNA polymerase gene Side Effects: hypo- or hypercalcemia and phosphotemia Side Effects: hypo- or hypercalcemia and phosphotemia

29. HIV AIDS- treatment

30. HIV

31. HIV

33. Antiretroviral Agents 1) Nucleoside Reverse Transcriptase Inhibitors (NRTIs) 2) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) 3)Protease inhibitors

36. Reverse Transcriptase Inhibitors Zidovudine (AZT) Zidovudine (AZT) Didanosine- causes pancreatitis* Didanosine- causes pancreatitis* Lamivudine- causes pancreatitis Lamivudine- causes pancreatitis Zalcitabine- causes peripheral neuropathy * Zalcitabine- causes peripheral neuropathy * Stavudine- causes peripheral neuropathy* Stavudine- causes peripheral neuropathy* Abacavir Abacavir

38. Mechanism of Action Zidovudine (AZT) A deoxythymidine analog A deoxythymidine analog enters the cell via passive diffusion enters the cell via passive diffusion must be converted to the triphosphate form by mammalian thymidine kinase must be converted to the triphosphate form by mammalian thymidine kinase competitively inhibits deoxythymidine triphosphate for the reverse transcriptase enzyme competitively inhibits deoxythymidine triphosphate for the reverse transcriptase enzyme causes chain termination causes chain termination

39. Mechanism of Resistance Zidovudine Due to mutations in the reverse transcriptase gene Due to mutations in the reverse transcriptase gene more frequent after prolong therapy and in persons with HIV more frequent after prolong therapy and in persons with HIV

40. Clinical Uses Zidovudine Available in IV and oral formulations Available in IV and oral formulations activity against HIV-1, HIV-2, and human T cell lymphotropic viruses activity against HIV-1, HIV-2, and human T cell lymphotropic viruses mainly used for treatment of HIV, decreases rate of progression and prolongs survival mainly used for treatment of HIV, decreases rate of progression and prolongs survival prevents mother to newborn transmission of HIV prevents mother to newborn transmission of HIV

41. Side Effects Zidovudine Myelosuppression, including anemia and neutropenia Myelosuppression, including anemia and neutropenia GI intolerance, headaches, and insomnia GI intolerance, headaches, and insomnia

42. Other NRTIs Didanosine- synthetic deoxy- adenosine analog; causes pancreatitis* Didanosine- synthetic deoxy- adenosine analog; causes pancreatitis* Lamivudine- cytosine analog Lamivudine- cytosine analog Zalcitabine- cytosine analog; causes peripheral neuropathy* Zalcitabine- cytosine analog; causes peripheral neuropathy* Stavudine- thymidine analog;causes peripheral neuropathy* Stavudine- thymidine analog;causes peripheral neuropathy* Abacavir- guanosine analog; more effective than the other agents; fatal hypersensitivity reactions can occur Abacavir- guanosine analog; more effective than the other agents; fatal hypersensitivity reactions can occur

43. Nucleotide Inhibitors Tenofovir Tenofovir Adefovir Adefovir

44. Tenofovir An acyclic nucleoside phosphonate analog of adenosine An acyclic nucleoside phosphonate analog of adenosine M.O.A.- competively inhibits HIV reverse transcriptase and causes chain termination after incorporation into DNA M.O.A.- competively inhibits HIV reverse transcriptase and causes chain termination after incorporation into DNA Uses – in combination with other antiretrovirals for HIV-1 suppression Uses – in combination with other antiretrovirals for HIV-1 suppression

45. Adefovir An analog of adenosine monophosphate An analog of adenosine monophosphate Phosphorylated by cellular kinases Phosphorylated by cellular kinases M.O.A. - Competitively inhibits HBV DNA polymerase and results in chain termination after incorporation into viral DNA M.O.A. - Competitively inhibits HBV DNA polymerase and results in chain termination after incorporation into viral DNA Uses - Hepatitis B Uses - Hepatitis B Side effects - nephrotoxicity Side effects - nephrotoxicity

46. Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Nevirapine Nevirapine Delavirdine Delavirdine Efavirenz Efavirenz

