Antivirals Antiprotozoals


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Antivirals Antiprotozoals

  1. 1. Antivirals & Antiprotozoals
  2. 2. Virus Types <ul><li>DNA viruses </li></ul><ul><ul><li>Herpes viruses – chicken pox, shingles, herpes </li></ul></ul><ul><ul><li>Adenoviruses – conjunctivitis, pharyngitis </li></ul></ul><ul><ul><li>Hepadnaviruses – hepatitis B </li></ul></ul><ul><ul><li>Papillomaviruses – warts </li></ul></ul><ul><li>RNA viruses </li></ul><ul><ul><li>Rubella – German measles </li></ul></ul><ul><ul><li>Rhabdoviruses - rabies </li></ul></ul><ul><ul><li>Picornaviruses – poliomyelitis, meningitis, colds </li></ul></ul><ul><ul><li>Arboviruses – yellow fever </li></ul></ul><ul><ul><li>Orthomyxoviruses – influenza </li></ul></ul><ul><ul><li>Paramyxoviruses – measles & mumps </li></ul></ul><ul><ul><li>Retroviruses - HIV </li></ul></ul>
  3. 3. Parasites <ul><li>Small, unicellular organisms </li></ul><ul><li>Include: </li></ul><ul><ul><li>Protozoa </li></ul></ul><ul><ul><li>Helminths </li></ul></ul><ul><ul><li>Arthropods </li></ul></ul><ul><li>Broken into categories based on locomotion </li></ul><ul><li>Examples of protozoal infections </li></ul><ul><ul><li>Amebiasis – Entamoeba histolytica </li></ul></ul><ul><ul><li>Giardiasis – Giardia Lamblia </li></ul></ul><ul><ul><li>Trichomoniasis – Trichomonas vaginalis </li></ul></ul><ul><ul><li>Malaria – Plasmodium falciparum, p. vivax, P. malariae, P. ovale </li></ul></ul>
  4. 4. Other Antivirals/Antiinfectives Antiinfluenza Antiherpes Flagyl Plaquenil Metronidazole Chloroquine Other Symmetrel Flumadine Relenza Tamiflu Amantadine Rimantadine Zanamivir Oseltamivir Zovirax Famvir Valtrex Denavir Acyclovir Famciclovir Valacyclovir Penciclovir Antivirals TRADE GENERIC CLASS
  5. 5. Antivirals: Indications <ul><li>Acyclovir, famciclovir, valacyclovir, penciclovir (only used topically)  inhibit viral DNA synthesis – highly selective for infected cells (all have similar chemical structure) </li></ul><ul><ul><li>HSV 1 & 2: acute infection & chronic suppression </li></ul></ul><ul><ul><li>VZV: chicken pox & shingles </li></ul></ul><ul><ul><li>EBV: mononucleosis </li></ul></ul><ul><li>Amantadine (also used in Parkinsons), rimantadine, zanamivir, oseltamivir – structurally similar to tricyclic amines  inhibit an early step in viral replication, also affect viral assembly </li></ul><ul><ul><li>Influenza A: amantadine & rimantadine </li></ul></ul><ul><ul><li>Influenza A & B: zanamivir & oseltamivir </li></ul></ul><ul><li>Metronidazole </li></ul><ul><ul><li>Many protozoa, also used in many bacterial and amebic infections </li></ul></ul><ul><li>Chloroquine </li></ul><ul><ul><li>Malaria </li></ul></ul>
  6. 6. Important Principles <ul><li>Peak viral activity occurs prior to Sx’s  effectiveness of drug depends on early initiation of Tx </li></ul><ul><li>Viral agents work by inhibiting reproduction BUT do not eradicate latent viruses  elimination of virus is NOT complete BUT can assist in reducing & suppressing Sx’s </li></ul><ul><li>Tx can reduce transmission rates in pregnancy & decreases morbidity/mortality associate with HSV infection </li></ul>
  7. 7. Antivirals: Patient Variables <ul><li>Geriatrics </li></ul><ul><ul><li>Generally effective & well tolerated </li></ul></ul><ul><li>Pediatrics </li></ul><ul><ul><li>Famciclovir & Valacyclovir: S&E in children < 18 yrs NOT established </li></ul></ul><ul><ul><li>Acyclovir: S&E in children < 2 yr NOT established </li></ul></ul><ul><ul><li>Amantadine & Rimantadine: S&E in children < 1 yr NOT established </li></ul></ul><ul><li>Pregnancy </li></ul><ul><ul><li>Famciclovir & Valacyclovir: Category B </li></ul></ul><ul><ul><li>Acyclovir, Amantadine & Rimantadine: Category C </li></ul></ul><ul><li>Lactation </li></ul><ul><ul><li>Acyclovir, Amantadine & Rimantadine: in breast milk </li></ul></ul><ul><ul><li>Famciclovir & Valacyclovir: Unknown </li></ul></ul>
