Chapter 5 Therapy for Fungi and Viruses BY : SANJAY RAJPUROHIT
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Chapter 5
Therapy for Fungi and Viruses
BY : SANJAY RAJPUROHIT
Chapter 5 Topics
• Fungi and Antifungals
• Viruses and Antivirals
• Antiretrovirals
Learning Objectives
• Understand the differences between fungi and viruses and why the drugs to treat them must have very different mechanisms of action.
• Differentiate antifungals, antivirals, and antiretrovirals by their indications, therapeutic effects, side effects, dosages, and administration.
• Use antifungal, antiviral, and antiretroviral terminology correctly in written and oral communication.
• Define differences in mechanisms of action of antibiotics, antifungals, antivirals, and antiretrovirals.
Fungi and Their Characteristics
Fungus – Single-cell
organism– Lack of chlorophyll– Rigid cell wall and
nucleus– Reproduction by
spores
Discussion
In what ways are fungal cells similar to human cells? How are they different?
Discussion
In what ways are fungal cells similar to human cells? How are they different?
Answer: Human cell membranes contain cholesterol, and cell membranes of fungi contain ergosterol.
Fungi and Their Characteristics
Organism Disease
Aspergillus Aspergillosis
Blastomyces Blastomycosis
Candida (yeast) Candidiasis
Coccidioides Coccidioidomycosis
Cryptococcus Cryptococcosis
Histoplasma Histoplasmosis
Antifungals
How They Work– Prevent synthesis of ergosterol– Because human cells use cholesterol,
human cells are affected minimally
Antifungals
Dispensed in Two Forms– Topical Agents– Systemic Agents
Antifungals
• amphotericin B (Abelcet, AmBisome, Amphocin, Amphotec, Fungizone)
• butenafine (Mentax)• caspofungin (Cancidas)• ciclopirox (Loprox, Penlac)• clotrimazole (Gyne-Lotrimin, Mycelex-7)• clotrimazole-betamethasone (Lotrisone)• fluconazole (Diflucan)• flucytosine (Ancobon)• griseofulvin (Fulvicin P/G, Gris-PEG)
Drug List
Antifungals
• itraconazole (Sporanox)• ketoconazole (Nizoral)• miconazole (Lotrimin AF, Monistat Derm, Monistat 3)• nystatin (Mycostatin)• sertaconazole (Ertaczo)• terbinafine (Lamisil)• terconazole (Terazol)• voriconazole (VFEND)
Drug List
Antifungal Side Effects
• Serious side effects have been reported, even for topical agents.
• Pay close attention to dosing regimen to avoid overdosing.
amphotericin B (Fungizone)
• Used for blood-born, life-threatening fungal infections
• Infused slowly, not piggybacked, and not mixed with normal saline
• Blood levels of drug monitored and vitals monitored during infusion
• During treatment, monitor electrolytes, BUN, serum creatinine, temperature, CBC, fluid input and output
• Side effects: renal toxicity, anemia, fever, chills, shaking, headache
voriconazole (VFEND)
• Alternative to amphotericin B
• Can be started IV and switched to oral
• Can cause liver toxicity and blurred vision
fluconazole (Diflucan)
• Oral form used for vaginal or oral candidiasis
• IV used for patients who cannot tolerate oral
• Commonly prescribed medication
• Side effects: headache, rash, GI upset
itraconazole (Sporanox)
• Fungal infections of nails• Capsule taken twice a day with a fatty meal
and taken with a cola to increase stomach acidity and increase absorption
• Not in conjunction with antacids or H2 blockers
• Can cause liver toxicity• Capsules not substituted for oral solution due
to absorption issues
terbinafine (Lamisil)
• Kills fungus instead of just inhibiting growth• Oral form taken once daily
– Six weeks for fingernails – Twelve weeks for toenails
• Pulse dosing works well• Topical form for athlete’s foot, jock itch, and
ringworm– Do not use vaginally– Do not exceed four weeks
Antifungal Dispensing Issues
Lamisil, Lomotil, and Lamictal look alike.Use dose and dosage form to help keep these drugs from being dispensed incorrectly.