47. Mechanism of Action NNRTIs Bind to site on viral reverse transcriptase, different from NRTIs Bind to site on viral reverse transcriptase, different from NRTIs results in blockade of RNA and DNA dependent DNA polymerase activity results in blockade of RNA and DNA dependent DNA polymerase activity do not compete with nucleoside triphosphates do not compete with nucleoside triphosphates do not require phosphorylation do not require phosphorylation these drugs can not be given alone these drugs can not be given alone substrates and inhibitors of CYP3A4 substrates and inhibitors of CYP3A4

48. Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Nevirapine- prevents transmission of HIV from mother to newborn when given at onset of labor and to the neonate at delivery Nevirapine- prevents transmission of HIV from mother to newborn when given at onset of labor and to the neonate at delivery Delavirdine- teratogenic, therefore can not be given during pregnancy Delavirdine- teratogenic, therefore can not be given during pregnancy Efavirenz- teratogenic, therefore can not be given during pregnancy Efavirenz- teratogenic, therefore can not be given during pregnancy

49. Protease Inhibitors Indinavir Indinavir Ritonavir Ritonavir Saquinavir Saquinavir Nelfinavir Nelfinavir Amprenavir Amprenavir

50. Protease Inhibitors The protease enzyme cleaves precursor molecules to produce mature, infectious virions The protease enzyme cleaves precursor molecules to produce mature, infectious virions these agents inhibit protease and prevent the spread of infection these agents inhibit protease and prevent the spread of infection These agents cause a syndrome of altered body fat distribution, insulin resistance, and hyperlipidemia These agents cause a syndrome of altered body fat distribution, insulin resistance, and hyperlipidemia

51. Indinavir and Ritonavir M.O.A.: Specific inhibitors of the HIV-1 protease enzyme M.O.A.: Specific inhibitors of the HIV-1 protease enzyme M.O.R.: mediated by expression of multiple and variable protease amino acid substitutions M.O.R.: mediated by expression of multiple and variable protease amino acid substitutions Side Effects: hyperbilirubinemia Side Effects: hyperbilirubinemia Contraindications:inhibitor/substrate for CPY3A4, do not give with antifungal azoles Contraindications:inhibitor/substrate for CPY3A4, do not give with antifungal azoles

52. Saquinavir A synthetic peptide-like substrate analog A synthetic peptide-like substrate analog inhibits HIV-1 protease inhibits HIV-1 protease prevents cleavage of viral polyproteins prevents cleavage of viral polyproteins

53. Nelfinavir and Amprenavir M.O.A.: Specific inhibitors of the HIV-1 protease enzyme M.O.A.: Specific inhibitors of the HIV-1 protease enzyme M.O.R.: mediated by expression of multiple and variable protease amino acid substitutions M.O.R.: mediated by expression of multiple and variable protease amino acid substitutions Less cross-resistance with Amprenavir Less cross-resistance with Amprenavir Side Effects: diarrhea and flatulence Side Effects: diarrhea and flatulence Amprenavir can cause Stevens- Johnson syndrome Amprenavir can cause Stevens- Johnson syndrome Contraindications:inhibitor/substra te for CPY3A4 Contraindications:inhibitor/substra te for CPY3A4

54. Fusion Inhibitors Enfuvirtide (T-20)- binds to the gp41 subunit of the viral envelope glycoprotein, preventing the conformational changes required for fusion of the viral and cellular membranes Enfuvirtide (T-20)- binds to the gp41 subunit of the viral envelope glycoprotein, preventing the conformational changes required for fusion of the viral and cellular membranes By blocking fusion (entry into cell), FUZEON prevents HIV from infecting CD4 cells By blocking fusion (entry into cell), FUZEON prevents HIV from infecting CD4 cells

55. Anti-Hepatitis Agents Lamivudine - Nucleoside Reverse Transcriptase Inhibitor (NRTI) Lamivudine - Nucleoside Reverse Transcriptase Inhibitor (NRTI) Adefovir - Nucleotide Inhibitor Adefovir - Nucleotide Inhibitor Interferon Alfa Interferon Alfa Pegylated Interferon Alfa Pegylated Interferon Alfa Ribavirin Ribavirin