  8. 8. Patient Ed: Genital Herpes <ul><li>Avoid sexual contact when visible lesions are present </li></ul><ul><li>Does not cure viral infection, but can decrease severity & duration of outbreak </li></ul><ul><li>Women may be at higher risk of cervical cancer  annual PAP </li></ul>
  9. 9. Acyclovir (Zovirax) <ul><li>Pharmacokinetics </li></ul><ul><ul><li>Absorption </li></ul></ul><ul><ul><ul><li>15-30% from GI; not affected by food; bioavailability decreases with increasing doses </li></ul></ul></ul><ul><ul><ul><li>Can achieve therapeutic serum levels </li></ul></ul></ul><ul><ul><li>Distribution </li></ul></ul><ul><ul><ul><li>WIDE including: brain, kidney, lung, liver, muscles, spleen, uterus, vaginal mucosa, CSF (50% plasma), herpetic vesicular fluid </li></ul></ul></ul><ul><ul><ul><li>Peak 1.5-2 hr; ½ life 3 hrs </li></ul></ul></ul><ul><ul><ul><li>Protein-binding 9-33% </li></ul></ul></ul><ul><ul><li>Metabolism </li></ul></ul><ul><ul><ul><li>Liver </li></ul></ul></ul><ul><ul><li>Excretion - dependent on renal function </li></ul></ul><ul><ul><ul><li>Kidneys (parenteral 62-91% unchanged) </li></ul></ul></ul>
  10. 10. Acyclovir (Zovirax) <ul><li>Contraindications </li></ul><ul><ul><li>Hypersensitivity or intolerance </li></ul></ul><ul><li>Warnings / Precautions </li></ul><ul><ul><li>Extreme caution in decreased renal function </li></ul></ul><ul><ul><li>Caution in poor hydration or w/nephrotoxic drugs  can precipitate ARF </li></ul></ul><ul><ul><li>Consider obtaining viral culture </li></ul></ul><ul><ul><li>1% neurologic reaction – lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, coma </li></ul></ul><ul><ul><li>Testicular atrophy in rats </li></ul></ul><ul><ul><li>Emergence of resistant viruses </li></ul></ul>
  11. 11. Acyclovir (Zovirax) <ul><li>Adverse effects </li></ul><ul><ul><li>COMMON: PO  GI: nausea, vomiting, diarrhea </li></ul></ul><ul><ul><li>IV  inflammation or phlebitis </li></ul></ul><ul><ul><li>Increased SE’s w/longer term use </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Probenecid  increases bioavailability & ½ life; may also decrease renal clearance & excretion </li></ul></ul><ul><ul><li>AZT + Zovirax  may cause severe lethargy </li></ul></ul>
  12. 12. Famciclovir (Famvir) <ul><li>Structurally similar to acyclovir – used as an alternative </li></ul><ul><li>Decreased duration but not incidence of post-herpetic neuralgia age>50 </li></ul><ul><li>Effective in treating first episodes & recurrences of HSV; also for chronic suppression of HSV as well as HBV </li></ul><ul><li>Cross resistance observed </li></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Cimetidine, probenecid, theophylline increase levels; drug increases digoxin levels </li></ul></ul><ul><li>COMMON SE’s: headache, nausea, diarrhea </li></ul>
  13. 13. Valacyclovir (Valtrex) <ul><li>Warnings </li></ul><ul><ul><li>Thrombotic thrombocytopenic purpura / hemolytic uremic syndrome in HIV </li></ul></ul><ul><ul><li>Caution in renal impairment </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Cimetidine & probenecid reduce rate but not extent of conversion of drug </li></ul></ul>
