Chapter 18: non-bacterial infections Flashcards
what has extensive use of ABTs worldwide led to?
emergence of viral and fungal superinfections
What population is most affected by superinfections
immunocompromise
effective, specific agents are often based on
genetic sequencing and understanding of pathogens
how does a virus reproduce
enters a host cell and take over the cell’s protein and nucleic acid synthesis
effective antiviral agents need to stop one of the steps in the viral replication process
attachment of the virus to the host cell -release of the virus’s genes into the host cell
replication and assembly of new viral components -release of viral components into a new host cell
regimen of medications used to treat HIV
highly active antiretroviral therapy (HAART)
clinical syndrome review of HIV/AIDS
“clinical syndrome”
opportunistic infections
cancer
“set point”
HIV replication
reverse transcribe RNA genome into DNA thus reversing the usual flow of genetic information. DNA is then incorporated into host cell’s genome allowing replication
reasons for noncompliance with HIV treatment regimen
length of treatment, side effects, cost of medications,
Patient education regarding HAART treatment
how to take med
adverse effects
fitting regimen into lifestyle longterm
cost management
safe sex practices
avoiding opportunistic infections
how to live with chronic infectious disease
purpose of antiretrovirals in HIV treatment
combination of drugs to suppress viral replication to undetectable plasma HIV RNA to prevent further immune system damage as well as any possibility of emergingresistant strains
6 classes of antiretrovirals
NRTI
NNRTI
PI
CCRS
FI
INTEGRASE
most common combinations of antiretrovirals for treatment of HIV
NRTI with PI one NNRTI
initial antiretroviral regimen consist of
2 NRTIs with with either an NNRTI, PI, Integrase inhibitor, or CCR5 antagonist
examples of NRTIs
abacavir (Ziagen)
didanosine (Videx)
emtricitabine (Emtriva)
lamivudine (Retrovir)
zalcitabine (Hivid)
stavudine (Zerit)
NRTIs are synthetic agents thast mimic
natural nucleotides (building blocks of RNA)
NRTI mechanism of action
compete with natural nucleotides in the HIV virus that would otherwise be used in the reverse transcriptase enzyme in newly synthesized viral DNA chains
common adverse effects of NRTIs
rash
abdominal distress
thrombocytosis
fatigue
lactic acidosis
back pain
tremor, headache, weakness
things to watch for with NRTIs
leukopenia, anemia, anaphylaxis, heptomegaly
concomittent use of any 2 NRTIs
not recommended
labs that need monitored with antiretroviral treatment
CBC
met panal
CD4
lymphocytes
HIV levels
what else should HIV patients be tested for prior to initiating therapy
Hep B
patients on abacavir must be monitored for
signs of hypersensitivity and elevated liver function
target of PIs
later stage in viral replication cycle than NRTIs
PI mechanism of action
bind to active sites that are used by viral protease enzymes so they can’t process viral precursors critical to the maturation of an HIV virus
examples of PPIs
amprenavir (Agnerase)
atazaniavir (ATV, Reyataz)
fosamprenavir (Lexiva, Telzir)
indinavir (Crixivan)
ritonavir (Norvir)
saquinavir (Fortovase)
nelfinavir (Viracept)
hypersensitivity reactions of PIs
can be severe
interactions with drugs metabolized in the liver that can cause serious life threatening events
nonsedating antihistamines
sedative hypnotics
Astemizole, triazolam, midazolam
ergot alkaloid preparation
antiarrhythmics (amiodarone, quinidine)
CCBs
amphetamines
PI contraindications
hypersensitivity to sulfonamides
patients taking vitamin E
NNRTI mechanism of action
bind to active site of HIV reverse transcriptase
is additive or synergistic with most other antiretrovirals
examples of NNRTIs
delavirdine (Rescriptor)
evavirenz (Sustiva)
nevirapine (Viramune)
DERM side effect of NNRTIs
rash that progresses to epidermal necrosis
NNRTIs patient education
stay well hydrated to avoid renal failure
why should efavirenz be taken at bedtime
improve CNS tolerability and psychiatric effects
what follows initial herpes infection
latent state with the potential to reactivate later in life
efficacy of episodic therapy for herpes
shortens the duration of an outbreak if started within 24 hours of lesions or prodromal symptoms
mechanism of action for antivirals used for herpes infections
nucleic acid analogues host enzymes cause them to convert to active compounds and become part of the DNA chain. This inhibits viral RNA to interferen with viral DNA synthesis
examples of antivirals used to treat herpes infections
acyclovir (Zovirax)
cidofovir (Vistide)
ganciclovir (Cytovene)
famciclovir (Famvir)
penciclovir (Denavir)
foscarnet (Foscavir)
trifluridine (Viroptic)
valacyclovir (Valtrex)
valganciclovir (Valcyte)
interactions with antivirals used for herpes infections
minimal.
