Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Antiviral Agents 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 cell’s energy to synthesize protein, DNA, and RNA. Understanding Viruses Viruses are difficult to kill because they live inside our cells. Any drug that kills a virus may also kill our cells. Viral Infections Competent immune system: Best response to viral infections A well-functioning immune system will eliminate or effectively destroy virus replication Immunocompromised patients have frequent viral infections Cancer patients, especially leukemia or Antivirals Key characteristics of antiviral drugs: 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. Antivirals Viruses killed by current antiviral therapy: cytomegalovirus (CMV) herpes simplex virus (HSV) human immunodeficiency virus (HIV) influenza A (the “flu”) respiratory syncytial virus (RSV) Antivirals: Mechanism of Action Inhibit viral replication Inhibit viral attachment Prevent genetic copying of virus Prevent viral protein production Sites of Drug Action Sites of Drug Action Antiviral Agents Block viral entry into the cell or must work inside the cell Most agents are pyrimidine or purine nucleoside analogs Antivirals Synthetic Purine Nucleoside Analogues Two types of nucleosides: Purine nucleosides guanine adenosine Pyrimidine nucleosides thymine cytosine Antivirals: Purine Nucleosides Agent Antiviral Activity guanines acyclovir HSV 1 & 2, VZV ganciclovir (DHPG) systemic CMV retinitis and CMV infection ribavirin (RTCD) B, Influenza types A and RSV, LV, HV adenosines didanosine (ddl) HIV vidarabine (Ara-A) HSV, herpes zoster Antivirals: Pyrimidine Nucleosides Agent Antiviral Activity cytosines lamivudine (3TC) zalcitabine (ddC) HIV HIV thymine idoxuridine (IDU) stavudine (d4T) trifluridine HSV HIV HSV Other Antivirals amantadine (Symmetrel) and rimantadine (Flumadine) influenza A foscarnet (Foscavir) CMV (retinitis and systemic) Neuraminidase Inhibitors: oseltamivir (Tamiflu) and zanamivir (Relenza) Antivirals: Side Effects acyclovir Burning when topically applied, nausea, vomiting, diarrhea, headache amantadine and rimantadine Anticholinergic effects, insomnia, lightheadedness, anorexia, nausea didanosine (ddl) Antivirals: Side Effects zidovudine (AZT) Bone marrow suppression, nausea, headache foscarnet (Foscavir) Headache, seizures, acute renal failure, nausea, vomiting, diarrhea ganciclovir (Cytovene) Antiherpes Agents Acyclovir- prototype Valacyclovir Famciclovir Penciclovir Trifluridine Vidarabine Mechanism of Action Acyclovir an acyclic guanosine derivative Phosphorylated by viral thymidine kinase Di-and tri-phosphorylated by host cellular enzymes Inhibits viral DNA synthesis by: 1) competing with dGTP for viral DNA polymerase 2) chain termination Clinical Uses Acyclovir Oral, IV, and Topical formulations Cleared by glomerular filtration and tubular secretion Uses: Herpes Simplex Virus 1 and 2 (HSV) Varicella-zoster virus (VZV) Side Effects: nausea, diarrhea, headache, tremors, and delirium Valacyclovir L-valyl ester of acyclovir Converted to acyclovir when ingested M.O.A.: same as acyclovir Uses: 1) recurrent genital herpes 2) herpes zoster infections Side Effects: nausea, diarrhea, and headache Famciclovir Prodrug of penciclovir (a guanosine analog) M.O.A.: same as acyclovir does not cause chain termination Uses: HSV-1, HSV-2, VZV, EBV, and hepatitis B Side Effects: nausea, diarrhea, and headache Trifluridine Trifluridine- fluorinated pyrimidine inhibits viral DNA synthesis same as acyclovir incorporates into viral and cellular DNA Uses: HSV-1 and HSV-2 (topically) Vidarabine An adenosine analog inhibits viral DNA polymerase incorporated into viral and cellular DNA metabolized to hypoxanthine arabinoside Side Effects: GI intolerance and myelosuppression Anti-Cytomegalovirus Agents Gancyclovir Valgancyclovir Cidofovir Foscarnet Fomivirsen Ganciclovir An acyclic guanosine analog requires triphosphorylation for activation monophosphorylation is catalyzed by a phosphotransferase in CMV and by thymidine kinase in HSV cells M.O.A.: same as acyclovir Uses: CMV*, HSV, VZV,and EBV Side Effect: myelosuppression HIV HIV Valgancyclovir Monovalyl ester prodrug of gancyclovir Metabolized by intestinal and hepatic esterases when administered orally M.O.A.: same as gancyclovir Uses: CMV* Side Effect: myelosuppression Foscarnet An inorganic pyrophosphate inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase does not have to be phosphorylated Uses: HSV, VZV, CMV, EBV, HHV-6, HBV, and HIV Resistance due to mutations in DNA polymerase gene Side Effects: hypo- or