Download Antiviral, Antitubercular, Antifunginal Agents.Antimalarial

Antiviral Agents
Understanding Viruses
Viral Replication
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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.
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Any drug that kills a virus may also kill our cells.
Viral Infections
Competent immune system:
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Best response to viral infections
A well-functioning immune system will
eliminate
or effectively destroy virus replication
Immunocompromised patients have
frequent viral infections
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Cancer patients, especially leukemia or
Antivirals
Key characteristics of antiviral drugs:
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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:
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cytomegalovirus (CMV)
herpes simplex virus (HSV)
human immunodeficiency virus (HIV)
influenza A (the “flu”)
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respiratory syncytial virus (RSV)
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Antivirals: Mechanism of Action
Inhibit viral replication
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Inhibit viral attachment
Prevent genetic copying of virus
Prevent viral protein production
Sites of Drug Action
Sites of Drug Action
Antiviral Agents
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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)
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influenza A
foscarnet (Foscavir)
 CMV (retinitis and systemic)
Neuraminidase Inhibitors: oseltamivir (Tamiflu)
and zanamivir (Relenza)
Antivirals: Side Effects
acyclovir
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Burning when topically applied, nausea,
vomiting, diarrhea, headache
amantadine and rimantadine
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Anticholinergic effects, insomnia,
lightheadedness, anorexia, nausea
didanosine (ddl)
Antivirals: Side Effects
zidovudine (AZT)
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Bone marrow suppression, nausea,
headache
foscarnet (Foscavir)
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Headache, seizures, acute renal failure,
nausea, vomiting, diarrhea
ganciclovir (Cytovene)
Antiherpes Agents
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Acyclovir- prototype
Valacyclovir
Famciclovir
Penciclovir
Trifluridine
Vidarabine
Mechanism of Action
Acyclovir
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an acyclic guanosine derivative
Phosphorylated by viral thymidine kinase
Di-and tri-phosphorylated by host cellular
enzymes
Inhibits viral DNA synthesis by:
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1) competing with dGTP for viral DNA
polymerase
2) chain termination
Clinical Uses
Acyclovir
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Oral, IV, and Topical formulations
Cleared by glomerular filtration and
tubular secretion
Uses:
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Herpes Simplex Virus 1 and 2 (HSV)
Varicella-zoster virus (VZV)
Side Effects: nausea, diarrhea,
headache, tremors, and delirium
Valacyclovir
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L-valyl ester of acyclovir
Converted to acyclovir when ingested
M.O.A.: same as acyclovir
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Uses:
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1) recurrent genital herpes
2) herpes zoster infections
Side Effects: nausea, diarrhea, and
headache
Famciclovir
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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
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Trifluridine- fluorinated pyrimidine
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inhibits viral DNA synthesis same as acyclovir
incorporates into viral and cellular DNA
Uses: HSV-1 and HSV-2 (topically)
Vidarabine
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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
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Gancyclovir
Valgancyclovir
Cidofovir
Foscarnet
Fomivirsen
Ganciclovir
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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
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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
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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
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Mechanism of Action
Zidovudine (AZT)
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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
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Due to mutations in the reverse
transcriptase gene
more frequent after prolong therapy and
in persons with HIV
Clinical Uses
Zidovudine
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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
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Myelosuppression, including anemia and
neutropenia
GI intolerance, headaches, and insomnia
Other NRTIs
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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
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Tenofovir
Adefovir
Tenofovir
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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
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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)
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Nevirapine
Delavirdine
Efavirenz
Mechanism of Action
NNRTIs
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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)
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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
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Indinavir
Ritonavir
Saquinavir
Nelfinavir
Amprenavir
Protease Inhibitors
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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
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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
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A synthetic peptide-like substrate analog
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inhibits HIV-1 protease
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prevents cleavage of viral polyproteins
Nelfinavir and Amprenavir
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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
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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
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Lamivudine -Nucleoside Reverse
Transcriptase Inhibitor (NRTI)
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Adefovir -Nucleotide Inhibitor
Interferon Alfa
Pegylated Interferon Alfa
Ribavirin
Interferons
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Interferon Alfa
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Endogenous proteins
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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
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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
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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
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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
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Zanamivir and Oseltamivir
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Inhibits the enzyme neuraminidase
inhibit the replication of influenza A and
Influenza B
treats uncomplicated influenza infections
administered intranasally
Antivirals: Nursing Implications
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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
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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
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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
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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:
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effects are varied and specific to each agent
Antivirals: Nursing Implications
Monitor for therapeutic effects:
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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
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Tuberculosis, “TB”
Caused by Mycobacterium tuberculosis
Antitubercular agents treat all forms of
mycobacterium
Mycobacterium Infections
Common Infection Sites
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lung (primary site)
brain
bone
liver
kidney
Mycobacterium Infections
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Aerobic bacillus
Passed from infected:
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Humans
Cows (bovine)
Birds (avian)
Mycobacterium Infections
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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
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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)
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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:
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Type of infection
Adequate dosing
Sufficient duration of treatment
Drug compliance
Selection of an effective drug combination
Antitubercular Agents: Side
Effects
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INH
peripheral neuritis, hepatotoxicity
ethambutol
retrobulbar neuritis, blindness
rifampin
hepatitis, discoloration of urine, stools
Antitubercular Agents:
Nursing Implications
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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:
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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:
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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
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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
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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
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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:
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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
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malaria
leishmaniasis
amebiasis
giardiasis
trichomoniasis
Malaria
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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
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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
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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
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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
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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
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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
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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
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Only exoerythrocytic drug.
Binds and alters DNA.
sulfonamides, tetracyclines, clindamycin
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Used in combination with antimalarials to
increase protozoacidal effects
Antimalarials: Drug Effects
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Kill parasitic organisms.
Chloroquine and hydroxychloroquine also
have antiinflammatory effects.
Antimalarials: Therapeutic Uses
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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
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Many side effects for the various agents
Primarily gastrointestinal: nausea,
vomiting, diarrhea,
anorexia, and
abdominal pain
Antiprotozoals
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atovaquone (Mepron)
metronidazole (Flagyl)
pentamidine (Pentam)
iodoquinol (Yodoxin, Di-Quinol)
paromomycin (Humatin)
Protozoal Infections
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amebiasis
giardiasis
pneumocystosis
toxoplasmosis
trichomoniasis
Protozoal Infections
Transmission
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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
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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
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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
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Inhibits DNA and RNA
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Binds to and aggregates ribosomes
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Directly lethal to Pneumocystis carinii
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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
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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
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“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
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nausea, vomiting, diarrhea, anorexia
metronidazole
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metallic taste, nausea, vomiting, diarrhea,
abdominal cramps
iodoquinol
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nausea, vomiting, diarrhea, anorexia,
agranulocytosis
Antiprotozoals: Side Effects
pentamidine
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bronchospasms, leukopenia, thrombocytopenia,
acute pancreatitis, acute renal failure, increased
liver function studies
paromomycin
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nausea, vomiting, diarrhea, stomach cramps
Antihelmintics
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




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.