Post on 14-Dec-2015
Antiviral AgentsAntiviral Agents
Understanding VirusesUnderstanding Viruses
Viral ReplicationViral Replication A virus cannot replicate on its own.A virus cannot replicate on its own. It must attach to and enter a host cell.It must attach to and enter a host cell. It then uses the host cell’s energy to It then uses the host cell’s energy to
synthesize protein, DNA, and RNA.synthesize protein, DNA, and RNA.
Understanding VirusesUnderstanding Viruses
Viruses are difficult to kill because they Viruses are difficult to kill because they liveliveinside our cells.inside our cells.
Any drug that kills a virus may also kill our Any drug that kills a virus may also kill our cells.cells.
Viral InfectionsViral InfectionsCompetent immune system:Competent immune system: Best response to viral infectionsBest response to viral infections A well-functioning immune system will eliminate A well-functioning immune system will eliminate
or effectively destroy virus replicationor effectively destroy virus replication
Immunocompromised patients have frequent Immunocompromised patients have frequent viral infectionsviral infections
Cancer patients, especially leukemia or lymphomaCancer patients, especially leukemia or lymphoma Transplant patients, due to pharmacological Transplant patients, due to pharmacological
therapytherapy AIDS patients, disease attacks immune systemAIDS patients, disease attacks immune system
AntiviralsAntivirals
Key characteristics of antiviral drugs:Key characteristics of antiviral drugs: Able to enter the cells infected with virus.Able to enter the cells infected with virus.
Interfere with viral nucleic acid synthesis Interfere with viral nucleic acid synthesis and/or regulation.and/or regulation.
Some agents interfere with ability of virus Some agents interfere with ability of virus to bind to cells.to bind to cells.
Some agents stimulate the body’s immune Some agents stimulate the body’s immune system.system.
AntiviralsAntivirals
Viruses killed by current antiviral Viruses killed by current antiviral therapy:therapy:
cytomegalovirus (CMV)cytomegalovirus (CMV) herpes simplex virus (HSV)herpes simplex virus (HSV) human immunodeficiency virus (HIV)human immunodeficiency virus (HIV) influenza A (the “flu”)influenza A (the “flu”) respiratory syncytial virus (RSV)respiratory syncytial virus (RSV)
Antivirals: Mechanism of Antivirals: Mechanism of ActionAction
Inhibit viral replicationInhibit viral replication Inhibit viral attachmentInhibit viral attachment Prevent genetic copying of virusPrevent genetic copying of virus Prevent viral protein productionPrevent viral protein production
Sites of Drug ActionSites of Drug Action
Sites of Drug ActionSites of Drug Action
Antiviral AgentsAntiviral Agents Block viral entry into the cell or must Block viral entry into the cell or must
work inside the cellwork inside the cell Most agents are pyrimidine or purine Most agents are pyrimidine or purine
nucleoside analogsnucleoside analogs
Antivirals Antivirals Synthetic Purine Nucleoside Synthetic Purine Nucleoside
AnaloguesAnaloguesTwo types of nucleosides:Two types of nucleosides:Purine nucleosidesPurine nucleosides guanineguanine adenosineadenosine
Pyrimidine nucleosidesPyrimidine nucleosides thyminethymine cytosinecytosine
Antivirals: Purine Antivirals: Purine NucleosidesNucleosides
AgentAgent Antiviral ActivityAntiviral Activity
guaninesguanines
acycloviracyclovir HSV 1 & 2, VZVHSV 1 & 2, VZV
ganciclovir (DHPG)ganciclovir (DHPG) CMV retinitis and CMV retinitis and systemicsystemic CMV infectionCMV infection
ribavirin (RTCD)ribavirin (RTCD) Influenza types A and Influenza types A and B,B, RSV, LV, HVRSV, LV, HV
adenosinesadenosines
didanosine (ddl)didanosine (ddl) HIVHIV
vidarabine (Ara-A)vidarabine (Ara-A) HSV, herpes zosterHSV, herpes zoster
Antivirals: Pyrimidine Antivirals: Pyrimidine NucleosidesNucleosides
AgentAgent Antiviral ActivityAntiviral Activitycytosinescytosines
lamivudine (3TC)lamivudine (3TC) HIVHIVzalcitabine (ddC)zalcitabine (ddC) HIVHIV
thyminethymineidoxuridine (IDU)idoxuridine (IDU) HSVHSVstavudine (d4T)stavudine (d4T) HIVHIVtrifluridinetrifluridine HSVHSVzidovudine (AZT)zidovudine (AZT) HIVHIV
Other AntiviralsOther Antivirals
amantadine amantadine (Symmetrel) and rimantadine (Symmetrel) and rimantadine (Flumadine)(Flumadine)
influenza Ainfluenza A
foscarnet (Foscavir)foscarnet (Foscavir) CMV (retinitis and systemic)CMV (retinitis and systemic)
Neuraminidase Inhibitors: oseltamivir (Tamiflu) Neuraminidase Inhibitors: oseltamivir (Tamiflu) and zanamivir (Relenza)and zanamivir (Relenza)
influenza types A and Binfluenza types A and B
Antivirals: Side EffectsAntivirals: Side Effects
acycloviracyclovir Burning when topically applied, nausea, Burning when topically applied, nausea,
vomiting, diarrhea, headachevomiting, diarrhea, headache
amantadine and rimantadineamantadine and rimantadine Anticholinergic effects, insomnia, Anticholinergic effects, insomnia,
lightheadedness, anorexia, nausealightheadedness, anorexia, nausea
didanosine (ddl)didanosine (ddl) Pancreatitis, peripheral neuropathies, seizuresPancreatitis, peripheral neuropathies, seizures
Antivirals: Side EffectsAntivirals: Side Effects
zidovudine (AZT)zidovudine (AZT) Bone marrow suppression, nausea, headacheBone marrow suppression, nausea, headache
foscarnet (Foscavir)foscarnet (Foscavir) Headache, seizures, acute renal failure, nausea, Headache, seizures, acute renal failure, nausea,
vomiting, diarrheavomiting, diarrhea
ganciclovir (Cytovene)ganciclovir (Cytovene) Bone marrow toxicity, nausea, anorexia, vomitingBone marrow toxicity, nausea, anorexia, vomiting
Antiherpes AgentsAntiherpes Agents
Acyclovir- Acyclovir- prototypeprototype ValacyclovirValacyclovir FamciclovirFamciclovir PenciclovirPenciclovir TrifluridineTrifluridine VidarabineVidarabine
Mechanism of Action Mechanism of Action AcyclovirAcyclovir
an acyclic guanosine derivativean acyclic guanosine derivative Phosphorylated by Phosphorylated by viral thymidine viral thymidine
kinasekinase Di-and tri-phosphorylated by host Di-and tri-phosphorylated by host
cellular enzymescellular enzymes Inhibits viral DNA synthesis by:Inhibits viral DNA synthesis by:
1) competing with dGTP for viral DNA 1) competing with dGTP for viral DNA polymerasepolymerase
2) chain termination2) chain termination
Clinical Uses Clinical Uses AcyclovirAcyclovir
Oral, IV, and Topical formulationsOral, IV, and Topical formulations Cleared by glomerular filtration and Cleared by glomerular filtration and
tubular secretiontubular secretion UsesUses::
Herpes Simplex Virus 1 and 2 (HSV)Herpes Simplex Virus 1 and 2 (HSV) Varicella-zoster virus (VZV)Varicella-zoster virus (VZV)
Side EffectsSide Effects: : nausea, diarrhea, nausea, diarrhea, headache, tremors, and deliriumheadache, tremors, and delirium
ValacyclovirValacyclovir L-valyl ester of acyclovirL-valyl ester of acyclovir Converted to acyclovir when ingestedConverted to acyclovir when ingested M.O.A.M.O.A.:: same as acyclovir same as acyclovir UsesUses: :
1) recurrent genital herpes1) recurrent genital herpes 2) herpes zoster infections2) herpes zoster infections
Side EffectsSide Effects:: nausea, diarrhea, and nausea, diarrhea, and headacheheadache
FamciclovirFamciclovir Prodrug of Prodrug of penciclovirpenciclovir (a guanosine (a guanosine
analog)analog) M.O.A.:M.O.A.: same as acyclovir same as acyclovir does does not not cause chain terminationcause chain termination Uses: Uses: HSV-1, HSV-2, VZV, EBV, and HSV-1, HSV-2, VZV, EBV, and
hepatitis Bhepatitis B Side EffectsSide Effects:: nausea, diarrhea, and nausea, diarrhea, and
headacheheadache
TrifluridineTrifluridine
TrifluridineTrifluridine- fluorinated pyrimidine - fluorinated pyrimidine inhibits viral DNA synthesis same as inhibits viral DNA synthesis same as
acycloviracyclovir incorporates into viral and cellular DNAincorporates into viral and cellular DNA UsesUses: HSV-1 and HSV-2 (topically): HSV-1 and HSV-2 (topically)
VidarabineVidarabine An adenosine analogAn adenosine analog inhibits viral DNA polymeraseinhibits viral DNA polymerase incorporated into viral and cellular incorporated into viral and cellular