56. Interferons Interferon Alfa Interferon Alfa Endogenous proteins Endogenous proteins induce host cell enzymes that inhibit viral RNA translation and cause degradation of viral mRNA and tRNA induce host cell enzymes that inhibit viral RNA translation and cause degradation of viral mRNA and tRNA Bind to membrane receptors on cell surface Bind to membrane receptors on cell surface May also inhibit viral penetration, uncoating, mRNA synthesis, and translation, and virion assembly and release May also inhibit viral penetration, uncoating, mRNA synthesis, and translation, and virion assembly and release

57. Interferons Pegylated interferon Alfa Pegylated interferon Alfa A linear or branced polyethylene gylcol (PEG) moiety is attached to covalently to interferon A linear or branced polyethylene gylcol (PEG) moiety is attached to covalently to interferon Increased half-life and steady drug concentrations Increased half-life and steady drug concentrations Less frequent dosing Less frequent dosing Tx chronic hepatitis C in combination with ribavirin Tx chronic hepatitis C in combination with ribavirin

58. Ribavirin A guanosine analog A guanosine analog phosphorylated intracellularly by host enzymes phosphorylated intracellularly by host enzymes inhibits capping of viral messenger RNA inhibits capping of viral messenger RNA inhibits the viral RNA-dependent RNA polymerase inhibits the viral RNA-dependent RNA polymerase inhibits replication of DNA and RNA viruses inhibits replication of DNA and RNA viruses

59. Anti-Influenza Agents Amantadine Amantadine Rimantadine Rimantadine Zanamivir Zanamivir

60. Amantadine and Rimantadine cyclic aminescyclic amines inhibit the uncoating of viral RNA therefore inhibiting replicationinhibit the uncoating of viral RNA therefore inhibiting replication resistance due to mutations in the RNA sequence coding for the structural M2 proteinresistance due to mutations in the RNA sequence coding for the structural M2 protein used in the prevention and treatment of Influenza Aused in the prevention and treatment of Influenza A

61. Zanamivir and Oseltamivir Inhibits the enzyme neuraminidase Inhibits the enzyme neuraminidase inhibit the replication of influenza A and Influenza B inhibit the replication of influenza A and Influenza B treats uncomplicated influenza infections treats uncomplicated influenza infections administered intranasally administered intranasally

62. Antivirals: Nursing Implications Before beginning therapy, thoroughly assess underlying disease and medical history, including allergies. Before beginning therapy, thoroughly assess underlying disease and medical history, including allergies. Assess baseline VS and nutritional status. Assess baseline VS and nutritional status. Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions. Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions.

63. Antivirals: Nursing Implications Be sure to teach proper application technique for ointments, aerosol powders, etc. Be sure to teach proper application technique for ointments, aerosol powders, etc. Emphasize hand washing before and after administration of medications to prevent site contamination and spread of infection. Emphasize hand washing before and after administration of medications to prevent site contamination and spread of infection. Patients should wear a glove or finger cot when applying ointments or solutions to affected areas. Patients should wear a glove or finger cot when applying ointments or solutions to affected areas.

64. Antivirals: Nursing Implications Instruct patients to consult their physician before taking any other medication, including OTC medications. Instruct patients to consult their physician before taking any other medication, including OTC medications. Emphasize the importance of good hygiene. Emphasize the importance of good hygiene. Inform patients that antiviral agents are not cures, but do help to manage symptoms. Inform patients that antiviral agents are not cures, but do help to manage symptoms.

65. Antivirals: Nursing Implications Instruct patients on the importance of taking these medications exactly as prescribed and for the full course of treatment. Instruct patients on the importance of taking these medications exactly as prescribed and for the full course of treatment. With zidovudine: With zidovudine: Inform patients that hair loss MAY occur so that they are prepared for this rare adverse reaction. Inform patients that hair loss MAY occur so that they are prepared for this rare adverse reaction. This medication should be taken on an empty stomach. This medication should be taken on an empty stomach.