Warning!
grisefulvin (Fulvicin P/G, Gris-PEG)
• Fungal infections of the hair, skin, and nails
• Take with a fatty meal
• Avoid exposure to sunlight
• Dizziness and drowsiness are side effects, as well as passing headache
clotrimazole(Gyne-Lotrimin, Mycelex-7)
• Effective against oral candidiasis
• Supplied as a troche
• Available as OTC vaginal cream
• Topical form is the DOC for ringworm
clotrimazole-betamethasone (Lotrisone)
• Cream and lotion
• Commonly prescribed medication
miconazole(Lotrimin AF, Monistat Derm,
Monistat 3)
• Treatment of vulvovaginal candidiasis
• Available OTC
nystatin(Mycostatin)
• For patients with oral candidiasis
• Often used in liquid form, swish and swallow
ciclopirox (Loprox, Penlac)
• “Nail polish” treats nail tissue infections
• Do not take in combination with other oral antifungals
• Dispensed in amber-colored container
• Apply at bedtime to avoid exposure to light
Viruses and Their Characteristics
Virus – Does not have
components of a cell
– Unable to replicate outside of a living host cell
A virus infecting a bacterium.
Viruses and Their Characteristics
Most viruses are spread through the following routes:
– Direct contact– Ingestion of contaminated food and water– Inhalation of airborne particles– Exposure to contaminated body
fluids/equipment
Viruses and Their Characteristics
• Parts of a virus particle, virion– Nucleic acid consisting of either DNA or
RNA, not both– Capsid (protein shell) that surrounds and
protects the nucleic acid
• Naked virus– Virus without an envelope covering the
capsid
Stages of Viral Infection
1. Virus attaches to a cell receptor.
Stages of Viral Infection
1. Virus attaches to a cell receptor.
2. Cell membrane indents and closes around the virus, thus the virus penetrates the cell.
Stages of Viral Infection
1. Virus attaches to a cell receptor.
2. Cell membrane indents and closes around the virus, thus the virus penetrates the cell.
3. Virus escapes into cytoplasm.
Stages of Viral Infection
1. Virus attaches to a cell receptor.2. Cell membrane indents and closes
around the virus, thus the virus penetrates the cell.
3. Virus escapes into cytoplasm.4. Virus uncoats, shedding its
covering and releasing DNA or RNA into cell nucleus.
Stages of Viral Infection
1. Virus attaches to a cell receptor.2. Cell membrane indents and closes around
the virus, thus the virus penetrates the cell.3. Virus escapes into cytoplasm.4. Virus uncoats, shedding its covering and
releasing DNA or RNA into cell nucleus.5. Virus thus converts nuclear activity in
the cell to viral activity and reproduces new viral particles.
Discussion
Provide an example of a common viral infection and the symptoms of this condition.
Discussion
Provide an example of a common viral infection and the symptoms of this condition.
Answer: The flu (influenza). Symptoms include malaise, myalgia (muscle pain), headache, chills, fever.
Viral Classification
Two ways that viral infections are classified
– Duration and severity– Infection
Viral Classification
• Duration and severity– Acute: quickly resolves with no latent
infection such as common cold and flu– Chronic: protracted course with long
periods of remission interspersed with reappearance such as herpes virus infection
– Slow: progressive course, ultimately ending in death
Viral Classification
• Infection– Local: affects tissues of a single system,
such as the respiratory tract, the eye, or the skin
– Generalized: has spread or is spreading to other tissues by way of bloodstream or tissues of the CNS
Virus and Cell Interaction
A virus can damage a host cell in the following ways:
– Kill the host cell– Alter the cell– Incorporate into the genetic material of the
host cell– Divide when the host cell divides
Virus and Cell Interaction
Immunoglobulinantibody that may prevent an organism from attaching to a cell receptor and may destroy the organism
Virus and Cell Interaction
Interferona substance that exerts virus-nonspecific but host-specific antiviral activity by inducing gene coding for antiviral proteins that inhibit the synthesis of viral RNA
Virus and Cell Interaction
Vaccination– Exposes the patient to a component of a
virus or a similar strain that does not produce infection.
– When a vaccinated patient encounters the actual virus, the infection cannot develop.
Discussion
Who should receive an influenza vaccine?
Discussion
Who should receive an influenza vaccine?
Answer: High-risk patients such as healthcare workers, nursing home residents, public safety workers, individuals over 65 years old, immunocompromised patients.
Antivirals
Prevent virus cell replication without interfering with host cell’s normal function.
