Transcript Antiviral, Antifungal and Antiparasitic Drugs

Antiviral, Antifungal and
Antiparasitic Drugs
Nursing 3703
Pharmacology
By Linda Self
Viruses
• Intracellular parasites
• Enter host, bind to receptors on cell
membranes
• Use cellular metabolic activities for replication
• May be DNA or RNA viruses
Viruses
• DNA viruses incorporate into chromosomal
DNA, produce new viruses
• RNA viruses must be converted to DNA by
reverse transcriptase in order to replicate
Viruses
• Induce antibodies and immunity
• Protein coat allows host recognition as foreign
vs. self
• Exception is influenza
Viral illnesses
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Herpes Simplex 1 and 2
Cytomegalovirus
Influenza
RSV
Rotavirus
HIV and AIDS
Antiviral Drugs
• Catalyst was AIDS
• Both for Tx of AIDS and for opportunistic
infections
Viral Vaccines
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Poliomyelitis
Measles
Rubella
Varicella
RSV
HPV
Herpes Zoster
Yellow Fever
others
Viral Vaccines
• Attenuated vaccines generally safe
• Do not use in patients who are: pregnant, on
steroids, receiving immunosuppressants or
antineoplastiacs, undergoing radiation Tx or
who are immunodeficient
Drugs for Herpes Virus Infections
• Zovirax (acyclovir) for herpes labialis, varicella,
herpes zoster, genital herpes
• Famvir (famciclovir) for zoster and genital
herpes
• Valtrex (valacyclovir) for herpes labialis, zoster,
recurrent genital herpes
• Famvir and Valtrex need titration in renally
impaired
Influenza
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H=hemagglutinin
N=neuramidase
April 2009
Quadruple reassortment
Tx—Tamiflu (oseltamivir) or Relenza
(zanamivir) or Flumadine (rimantadine)
• Tx for 5 days
• Relenza can cause bronchospasm
Influenza
• To short course of infection, must be started
within 48h
• Thereafter, ? may decrease severity
RSV
• Virazole (ribavirin)
• Administered by inhalation
• Can cause bronchospasm
Viral hepatitis
• Hepatitis B—Hepsera (adefovir), Epivir
(lamivudine)
• Hepatitis C—peginterferon alfa 2a and
Virazole (ribavirin)
HIV
• Unique features
• 2 proteins on surface of virus bind with 2 sites
on CD4+ cell
• Virus infiltrates into genetic material
• Reverse transcriptase enzyme enables virus to
become double stranded DNA
HIV
• Once double-stranded DNA, like the host cell,
HIV can infiltrate cell nucleus of target cell
• Gains entry into target cell nucleus with aid of
Integrase
• Following integration and replication, long
protein chain is cleaved. Pieces then form into
new viral particle
HIV
• Cleavage is accomplished with aid of protease
• See page 568
Drugs for HIV Infection
• Nucleoside reverse transcriptase inhibitors
• Nucleotide reverse transcriptase inhibitors
• Non-nucleoside reverse transcriptase
inhibitors
• Protease inhibitors
• Entry inhibitors
Antiretrovirals
• Always used in combination
• Target enzymes or receptor sites
• Specific guidelines for pregnancy
Nucleoside Reverse Transcriptase
Inhibitors
• Prototype is AZT
• Similar structurally to DNA components
(adenosine, guanosine, cytosine or thymidine)
• Affect thymidine, thus inhibit reverse
transcriptase
• Slow progression but do not cure
• Didanosine, Ziagen (abacavir), AZT
(zidovudine), Epivir (lamivudine)
Nucleotide Reverse Transcriptase
Inhibitors
• Also inhibit reverse transcriptase
• Differ structurally from nucleoside RTI so
circumvent resistance
• Viread (tenofovir)
• Used to Tx hep B as well
Non-nucleoside Reverse Transcriptase
Inhibitors
• Directly bind with reverse transcriptase
• Used in combination with NRTIs
• Viramune (nevirapine) and Sustiva (efavirenz)
Protease Inhibitors
• Inhibit action of protease
• Most protease inhibitors metabolized by
cytochrome p450 system
• Many drug interactions
• Liver toxicities
• Lipid abnormalities
• Hyperglycemia
• lipodystrophies
Protease Inhibitors
• Prezista (darunavir), Crixivan (indinavir),
Viracept (nelfinavir), Norvir (ritonavir),
Invirase (saquinavir)
Combination Antiretrovirals
• Combovir (stavudine and zidovudine)
• Trizivir (abacavir, lamivudine and zidovudine)