66. Antivirals: Nursing Implications Monitor for side effects: effects are varied and specific to each agent effects are varied and specific to each agent

67. Antivirals: Nursing Implications Monitor for therapeutic effects: effects will vary depending on the type of viral infection effects will vary depending on the type of viral infection Effects range from delayed progression of AIDS and ARC to decrease in flu-like symptoms, decreased frequency of herpes-like flare- ups, or crusting over of herpetic lesions. Effects range from delayed progression of AIDS and ARC to decrease in flu-like symptoms, decreased frequency of herpes-like flare- ups, or crusting over of herpetic lesions.

68. Antitubercular Agents

69. Tuberculosis, “TB” Tuberculosis, “TB” Caused by Mycobacterium tuberculosis Caused by Mycobacterium tuberculosis Antitubercular agents treat all forms of mycobacterium Antitubercular agents treat all forms of mycobacterium

70. Mycobacterium Infections Common Infection Sites lung (primary site) lung (primary site) brain brain bone bone liver liver kidney kidney

71. Mycobacterium Infections Aerobic bacillus Aerobic bacillus Passed from infected: Passed from infected: HumansHumans Cows (bovine)Cows (bovine) Birds (avian)Birds (avian)

72. Mycobacterium Infections Tubercle bacilli are conveyed by droplets. Tubercle bacilli are conveyed by droplets. Droplets are expelled by coughing or sneezing, then gain entry into the body by inhalation. Droplets are expelled by coughing or sneezing, then gain entry into the body by inhalation. Tubercle bacilli then spread to other body organs via blood and lymphatic systems. Tubercle bacilli then spread to other body organs via blood and lymphatic systems. Tubercle bacilli may become dormant, or walled off by calcified or fibrous tissue. Tubercle bacilli may become dormant, or walled off by calcified or fibrous tissue.

73. Antitubercular Agents Primary AgentsSecondary Agents isoniazid*capreomycin ethambutolcycloserine pyrazinamide (PZA)ethionamide rifampinkanamycin streptomycinpara-aminosalicyclic acid(PSA) *most frequently used

74. Antitubercular Agents: Mechanism of Action Three Groups Protein wall synthesis inhibitors streptomycin, kanamycin, capreomycin, rifampin, rifabutin Protein wall synthesis inhibitors streptomycin, kanamycin, capreomycin, rifampin, rifabutin Cell wall synthesis inhibitors cycloserine, ethionamide, isoniazid Cell wall synthesis inhibitors cycloserine, ethionamide, isoniazid Other mechanisms of action Other mechanisms of action

75. Antitubercular Agents: Mechanism of Action isoniazid (INH) Drug of choice for TB Drug of choice for TB Resistant strains of mycobacterium emerging Resistant strains of mycobacterium emerging Metabolized in the liver through acetylation—watch for “slow acetylators” Metabolized in the liver through acetylation—watch for “slow acetylators”

76. Used for the prophylaxis or treatment of TB Antitubercular Agents: Therapeutic Uses

77. Antitubercular Therapy Effectiveness depends upon: Type of infection Type of infection Adequate dosing Adequate dosing Sufficient duration of treatment Sufficient duration of treatment Drug compliance Drug compliance Selection of an effective drug combination Selection of an effective drug combination

78. Antitubercular Agents: Side Effects INH peripheral neuritis, hepatotoxicity INH peripheral neuritis, hepatotoxicity ethambutol retrobulbar neuritis, blindness ethambutol retrobulbar neuritis, blindness rifampin hepatitis, discoloration of urine, stools rifampin hepatitis, discoloration of urine, stools

79. Antitubercular Agents: Nursing Implications Obtain a thorough medical history and assessment. Obtain a thorough medical history and assessment. Perform liver function studies in patients who are to receive isoniazid or rifampin (especially in elderly patients or those who use alcohol daily). Perform liver function studies in patients who are to receive isoniazid or rifampin (especially in elderly patients or those who use alcohol daily). Assess for contraindications to the various agents, conditions for cautious use, and potential drug interactions. Assess for contraindications to the various agents, conditions for cautious use, and potential drug interactions.