DNADNA metabolized to hypoxanthine metabolized to hypoxanthine
arabinosidearabinoside Side EffectsSide Effects: GI intolerance and : GI intolerance and
myelosuppressionmyelosuppression
Anti-Cytomegalovirus Anti-Cytomegalovirus AgentsAgents
GancyclovirGancyclovir ValgancyclovirValgancyclovir CidofovirCidofovir FoscarnetFoscarnet FomivirsenFomivirsen
GanciclovirGanciclovir An acyclic guanosine analogAn acyclic guanosine analog requires triphosphorylation for activationrequires triphosphorylation for activation monophosphorylation is catalyzed by a monophosphorylation is catalyzed by a
phosphotransferase in CMV and by phosphotransferase in CMV and by thymidine kinase in HSV cellsthymidine kinase in HSV cells
M.O.A.: M.O.A.: same as acyclovirsame as acyclovir UsesUses: CMV*, HSV, VZV,and EBV: CMV*, HSV, VZV,and EBV Side EffectSide Effect: myelosuppression: myelosuppression
HIVHIV
HIVHIV
ValgancyclovirValgancyclovir Monovalyl ester prodrug of gancyclovirMonovalyl ester prodrug of gancyclovir Metabolized by intestinal and hepatic Metabolized by intestinal and hepatic
esterases when administered orallyesterases when administered orally
M.O.A.: M.O.A.: same as gancyclovirsame as gancyclovir UsesUses: CMV*: CMV* Side EffectSide Effect: myelosuppression: myelosuppression
FoscarnetFoscarnet An inorganic pyrophosphateAn inorganic pyrophosphate inhibits viral DNA polymerase, RNA inhibits viral DNA polymerase, RNA
polymerase, and HIV reverse polymerase, and HIV reverse transcriptasetranscriptase
does not have to be phosphorylateddoes not have to be phosphorylated Uses: Uses: HSV, VZV, CMV, EBV, HHV-6, HSV, VZV, CMV, EBV, HHV-6,
HBV, and HIVHBV, and HIV Resistance due to mutations in DNA Resistance due to mutations in DNA
polymerase genepolymerase gene Side Effects:Side Effects: hypo- or hypercalcemia hypo- or hypercalcemia
and phosphotemiaand phosphotemia
HIVHIV
AIDS- treatmentAIDS- treatment
Antiretroviral AgentsAntiretroviral Agents
1) Nucleoside Reverse Transcriptase 1) Nucleoside Reverse Transcriptase Inhibitors (NRTIs)Inhibitors (NRTIs)
2) Nonnucleoside Reverse 2) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)Transcriptase Inhibitors (NNRTIs)
3)Protease inhibitors3)Protease inhibitors
Reverse Transcriptase Reverse Transcriptase InhibitorsInhibitors
Zidovudine (AZT)Zidovudine (AZT) Didanosine- Didanosine- causes pancreatitis*causes pancreatitis* Lamivudine- Lamivudine- causes pancreatitiscauses pancreatitis Zalcitabine- Zalcitabine- causes peripheral causes peripheral
neuropathyneuropathy**
Stavudine- Stavudine- causes peripheral neuropathy*causes peripheral neuropathy* AbacavirAbacavir
Mechanism of Action Mechanism of Action Zidovudine (AZT)Zidovudine (AZT)
A deoxythymidine analogA deoxythymidine analog enters the cell via passive diffusionenters the cell via passive diffusion must be converted to the must be converted to the
triphosphate form by mammalian triphosphate form by mammalian thymidine kinasethymidine kinase
competitively inhibits competitively inhibits deoxythymidine triphosphate for the deoxythymidine triphosphate for the reverse transcriptase enzymereverse transcriptase enzyme
causes chain terminationcauses chain termination
Mechanism of Resistance Mechanism of Resistance ZidovudineZidovudine
Due to mutations in the reverse Due to mutations in the reverse transcriptase genetranscriptase gene
more frequent after prolong therapy more frequent after prolong therapy and in persons with HIVand in persons with HIV
Clinical Uses Clinical Uses ZidovudineZidovudine
Available in IV and oral formulationsAvailable in IV and oral formulations activity against HIV-1, HIV-2, and activity against HIV-1, HIV-2, and
human T cell lymphotropic viruseshuman T cell lymphotropic viruses mainly used for treatment of HIV, mainly used for treatment of HIV,
decreases rate of progression and decreases rate of progression and prolongs survivalprolongs survival
prevents mother to newborn prevents mother to newborn transmission of HIVtransmission of HIV
Side Effects Side Effects ZidovudineZidovudine
Myelosuppression, including anemia Myelosuppression, including anemia and neutropeniaand neutropenia
GI intolerance, headaches, and GI intolerance, headaches, and insomniainsomnia
Other NRTIsOther NRTIs
Didanosine- Didanosine- synthetic synthetic deoxy-deoxy-adenosineadenosine analog; causes pancreatitis* analog; causes pancreatitis*
Lamivudine- Lamivudine- cytosinecytosine analog analog Zalcitabine- Zalcitabine- cytosinecytosine analog; causes analog; causes
peripheral neuropathy*peripheral neuropathy* Stavudine- Stavudine- thymidinethymidine analog;causes analog;causes
peripheral neuropathy*peripheral neuropathy* Abacavir- Abacavir- guanosine analog; more guanosine analog; more
effective than the other agents; fatal effective than the other agents; fatal hypersensitivity reactions can occur hypersensitivity reactions can occur
Nucleotide InhibitorsNucleotide Inhibitors TenofovirTenofovir AdefovirAdefovir
TenofovirTenofovir An acyclic nucleoside phosphonate An acyclic nucleoside phosphonate
analog of adenosineanalog of adenosine M.O.AM.O.A.- competively inhibits HIV .- competively inhibits HIV
reverse transcriptase and causes reverse transcriptase and causes chain termination after incorporation chain termination after incorporation into DNAinto DNA
UsesUses – in combination with other – in combination with other antiretrovirals for HIV-1 suppressionantiretrovirals for HIV-1 suppression
AdefovirAdefovir An analog of adenosine monophosphateAn analog of adenosine monophosphate Phosphorylated by cellular kinases Phosphorylated by cellular kinases M.O.A.M.O.A. - Competitively inhibits HBV - Competitively inhibits HBV
DNA polymerase and results in chain DNA polymerase and results in chain termination after incorporation into viral termination after incorporation into viral DNADNA
UsesUses - Hepatitis B - Hepatitis B Side effectsSide effects - nephrotoxicity - nephrotoxicity
Nonnucleoside Reverse Nonnucleoside Reverse Transcriptase Inhibitors Transcriptase Inhibitors
(NNRTIs)(NNRTIs)
NevirapineNevirapine DelavirdineDelavirdine EfavirenzEfavirenz
Mechanism of ActionMechanism of ActionNNRTIsNNRTIs
Bind to site on viral reverse transcriptase, Bind to site on viral reverse transcriptase, different from NRTIsdifferent from NRTIs
results in blockade of RNA and DNA results in blockade of RNA and DNA dependent DNA polymerase activitydependent DNA polymerase activity
do do notnot compete with nucleoside compete with nucleoside triphosphatestriphosphates
do do notnot require phosphorylation require phosphorylation these drugs can these drugs can notnot be given alone be given alone substrates and inhibitors of CYP3A4substrates and inhibitors of CYP3A4
Nonnucleoside Reverse Nonnucleoside Reverse Transcriptase Inhibitors Transcriptase Inhibitors
(NNRTIs)(NNRTIs)
Nevirapine- Nevirapine- prevents transmission prevents transmission of HIV from mother to newborn when of HIV from mother to newborn when given at onset of labor and to the given at onset of labor and to the neonate at deliveryneonate at delivery
Delavirdine- Delavirdine- teratogenic, therefore teratogenic, therefore can not be given during pregnancycan not be given during pregnancy
Efavirenz- Efavirenz- teratogenic, therefore teratogenic, therefore can not be given during pregnancycan not be given during pregnancy
Protease InhibitorsProtease Inhibitors IndinavirIndinavir RitonavirRitonavir SaquinavirSaquinavir NelfinavirNelfinavir AmprenavirAmprenavir
Protease InhibitorsProtease Inhibitors The protease enzyme cleaves The protease enzyme cleaves
precursor molecules to produce precursor molecules to produce mature, infectious virionsmature, infectious virions
these agents inhibit protease and these agents inhibit protease and prevent the spread of infectionprevent the spread of infection
These agents cause a syndrome of These agents cause a syndrome of altered body fat distribution, insulin altered body fat distribution, insulin resistance, and hyperlipidemiaresistance, and hyperlipidemia