• Decrease pill burden
Entry Inhibitors
• Fuzeon (enfuvirtide)
• Selzentry (maraviroc)
• Do not act on enzymes but rather affect
glycoproteins that allow binding and fusion of
the virus to the CD4+ cell
Integrase inhibitors
• Still in clinical trials
Fungi (mycoses)
• Mild or life threatening
• Widely present in environment
• Dermatophytes—tinea capitis, tinea pedis,
tinea cruris, tinea corporis
• Examples: Candida, Aspergillosis,
Cryptococcus, Histoplasmosis, B
Antifungal Drugs
• Development of antifungals difficult because
fungal cells closely resemble human cells
• Polyenes—Amphotericin B, Nystatin
• Azoles—Sporonox (itraconazole), Nizoral
(ketoconazole), Diflucan (fluconazole)
• Echinocandins—Eraxis (anidulafungin),
Cancidas (caspofungin)
Fungizone (amphotericin B)
• Give in D5W
• Use separate line
• In line filter depending on formulation
• Adverse effects:
Infusion reaction with chills, fever, tachypnea
Treat with Benadryl, Tylenol or steroids
• Nephrotoxicity most serious SE
Amphotericin B
• Indicated for life-threatening fungal infections
such as aspergillosis, blastomycosis,
candidiasis, coccinioidomycosis, crytococcis
and histoplasmosis
• Drug concentrations are highest in inflamed
tissues
Miscellaneous Antifungals
• Lamisil (terbinafine)
• griseofulvin
Mycostatin (nystatin)
• Same mechanism of action as Amphotericin B
• Too toxic for systemic use
Azoles
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Largest group of commonly used antifungals
Can be used topically or systemically
Prototype is Nizoral (ketoconazole0
All azoles are contraindicated in pregnancy
Azoles
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Less toxic than ampho
Many drug interactions
Poor absorption if achlorhydric
Some hepatotoxicity
Can be given orally
Diflucan (fluconazole)
• Synthetic, broad spectrum against candidiasis,
cryptococcis, coccidioidomycosis
• Not effective against aspergillosis
• PO or IV
• Fewer side effects than ketoconazole
• Does not require gastric acidity, does not cross
blood-brain barrier
• Reduce dosage in renal failure
Sporanox (itraconazole)
• Similar to Diflucan
• Drug of choice for blastomycosis, histoplasmosis
and sporotrichosis
• Good for suppressive Tx in AIDS patients w/histo
• Contraindicated for dermatophytic infections and
onychomycoses in heart failure patients
• IV or PO
• Many drug interactions
Cancidas (caspofungin)
• First chicocandin antifungal
• Affects glucan in fungal cell wall leading to
leakage of cellular contents
• Indicated for Tx of invasive aspergillosis who
cannot take or do not respond to Fungizone or
Sporanox
Cancidas
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Can cause thrombophlebitis
Abnormalities in blood count
Liver impairment
Drug interactions
Mix only with normal saline, infuse over at
least one hour
Fulvicin (griseofulvin)
• For dermatophyte infections of the scalp and
nails and for extensive skin eruptions
• Drug binds to keratin, over time the infected
tissues are shed and replaced by uninfected
tissues
• Need 3-8 weeks to Tx ringworm
• Up to one year for onychomycoses
Fulvicin
• Side effects: GI upset, skin rash, insomnia,
fatigue, hepatotoxicity, blood dyscrasias and
peripheral neuritis
• Take with fatty meal
• May affect efficacy of OCP
• Coumadin may warrant adjustment
Lamisil (terbinafine)
• Synthetic with broad spectrum of activity
• Inhibits an enzyme needed for synthesis of
ergosterol, a structural component of fungal
cell membranes
• Good for Tx of ringworm, nails
• hepatotoxic
Drug Treatment for Specific Infections
• Aspergillosis—Sporonox, Amphotericin B
• Blastomycosis—Sporonox, Amphotericin B
• Candidiasis—varies r/t area of infection
Oral
Cutaneous
Vaginal
Systemic
Drug Treatment for Fungal Infections
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Histoplasmosis—Sporanox
PCP—Bactrim, pentamidine, dapsone, others
Cryptococcis-Amphotericin B
Coccidioidomycosis- azole to Amphotericin B
Aspergillosis
• Found in soil, decaying plant matter, cellars
• May be found in cereals, powdered milk,