80. Antitubercular Agents: Nursing Implications Patient education is CRITICAL: Therapy may last for up to 24 months. Therapy may last for up to 24 months. Take medications exactly as ordered, at the same time every day. Take medications exactly as ordered, at the same time every day. Emphasize the importance of strict compliance to regimen for improvement of condition or cure. Emphasize the importance of strict compliance to regimen for improvement of condition or cure.

81. Antitubercular Agents: Nursing Implications Patient education is CRITICAL: Remind patients that they are contagious during the initial period of their illness—instruct in proper hygiene and prevention of the spread of infected droplets. Remind patients that they are contagious during the initial period of their illness—instruct in proper hygiene and prevention of the spread of infected droplets. Emphasize to patients to take care of themselves, including adequate nutrition and rest. Emphasize to patients to take care of themselves, including adequate nutrition and rest.

82. Antitubercular Agents: Nursing Implications Patients should not consume alcohol while on these medications nor take other medications, including OTC, unless they check with their physician. Patients should not consume alcohol while on these medications nor take other medications, including OTC, unless they check with their physician. Diabetic patients taking INH should monitor their blood glucose levels because hyperglycemia may occur. Diabetic patients taking INH should monitor their blood glucose levels because hyperglycemia may occur. INH and rifampin cause oral contraceptives to become ineffective; another form of birth control will be needed. INH and rifampin cause oral contraceptives to become ineffective; another form of birth control will be needed.

83. Antitubercular Agents: Nursing Implications Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish- orange; even contact lenses may be stained. Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish- orange; even contact lenses may be stained. Vitamin B 6 may is needed to combat peripheral neuritis associated with INH therapy. Vitamin B 6 may is needed to combat peripheral neuritis associated with INH therapy.

84. Antitubercular Agents: Nursing Implications Monitor for side effects Instruct patients on the side effects that should be reported to the physician immediately. Instruct patients on the side effects that should be reported to the physician immediately. These include fatigue, nausea, vomiting, numbness and tingling of the extremities, fever, loss of appetite, depression, jaundice. These include fatigue, nausea, vomiting, numbness and tingling of the extremities, fever, loss of appetite, depression, jaundice.

85. Antitubercular Agents: Nursing Implications Monitor for therapeutic effects: Decrease in symptoms of TB, such as cough and fever Decrease in symptoms of TB, such as cough and fever Lab studies (culture and sensitivity tests) and CXR should confirm clinical findings Lab studies (culture and sensitivity tests) and CXR should confirm clinical findings Watch for lack of clinical response to therapy, indicating possible drug resistance Watch for lack of clinical response to therapy, indicating possible drug resistance

86. Antimalarial, Antiprotozoal, and Antihelmintic Agents

87. Protozoal Infections Parasitic protozoa: live in or on humans malaria malaria leishmaniasis leishmaniasis amebiasis amebiasis giardiasis giardiasis trichomoniasis trichomoniasis

88. Malaria Caused by the plasmodium protozoa. Caused by the plasmodium protozoa. Four different plasmodium species. Four different plasmodium species. Cause: the bite of an infected adult mosquito. Cause: the bite of an infected adult mosquito. Can also be transmitted by infected individuals via blood transfusion, congenitally, or via infected needles by drug abusers. Can also be transmitted by infected individuals via blood transfusion, congenitally, or via infected needles by drug abusers.

89. Malaria Endemic countries

94. Malarial Parasite (plasmodium) Two Interdependent Life Cycles Sexual cycle: in the mosquito Sexual cycle: in the mosquito Asexual cycle: in the human Asexual cycle: in the human Knowledge of the life cycles is essential in understanding antimalarial drug treatment.Knowledge of the life cycles is essential in understanding antimalarial drug treatment. Drugs are only effective during the asexual cycle.Drugs are only effective during the asexual cycle.