Indinavir Indinavir andand Ritonavir Ritonavir M.O.A.M.O.A.: Specific inhibitors of the HIV-1 : Specific inhibitors of the HIV-1
protease enzymeprotease enzyme M.O.R.M.O.R.: mediated by expression of : mediated by expression of
multiple and variable protease amino acid multiple and variable protease amino acid substitutionssubstitutions
Side EffectsSide Effects:: hyperbilirubinemiahyperbilirubinemia ContraindicationsContraindications:inhibitor/substrate for :inhibitor/substrate for
CPY3A4, do CPY3A4, do not not give with antifungal azolesgive with antifungal azoles
SaquinavirSaquinavir A synthetic peptide-like substrate A synthetic peptide-like substrate
analoganalog
inhibits HIV-1 proteaseinhibits HIV-1 protease
prevents cleavage of viral prevents cleavage of viral polyproteinspolyproteins
Nelfinavir Nelfinavir andand AmprenavirAmprenavir
M.O.A.M.O.A.: Specific inhibitors of the HIV-: Specific inhibitors of the HIV-1 protease enzyme1 protease enzyme
M.O.R.M.O.R.: mediated by expression of : mediated by expression of multiple and variable protease amino multiple and variable protease amino acid substitutionsacid substitutions
Less cross-resistance with Less cross-resistance with AmprenavirAmprenavir Side EffectsSide Effects: diarrhea and flatulence: diarrhea and flatulence AmprenavirAmprenavir can cause Stevens- can cause Stevens-
Johnson syndromeJohnson syndrome ContraindicationsContraindications:inhibitor/:inhibitor/
substrate for CPY3A4substrate for CPY3A4
Fusion InhibitorsFusion Inhibitors EnfuvirtideEnfuvirtide (T-20)- binds to the gp41 (T-20)- binds to the gp41
subunit of the viral envelope glycoprotein, subunit of the viral envelope glycoprotein, preventing the conformational changes preventing the conformational changes required for fusion of the viral and cellular required for fusion of the viral and cellular membranesmembranes
By blocking fusion (entry into cell), By blocking fusion (entry into cell), FUZEON prevents HIV from infecting CD4 FUZEON prevents HIV from infecting CD4 cellscells
Anti-Hepatitis AgentsAnti-Hepatitis Agents LamivudineLamivudine - -Nucleoside Reverse Nucleoside Reverse
Transcriptase Inhibitor (NRTI)Transcriptase Inhibitor (NRTI) Adefovir Adefovir --Nucleotide InhibitorNucleotide Inhibitor InterferonInterferon AlfaAlfa Pegylated Interferon AlfaPegylated Interferon Alfa RibavirinRibavirin
InterferonsInterferons Interferon AlfaInterferon Alfa
Endogenous proteins Endogenous proteins
induce host cell enzymes that inhibit viral induce host cell enzymes that inhibit viral RNA translation and cause degradation of RNA translation and cause degradation of viral mRNA and tRNAviral mRNA and tRNA
Bind to membrane receptors on cell Bind to membrane receptors on cell surfacesurface
May also inhibit viral penetration, May also inhibit viral penetration, uncoating, mRNA synthesis, and uncoating, mRNA synthesis, and translation, and virion assembly and translation, and virion assembly and releaserelease
InterferonsInterferons Pegylated interferon AlfaPegylated interferon Alfa A linear or branced polyethylene A linear or branced polyethylene
gylcol (PEG) moiety is attached to gylcol (PEG) moiety is attached to covalently to interferoncovalently to interferon
Increased half-life and steady drug Increased half-life and steady drug concentrationsconcentrations
Less frequent dosingLess frequent dosing Tx chronic hepatitis C in combination Tx chronic hepatitis C in combination
with ribavirinwith ribavirin
RibavirinRibavirin A guanosine analogA guanosine analog phosphorylated intracellularly by host phosphorylated intracellularly by host
enzymesenzymes inhibits capping of viral messenger RNAinhibits capping of viral messenger RNA inhibits the viral RNA-dependent RNA inhibits the viral RNA-dependent RNA
polymerasepolymerase inhibits replication of DNA and RNA inhibits replication of DNA and RNA
virusesviruses
Anti-Influenza AgentsAnti-Influenza Agents
AmantadineAmantadine RimantadineRimantadine ZanamivirZanamivir
AmantadineAmantadine and and RimantadineRimantadine
cyclic aminescyclic amines inhibit the uncoating of viral RNA inhibit the uncoating of viral RNA
therefore inhibiting replicationtherefore inhibiting replication resistance due to mutations in the resistance due to mutations in the
RNA sequence coding for the RNA sequence coding for the structural M2 proteinstructural M2 protein
used in the prevention and used in the prevention and treatment of Influenza Atreatment of Influenza A
Zanamivir Zanamivir andand OseltamivirOseltamivir
Inhibits the enzyme neuraminidaseInhibits the enzyme neuraminidase inhibit the replication of influenza A inhibit the replication of influenza A
and Influenza Band Influenza B treats uncomplicated influenza treats uncomplicated influenza
infectionsinfections administered intranasallyadministered intranasally
Antivirals: Nursing Antivirals: Nursing ImplicationsImplications
Before beginning therapy, thoroughly Before beginning therapy, thoroughly assess underlying disease and medical assess underlying disease and medical history, including allergies.history, including allergies.
Assess baseline VS and nutritional status.Assess baseline VS and nutritional status. Assess for contraindications, conditions Assess for contraindications, conditions
that may indicate cautious use, and that may indicate cautious use, and potential drug interactions.potential drug interactions.
Antivirals: Nursing Antivirals: Nursing ImplicationsImplications
Be sure to teach proper application Be sure to teach proper application technique for ointments, aerosol technique for ointments, aerosol powders, etc.powders, etc.
Emphasize hand washing before and after Emphasize hand washing before and after administration of medications to prevent administration of medications to prevent site contamination and spread of infection.site contamination and spread of infection.
Patients should wear a glove or finger cot Patients should wear a glove or finger cot when applying ointments or solutions to when applying ointments or solutions to affected areas.affected areas.
Antivirals: Nursing Antivirals: Nursing ImplicationsImplications
Instruct patients to consult their Instruct patients to consult their physician before taking any other physician before taking any other medication, including OTC medications.medication, including OTC medications.
Emphasize the importance of good Emphasize the importance of good hygiene.hygiene.
Inform patients that antiviral agents Inform patients that antiviral agents are not cures, but do help to manage are not cures, but do help to manage symptoms.symptoms.
Antivirals: Nursing Antivirals: Nursing ImplicationsImplications
Instruct patients on the importance of taking Instruct patients on the importance of taking these medications exactly as prescribed and these medications exactly as prescribed and for the full course of treatment.for the full course of treatment.
With zidovudine:With zidovudine: Inform patients that hair loss MAY occur so Inform patients that hair loss MAY occur so
that they are prepared for this rare adverse that they are prepared for this rare adverse reaction.reaction.
This medication should be taken on an This medication should be taken on an empty stomach.empty stomach.
Antivirals: Nursing Antivirals: Nursing ImplicationsImplications
Monitor for side effects:Monitor for side effects: effects are varied and specific to each effects are varied and specific to each
agentagent
Antivirals: Nursing Antivirals: Nursing ImplicationsImplications
Monitor for therapeutic effects:Monitor for therapeutic effects: effects will vary depending on the type of effects will vary depending on the type of
viral infectionviral infection Effects range from delayed progression of Effects range from delayed progression of
AIDS AIDS and ARC to decrease in flu-like symptoms, and ARC to decrease in flu-like symptoms, decreased frequency of herpes-like flare-decreased frequency of herpes-like flare-ups, ups, or crusting over of herpetic lesions.or crusting over of herpetic lesions.