  14. 14. Amantadine (Symmetrel) <ul><li>Warnings / Precautions </li></ul><ul><ul><li>Observe closely if seizure Hx </li></ul></ul><ul><ul><li>Caution in liver disease, psychosis or psychoneurosis, cardiac Hx (CHF), renal impairment </li></ul></ul><ul><ul><li>CNS effects: blurred vision </li></ul></ul><ul><ul><li>Development of resistant strains </li></ul></ul><ul><ul><li>Do NOT D/C abruptly in Parkinsons </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Nausea, dizziness, lightheadedness, insomnia </li></ul></ul>
  15. 15. Amantadine (Symmetrel) <ul><li>Drug interactions </li></ul><ul><ul><li>Anticholinergic – may need to reduce dose if atropine-like effect occurs </li></ul></ul><ul><ul><li>HCTZ – decreases urinary excretion  increases plasma concentration </li></ul></ul><ul><li>Overdosage </li></ul><ul><ul><li>Nausea, vomiting, anorexia, CNS effects </li></ul></ul><ul><ul><li>Can cause death </li></ul></ul><ul><ul><li>Notify HCP if </li></ul></ul><ul><ul><ul><li>Mood or mental changes, swelling of extremities, difficulty urinating, SOB </li></ul></ul></ul>
  16. 16. Rimantadine (Flumadine) <ul><li>Adverse effects </li></ul><ul><ul><li>MOST COMMON: GI & CNS </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Acetaminophen & ASA decrease peak concentration </li></ul></ul><ul><ul><li>Cimetidine increases serum concentration </li></ul></ul>
  17. 17. Vancomycin (Vancocin) <ul><li>Mechanism of action </li></ul><ul><ul><li>Rarely used in primary care </li></ul></ul><ul><ul><li>Prevents synthesis of bacterial cell wall by block peptidoglycan strand formation </li></ul></ul><ul><li>Indications </li></ul><ul><ul><li>IV for serious life-threatening staph or strept infections </li></ul></ul><ul><ul><li>Drug of choice for severe cases of C. difficile </li></ul></ul><ul><ul><li>Primary care use: Tx of pseudomembranous colitis caused by C. difficile & given PO if metronidazole contraindicated or ineffective </li></ul></ul>
  18. 18. Clindamycin (Cleocin) <ul><li>Indications </li></ul><ul><ul><li>Reserved for serious infections where less toxic drugs are inappropriate </li></ul></ul><ul><ul><li>Used for serious infections caused by strepto-, pneumo-, and staphylococci </li></ul></ul><ul><ul><li>In primary care used in combination with tretinoin gel for Tx of acne vulgaris </li></ul></ul><ul><li>Can cause severe & possibly fatal colitis </li></ul><ul><li>PCPs should work closely w/specialist in Tx of patients with this drug </li></ul>
  19. 19. Nitrofurantoin (Macrobid et al) <ul><li>Indications </li></ul><ul><ul><li>UTI caused by: E. coli , enterococci, S. aureus , Kleibsiella and Enterobacter species </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Not for use in impaired renal function or pregnancy </li></ul></ul><ul><li>Warnings/Precautions </li></ul><ul><ul><li>Acute pulmonary reactions: dyspnea, chest pain, cough, fever, chills </li></ul></ul><ul><ul><li>Chronic pulmonary reactions seen in prolonged therapy </li></ul></ul><ul><ul><li>Hemolytic anemia </li></ul></ul><ul><ul><li>Hepatic reactions: hepatitis, cholestatic jaundice (rare fatalities) </li></ul></ul>
  20. 20. Nitrofurantoin (Macrobid et al) <ul><li>Patient variables </li></ul><ul><ul><li>Pediatric: contraindicated in age <1 mo </li></ul></ul><ul><ul><li>Pregnancy: Category B </li></ul></ul><ul><ul><li>Lactation: excreted in milk </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Peripheral neuropathy: may be severe or irreversible </li></ul></ul><ul><ul><li>Superinfection </li></ul></ul><ul><ul><li>MOST COMMON: anorexia, nausea, emesis </li></ul></ul><ul><li>Overdosage </li></ul><ul><ul><li>Vomiting </li></ul></ul>