96. Plasmodium Life Cycle Asexual cycle: two phases Exoerythrocytic phase:occurs “outside” the erythrocyte Exoerythrocytic phase:occurs “outside” the erythrocyte Erythrocytic phase:occurs “inside” the erythrocyte Erythrocytic phase:occurs “inside” the erythrocyte Erythrocytes = RBCs

102. Antimalarial Agents Attack the parasite during the asexual phase, when it is vulnerable Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquine Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquine Exoerythrocytic phase drug: primaquine Exoerythrocytic phase drug: primaquine May be used together for synergistic or additive killing power.

103. Antimalarials: Mechanism of Action 4-aminoquinoline derivatives chloroquine and hydroxychloroquine Bind to parasite nucleoproteins and interfere with protein synthesis. Bind to parasite nucleoproteins and interfere with protein synthesis. Prevent vital parasite-sustaining substances from being formed. Prevent vital parasite-sustaining substances from being formed. Alter pH within the parasite. Alter pH within the parasite. Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin. Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin. Effective only during the erythrocytic phase Effective only during the erythrocytic phase

104. Antimalarials: Mechanism of Action 4-aminoquinoline derivatives quinine and mefloquine Alter pH within the parasite. Alter pH within the parasite. Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin. Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin. Effective only during the erythrocytic phase. Effective only during the erythrocytic phase.

105. Antimalarials: Mechanism of Action diaminophyrimidines pyrimethamine and trimethoprim Inhibit dihydrofolate reductase in the parasite. Inhibit dihydrofolate reductase in the parasite. This enzyme is needed by the parasite to make essential substances. This enzyme is needed by the parasite to make essential substances. Also blocks the synthesis of tetrahydrofolate. Also blocks the synthesis of tetrahydrofolate. These agents may be used with sulfadoxine or dapsone for synergistic effects.

106. Antimalarials: Mechanism of Action primaquine Only exoerythrocytic drug. Only exoerythrocytic drug. Binds and alters DNA. Binds and alters DNA. sulfonamides, tetracyclines, clindamycin Used in combination with antimalarials to increase protozoacidal effects Used in combination with antimalarials to increase protozoacidal effects

107. Antimalarials: Drug Effects Kill parasitic organisms. Kill parasitic organisms. Chloroquine and hydroxychloroquine also have antiinflammatory effects. Chloroquine and hydroxychloroquine also have antiinflammatory effects.

108. Antimalarials: Therapeutic Uses Used to kill plasmodium organisms, the parasites that cause malaria. Used to kill plasmodium organisms, the parasites that cause malaria. The drugs have varying effectiveness on the different malaria organisms. The drugs have varying effectiveness on the different malaria organisms. Some agents are used for prophylaxis against malaria. Some agents are used for prophylaxis against malaria. Chloroquine is also used for rheumatoid arthritis and lupus. Chloroquine is also used for rheumatoid arthritis and lupus.

109. Antimalarials: Side Effects Many side effects for the various agents Many side effects for the various agents Primarily gastrointestinal: nausea, vomiting, diarrhea,anorexia, and abdominal pain Primarily gastrointestinal: nausea, vomiting, diarrhea,anorexia, and abdominal pain

110. Antiprotozoals atovaquone (Mepron) atovaquone (Mepron) metronidazole (Flagyl) metronidazole (Flagyl) pentamidine (Pentam) pentamidine (Pentam) iodoquinol (Yodoxin, Di-Quinol) iodoquinol (Yodoxin, Di-Quinol) paromomycin (Humatin) paromomycin (Humatin)

111. Protozoal Infections amebiasis amebiasis giardiasis giardiasis pneumocystosis pneumocystosis toxoplasmosis toxoplasmosis trichomoniasis trichomoniasis

114. Protozoal Infections Transmission Person-to-person Person-to-person Ingestion of contaminated water or food Ingestion of contaminated water or food Direct contact with the parasite Direct contact with the parasite Insect bite (mosquito or tick) Insect bite (mosquito or tick)

115. Antiprotozoals: Mechanism of Action and Uses atovaquone (Mepron) Protozoal energy comes from the mitochondria Protozoal energy comes from the mitochondria Atovaquone: selective inhibition of mitochondrial electron transport Atovaquone: selective inhibition of mitochondrial electron transport Result: no energy, leading to cellular death Result: no energy, leading to cellular death Used to treat mild to moderate P. carinii