Antivirals
Systemic Agents• acyclovir (Zovirax)• amantadine (Symmetrel)• cidofovir (Vistide)• famciclovir (Famvir)• foscarnet (Foscavir)• ganciclovir (Cytovene)
Drug List
Antivirals
Systemic Agents• oseltamivir (Tamiflu)• ribavirin (Copegus, Rebetol, Virazole)• rimantadine (Flumadine)• valacyclovir (Valtrex)• valganciclovir (Valcyte)• zanamivir (Relenza)
Drug List
Antivirals
Ocular Agent
• ganciclovir (Vitrasert)
Drug List
Therapeutic Uses of Antivirals
• Cytomegalovirus (CMV) retinitis
• Herpes simplex
• Herpes simplex keratitis
• Herpes zoster (shingles)
• Influenza prophylaxis
• Varicella (chicken pox)
Antiviral Side Effects
Range from mild to severe.– Mild: headache– Severe: renal disorders
Antiviral Dispensing Issues
Amatadine, rimantadine, and ranitidine can be easily confused.
Dosing and indications will help keep them straight.
Warning!
acyclovir (Zovirax)
• Treatment of– Genital herpes– Herpes zoster (shingles)– Varicella (chicken pox) – Herpes encephalitis (in IV form)
• Range of short- and long-term side effects reported
famciclovir (Famvir)
• Treatment of – Acute herpes zoster– Herpes simplex in immunocompromised
patients– Genital herpes
• Dosed less frequently than acyclovir
• Prodrug
valacyclovir (Valtrex)
• Treats herpes zoster in immunocompetent adults and genital herpes
• Take with water and within forty-eight hours of the onset of zoster rash
• Shortens duration of postherpetic neuralgia• Commonly prescribed medication• Side effects: nausea, vomiting, diarrhea,
constipation
zanamivir (Relenza)
• Treatment of influenza A and B• Therapy initiated within 48 hr of symptom
onset• 2 inhalations daily, at 12 hr intervals, for 5
days• If using brochodilator, use it immediately
prior to admin of zanamivir• Sometimes Rx as prophylactic
oseltamivir (Tamiflu)
• Prevents influenza A and B
• Initiated within forty-eight hours of symptom onset
• Food improves tolerance
ganciclovir (Cytovene)
• Treating cytomegalovirus (CMV) infections in immunocompromised patients
• Follow chemotherapy preparations and dispensing guidelines when mixing, labeling, and packaging
• IV form not used for rapid or bolus injection
Antiviral Dispensing Issues
• Cytovene and Cytosar might be confused. – Cytovene: 250 mg, 500 mg– Cytosar: Chemotherapy agent, 10 mg
Warning!
foscarnet (Foscavir)
• Treatment of CMV infections in immunocompromised patients
• IV infusion, not rapid or bolus injection
• Patient must be hydrated, and Rx for hydration should be included with order for drug
Antiviral Dispensing Issues
• Patients who are given ganciclovir (Cytovene) or foscarnet (Foscavir) IV must be well hydrated.
• Typically there are “standing orders” for hydration when these drugs are prescribed.
Warning!
ribavirin (Virazole)
• Treating viral infections and pediatric patients with RSV
• Absorbed systemically from the respiratory tract following nasal and oral inhalation
• Side effects: fatigue, headache, insomnia, nausea, anorexia
Antiretrovirals
• Developed to limit the progression of the retrovirus HIV, the cause of AIDS
Antiretrovirals
• Developed to limit the progression of the retrovirus HIV, the cause of AIDS
• Five classes of antiretroviral drugs
Antiretrovirals
• Developed to limit the progression of the retrovirus HIV, the cause of AIDS
• Five classes of antiretroviral drugs– NRTIs– NNRTIs– NtRTIs– PIs– Fusion inhibitors
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
• Inhibit the action of reverse transcriptase to prevent the formation of viral RNA from proviral DNA
• Cause a decrease in the amount of virus in the body and subsequent spread to other healthy cells
NRTI Side Effects
• Lactic acidosis
• Degeneration of the liver
NRTI Dispensing Issues
• Taken with or without food
• Generally do not interfere with other drugs
• Administered in two or three doses per day
NRTIs
• abacavir (Ziagen)• didanosine (Videx)• emtricitabine (Emtriva)• lamivudine (Epivir)• stavudine (Zerit)• zalcitabine (Hivid)• zidovudine, AZT (Retrovir)• zidovudine-lamivudine (Combivir)• zidovudine-lamivudine-abacavir (Trizivir)
Drug List
zidovudine (Retrovir)
• Previously called AZT• One of first drugs developed specifically for