peanuts, cashews, coffee beans
• Characterized by granulomatous lesions of
lungs,skin, eyes, nose, urethra and may
infiltrate to vital organs
• Occurs in debilitated and
immunocompromised
• Tx w/ Amphotericin or Sporonox
Histoplasmosis
• Found in soil, organic debris around chicken
houses, bird roosts and caves inhabited by
bats
• Develops when spores are inhaled
• Tx with Sporanox, possibly Ampho
Candidiasis
• Yeast infection commonly affects those on abx
therapy, inhaled steroids, diabetics, those on
antineoplastic Tx or on steroids or who have
AIDS
• Presents as: vaginal candidiasis, skin
candidiasis, oral candidiasis or systemic
disease
Tx for Candidiasis
• Systemically—Amphotericin B
• Vaginally-Lotrimin (clotrimazole), Diflucan
• Oropharyngeal, esophageal, vaginal and
systemic—Diflucan PO or IV
Parasites
• Organisms that live within, upon or at expense
of another organism to survive
• Include protozoa, helminths, scabies and
pediculi
Protozoa
• Include amebiasis, giardiasis, malaria,
toxoplasmosis and trichomoniasis
• Single celled, may be saprophytes. Usually
contracted by oral-fecal route, by
contaminated water or by bite of an insect.
Amebiasis
• Common in Africa, Asia and Latin America
• In US, more likely in homosexuals and bisexual
men and in those who travel to areas with
poor sanitation
Amebiasis
• Drugs used are classified according to site of
action
• Extraintestinal e.g. liver—use Aralen
(chloroquine)
• For Intestinal use Yodoxin (lodoquinol)
• Flagyl is effective for intestinal and
extraintestinal amebiasis
• May also use tetracycline or doxycycline as
they alter bacterial flora
Giardiasis
• Caused by Giardia lamblia
• Spread by food or water contaminated with
feces with encysted forms of organism
• Also can contract by person to person
transmission in day cares, institutions and in
homosexual or bisexual men
Giardiasis
• Seen in campers who drink water
• Causes diarrhea
• Can progress to chronic condition with
malabsorption, wt. loss, anorexia
• Can result in B12 deficiency
• Tx is Flagyl
Malaria
• Seen in tropics
• Rare in US
• Caused by four species of protozoa of genus
Plasmodium-vivax, malariae, ovale and
falciparum
• Transmitted by the Anopholes mosquito
• Antimalarials act at different stages in life
cycle
Malaria
• Chloroquine with primaquine is used for
prophylaxis
• Lariam (mefloquine) for prevention and Tx,
better in more resistant forms
• Plaquenil (hydroxychloroquine) used to Tx
erythrocytic malaria
• Daraprim (pyrimethamine) folic acid
antagonist also used in prevention
Malaria
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Quinamm (quinine) prototype
Derived from bark of cinchona tree
Sometimes still used for leg cramps
Replaced by agents with fewer SE
Trichomoniasis
• Vaginal infection caused by Trichomonas
vaginalis
• Contracted sexually
• Treat both partners
• Flagyl is Tx
Helminthiasis
• Infestation with parasitic worms
• Some types of worms penetrate body tissues
or produce larvae that migrate to blood,
lymph, lungs, liver or other sites
• Some anthelminthics act locally, some
systemically
Vermox (mebendazole)
• Effective for hookworms, pinworms,
roundworms, whipworms
• May be useful with tapeworms
• Prevents uptake of glucose necessary for
parasitic metabolism
• Only 10% is absorbed systemically
Stromectrol (vermectin)
• Used for various parasitic infections, most
useful in stronguloidiasis
• Also used for resistant lice
Scabies and Pediculosis
• Parasitic infestations of the skin
• Scabies by the itch mite called the Sarcoptes
scabeii
• Scabies caused by one of three types of lice:
pediculosis capitis, pediculosis corporis and
pediculosis pubis
Scabicides and Pediculocides
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Permethrins drug of choice for both
Two applications recommended
Pediculosis is a 1% preparation (Nix)
Scabies used a 5% cream (Elimite)
Permethrins safest
Second line use Lindane (gamma benzene
hexachloride)
Scabicides and Pediculosis
• Ovide (malathion) is a pediculicide for head
lice
• Rid (pyrethrin) for pediculosis