116. Antiprotozoals: Mechanism of Action and Uses metronidazole Disruption of DNA synthesis as well as nucleic acid synthesis Disruption of DNA synthesis as well as nucleic acid synthesis Bactericidal, amebicidal, trichomonacidal Bactericidal, amebicidal, trichomonacidal Used for treatment of trichomoniasis, amebiasis, giardiasis, anaerobic infections, and antibiotic-associated pseudomembranous colitis

117. Antiprotozoals: Mechanism of Action and Uses pentamidine Inhibits DNA and RNA Inhibits DNA and RNA Binds to and aggregates ribosomes Binds to and aggregates ribosomes Directly lethal to Pneumocystis carinii Directly lethal to Pneumocystis carinii Inhibits glucose metabolism, protein and RNA synthesis, and intracellular amino acid transport Inhibits glucose metabolism, protein and RNA synthesis, and intracellular amino acid transport Mainly used to treat P. carinii pneumonia and other protozoal infections

118. Antiprotozoals: Mechanism of Action and Uses iodoquinol (Yodoxin, Di-Quinol) “Luminal” or “contact” amebicide “Luminal” or “contact” amebicide Acts primarily in the intestinal lumen of the infected host Acts primarily in the intestinal lumen of the infected host Directly kills the protozoa Directly kills the protozoa Used to treat intestinal amebiasis

119. Antiprotozoals: Mechanism of Action and Uses paromomycin “Luminal” or “contact” amebicide “Luminal” or “contact” amebicide Kills by inhibiting protein synthesis Kills by inhibiting protein synthesis Used to treat amebiasis and intestinal protozoal infections, and also adjunct therapy in management of hepatic coma

120. Antiprotozoals: Side Effects atovaquone nausea, vomiting, diarrhea, anorexia nausea, vomiting, diarrhea, anorexiametronidazole metallic taste, nausea, vomiting, diarrhea, abdominal cramps metallic taste, nausea, vomiting, diarrhea, abdominal crampsiodoquinol nausea, vomiting, diarrhea, anorexia, agranulocytosis nausea, vomiting, diarrhea, anorexia, agranulocytosis

121. Antiprotozoals: Side Effects pentamidine bronchospasms, leukopenia, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver function studies bronchospasms, leukopenia, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver function studiesparomomycin nausea, vomiting, diarrhea, stomach cramps nausea, vomiting, diarrhea, stomach cramps

122. Antihelmintic drugs

124. Roundworm characteristics Round in cross section Digestive system complete – mouth to anus Acellular cuticle Four larval stages Subcuticular layer of muscle Separate sexes Terms: egg (ova) embryo larva adult

126. Pin worms

130. Antihelmintics diethylcarbamazine (Hetrazan) diethylcarbamazine (Hetrazan) mebendazole (Vermox) mebendazole (Vermox) niclosamide (Niclocide) niclosamide (Niclocide) oxamniquine (Vansil) oxamniquine (Vansil) piperazine (Vermizine) piperazine (Vermizine) praziquantel (Biltricide) praziquantel (Biltricide) pyrantel (Antiminth) pyrantel (Antiminth) thiabendazole (Mintezol) thiabendazole (Mintezol)

131. Antihelmintics Drugs used to treat parasitic worm infections: helmintic infections Drugs used to treat parasitic worm infections: helmintic infections Unlike protozoa, helminths are large and have complex cellular structures Unlike protozoa, helminths are large and have complex cellular structures Drug treatment is very specific Drug treatment is very specific

132. Antihelmintics It is VERY IMPORTANT to identify the causative worm It is VERY IMPORTANT to identify the causative worm Done by finding the parasite ova or larvae in feces, urine, blood, sputum, or tissue Done by finding the parasite ova or larvae in feces, urine, blood, sputum, or tissue cestodes (tapeworms)cestodes (tapeworms) nematodes (roundworms)nematodes (roundworms) trematodes (flukes)trematodes (flukes)