  21. 21. Nitrofurantoin (Macrobid et al) <ul><li>Drug interactions </li></ul><ul><ul><li>Anticholinergics increase bioavailability </li></ul></ul><ul><ul><li>Mg salts decrease absorption </li></ul></ul><ul><ul><li>Uricosurics (probenecid) increase serum levels </li></ul></ul><ul><li>Patient education </li></ul><ul><ul><li>GI upset  may take with food or milk </li></ul></ul><ul><ul><li>Brown discoloration of urine </li></ul></ul><ul><ul><li>Notify HCP if: </li></ul></ul><ul><ul><ul><li>Fever, chills, cough, chest pain, difficulty breathing, skin rash, numbness or tingling of fingers or toes, intolerable GI upset </li></ul></ul></ul>
  22. 22. Fosfomycin (Monurol) <ul><li>Indication </li></ul><ul><ul><li>UTI </li></ul></ul><ul><li>Patient variables </li></ul><ul><ul><li>Pediatrics: contraindicated in children </li></ul></ul><ul><ul><li>Pregnancy: Category B </li></ul></ul><ul><ul><li>Lactation: Use NOT recommended </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Diarrhea, nausea, dyspepsia, vaginitis, headache, dizziness, asthenia (muscle weakness) </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Serum levels lowered by drugs that slow GI motility </li></ul></ul>
  23. 23. Metronidazole (Flagyl) <ul><li>Indications </li></ul><ul><ul><li>Short-acting synthetic antiprotozoal & antibacterial </li></ul></ul><ul><ul><li>Active against most anaerobic bacteria, certain protozoa, and H. pylori </li></ul></ul><ul><ul><li>Outpatient: most often used to Tx T. vaginalis and non-specific BV </li></ul></ul><ul><ul><li>Excellent tissue penetration  used in Tx of many pelvic & intra-abdominal infections </li></ul></ul><ul><ul><li>Can lower potential for overgrowth of C. difficile associated with certain antibiotics </li></ul></ul><ul><li>Mechanism of action </li></ul><ul><ul><li>Cytotoxic BUT mechanism NOT well understood  directly damages DNA synthesis  cell death </li></ul></ul>
  24. 24. Metronidazole (Flagyl) <ul><li>Drug Tx principles </li></ul><ul><ul><li>Excellent activity against G(-) & G(+) anaerobes </li></ul></ul><ul><ul><li>Indicated for use in serious infections </li></ul></ul><ul><ul><li>Reaches high concentrations in most body tissues </li></ul></ul><ul><ul><li>Does NOT cover G(+) cocci or aerobic organisms </li></ul></ul><ul><ul><li>Primary care: drug of choice for Trichomonas vaginalis (both partners require Tx) & bacterial or non-specific vaginitis </li></ul></ul><ul><ul><li>Tx of choice for symptomatic Giardia </li></ul></ul><ul><ul><li>Recommended initial Tx for C. difficile (vanco for severe cases) </li></ul></ul><ul><ul><li>Tx for H. pylori in gastritis & PUD in conjunction with bismuth & tetracycline </li></ul></ul>
  25. 25. Metronidazole (Flagyl) <ul><li>Pharmacokinetics </li></ul><ul><ul><li>Absorption </li></ul></ul><ul><ul><ul><li>Well absorbed; peak 1-2 hr; ½ life 8 hrs </li></ul></ul></ul><ul><ul><ul><li>Food does NOT alter bioavailability BUT can delay peak </li></ul></ul></ul><ul><ul><ul><li>Plasma concentration proportional to administered dose </li></ul></ul></ul><ul><ul><li>Distribution </li></ul></ul><ul><ul><ul><li>Large Vd; 20% protein binding </li></ul></ul></ul><ul><ul><ul><li>Reaches all body tissues & fluids including: bone, pelvic tissue, CSF, meninges, bile, saliva, seminal fluid, breast milk, placenta, abscesses (including brain & hepatic), empyema fluid, middle ear fluid </li></ul></ul></ul><ul><ul><li>Metabolism </li></ul></ul><ul><ul><ul><li>Liver; plasma clearance decreased in liver dysfunction </li></ul></ul></ul><ul><ul><li>Excretion </li></ul></ul><ul><ul><ul><li>Urine; accumulation in renal failure BUT rarely toxic </li></ul></ul></ul>