hypercalcemia and phosphotemia HIV AIDS- treatment Antiretroviral Agents 1) Nucleoside Reverse Transcriptase Inhibitors (NRTIs) 2) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) 3)Protease inhibitors Reverse Transcriptase Inhibitors Zidovudine (AZT) Didanosine- causes pancreatitis* Lamivudine- causes pancreatitis Zalcitabine- causes peripheral neuropathy* Stavudine- causes peripheral neuropathy* Abacavir Mechanism of Action Zidovudine (AZT) A deoxythymidine analog enters the cell via passive diffusion must be converted to the triphosphate form by mammalian thymidine kinase competitively inhibits deoxythymidine triphosphate for the reverse transcriptase enzyme causes chain termination Mechanism of Resistance Zidovudine Due to mutations in the reverse transcriptase gene more frequent after prolong therapy and in persons with HIV Clinical Uses Zidovudine Available in IV and oral formulations 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 prevents mother to newborn transmission of HIV Side Effects Zidovudine Myelosuppression, including anemia and neutropenia GI intolerance, headaches, and insomnia Other NRTIs Didanosine- synthetic deoxy-adenosine analog; causes pancreatitis* Lamivudine- cytosine analog Zalcitabine- cytosine analog; causes peripheral neuropathy* Stavudine- thymidine analog;causes peripheral neuropathy* Abacavir- guanosine analog; more effective than the other agents; fatal hypersensitivity reactions can occur Nucleotide Inhibitors Tenofovir Adefovir Tenofovir An acyclic nucleoside phosphonate analog of adenosine 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 Adefovir An analog of adenosine monophosphate Phosphorylated by cellular kinases M.O.A. - Competitively inhibits HBV DNA polymerase and results in chain termination after incorporation into viral DNA Uses - Hepatitis B Side effects - nephrotoxicity Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Nevirapine Delavirdine Efavirenz Mechanism of Action NNRTIs Bind to site on viral reverse transcriptase, different from NRTIs results in blockade of RNA and DNA dependent DNA polymerase activity do not compete with nucleoside triphosphates do not require phosphorylation these drugs can not be given alone substrates and inhibitors of CYP3A4 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 Delavirdine- teratogenic, therefore can not be given during pregnancy Efavirenz- teratogenic, therefore can not be given during pregnancy Protease Inhibitors Indinavir Ritonavir Saquinavir Nelfinavir Amprenavir Protease Inhibitors The protease enzyme cleaves precursor molecules to produce mature, infectious virions these agents inhibit protease and prevent the spread of infection These agents cause a syndrome of altered body fat distribution, insulin resistance, and hyperlipidemia Indinavir and Ritonavir 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 Side Effects: hyperbilirubinemia Contraindications:inhibitor/substrate for CPY3A4, do not give with antifungal azoles Saquinavir A synthetic peptide-like substrate analog inhibits HIV-1 protease prevents cleavage of viral polyproteins Nelfinavir and Amprenavir 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 Less cross-resistance with Amprenavir Side Effects: diarrhea and flatulence Amprenavir can cause Stevens-Johnson syndrome Contraindications:inhibitor/substrate for CPY3A4 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 By blocking fusion (entry into cell), FUZEON prevents HIV from infecting CD4 cells Anti-Hepatitis Agents Lamivudine -Nucleoside Reverse Transcriptase Inhibitor (NRTI) Adefovir -Nucleotide Inhibitor Interferon Alfa Pegylated Interferon Alfa Ribavirin Interferons Interferon Alfa Endogenous proteins induce host cell enzymes that inhibit viral RNA translation and cause degradation of viral mRNA and tRNA Bind to membrane receptors on cell surface May also inhibit viral penetration, uncoating, mRNA synthesis, and translation, and virion assembly and release Interferons Pegylated interferon Alfa A linear or branced polyethylene gylcol (PEG) moiety is attached to covalently to interferon Increased half-life and steady drug concentrations Less frequent dosing Tx chronic hepatitis C in combination with ribavirin Ribavirin A guanosine analog phosphorylated intracellularly by host enzymes inhibits capping of viral messenger RNA inhibits the viral RNA-dependent RNA polymerase inhibits replication of DNA and RNA viruses Anti-Influenza Agents Amantadine Rimantadine Zanamivir Amantadine and Rimantadine cyclic amines inhibit the uncoating of viral RNA therefore inhibiting replication resistance due to mutations in the RNA sequence coding for the structural M2 protein used in the prevention and treatment of Influenza A Zanamivir and Oseltamivir Inhibits the enzyme neuraminidase inhibit the replication of influenza A and Influenza B treats uncomplicated influenza infections administered intranasally Antivirals: Nursing Implications Before beginning therapy, thoroughly assess underlying disease and medical history, including allergies. Assess baseline VS and nutritional status. Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions. Antivirals: Nursing Implications 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. Patients should wear a glove or finger cot when applying ointments or solutions to affected areas. Antivirals: Nursing Implications Instruct patients to consult their physician before taking any other medication, including OTC medications. Emphasize the importance of good hygiene. Inform patients that antiviral agents are not cures, but do help to manage symptoms. Antivirals: Nursing Implications Instruct patients on the importance of taking these medications exactly as prescribed and for the full course of treatment. With zidovudine: Inform patients that hair loss MAY occur so that they are prepared for this rare adverse reaction. This medication should be taken on an Antivirals: Nursing Implications Monitor for side effects: effects are varied and specific to each agent Antivirals: Nursing Implications Monitor for therapeutic effects: 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. Antitubercular Agents Antitubercular Agents Tuberculosis, “TB” Caused by Mycobacterium tuberculosis Antitubercular agents treat all forms of mycobacterium Mycobacterium Infections Common Infection Sites lung (primary site) brain bone liver kidney Mycobacterium Infections Aerobic bacillus Passed from infected: Humans Cows (bovine) Birds (avian) Mycobacterium Infections Tubercle bacilli are conveyed by droplets. 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 may become dormant, or walled off by calcified or fibrous tissue. Antitubercular Agents Primary Agents Secondary Agents isoniazid* ethambutol pyrazinamide (PZA) rifampin streptomycin capreomycin cycloserine ethionamide kanamycin para-aminosalicyclic acid (PSA) *most frequently used Antitubercular Agents: Mechanism of Action Three Groups Protein wall synthesis inhibitors streptomycin, kanamycin, capreomycin, rifampin, rifabutin Cell wall synthesis inhibitors cycloserine, ethionamide, isoniazid Other mechanisms of action Antitubercular Agents: Mechanism of Action isoniazid (INH) Drug of choice for TB Resistant strains of mycobacterium emerging Metabolized in the liver through acetylation—watch for “slow acetylators” Antitubercular Agents: Therapeutic Uses Used for the prophylaxis or treatment of TB Antitubercular Therapy Effectiveness depends upon: Type of infection Adequate dosing Sufficient duration of treatment Drug compliance Selection of an effective drug combination Antitubercular Agents: Side Effects INH peripheral neuritis, hepatotoxicity ethambutol retrobulbar neuritis, blindness rifampin hepatitis, discoloration of urine, stools Antitubercular Agents: Nursing Implications 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). Assess for contraindications to the various agents, conditions for cautious use, and potential drug interactions. Antitubercular Agents: Nursing Implications Patient education is CRITICAL: Therapy may last for up to 24 months. 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. 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. Emphasize to patients to take care of themselves, including adequate nutrition and rest. 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. 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. 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. Vitamin B6 may is needed to combat peripheral neuritis associated with INH therapy. Antitubercular Agents: Nursing Implications Monitor for side effects 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. Antitubercular Agents: Nursing Implications Monitor for therapeutic effects: Decrease in symptoms of TB, such as cough and fever Lab studies (culture and sensitivity tests) and CXR should confirm clinical findings Watch for lack of clinical response to therapy, indicating possible drug resistance Antimalarial, Antiprotozoal, and Antihelmintic Agents Protozoal Infections Parasitic protozoa: live in or on humans malaria leishmaniasis amebiasis giardiasis trichomoniasis Malaria Caused by the plasmodium protozoa. Four different plasmodium species. 