133. Antihelmintics: Mechanism of Action and Uses diethylcarbamazine (Hetrazan) Inhibits rate of embryogenesis Inhibits rate of embryogenesis thiabendazole (Mintezol) Inhibits the helminth-specific enzyme, fumarate reductase Inhibits the helminth-specific enzyme, fumarate reductase Both used for nematodes (tissue and some roundworms)

134. Antihelmintics: Mechanism of Action piperazine (Vermizine) and pyrantel (Antiminth) Blocks acetylcholine at the neuromuscular junction, resulting in paralysis of the worms, which are then expelled through the GI tract Blocks acetylcholine at the neuromuscular junction, resulting in paralysis of the worms, which are then expelled through the GI tract Used to treat nematodes (giant worm and pinworm)

135. Antihelmintics: Mechanism of Action mebendazole (Vermox) Inhibits uptake of glucose and other nutrients, leading to autolysis and death of the parasitic worm Inhibits uptake of glucose and other nutrients, leading to autolysis and death of the parasitic worm Used to treat cestodes and nematodes

136. Antihelmintics: Mechanism of Action niclosamide (Niclocide) Causes the worm to become dislodged from the GI wall Causes the worm to become dislodged from the GI wall They are then digested in the intestines and expelled They are then digested in the intestines and expelled Used to treat cestodes

137. Antihelmintics: Mechanism of Action oxamniquine (Vansil) and praziquantel (Biltricide) Cause paralysis of worms’ musculature and immobilization of their suckers 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 Cause worms to dislodge from mesenteric veins to the liver, then killed by host tissue reactions Used to treat trematodes, cestodes (praziquantel only)

138. Antihelmintics: Side Effects niclosamide, oxamniquine, praziquantel, thiabendazole, piperazine, pyrantel nausea, vomiting, diarrhea, dizziness, headache nausea, vomiting, diarrhea, dizziness, headachemebendazole diarrhea, abdominal pain, tissue necrosis diarrhea, abdominal pain, tissue necrosis

139. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications Before beginning therapy, perform a thorough health history and medication history, and assess for allergies. Before beginning therapy, perform a thorough health history and medication history, and assess for allergies. Check baseline VS. Check baseline VS. Check for conditions that may contraindicate use, and for potential drug interactions. Check for conditions that may contraindicate use, and for potential drug interactions.

140. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications Some agents may cause the urine to have an asparagus-like odor, or cause an unusual skin odor, or a metallic taste; be sure to warn the patient ahead of time. Some agents may cause the urine to have an asparagus-like odor, or cause an unusual skin odor, or a metallic taste; be sure to warn the patient ahead of time. Administer ALL agents as ordered and for the prescribed length of time. Administer ALL agents as ordered and for the prescribed length of time. Most agents should be taken with food to reduce GI upset. Most agents should be taken with food to reduce GI upset.

141. Antimalarial Agents: Nursing Implications Assess for presence of malarial symptoms. Assess for presence of malarial symptoms. When used for prophylaxis, these agents should be started 2 weeks before potential exposure to malaria, and for 8 weeks after leaving the area. When used for prophylaxis, these 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. Medications are taken weekly, with 8 ounces of water.

142. Antimalarial Agents: Nursing Implications Instruct patient to notify physician immediately if ringing in the ears, hearing decrease, visual difficulties, nausea, vomiting, profuse diarrhea, or abdominal pain occur. Instruct patient to notify physician immediately if ringing in the ears, hearing decrease, visual difficulties, nausea, vomiting, profuse diarrhea, or abdominal pain occur. Alert patients to the possible recurrence of the symptoms of malaria so that they will know to seek immediate treatment. Alert patients to the possible recurrence of the symptoms of malaria so that they will know to seek immediate treatment.

143. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications Monitor for side effects: Ensure that patients know the side effects that should be reported. Ensure that patients know the side effects that should be reported. Monitor for therapeutic effects and adverse effects with long-term therapy. Monitor for therapeutic effects and adverse effects with long-term therapy.