  26. 26. Metronidazole (Flagyl) <ul><li>Contraindications </li></ul><ul><ul><li>Avoid ALL alcohol  antabuse or disulfuram-like reaction </li></ul></ul><ul><ul><li>Hypersensitivity </li></ul></ul><ul><li>Warnings/Precautions </li></ul><ul><ul><li>CNS disease: seizures & peripheral neuropathy reported </li></ul></ul><ul><ul><li>Hepatic disease: accumulation of drug & metabolites  dose reduction required with impairment </li></ul></ul><ul><ul><li>Crohn’s: increased GI cancers </li></ul></ul><ul><ul><li>Hx blood dyscrasias: can induce mild leukopenia </li></ul></ul><ul><ul><li>Carcinogenesis in rodents with chronic oral administration </li></ul></ul>
  27. 27. Metronidazole (Flagyl) <ul><li>Patient variables </li></ul><ul><ul><li>Geriatrics </li></ul></ul><ul><ul><ul><li>Altered pharmacokinetics – monitor serum levels </li></ul></ul></ul><ul><ul><li>Pediatrics </li></ul></ul><ul><ul><ul><li>S&E NOT established in children except for Tx of amebiasis </li></ul></ul></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><ul><li>Category C </li></ul></ul></ul><ul><ul><ul><li>Crosses placenta & enters fetal circulation </li></ul></ul></ul><ul><ul><li>Lactation </li></ul></ul><ul><ul><ul><li>Found in breast milk </li></ul></ul></ul><ul><ul><ul><li>Safety in nursing NOT established </li></ul></ul></ul>
  28. 28. Metronidazole (Flagyl) <ul><li>Adverse effects </li></ul><ul><ul><li>MOST COMMON: GI  nausea, vomiting, diarrhea, epigastric discomfort </li></ul></ul><ul><ul><li>Also: Metallic taste, dizziness, headache, dysuria, vaginal dryness, dark urine </li></ul></ul><ul><ul><li>Less common BUT SERIOUS: seizures, ataxia, peripheral neuropathy </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Disulfuram-like reaction with alcohol (immediate n/v/d & CV effects) </li></ul></ul><ul><li>Patient education </li></ul><ul><ul><li>GI upset, darkens urine, metallic taste </li></ul></ul><ul><ul><li>Avoid alcohol </li></ul></ul><ul><ul><li>Trichomoniasis is STI  need to Tx both partners for cure </li></ul></ul><ul><ul><li>Finish all medication – do NOT share medication with others </li></ul></ul>
  29. 29. Chloroquine (Plaquenil) <ul><li>Indications </li></ul><ul><ul><li>Prophylaxis & Tx of acute attacks of malaria </li></ul></ul><ul><ul><li>Also: rheumatoid, SLE, scleroderma </li></ul></ul><ul><li>Mechanism of action </li></ul><ul><ul><li>Unknown – raises internal pH of parasites; may interfere with Hgb digestion or nucleoprotein synthesis </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Hypersensitivity </li></ul></ul><ul><ul><li>Retinal or visual changes </li></ul></ul>
  30. 30. Chloroquine (Plaquenil) <ul><li>Warnings/Precautions </li></ul><ul><ul><li>Resistance </li></ul></ul><ul><ul><li>Irreversible retinal damage  monitor vision frequently </li></ul></ul><ul><li>Patient variables </li></ul><ul><ul><li>Pediatric: sensitive  fatalities have occurred </li></ul></ul><ul><ul><li>Pregnancy: only if clearly indicated </li></ul></ul><ul><ul><li>Lactation: safety NOT established </li></ul></ul><ul><li>Monitoring </li></ul><ul><ul><li>Periodic CBC for blood disorders </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>SEVERE: CV, ophthalmic retinal damage, agranulocytosis </li></ul></ul>
  31. 31. Chloroquine (Plaquenil) <ul><li>Overdosage </li></ul><ul><ul><li>Headache, drowsiness, visual disturbances, CV collapse, convulsions, death </li></ul></ul><ul><ul><li>Tx symptomatic </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Cimetidine reduces clearance </li></ul></ul><ul><li>Patient eduation </li></ul><ul><ul><li>GI upset  take with food </li></ul></ul><ul><ul><li>Report: </li></ul></ul><ul><ul><ul><li>Visual disturbances, difficulty hearing or ringing in ears, diarrhea, vomiting, muscle weakness, or rash </li></ul></ul></ul>