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. Malarial Parasite (plasmodium) Two Interdependent Life Cycles Sexual cycle: in the mosquito Asexual cycle: in the human Knowledge of the life cycles is essential in understanding antimalarial drug treatment. Drugs are only effective during the asexual cycle. Plasmodium Life Cycle Asexual cycle: two phases Exoerythrocytic phase: occurs “outside” the erythrocyte Erythrocytic phase: occurs “inside” the erythrocyte Erythrocytes = RBCs Antimalarial Agents Attack the parasite during the asexual phase, when it is vulnerable Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquine Exoerythrocytic phase drug: primaquine May be used together for synergistic or additive killing power. Antimalarials: Mechanism of Action 4-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 Antimalarials: Mechanism of Action 4-aminoquinoline derivatives quinine and mefloquine Alter pH within the parasite. Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin. Effective only during the erythrocytic phase. Antimalarials: Mechanism of Action diaminophyrimidines pyrimethamine and trimethoprim Inhibit dihydrofolate reductase in the parasite. This enzyme is needed by the parasite to make essential substances. Also blocks the synthesis of tetrahydrofolate. These agents may be used with sulfadoxine or Antimalarials: Mechanism of Action primaquine Only exoerythrocytic drug. Binds and alters DNA. sulfonamides, tetracyclines, clindamycin Used in combination with antimalarials to increase protozoacidal effects Antimalarials: Drug Effects Kill parasitic organisms. Chloroquine and hydroxychloroquine also have antiinflammatory effects. Antimalarials: Therapeutic Uses Used to kill plasmodium organisms, the parasites that cause malaria. The drugs have varying effectiveness on the different malaria organisms. Some agents are used for prophylaxis against malaria. Chloroquine is also used for rheumatoid arthritis and lupus. Antimalarials: Side Effects Many side effects for the various agents Primarily gastrointestinal: nausea, vomiting, diarrhea, anorexia, and abdominal pain Antiprotozoals atovaquone (Mepron) metronidazole (Flagyl) pentamidine (Pentam) iodoquinol (Yodoxin, Di-Quinol) paromomycin (Humatin) Protozoal Infections amebiasis giardiasis pneumocystosis toxoplasmosis trichomoniasis Protozoal Infections Transmission Person-to-person Ingestion of contaminated water or food Direct contact with the parasite Insect bite (mosquito or tick) Antiprotozoals: Mechanism of Action and Uses atovaquone (Mepron) Protozoal energy comes from the mitochondria Atovaquone: selective inhibition of mitochondrial electron transport Result: no energy, leading to cellular death Used to treat mild to moderate P. carinii Antiprotozoals: Mechanism of Action and Uses metronidazole Disruption of DNA synthesis as well as nucleic acid synthesis Bactericidal, amebicidal, trichomonacidal Used for treatment of trichomoniasis, amebiasis, giardiasis, anaerobic infections, and antibiotic-associated pseudomembranous colitis Antiprotozoals: Mechanism of Action and Uses pentamidine Inhibits DNA and RNA Binds to and aggregates ribosomes Directly lethal to Pneumocystis carinii Inhibits glucose metabolism, protein and RNA synthesis, and intracellular amino acid transport Mainly used to treat P. carinii pneumonia Antiprotozoals: Mechanism of Action and Uses iodoquinol (Yodoxin, Di-Quinol) “Luminal” or “contact” amebicide Acts primarily in the intestinal lumen of the infected host Directly kills the protozoa Used to treat intestinal amebiasis Antiprotozoals: Mechanism of Action and Uses paromomycin “Luminal” or “contact” amebicide Kills by inhibiting protein synthesis Used to treat amebiasis and intestinal protozoal infections, and also adjunct therapy in management of hepatic coma Antiprotozoals: Side Effects atovaquone nausea, vomiting, diarrhea, anorexia metronidazole metallic taste, nausea, vomiting, diarrhea, abdominal cramps iodoquinol nausea, vomiting, diarrhea, anorexia, agranulocytosis Antiprotozoals: Side Effects pentamidine bronchospasms, leukopenia, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver function studies paromomycin nausea, vomiting, diarrhea, stomach cramps Antihelmintics diethylcarbamazine (Hetrazan) mebendazole (Vermox) niclosamide (Niclocide) oxamniquine (Vansil) piperazine (Vermizine) praziquantel (Biltricide) pyrantel (Antiminth) thiabendazole (Mintezol) Antihelmintics Drugs used to treat parasitic worm infections: helmintic infections Unlike protozoa, helminths are large and have complex cellular structures Drug treatment is very