May affect bioavailability if acyclovir anf famciclovir are given with antihistamines
most important variable in selecting antiviral for herpes treatment
renal function
examples of antivirals used for respiratory infections
amantadine (Symmetrel)
oseltamivir (Tamiflu)
rimantadine (Flumadine)
zanamivir (Relenza)
zanamivir (Relenza) mechanism of action
prevents viral replication by inhibiting the enzyme neuraminidase
amantadine (Symmetrel) mechanism of action
dopaminergic agonsit with the ability to block the uncoating of influenza A virus
rimantadine (Flumadine) mechanism of action
tricyclic amine that affects the release of newly replicated virus strands from host cells, possibly by inhibiting uncoating of the virus
osteltamivir (Tamiflu)
analogue of sialic acid and is potent selective inhibitor of influenza A and B virus neuraminidase
clinical use for osteltamivir and zanamivir
prevention and treatment of influenza A or B
clinical use for amantadine and rimantadine
prevention and treatment for influenza A
susceptibility of vast majority of H1N1 strains
susceptible to osteltamivir and zanamivir
resistant to amantadine and rimantadine
antivirals for respiratory infections administered with antihistamines or antidepressants
cause dry mouth, blurry vision, and constipation
what drug causes increased toxicity if given with amantadine and rimantadine
triamterine
contraindications for amantadine and rimantadine
pregnancy
types of antifungals
polyene macrolides
azoles
terbinafine (Lamisil)
griseofluvin (Fluvicin)
examples of polyene macrolides
amphotericin B
Nystatin
examples of Azoles
imidazole
triazole
patient education on antivirals used for respiratory infections
only shortens flu duration by 1-2 days
alcohol compounds dizziness
take 4 hours prior to bed to avoid insomnia
drug of choice for topical fungal infections
nystatin
clinical uses of amphotericin B
cryptococcal meningitis in HIV patients
invasive and rapidly progressing, potentially fatal fungul infections
treatment of visceral leishmaniasis
polyene macrolides mechanism of action
bind to sterols in the fungal cell membrane altering the membranes permeability to K+, Mg+, and other celll components
polyene macrolide interactions
synergistic nephrotoxicity with aminoglycosides or cyclosporine
patient education about polyene macrolides
long term treatment may be necessary to clear infection (weeks to months)
azoles mechanism of action
inhibits fungal demethylase (a CYP450 dependent enzyme present in fungi) affects the synthesis of the fungal cell wall and causes leakage of cell contents
types of azoles
imidazole
triazole
examples of imidazoles
fluconazole (Diflucan)
ketoconazole (Nizoral)
itraconazole (Sporanox)
clinical uses of oral antifungals
superficial infections caused by yeast
dermatophytes, and invase systemic mycoses (page 351)
clinical uses for topical antifungals
treat tinea infections and superficial yeast infections
which antifungal should NOT be used with history of HF
itraconazole
why should coadministration of ABTs and azoles be avoided
can lead to fungal resistance and fungal superinfection
patient education: itraconazole
take with food to enhance absorption
avoid antacids within 2 hours of ingestion
terbinafine (Lamisil)
mechanism of action
synthetic allylamine that inhibits squalene 2, 3-epoxidase
(enzyme needed for cell wall synthesis)
fungicidal to a wide variety of dermatophytes
clinical uses for lamisil
superficial fungal infections of hair, nail, and skin
examples:
tinea pedic (athletes foot)
tinea cruris (jock itch)
tinea corporis (ringworm)
lamisil interactions
alcohol increases liklihood of hepatotoxicity
drugs that inhibit hepatic metabolism (cimetidine, rifampin)
caffeine can increase side effects
patient education for lamisil
notify clinician if dark urine, rash, pale stool appear
take same time every day for entire course
discuss OTC and herbal medications prior to use
griseofulvin (Fulvicin)
mechanism of action
binds to microtubules that comprise the spindles to inhibit fungal mitosis
fungistatic
what is griseofulvin NOT used for
subcutaneous or deep fungal infections
candidiasis
tinea versicolor
clinical uses of fluvicin
treatment of superficial fungal infections of hair, nails, and skin
griseofulvin interactions
reduces plasma salicylate levels when taken with ASA
oral contraceptives
reduces anticoagulant effect of warfarin
can increase effects of alcohol (tachycardia, diaphoresis, flushing)
griseofulvin contraindications
severe liver disease
active alcoholism
pregnancy
most common adverse effect of griseofulvin
skin eruptions and rash, sore throat
types of antiprotozoals
metronidazole (Flagyl)
nitazoxanide (Alinia)