Antitubercular AgentsAntitubercular Agents
Antitubercular AgentsAntitubercular Agents
Tuberculosis, “TB”Tuberculosis, “TB” Caused by Mycobacterium Caused by Mycobacterium
tuberculosistuberculosis Antitubercular agents treat all forms Antitubercular agents treat all forms
of mycobacteriumof mycobacterium
Mycobacterium InfectionsMycobacterium Infections
Common Infection SitesCommon Infection Sites lung (primary site)lung (primary site) brainbrain bonebone liverliver kidneykidney
Mycobacterium InfectionsMycobacterium Infections
Aerobic bacillusAerobic bacillus Passed from infected:Passed from infected:
HumansHumans Cows (bovine)Cows (bovine) Birds (avian)Birds (avian)
Mycobacterium InfectionsMycobacterium Infections
Tubercle bacilli are conveyed by droplets.Tubercle bacilli are conveyed by droplets. Droplets are expelled by coughing or sneezing, Droplets are expelled by coughing or sneezing,
then gain entry into the body then gain entry into the body by inhalation.by inhalation.
Tubercle bacilli then spread to other body Tubercle bacilli then spread to other body organs organs via blood and lymphatic systems.via blood and lymphatic systems.
Tubercle bacilli may become dormant, or Tubercle bacilli may become dormant, or walled walled off by calcified or fibrous tissue.off by calcified or fibrous tissue.
Antitubercular AgentsAntitubercular Agents
Primary AgentsPrimary Agents Secondary AgentsSecondary Agentsisoniazid*isoniazid* capreomycincapreomycin
ethambutolethambutol cycloserinecycloserine
pyrazinamide (PZA)pyrazinamide (PZA) ethionamideethionamide
rifampinrifampin kanamycinkanamycin
streptomycinstreptomycin para-aminosalicyclic para-aminosalicyclic acidacid (PSA)(PSA)
*most frequently used*most frequently used
Antitubercular Agents: Antitubercular Agents: Mechanism of ActionMechanism of Action
Three GroupsThree Groups Protein wall synthesis inhibitors Protein wall synthesis inhibitors
streptomycin, kanamycin, capreomycin, streptomycin, kanamycin, capreomycin, rifampin, rifabutinrifampin, rifabutin
Cell wall synthesis inhibitors cycloserine, Cell wall synthesis inhibitors cycloserine, ethionamide, isoniazidethionamide, isoniazid
Other mechanisms of actionOther mechanisms of action
Antitubercular Agents:Antitubercular Agents:Mechanism of Action Mechanism of Action
isoniazid (INH)isoniazid (INH) Drug of choice for TBDrug of choice for TB Resistant strains of mycobacterium Resistant strains of mycobacterium
emergingemerging Metabolized in the liver through Metabolized in the liver through
acetylation—watch for “slow acetylation—watch for “slow acetylators”acetylators”
Used for the prophylaxisUsed for the prophylaxisor treatment of TBor treatment of TB
Antitubercular Antitubercular Agents:Agents:
Therapeutic UsesTherapeutic Uses
Antitubercular TherapyAntitubercular Therapy
Effectiveness depends upon:Effectiveness depends upon: Type of infectionType of infection Adequate dosingAdequate dosing Sufficient duration of treatmentSufficient duration of treatment Drug complianceDrug compliance Selection of an effective drug Selection of an effective drug
combinationcombination
Antitubercular Agents: Side Antitubercular Agents: Side EffectsEffects
INHINHperipheral neuritis, hepatotoxicityperipheral neuritis, hepatotoxicity
ethambutolethambutolretrobulbar neuritis, blindnessretrobulbar neuritis, blindness
rifampinrifampinhepatitis, discoloration of urine, hepatitis, discoloration of urine, stoolsstools
Antitubercular Agents: Antitubercular Agents: Nursing ImplicationsNursing Implications
Obtain a thorough medical history and Obtain a thorough medical history and assessment.assessment.
Perform liver function studies in patients Perform liver function studies in patients who are to receive isoniazid or rifampin who are to receive isoniazid or rifampin (especially in elderly patients or those who (especially in elderly patients or those who use alcohol daily).use alcohol daily).
Assess for contraindications to the various Assess for contraindications to the various agents, conditions for cautious use, and agents, conditions for cautious use, and potential drug interactions.potential drug interactions.
Antitubercular Agents: Antitubercular Agents: Nursing ImplicationsNursing Implications
Patient education is CRITICAL:Patient education is CRITICAL: Therapy may last for up to 24 months.Therapy may last for up to 24 months. Take medications exactly as ordered, Take medications exactly as ordered,
at the same time every day.at the same time every day. Emphasize the importance of strict Emphasize the importance of strict
compliance compliance to regimen for improvement of condition to regimen for improvement of condition or cure.or cure.
Antitubercular Agents: Antitubercular Agents: Nursing ImplicationsNursing Implications
Patient education is CRITICAL:Patient education is CRITICAL: Remind patients that they are contagious Remind patients that they are contagious
during during the initial period of their illness—instruct in the initial period of their illness—instruct in proper hygiene and prevention of the proper hygiene and prevention of the spread of infected droplets.spread of infected droplets.
Emphasize to patients to take care of Emphasize to patients to take care of themselves, including adequate nutrition themselves, including adequate nutrition and rest.and rest.
Antitubercular Agents: Antitubercular Agents: Nursing ImplicationsNursing Implications
Patients should not consume alcohol while Patients should not consume alcohol while on these medications nor take other on these medications nor take other medications, including OTC, unless they medications, including OTC, unless they check with their physician.check with their physician.
Diabetic patients taking INH should monitor Diabetic patients taking INH should monitor their blood glucose levels because their blood glucose levels because hyperglycemia may occur.hyperglycemia may occur.
INH and rifampin cause oral contraceptives INH and rifampin cause oral contraceptives to become ineffective; another form of birth to become ineffective; another form of birth control control will be needed.will be needed.
Antitubercular Agents: Antitubercular Agents: Nursing ImplicationsNursing Implications
Patients who are taking rifampin should be Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, told that their urine, stool, saliva, sputum, sweat, or tears may become reddish-sweat, or tears may become reddish-orange; even contact lenses may be orange; even contact lenses may be stained.stained.
Vitamin BVitamin B66 may is needed to combat may is needed to combat peripheral neuritis associated with INH peripheral neuritis associated with INH therapy.therapy.
Antitubercular Agents:Antitubercular Agents:Nursing ImplicationsNursing Implications
Monitor for side effectsMonitor for side effects Instruct patients on the side effects that Instruct patients on the side effects that
should be reported to the physician should be reported to the physician immediately.immediately.
These include fatigue, nausea, vomiting, These include fatigue, nausea, vomiting, numbness and tingling of the extremities, numbness and tingling of the extremities, fever, loss of appetite, depression, fever, loss of appetite, depression, jaundice.jaundice.
Antitubercular Agents:Antitubercular Agents:Nursing ImplicationsNursing Implications
Monitor for therapeutic effects:Monitor for therapeutic effects: Decrease in symptoms of TB, such as Decrease in symptoms of TB, such as
cough cough and feverand fever
Lab studies (culture and sensitivity tests) Lab studies (culture and sensitivity tests) and CXR should confirm clinical findingsand CXR should confirm clinical findings
Watch for lack of clinical response to Watch for lack of clinical response to therapy, indicating possible drug therapy, indicating possible drug resistanceresistance
Antimalarial, Antimalarial, Antiprotozoal, and Antiprotozoal, and
Antihelmintic AgentsAntihelmintic Agents
Protozoal InfectionsProtozoal Infections
Parasitic protozoa: live in or on Parasitic protozoa: live in or on humanshumans
malariamalaria leishmaniasisleishmaniasis amebiasisamebiasis giardiasisgiardiasis trichomoniasistrichomoniasis
MalariaMalaria
Caused by the plasmodium protozoa.Caused by the plasmodium protozoa. Four different plasmodium species.Four different plasmodium species. Cause: the bite of an infected adult Cause: the bite of an infected adult
mosquito.mosquito. Can also be transmitted by infected Can also be transmitted by infected
individuals via blood transfusion, individuals via blood transfusion, congenitally, or via infected needles congenitally, or via infected needles by drug abusers.by drug abusers.