specific 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) Antihelmintics: Mechanism of Action and Uses diethylcarbamazine (Hetrazan) Inhibits rate of embryogenesis thiabendazole (Mintezol) Inhibits the helminth-specific enzyme, fumarate reductase Both used for nematodes 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 Used to treat nematodes (giant worm and pinworm) Pin worms Pin worms Antihelmintics: Mechanism of Action mebendazole (Vermox) Inhibits uptake of glucose and other nutrients, leading to autolysis and death of the parasitic worm Used to treat cestodes and nematodes Antihelmintics: Mechanism of Action niclosamide (Niclocide) Causes the worm to become dislodged from the GI wall They are then digested in the intestines and expelled Used to treat cestodes Antihelmintics: Mechanism of Action oxamniquine (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 treat trematodes, cestodes (praziquantel only) Antihelmintics: Side Effects niclosamide, oxamniquine, praziquantel, thiabendazole, piperazine, pyrantel nausea, vomiting, diarrhea, dizziness, headache mebendazole diarrhea, abdominal pain, tissue necrosis Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications Before beginning therapy, perform a thorough health history and medication history, and assess for allergies. Check baseline VS. Check for conditions that may contraindicate use, and for potential drug interactions. 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. Administer ALL agents as ordered and for the prescribed length of time. Most agents should be taken with food to reduce GI upset. Antimalarial Agents: Nursing Implications 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. Medications are taken weekly, with 8 ounces of water. 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. Alert patients to the possible recurrence of the symptoms of malaria so that they will know to seek immediate treatment. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications Monitor for side effects: Ensure that patients know the side effects that should be reported. Monitor for therapeutic effects and adverse effects with long-term therapy. Antimalarial, Antiprotozoal, and Antihelmintic Agents Protozoal Infections Parasitic protozoa: live in or on humans malaria leishmaniasis amebiasis giardiasis trichomoniasis Malaria Endemic countries Malaria Caused by the plasmodium protozoa. Four different plasmodium species. 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. Malarial Parasite (plasmodium) Two Interdependent Life Cycles Sexual cycle: in the mosquito Asexual cycle: in the human Knowledge of the life cycles is essential in understanding antimalarial drug treatment. Drugs are only effective during the asexual cycle. Malaria Cycle Plasmodium Life Cycle Asexual cycle: two phases Exoerythrocytic phase: occurs “outside” the erythrocyte Erythrocytic phase: occurs “inside” the erythrocyte Erythrocytes = RBCs Antimalarial Agents Attack the parasite during the asexual phase, when it is vulnerable Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquine Exoerythrocytic phase drug: primaquine May be used together for synergistic or additive killing power. Antimalarials: Mechanism of Action 4-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 Antimalarials: Mechanism of Action 4-aminoquinoline derivatives quinine and mefloquine Alter pH within the parasite. Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin. Effective only during the erythrocytic phase. Antimalarials: Mechanism of Action diaminophyrimidines pyrimethamine and trimethoprim Inhibit dihydrofolate reductase in the parasite. This enzyme is needed by the parasite to make essential substances. Also blocks the synthesis of tetrahydrofolate. These agents may be used with sulfadoxine or Antimalarials: Mechanism of Action primaquine Only exoerythrocytic drug. Binds and alters DNA. sulfonamides, tetracyclines, clindamycin Used in combination with antimalarials to increase protozoacidal effects Antimalarials: Drug Effects Kill parasitic organisms. Chloroquine and hydroxychloroquine also have antiinflammatory effects. Antimalarials: Therapeutic Uses Used to kill plasmodium organisms, the parasites that cause malaria. The drugs have varying effectiveness on the different malaria organisms. Some agents are used for prophylaxis against malaria. Chloroquine is also used for rheumatoid arthritis and lupus. Antimalarials: Side Effects Many side effects for the various agents Primarily gastrointestinal: nausea, vomiting, diarrhea, anorexia, and abdominal pain Antiprotozoals atovaquone (Mepron) metronidazole (Flagyl) pentamidine (Pentam) iodoquinol (Yodoxin, Di-Quinol) paromomycin (Humatin) Protozoal Infections amebiasis giardiasis pneumocystosis toxoplasmosis trichomoniasis Protozoal Infections Transmission Person-to-person Ingestion of contaminated water or food Direct contact with the parasite Insect bite (mosquito or tick) Antiprotozoals: Mechanism of Action and Uses atovaquone (Mepron) Protozoal energy comes from the mitochondria Atovaquone: selective inhibition of mitochondrial electron transport Result: no energy, leading to cellular death Used to treat mild to moderate P. carinii Antiprotozoals: Mechanism of Action and Uses metronidazole Disruption of DNA synthesis as well as nucleic acid synthesis Bactericidal, amebicidal, trichomonacidal Used for treatment of trichomoniasis, amebiasis, giardiasis, anaerobic infections, and antibiotic-associated pseudomembranous colitis Antiprotozoals: Mechanism of Action and Uses pentamidine Inhibits DNA and RNA Binds to and aggregates ribosomes Directly lethal to Pneumocystis carinii Inhibits glucose metabolism, protein and RNA synthesis, and intracellular amino acid transport Mainly used to treat P. carinii pneumonia Antiprotozoals: Mechanism of Action and Uses iodoquinol (Yodoxin, Di-Quinol) “Luminal” or “contact” amebicide Acts primarily in the intestinal lumen of the infected host Directly kills the protozoa Used to treat intestinal amebiasis Antiprotozoals: Mechanism of Action and Uses paromomycin “Luminal” or “contact” amebicide Kills by inhibiting protein synthesis Used to treat amebiasis and intestinal protozoal infections, and also adjunct therapy in management of hepatic coma Antiprotozoals: Side Effects atovaquone nausea, vomiting, diarrhea, anorexia metronidazole metallic taste, nausea, vomiting, diarrhea, abdominal cramps iodoquinol nausea, vomiting, diarrhea, anorexia, agranulocytosis Antiprotozoals: Side Effects pentamidine bronchospasms, leukopenia, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver function studies paromomycin nausea, vomiting, diarrhea, stomach cramps Antihelmintics diethylcarbamazine (Hetrazan) mebendazole (Vermox) niclosamide (Niclocide) oxamniquine (Vansil) piperazine (Vermizine) praziquantel (Biltricide) pyrantel (Antiminth) thiabendazole (Mintezol) Antihelmintics Drugs used to treat parasitic worm infections: helmintic infections Unlike protozoa, helminths are large and have complex cellular structures Drug treatment is very specific 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) Brain worms Antihelmintics: Mechanism of Action and Uses diethylcarbamazine (Hetrazan) Inhibits rate of embryogenesis thiabendazole (Mintezol) Inhibits the helminth-specific enzyme, fumarate reductase Both used for nematodes 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 Used to treat nematodes (giant worm and pinworm) Antihelmintics: Mechanism of Action mebendazole (Vermox) Inhibits uptake of glucose and other nutrients, leading to autolysis and death of the parasitic worm Used to treat cestodes and nematodes Antihelmintics: Mechanism of Action niclosamide (Niclocide) Causes the worm to become dislodged from the GI wall They are then digested in the intestines and expelled Used to treat cestodes Antihelmintics: Mechanism of Action oxamniquine (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 treat trematodes, cestodes (praziquantel only) Antihelmintics: Side Effects niclosamide, oxamniquine, praziquantel, thiabendazole, piperazine, pyrantel nausea, vomiting, diarrhea, dizziness, headache mebendazole diarrhea, abdominal pain, tissue necrosis Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications Before beginning therapy, perform a thorough health history and medication history, and assess for allergies. Check baseline VS. Check for conditions that may contraindicate use, and for potential drug interactions. 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. Administer ALL agents as ordered and for the prescribed length of time. Most agents should be taken with food to reduce GI upset. Antimalarial Agents: Nursing Implications 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. Medications are taken weekly, with 8 ounces of water. 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. Alert patients to the possible recurrence of the symptoms of malaria so that they will know to seek immediate treatment. Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing Implications Monitor for side effects: Ensure that patients know the side effects that should be reported. Monitor for therapeutic effects and adverse effects with long-term therapy.