tinidazole (Tindamax)
conscientious prescribing of antiprotozoals
include sexual partner in treatment for trichomoniasis
disulfiram-like reaction can occur to alcohol base in other preparations
efficacy unknown in immunocompromised patients
what should be done if antiprotozoal re-treatment is necessary
CBC
white blood cell differential
antiprotozoal patient education
avoid alcohol for at least 24 hours after last dose
expect metallic taste
may cause reddish-brown urine
take with food to avoid GI upset
metronidazole (Flagyl)
mechanism of action
anaerobic bactericide, trichomonacide, amebicide
diffuses into a susceptible organisma and disrupts DNA and protein synthesis
clinical use of flagyl
oral therapy for anaerobic infections, amebiasis, giardiasis, trichomoniasis, and colitis d/t C-diff
nitazoxanide (Alinia)
mechanism of action
interferes with the pyruvate ferrodoxin enzyme pathway
clinical uses of nitazoxanide (Alinia)
diarrhea associated with Giardia lamblia and Cryptosporidium parvum
tinidazole (Tindamax)
mechanism of action
similar to flagyl but is converted to an active metabolite by cell extracts of the pathogen
clinical uses for tinidazole (Tindamax)
intestinal amebiasis, giardiasis, and trichomoniasis
clinical uses of antiprotozoals
topically for rosacea and bacterial vaginosis
used in combo therapy for H. pylori ulcers
antiprotozoal interactions
flagyl and warfarin may induce bleeding
cimetidine may decrease metabolism of flagyl
disulfram-like reaction with alcohol
antiprotozoals contraindications
first trimester of pregnancy
lactation
antihelminthics
used to treat parasitic infections
classes of antihelminths
benzimidazoles
pyrantel pamoate
ivermectin
axamples of benzimidazoles
mebendazole (Vermox)
thiabendazole (Mintezol)
albendazole (Albenza)
appropriate treatment for all helminthic infestations except pinworms
mebendazole 100mg BID x 3days
OR
albendazole 400mg daily
most pressing concern when fighting a nematode infestation
seeing resistance develop
monitor patients closely
why should patients be monitored closely when taking a banzimidazole
propensity of medication to cause bone marrow depression, aplastic anemia, or agranulocytosis
benzimidazoles mechanism of action
each act directly on different parasites to treat systemic infections
uses for mebendazole (Vermox)
treatment of ascariasis, trichuriasis, hookworm, and pinworm infections
uses of thiabendazole (Mintezol)
treatment of strongyloidiasis (threadworm)
uses of albendazole (Albenza)
treatment of ascariasis enterobiasis (pinworm), hookworm, and after surgical removal or aspiration of hydatid cysts
antihelminths interactions
mebendazole metabolism is inhibited by cimetidine and anticonvulsants
thiabendazole and xanthine derivatives can cause toxicity
antihelminths contraindications
pregnancy
renal disease
cirrhosis
antihelminths patient education
chew tablets before swallowing
stool should be rechecked 3 days after treatment
strict hygiene to prevent reinfection
pyrantel pamoate
mechanism of action
acts as a neuromuscular blocking agent in susceotible mature and immature helminths within the GI tract
pyrantel pamoate is only effective where
within the GI lumen
clinical uses of pyrantel pamoate
pinworm, roundworm, hookworm
pyrantel and piperazine
mutually antagonize each other
ivermectin (Stromectol)
mechanims of action
related to macrolide ABTs
causes paralysis and death of parasite by binding to chloride channels in parasite’s nerve and muscle cells
clinical uses of ivermectin
river blindness (Onchocera volvulus)
control of head lice and scabies
ivermectin interactions
can affect LFTs
barbituates and benzodiazepines can cause increased sedation
ivermectin contraindications
pregnancy
lactation
drugs used to treat malaria
chloroquine
primaquine
atovaquone/proguanil (Malarone)
chloroquine mechanism of action
interfers with parasite protein synthesis and inhibits it’s growth
what is the most widely used drug to treat malaria
chloroquine
(prophylaxis and treatment)
mechanism of action for primaquine and mefloquine
destroy the asexual blood forms of malarial pathogens
inhibits parasite growth
when are primaquine and mefloquine used
when there is known resistance to chloroquine
malarone use
malria prophylaxis
antimalarial drugs when patient is on cardiac medications such as beta-blockers
take cardiac medication at least 12 hours after antimalarial
contraindications for antimalarials
history of seizures, psychiatric disorders, cardiac abnormalities
pregnancy
lab values that require d/c of antimalarial medication
drop in LFTs, HGB concentrations, or leukocyte counts
antimalarials in patients with G6PD
watch for hemolytic anemia or leukopenia