Malarial Parasite Malarial Parasite (plasmodium)(plasmodium)
Two Interdependent Life CyclesTwo Interdependent Life Cycles Sexual cycle: in the mosquitoSexual cycle: in the mosquito Asexual cycle: in the humanAsexual cycle: in the human
Knowledge of the life cycles is essential Knowledge of the life cycles is essential in understanding antimalarial drug in understanding antimalarial drug treatment.treatment.
Drugs are only effective during the Drugs are only effective during the asexual cycle.asexual cycle.
Plasmodium Life CyclePlasmodium Life Cycle
Asexual cycle: two phasesAsexual cycle: two phases Exoerythrocytic phase:Exoerythrocytic phase:occurs “outside” occurs “outside”
the erythrocytethe erythrocyte Erythrocytic phase:Erythrocytic phase: occurs “inside” occurs “inside”
the erythrocytethe erythrocyte
Erythrocytes = RBCsErythrocytes = RBCs
Antimalarial AgentsAntimalarial Agents
Attack the parasite during the asexual Attack the parasite during the asexual phase, when it is phase, when it is vulnerablevulnerable
Erythrocytic phase drugs: chloroquine, Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquinehydroxychloroquine, quinine, mefloquine
Exoerythrocytic phase drug: primaquineExoerythrocytic phase drug: primaquine
May be used together for synergistic or additive May be used together for synergistic or additive killing power.killing power.
Antimalarials: Antimalarials: Mechanism of ActionMechanism of Action
4-aminoquinoline derivatives chloroquine 4-aminoquinoline derivatives chloroquine and hydroxychloroquineand hydroxychloroquine
Bind to parasite nucleoproteins and interfere with Bind to parasite nucleoproteins and interfere with protein synthesis.protein synthesis.
Prevent vital parasite-sustaining substances from Prevent vital parasite-sustaining substances from being formed.being formed.
Alter pH within the parasite.Alter pH within the parasite.
Interfere with parasite’s ability to metabolize andInterfere with parasite’s ability to metabolize anduse erythrocyte hemoglobin.use erythrocyte hemoglobin.
Effective only during the erythrocytic phaseEffective only during the erythrocytic phase
Antimalarials: Mechanism of Antimalarials: Mechanism of ActionAction
4-aminoquinoline derivatives quinine 4-aminoquinoline derivatives quinine and mefloquineand mefloquine
Alter pH within the parasite.Alter pH within the parasite. Interfere with parasite’s ability to Interfere with parasite’s ability to
metabolize and use erythrocyte metabolize and use erythrocyte hemoglobin.hemoglobin.
Effective only during the erythrocytic Effective only during the erythrocytic phase.phase.
Antimalarials: Mechanism of Antimalarials: Mechanism of Action Action
diaminophyrimidines pyrimethamine and diaminophyrimidines pyrimethamine and trimethoprimtrimethoprim
Inhibit dihydrofolate reductase in the parasite.Inhibit dihydrofolate reductase in the parasite. This enzyme is needed by the parasite to make This enzyme is needed by the parasite to make
essential substances.essential substances. Also blocks the synthesis of tetrahydrofolate.Also blocks the synthesis of tetrahydrofolate.
These agents may be used with sulfadoxine or These agents may be used with sulfadoxine or dapsone dapsone for synergistic effects.for synergistic effects.
Antimalarials: Mechanism Antimalarials: Mechanism of Actionof Action
primaquineprimaquine Only exoerythrocytic drug.Only exoerythrocytic drug. Binds and alters DNA.Binds and alters DNA.
sulfonamides, tetracyclines, sulfonamides, tetracyclines, clindamycinclindamycin
Used in combination with antimalarials to Used in combination with antimalarials to increase protozoacidal effectsincrease protozoacidal effects
Antimalarials: Drug EffectsAntimalarials: Drug Effects
Kill parasitic organisms.Kill parasitic organisms. Chloroquine and hydroxychloroquine Chloroquine and hydroxychloroquine
also have antiinflammatory effects.also have antiinflammatory effects.
Antimalarials: Therapeutic Antimalarials: Therapeutic UsesUses
Used to kill plasmodium organisms, the Used to kill plasmodium organisms, the parasites that cause malaria.parasites that cause malaria.
The drugs have varying effectiveness on The drugs have varying effectiveness on the different malaria organisms.the different malaria organisms.
Some agents are used for prophylaxis Some agents are used for prophylaxis against malaria.against malaria.
Chloroquine is also used for rheumatoid Chloroquine is also used for rheumatoid arthritis and lupus.arthritis and lupus.
Antimalarials: Side EffectsAntimalarials: Side Effects
Many side effects for the various Many side effects for the various agentsagents
Primarily gastrointestinal: nausea, Primarily gastrointestinal: nausea, vomiting, diarrhea,vomiting, diarrhea, anorexia, and anorexia, and abdominal painabdominal pain
AntiprotozoalsAntiprotozoals
atovaquone (Mepron)atovaquone (Mepron) metronidazole (Flagyl)metronidazole (Flagyl) pentamidine (Pentam)pentamidine (Pentam) iodoquinol (Yodoxin, Di-Quinol)iodoquinol (Yodoxin, Di-Quinol) paromomycin (Humatin)paromomycin (Humatin)
Protozoal InfectionsProtozoal Infections
amebiasisamebiasis giardiasisgiardiasis pneumocystosispneumocystosis toxoplasmosistoxoplasmosis trichomoniasistrichomoniasis
Protozoal InfectionsProtozoal Infections
TransmissionTransmission Person-to-personPerson-to-person Ingestion of contaminated water or foodIngestion of contaminated water or food Direct contact with the parasiteDirect contact with the parasite Insect bite (mosquito or tick)Insect bite (mosquito or tick)
Antiprotozoals: Antiprotozoals: Mechanism of Action Mechanism of Action and Uses atovaquone and Uses atovaquone
(Mepron)(Mepron) Protozoal energy comes from the Protozoal energy comes from the mitochondriamitochondria
Atovaquone: selective inhibition of Atovaquone: selective inhibition of mitochondrial electron transportmitochondrial electron transport
Result: no energy, leading to cellular Result: no energy, leading to cellular deathdeath
Used to treat mild to moderate P. carinii Used to treat mild to moderate P. carinii
Antiprotozoals: Antiprotozoals: Mechanism of Action and Mechanism of Action and
Uses metronidazoleUses metronidazole Disruption of DNA synthesis as well as Disruption of DNA synthesis as well as
nucleic acid synthesisnucleic acid synthesis Bactericidal, amebicidal, Bactericidal, amebicidal,
trichomonacidaltrichomonacidal
Used for treatment of trichomoniasis, Used for treatment of trichomoniasis, amebiasis, giardiasis, anaerobic amebiasis, giardiasis, anaerobic infections, and antibiotic-associated infections, and antibiotic-associated pseudomembranous colitispseudomembranous colitis
Antiprotozoals: Antiprotozoals: Mechanism of Action and Mechanism of Action and
Uses pentamidineUses pentamidine Inhibits DNA and RNAInhibits DNA and RNA
Binds to and aggregates ribosomesBinds to and aggregates ribosomes
Directly lethal to Pneumocystis cariniiDirectly lethal to Pneumocystis carinii
Inhibits glucose metabolism, protein and RNA Inhibits glucose metabolism, protein and RNA synthesis, and intracellular amino acid synthesis, and intracellular amino acid transporttransport
Mainly used to treat P. carinii pneumonia Mainly used to treat P. carinii pneumonia and other protozoal infectionsand other protozoal infections
Antiprotozoals: Mechanism Antiprotozoals: Mechanism of Action of Action
and Uses iodoquinol and Uses iodoquinol (Yodoxin, Di-Quinol)(Yodoxin, Di-Quinol) ““Luminal” or “contact” amebicideLuminal” or “contact” amebicide
Acts primarily in the intestinal lumen Acts primarily in the intestinal lumen of the infected hostof the infected host
Directly kills the protozoaDirectly kills the protozoa
Used to treat intestinal amebiasisUsed to treat intestinal amebiasis
Antiprotozoals: Antiprotozoals: Mechanism of Action and Mechanism of Action and
Uses paromomycinUses paromomycin ““Luminal” or “contact” amebicideLuminal” or “contact” amebicide Kills by inhibiting protein synthesisKills by inhibiting protein synthesis
