Download Virus attaches to a cell receptor.

Chapter 5
Therapy for Fungi
and Viruses
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
Drug List
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)
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
Warning!
Lamisil, Lomotil, and Lamictal look alike.
Use dose and dosage form to help keep these
drugs from being dispensed incorrectly.
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
Immunoglobulin
antibody that may prevent an organism from
attaching to a cell receptor and may destroy
the organism
Virus and Cell Interaction
Interferon
a 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.
Drug List
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)
Therapeutic Uses of Antivirals
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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
Warning!
Amatadine, rimantadine, and ranitidine can be
easily confused.
Dosing and indications will help keep them
straight.
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
Warning!
• Cytovene and Cytosar might be confused.
– Cytovene: 250 mg, 500 mg
– Cytosar: Chemotherapy agent, 10 mg
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
Warning!
• 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.
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
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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
Drug List
NRTIs
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•
•
abacavir (Ziagen)
didanosine (Videx)
emtricitabine (Emtriva)
lamivudine (Epivir)
stavudine (Zerit)
zalcitabine (Hivid)
zidovudine, AZT (Retrovir)
zidovudine-lamivudine (Combivir)
zidovudine-lamivudine-abacavir (Trizivir)
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
Drug List
NNRTIs
• delavirdine (Rescriptor)
• efavirenz (Sustiva)
• nevirapine (Viramune)
efavirenz (Sustiva)
• Dosed once a day, preferably at
bedtime
• Patients should avoid high-fat meals
• Side effects
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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
Drug List
NtRTIs
• tenofovir (Viread)
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
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•
•
•
•
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Protease paunch
Facial atrophy
Breast enlargement
Hyperglycemia
Hyperlipidemia
Increase in bleeding episodes in
hemophiliacs
Drug List
PIs
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•
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•
•
•
amprenavir (Agenerase)
atazanavir (Reyataz)
fosamprenavir (Lexiva)
indinavir (Crixivan)
lopinavir-ritonavir (Kaletra)
nelfinavir (Viracept)
ritonavir (Norvir)
saquinavir (Fortovase, Invirase)
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.
Drug List
Fusion Inhibitors
• enfuvirtide (Fuzeon)
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 Antiretrovirals
Regimen Type
standard therapy
alternative therapy
post-exposure prophylaxis
(PEP)
Recommendation
NNRTI: efavirenz +
lamivudine + (zidovudine or
tenofovir or stavudine)
PI: lopinavir-ritonavir +
lamivudine + (zidovudine or
stavudine)
3 × NRTI: abacavir +
lamivudine + (zidovudine or
stavudine)
zidovudine + lamivudine +
(indinavir or nelfinavir)
Antiretroviral Dispensing Issues
Warning!
Avoid the following antiretroviral drug combinations:
–
–
–
–
didanosine with zalcitabine
zidovudine with stavudine
lamivudine with zalcitabine
stavudine with zalcitabine
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.