treatment of HIV• Can be combined with all NRTIs except
stavudine • Used in combination with lamivudine (with
or without PI) used for needlestick or sexual exposure treatment
lamivudine (Epivir)
• Treatment– HIV– Chronic hepatitis B
• Must be taken exactly as prescribed
• Fewest side effects of any of the NRTIs
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• Inhibit the action of HIV reverse transcriptase but at a different site on the enzyme than the site targeted by NRTIs
• Block RNA-dependent DNA polymerase activities
NNRTIs
• delavirdine (Rescriptor)
• efavirenz (Sustiva)
• nevirapine (Viramune)
Drug List
efavirenz (Sustiva)
• Dosed once a day, preferably at bedtime
• Patients should avoid high-fat meals• Side effects
– Dizziness, headache– Vivid dreams, nightmares, hallucinations– Typically occur 1-3 hr after administration– Typically subside after 2-4 weeks on drug
nevirapine (Viramune)
• Lower dose first 2 weeks and then increased to appropriate therapeutic level to avoid rash
• The antibiotic rifampin interferes with this drug
• This drug decreases serum concentration of PIs
• Must monitor liver functions
Nucleotide Reverse Transcriptase Inhibitors (NtRTIs)
• Inhibit the activity of HIV-1 reverse transcriptase by competing with natural nucleic acid substrates
• Cause termination of chain formation after incorporating in viral nucleic acid
NtRTIs
• tenofovir (Viread)
Drug List
Protease Inhibitors (PIs)
• Inhibit the protease enzyme, which typically cleaves certain HIV protein precursors that are necessary for the replication of new infectious virons
• Results in production of immature, noninfectious virons
• Combined with other antiretroviral drugs
PI Side Effects
• Protease paunch
• Facial atrophy
• Breast enlargement
• Hyperglycemia
• Hyperlipidemia
• Increase in bleeding episodes in hemophiliacs
PIs
• amprenavir (Agenerase)• atazanavir (Reyataz)• fosamprenavir (Lexiva)• indinavir (Crixivan)• lopinavir-ritonavir (Kaletra)• nelfinavir (Viracept)• ritonavir (Norvir)• saquinavir (Fortovase, Invirase)
Drug List
indinavir (Crixivan)
• Do not take with– St. John’s wort– Grapefruit juice– With food, especially high-fat
• Do take with a lot of water (48 oz/day) to avoid kidney stones
• Package with a desiccant, and patient to store in original container
lopinavir-ritonavir (Kaletra)
• Combination inhibits metabolism of lopinavir, allowing increased plasma levels of lopinavir
• Side effects– Nausea and vomiting– Diarrhea– Pancreatitis
• Solution contains alcohol
nelfinavir (Viracept)
• Can cause diarrhea, but loperamide and calcium carbonate can help control
• Take with food
ritonavir (Norvir)
• Causes increase in serum concentrations and thus decreases dosage frequency of other PIs, thus decreasing side effects
• Given at a low dose• Take with food• Causes an altered sense of taste• Store in the refrigerator
Fusion Inhibitors
How do fusion inhibitors represent an advance in the treatment of HIV?
Fusion Inhibitors
How do fusion inhibitors represent an advance in the treatment of HIV?
Answer: Prevents AIDS virus from entering the immune cells.
Fusion Inhibitors
• enfuvirtide (Fuzeon)
Drug List
Responding to HIV Exposure
• Centers for Disease Control guidelines
• Post-exposure prophylaxis (PEP)
• Begin within two hours
• Can decrease risk of infection by 80%
Combining AntiretroviralsRegimen Type Recommendation
standard therapy NNRTI: efavirenz + lamivudine + (zidovudine or tenofovir or stavudine)
PI: lopinavir-ritonavir + lamivudine + (zidovudine or stavudine)
alternative therapy 3 × NRTI: abacavir + lamivudine + (zidovudine or stavudine)
post-exposure prophylaxis (PEP)
zidovudine + lamivudine + (indinavir or nelfinavir)
Antiretroviral Dispensing Issues
Avoid the following antiretroviral drug combinations:– didanosine with zalcitabine
– zidovudine with stavudine
– lamivudine with zalcitabine
– stavudine with zalcitabine
Warning!
Discussion
What is one of the biggest problems when treating HIV?
Discussion
What is one of the biggest problems when treating HIV?
Answer: Noncompliance with drug regimen due to problematic side effects and complex dosing.
Related Documents