Used to treat amebiasis and intestinal Used to treat amebiasis and intestinal protozoal infections, and also adjunct protozoal infections, and also adjunct therapy in management of hepatic comatherapy in management of hepatic coma
Antiprotozoals: Side EffectsAntiprotozoals: Side Effects
atovaquoneatovaquone nausea, vomiting, diarrhea, anorexianausea, vomiting, diarrhea, anorexia
metronidazolemetronidazole metallic taste, nausea, vomiting, diarrhea, metallic taste, nausea, vomiting, diarrhea,
abdominal crampsabdominal cramps
iodoquinoliodoquinol nausea, vomiting, diarrhea, anorexia, nausea, vomiting, diarrhea, anorexia,
agranulocytosisagranulocytosis
Antiprotozoals: Side EffectsAntiprotozoals: Side Effects
pentamidinepentamidine bronchospasms, leukopenia, bronchospasms, leukopenia,
thrombocytopenia, acute pancreatitis, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver function acute renal failure, increased liver function studiesstudies
paromomycinparomomycin nausea, vomiting, diarrhea, stomach nausea, vomiting, diarrhea, stomach
crampscramps
AntihelminticsAntihelmintics
diethylcarbamazine (Hetrazan)diethylcarbamazine (Hetrazan) mebendazole (Vermox)mebendazole (Vermox) niclosamide (Niclocide)niclosamide (Niclocide) oxamniquine (Vansil)oxamniquine (Vansil) piperazine (Vermizine)piperazine (Vermizine) praziquantel (Biltricide)praziquantel (Biltricide) pyrantel (Antiminth)pyrantel (Antiminth) thiabendazole (Mintezol)thiabendazole (Mintezol)
AntihelminticsAntihelmintics
Drugs used to treat parasitic worm Drugs used to treat parasitic worm infections: helmintic infectionsinfections: helmintic infections
Unlike protozoa, helminths are large Unlike protozoa, helminths are large and have complex cellular structuresand have complex cellular structures
Drug treatment is very specificDrug treatment is very specific
AntihelminticsAntihelmintics
It is VERY IMPORTANT to identify the It is VERY IMPORTANT to identify the causative wormcausative worm
Done by finding the parasite ova or Done by finding the parasite ova or larvae in feces, urine, blood, larvae in feces, urine, blood, sputum, or tissuesputum, or tissue cestodes (tapeworms)cestodes (tapeworms) nematodes (roundworms)nematodes (roundworms) trematodes (flukes)trematodes (flukes)
Antihelmintics: Mechanism Antihelmintics: Mechanism of Action and Usesof Action and Uses
diethylcarbamazine (Hetrazan)diethylcarbamazine (Hetrazan)
Inhibits rate of embryogenesisInhibits rate of embryogenesis
thiabendazole (Mintezol)thiabendazole (Mintezol) Inhibits the helminth-specific enzyme, fumarate Inhibits the helminth-specific enzyme, fumarate
reductasereductase
Both used for nematodes Both used for nematodes (tissue and some roundworms)(tissue and some roundworms)
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
piperazine (Vermizine) and pyrantel piperazine (Vermizine) and pyrantel (Antiminth)(Antiminth)
Blocks acetylcholine at the neuromuscular Blocks acetylcholine at the neuromuscular junction, resulting in paralysis of the junction, resulting in paralysis of the worms, which are then expelled through worms, which are then expelled through the GI tractthe GI tract
Used to treat nematodes (giant worm and Used to treat nematodes (giant worm and pinworm)pinworm)
Pin wormsPin worms
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
mebendazole (Vermox)mebendazole (Vermox) Inhibits uptake of glucose and other Inhibits uptake of glucose and other
nutrients, leading to autolysis and death of nutrients, leading to autolysis and death of the parasitic wormthe parasitic worm
Used to treat cestodes and nematodesUsed to treat cestodes and nematodes
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
niclosamide (Niclocide)niclosamide (Niclocide) Causes the worm to become dislodged Causes the worm to become dislodged
from the GI wallfrom the GI wall They are then digested in the intestines They are then digested in the intestines
and expelledand expelled
Used to treat cestodesUsed to treat cestodes
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
oxamniquine (Vansil) and praziquantel oxamniquine (Vansil) and praziquantel (Biltricide)(Biltricide)
Cause paralysis of worms’ musculature and Cause paralysis of worms’ musculature and immobilization of their suckersimmobilization of their suckers
Cause worms to dislodge from mesenteric Cause worms to dislodge from mesenteric veins veins to the liver, then killed by host tissue reactionsto the liver, then killed by host tissue reactions
Used to treat trematodes, cestodes Used to treat trematodes, cestodes (praziquantel only)(praziquantel only)
Antihelmintics: Side EffectsAntihelmintics: Side Effects
niclosamide, oxamniquine, niclosamide, oxamniquine, praziquantel, thiabendazole, praziquantel, thiabendazole, piperazine, pyrantelpiperazine, pyrantel
nausea, vomiting, diarrhea, dizziness, nausea, vomiting, diarrhea, dizziness, headacheheadache
mebendazolemebendazole diarrhea, abdominal pain, tissue necrosisdiarrhea, abdominal pain, tissue necrosis
Antimalarial, Antiprotozoal, Antimalarial, Antiprotozoal, Antihelmintic Agents: Antihelmintic Agents: Nursing ImplicationsNursing Implications
Before beginning therapy, perform a Before beginning therapy, perform a thorough health history and thorough health history and medication history, and assess for medication history, and assess for allergies.allergies.
Check baseline VS.Check baseline VS. Check for conditions that may Check for conditions that may
contraindicate use, and for potential contraindicate use, and for potential drug interactions.drug interactions.
Antimalarial, Antiprotozoal, Antimalarial, Antiprotozoal, Antihelmintic Agents: Antihelmintic Agents: Nursing ImplicationsNursing Implications
Some agents may cause the urine to Some agents may cause the urine to have an asparagus-like odor, or cause an have an asparagus-like odor, or cause an unusual skin odor, or a metallic taste; be unusual skin odor, or a metallic taste; be sure to warn the patient ahead of time.sure to warn the patient ahead of time.
Administer ALL agents as ordered and for Administer ALL agents as ordered and for the prescribed length of time.the prescribed length of time.
Most agents should be taken with food to Most agents should be taken with food to reduce GI upset.reduce GI upset.
Antimalarial Agents: Antimalarial Agents: Nursing ImplicationsNursing Implications
Assess for presence of malarial Assess for presence of malarial symptoms.symptoms.
When used for prophylaxis, these When used for prophylaxis, these agents should be started 2 weeks agents should be started 2 weeks before potential exposure to malaria, before potential exposure to malaria, and for 8 weeks after leaving the area.and for 8 weeks after leaving the area.
Medications are taken weekly, with 8 Medications are taken weekly, with 8 ounces of water.ounces of water.
Antimalarial Agents: Antimalarial Agents: Nursing ImplicationsNursing Implications
Instruct patient to notify physician Instruct patient to notify physician immediately if ringing in the ears, immediately if ringing in the ears, hearing decrease, visual difficulties, hearing decrease, visual difficulties, nausea, vomiting, profuse diarrhea, or nausea, vomiting, profuse diarrhea, or abdominal pain occur.abdominal pain occur.
Alert patients to the possible recurrence Alert patients to the possible recurrence of the symptoms of malaria so that they of the symptoms of malaria so that they will know to seek immediate treatment.will know to seek immediate treatment.
Antimalarial, Antiprotozoal, Antimalarial, Antiprotozoal, Antihelmintic Agents: Antihelmintic Agents: Nursing ImplicationsNursing Implications
Monitor for side effects:Monitor for side effects: Ensure that patients know the side effects Ensure that patients know the side effects
that should be reported.that should be reported. Monitor for therapeutic effects and Monitor for therapeutic effects and
adverse effects with long-term therapy.adverse effects with long-term therapy.
Antimalarial, Antimalarial, Antiprotozoal, and Antiprotozoal, and
Antihelmintic AgentsAntihelmintic Agents
Protozoal InfectionsProtozoal Infections
Parasitic protozoa: live in or on Parasitic protozoa: live in or on humanshumans
malariamalaria leishmaniasisleishmaniasis amebiasisamebiasis giardiasisgiardiasis trichomoniasistrichomoniasis
Malaria Endemic countriesMalaria Endemic countries
MalariaMalaria
Caused by the plasmodium protozoa.Caused by the plasmodium protozoa. Four different plasmodium species.Four different plasmodium species. Cause: the bite of an infected adult Cause: the bite of an infected adult
mosquito.mosquito. Can also be transmitted by infected Can also be transmitted by infected
individuals via blood transfusion, individuals via blood transfusion, congenitally, or via infected needles congenitally, or via infected needles by drug abusers.by drug abusers.
Malarial Parasite Malarial Parasite (plasmodium)(plasmodium)
Two Interdependent Life CyclesTwo Interdependent Life Cycles Sexual cycle: in the mosquitoSexual cycle: in the mosquito Asexual cycle: in the humanAsexual cycle: in the human
Knowledge of the life cycles is essential Knowledge of the life cycles is essential in understanding antimalarial drug in understanding antimalarial drug treatment.treatment.
Drugs are only effective during the Drugs are only effective during the asexual cycle.asexual cycle.
Malaria CycleMalaria Cycle
Plasmodium Life CyclePlasmodium Life Cycle
Asexual cycle: two phasesAsexual cycle: two phases Exoerythrocytic phase:Exoerythrocytic phase:occurs “outside” occurs “outside”
the erythrocytethe erythrocyte Erythrocytic phase:Erythrocytic phase: occurs “inside” occurs “inside”
the erythrocytethe erythrocyte
Erythrocytes = RBCsErythrocytes = RBCs
Antimalarial AgentsAntimalarial Agents
Attack the parasite during the asexual Attack the parasite during the asexual phase, when it is phase, when it is vulnerablevulnerable
Erythrocytic phase drugs: chloroquine, Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquinehydroxychloroquine, quinine, mefloquine
Exoerythrocytic phase drug: primaquineExoerythrocytic phase drug: primaquine
May be used together for synergistic or additive May be used together for synergistic or additive killing power.killing power.
Antimalarials: Antimalarials: Mechanism of ActionMechanism of Action
4-aminoquinoline derivatives chloroquine 4-aminoquinoline derivatives chloroquine and hydroxychloroquineand hydroxychloroquine
Bind to parasite nucleoproteins and interfere with Bind to parasite nucleoproteins and interfere with protein synthesis.protein synthesis.
Prevent vital parasite-sustaining substances from Prevent vital parasite-sustaining substances from being formed.being formed.
Alter pH within the parasite.Alter pH within the parasite.
Interfere with parasite’s ability to metabolize andInterfere with parasite’s ability to metabolize anduse erythrocyte hemoglobin.use erythrocyte hemoglobin.
Effective only during the erythrocytic phaseEffective only during the erythrocytic phase
Antimalarials: Mechanism of Antimalarials: Mechanism of ActionAction
4-aminoquinoline derivatives quinine 4-aminoquinoline derivatives quinine and mefloquineand mefloquine
Alter pH within the parasite.Alter pH within the parasite. Interfere with parasite’s ability to Interfere with parasite’s ability to
metabolize and use erythrocyte metabolize and use erythrocyte hemoglobin.hemoglobin.
Effective only during the erythrocytic Effective only during the erythrocytic phase.phase.
Antimalarials: Mechanism of Antimalarials: Mechanism of Action Action
diaminophyrimidines pyrimethamine and diaminophyrimidines pyrimethamine and trimethoprimtrimethoprim
Inhibit dihydrofolate reductase in the parasite.Inhibit dihydrofolate reductase in the parasite. This enzyme is needed by the parasite to make This enzyme is needed by the parasite to make
essential substances.essential substances. Also blocks the synthesis of tetrahydrofolate.Also blocks the synthesis of tetrahydrofolate.
These agents may be used with sulfadoxine or These agents may be used with sulfadoxine or dapsone dapsone for synergistic effects.for synergistic effects.
Antimalarials: Mechanism Antimalarials: Mechanism of Actionof Action
primaquineprimaquine Only exoerythrocytic drug.Only exoerythrocytic drug. Binds and alters DNA.Binds and alters DNA.
sulfonamides, tetracyclines, sulfonamides, tetracyclines, clindamycinclindamycin
Used in combination with antimalarials to Used in combination with antimalarials to increase protozoacidal effectsincrease protozoacidal effects
Antimalarials: Drug EffectsAntimalarials: Drug Effects
Kill parasitic organisms.Kill parasitic organisms. Chloroquine and hydroxychloroquine Chloroquine and hydroxychloroquine
also have antiinflammatory effects.also have antiinflammatory effects.
Antimalarials: Therapeutic Antimalarials: Therapeutic UsesUses
Used to kill plasmodium organisms, the Used to kill plasmodium organisms, the parasites that cause malaria.parasites that cause malaria.
The drugs have varying effectiveness on The drugs have varying effectiveness on the different malaria organisms.the different malaria organisms.
Some agents are used for prophylaxis Some agents are used for prophylaxis against malaria.against malaria.
Chloroquine is also used for rheumatoid Chloroquine is also used for rheumatoid arthritis and lupus.arthritis and lupus.
Antimalarials: Side EffectsAntimalarials: Side Effects
Many side effects for the various Many side effects for the various agentsagents
Primarily gastrointestinal: nausea, Primarily gastrointestinal: nausea, vomiting, diarrhea,vomiting, diarrhea, anorexia, and anorexia, and abdominal painabdominal pain
AntiprotozoalsAntiprotozoals
atovaquone (Mepron)atovaquone (Mepron) metronidazole (Flagyl)metronidazole (Flagyl) pentamidine (Pentam)pentamidine (Pentam) iodoquinol (Yodoxin, Di-Quinol)iodoquinol (Yodoxin, Di-Quinol) paromomycin (Humatin)paromomycin (Humatin)
Protozoal InfectionsProtozoal Infections
amebiasisamebiasis giardiasisgiardiasis pneumocystosispneumocystosis toxoplasmosistoxoplasmosis trichomoniasistrichomoniasis
Protozoal InfectionsProtozoal Infections
TransmissionTransmission Person-to-personPerson-to-person Ingestion of contaminated water or foodIngestion of contaminated water or food Direct contact with the parasiteDirect contact with the parasite Insect bite (mosquito or tick)Insect bite (mosquito or tick)
Antiprotozoals: Antiprotozoals: Mechanism of Action Mechanism of Action and Uses atovaquone and Uses atovaquone
(Mepron)(Mepron) Protozoal energy comes from the Protozoal energy comes from the mitochondriamitochondria
Atovaquone: selective inhibition of Atovaquone: selective inhibition of mitochondrial electron transportmitochondrial electron transport
Result: no energy, leading to cellular Result: no energy, leading to cellular deathdeath
Used to treat mild to moderate P. carinii Used to treat mild to moderate P. carinii
Antiprotozoals: Antiprotozoals: Mechanism of Action and Mechanism of Action and
Uses metronidazoleUses metronidazole Disruption of DNA synthesis as well as Disruption of DNA synthesis as well as
nucleic acid synthesisnucleic acid synthesis Bactericidal, amebicidal, Bactericidal, amebicidal,
trichomonacidaltrichomonacidal
Used for treatment of trichomoniasis, Used for treatment of trichomoniasis, amebiasis, giardiasis, anaerobic amebiasis, giardiasis, anaerobic infections, and antibiotic-associated infections, and antibiotic-associated pseudomembranous colitispseudomembranous colitis
Antiprotozoals: Antiprotozoals: Mechanism of Action and Mechanism of Action and
Uses pentamidineUses pentamidine Inhibits DNA and RNAInhibits DNA and RNA
Binds to and aggregates ribosomesBinds to and aggregates ribosomes
Directly lethal to Pneumocystis cariniiDirectly lethal to Pneumocystis carinii
Inhibits glucose metabolism, protein and RNA Inhibits glucose metabolism, protein and RNA synthesis, and intracellular amino acid synthesis, and intracellular amino acid transporttransport
Mainly used to treat P. carinii pneumonia Mainly used to treat P. carinii pneumonia and other protozoal infectionsand other protozoal infections
Antiprotozoals: Mechanism Antiprotozoals: Mechanism of Action of Action
and Uses iodoquinol and Uses iodoquinol (Yodoxin, Di-Quinol)(Yodoxin, Di-Quinol) ““Luminal” or “contact” amebicideLuminal” or “contact” amebicide
Acts primarily in the intestinal lumen Acts primarily in the intestinal lumen of the infected hostof the infected host
Directly kills the protozoaDirectly kills the protozoa
Used to treat intestinal amebiasisUsed to treat intestinal amebiasis
Antiprotozoals: Antiprotozoals: Mechanism of Action and Mechanism of Action and
Uses paromomycinUses paromomycin ““Luminal” or “contact” amebicideLuminal” or “contact” amebicide Kills by inhibiting protein synthesisKills by inhibiting protein synthesis
Used to treat amebiasis and intestinal Used to treat amebiasis and intestinal protozoal infections, and also adjunct protozoal infections, and also adjunct therapy in management of hepatic comatherapy in management of hepatic coma
Antiprotozoals: Side EffectsAntiprotozoals: Side Effects
atovaquoneatovaquone nausea, vomiting, diarrhea, anorexianausea, vomiting, diarrhea, anorexia
metronidazolemetronidazole metallic taste, nausea, vomiting, diarrhea, metallic taste, nausea, vomiting, diarrhea,
abdominal crampsabdominal cramps
iodoquinoliodoquinol nausea, vomiting, diarrhea, anorexia, nausea, vomiting, diarrhea, anorexia,
agranulocytosisagranulocytosis
Antiprotozoals: Side EffectsAntiprotozoals: Side Effects
pentamidinepentamidine bronchospasms, leukopenia, bronchospasms, leukopenia,
thrombocytopenia, acute pancreatitis, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver function acute renal failure, increased liver function studiesstudies
paromomycinparomomycin nausea, vomiting, diarrhea, stomach nausea, vomiting, diarrhea, stomach
crampscramps
AntihelminticsAntihelmintics
diethylcarbamazine (Hetrazan)diethylcarbamazine (Hetrazan) mebendazole (Vermox)mebendazole (Vermox) niclosamide (Niclocide)niclosamide (Niclocide) oxamniquine (Vansil)oxamniquine (Vansil) piperazine (Vermizine)piperazine (Vermizine) praziquantel (Biltricide)praziquantel (Biltricide) pyrantel (Antiminth)pyrantel (Antiminth) thiabendazole (Mintezol)thiabendazole (Mintezol)
AntihelminticsAntihelmintics
Drugs used to treat parasitic worm Drugs used to treat parasitic worm infections: helmintic infectionsinfections: helmintic infections
Unlike protozoa, helminths are large Unlike protozoa, helminths are large and have complex cellular structuresand have complex cellular structures
Drug treatment is very specificDrug treatment is very specific
AntihelminticsAntihelmintics
It is VERY IMPORTANT to identify the It is VERY IMPORTANT to identify the causative wormcausative worm
Done by finding the parasite ova or Done by finding the parasite ova or larvae in feces, urine, blood, larvae in feces, urine, blood, sputum, or tissuesputum, or tissue cestodes (tapeworms)cestodes (tapeworms) nematodes (roundworms)nematodes (roundworms) trematodes (flukes)trematodes (flukes)
Brain wormsBrain worms
Antihelmintics: Mechanism Antihelmintics: Mechanism of Action and Usesof Action and Uses
diethylcarbamazine (Hetrazan)diethylcarbamazine (Hetrazan)
Inhibits rate of embryogenesisInhibits rate of embryogenesis
thiabendazole (Mintezol)thiabendazole (Mintezol) Inhibits the helminth-specific enzyme, fumarate Inhibits the helminth-specific enzyme, fumarate
reductasereductase
Both used for nematodes Both used for nematodes (tissue and some roundworms)(tissue and some roundworms)
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
piperazine (Vermizine) and pyrantel piperazine (Vermizine) and pyrantel (Antiminth)(Antiminth)
Blocks acetylcholine at the neuromuscular Blocks acetylcholine at the neuromuscular junction, resulting in paralysis of the junction, resulting in paralysis of the worms, which are then expelled through worms, which are then expelled through the GI tractthe GI tract
Used to treat nematodes (giant worm and Used to treat nematodes (giant worm and pinworm)pinworm)
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
mebendazole (Vermox)mebendazole (Vermox) Inhibits uptake of glucose and other Inhibits uptake of glucose and other
nutrients, leading to autolysis and death of nutrients, leading to autolysis and death of the parasitic wormthe parasitic worm
Used to treat cestodes and nematodesUsed to treat cestodes and nematodes
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
niclosamide (Niclocide)niclosamide (Niclocide) Causes the worm to become dislodged Causes the worm to become dislodged
from the GI wallfrom the GI wall They are then digested in the intestines They are then digested in the intestines
and expelledand expelled
Used to treat cestodesUsed to treat cestodes
Antihelmintics: Mechanism Antihelmintics: Mechanism of Actionof Action
oxamniquine (Vansil) and praziquantel oxamniquine (Vansil) and praziquantel (Biltricide)(Biltricide)
Cause paralysis of worms’ musculature and Cause paralysis of worms’ musculature and immobilization of their suckersimmobilization of their suckers
Cause worms to dislodge from mesenteric Cause worms to dislodge from mesenteric veins veins to the liver, then killed by host tissue reactionsto the liver, then killed by host tissue reactions
Used to treat trematodes, cestodes Used to treat trematodes, cestodes (praziquantel only)(praziquantel only)
Antihelmintics: Side EffectsAntihelmintics: Side Effects
niclosamide, oxamniquine, niclosamide, oxamniquine, praziquantel, thiabendazole, praziquantel, thiabendazole, piperazine, pyrantelpiperazine, pyrantel
nausea, vomiting, diarrhea, dizziness, nausea, vomiting, diarrhea, dizziness, headacheheadache
mebendazolemebendazole diarrhea, abdominal pain, tissue necrosisdiarrhea, abdominal pain, tissue necrosis
Antimalarial, Antiprotozoal, Antimalarial, Antiprotozoal, Antihelmintic Agents: Antihelmintic Agents: Nursing ImplicationsNursing Implications
Before beginning therapy, perform a Before beginning therapy, perform a thorough health history and thorough health history and medication history, and assess for medication history, and assess for allergies.allergies.
Check baseline VS.Check baseline VS. Check for conditions that may Check for conditions that may
contraindicate use, and for potential contraindicate use, and for potential drug interactions.drug interactions.
Antimalarial, Antiprotozoal, Antimalarial, Antiprotozoal, Antihelmintic Agents: Antihelmintic Agents: Nursing ImplicationsNursing Implications
Some agents may cause the urine to Some agents may cause the urine to have an asparagus-like odor, or cause an have an asparagus-like odor, or cause an unusual skin odor, or a metallic taste; be unusual skin odor, or a metallic taste; be sure to warn the patient ahead of time.sure to warn the patient ahead of time.
Administer ALL agents as ordered and for Administer ALL agents as ordered and for the prescribed length of time.the prescribed length of time.
Most agents should be taken with food to Most agents should be taken with food to reduce GI upset.reduce GI upset.
Antimalarial Agents: Antimalarial Agents: Nursing ImplicationsNursing Implications
Assess for presence of malarial Assess for presence of malarial symptoms.symptoms.
When used for prophylaxis, these When used for prophylaxis, these agents should be started 2 weeks agents should be started 2 weeks before potential exposure to malaria, before potential exposure to malaria, and for 8 weeks after leaving the area.and for 8 weeks after leaving the area.
Medications are taken weekly, with 8 Medications are taken weekly, with 8 ounces of water.ounces of water.
Antimalarial Agents: Antimalarial Agents: Nursing ImplicationsNursing Implications
Instruct patient to notify physician Instruct patient to notify physician immediately if ringing in the ears, immediately if ringing in the ears, hearing decrease, visual difficulties, hearing decrease, visual difficulties, nausea, vomiting, profuse diarrhea, or nausea, vomiting, profuse diarrhea, or abdominal pain occur.abdominal pain occur.
Alert patients to the possible recurrence Alert patients to the possible recurrence of the symptoms of malaria so that they of the symptoms of malaria so that they will know to seek immediate treatment.will know to seek immediate treatment.
Antimalarial, Antiprotozoal, Antimalarial, Antiprotozoal, Antihelmintic Agents: Antihelmintic Agents: Nursing ImplicationsNursing Implications
Monitor for side effects:Monitor for side effects: Ensure that patients know the side effects Ensure that patients know the side effects
that should be reported.that should be reported. Monitor for therapeutic effects and Monitor for therapeutic effects and
adverse effects with long-term therapy.adverse effects with long-term therapy.