WEEK 2 Midterm review
Know how to treat
o Different types of Tinea
Tinea pedis.
Tinea pedis, the most common fungal infection, generally responds well
... [Show More] to
topical therapy. Patients should be advised to wear absorbent cotton socks,
change their shoes often, and dry their feet after bathing.
Tinea corporis.
Tinea corporis usually responds to a topical azole or allylamine. Treatment
should continue for at least 1 week after symptoms have cleared. Severe
infection may require a systemic antifungal agent (e.g., griseofulvin).
Tinea cruris.
Tinea cruris responds well to topical therapy. Treatment should continue for at
least 1 week after symptoms have cleared. If the infection is severely inflamed,
a systemic antifungal drug (e.g., clotrimazole) may be needed; topical or
systemic glucocorticoids may be needed as well.
Tinea capitis.
Tinea capitis is difficult to treat. Topical drugs are not likely to work. Oral
griseofulvin, taken for 6 to 8 weeks, is considered standard therapy. However,
oral terbinafine, taken for only 2 to 4 weeks, may be more effective.
o Oral candidiasis
Oral candidiasis.
Oral candidiasis, also known as thrush, is seen often. Topical
agents—nystatin, clotrimazole, and miconazole—are generally
effective. In the immunocompromised host, oral therapy
with fluconazole or ketoconazole is usually required.
o Aspergillosis
Voriconazole
- Voriconazole and Phenobarbital should not be combined due to CYP450O Phenobarbital is a CYP450 inhibitors which can reduce the levels of drugs like
voriconazole.
- Adverse reactions/Patient Teaching
o Itraconazole
Adverse effects.
Itraconazole is well tolerated in usual doses. Gastrointestinal reactions (nausea,
vomiting, diarrhea) are most common. Other reactions include rash, headache,
abdominal pain, and edema. Itraconazole may also cause two potentially serious
effects: cardiac suppression and liver injury.
Cardiac suppression.
Itraconazole has negative inotropic actions that can cause a
transient decrease in ventricular ejection fraction. Cardiac
function returns to normal by 12 hours after dosing. The drug
may still be used to treat serious fungal infections in patients
with heart failure but only with careful monitoring and only if
the benefts clearly outweigh the risks. If signs and symptoms
of heart failure worsen, itraconazole should be stopped.
Black Box Warning
Negative Inotropic Actions With Itraconazole
Because of its negative inotropic actions, itraconazole should
not be used for superfcial fungal infections (dermatomycoses,
onychomycosis) in patients with heart failure, a history of heart
failure, or other indications of ventricular dysfunction.
Summary of Key Prescribing
Considerations
Azoles
Therapeutic Goal: Treatment of systemic and
superfcial mycoses.
Baseline Data: Baseline tests of liver function.Monitoring: No recommended monitoring.
Identifying High-Risk Patients: Use with great caution
in patient with liver disease.
Evaluating Therapeutic Effects: Monitor for
indications of antifungal effects—reduction in fever, pain,
or inflammation.
Minimizing Adverse Effects: Instruct patients to report
signs of liver dysfunction. Avoid use with drugs
metabolized by CYP3A4 (warfarin, cyclosporine, digoxin,
quinidine).
o Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Adverse Effects
The NRTIs share a core of adverse effects associated with mitochondrial
toxicity. Recall that mitochondria are cellular organelles that take in nutrients
and convert them into adenosine triphosphate (ATP) for energy. NRTIs can
disrupt synthesis of mitochondrial DNA and can thereby impair mitochondrial
function.
Lactic acidosis.
A major consequence of mitochondrial impairment is lactic acidosis. Lactic acid
accumulates because dysfunctional mitochondria cannot break down lactic acid.
Symptoms include nausea, malaise, fatigue, anorexia, and hyperventilation
(blowing off carbon dioxide can reduce acidosis). Left untreated, the syndrome
can be fatal. Diagnosis is based on lactic acid measurement in arterial blood.
The United States Food and Drug Administration (FDA) requires all NRTIs to
carry black box warnings about this possibility, even though it is rare for most.
Those for which this is most likely to occur are didanosine and stavudine.
Hepatic steatosis.
Hepatic steatosis (fatty degeneration of the liver) and hepatomegaly are also
adverse effects of NRTIs. This is also associated with mitochondrial impairment
because there is decreased breakdown of fatty acids by mitochondria leading to
fatty deposits in the liver.
Other adverse effects.NRTIs may also cause pancreatitis and myopathies, which are likely tied to
lactic acidosis. Adverse effects of individual NRTIs are discussed separately.
▪ Example drugs of NRTIs
At this time, seven NRTIs are available: abacavir [Ziagen],
didanosine [Videx], emtricitabine [Emtriva], lamivudine [Epivir],
stavudine [Zerit], tenofovir [Viread], and zidovudine [Retrovir].
They are commonly identifed by assigned abbreviations:
abacavir (ABC), didanosine (ddI), emtricitabine (FTC),
lamivudine (3TC), stavudine (d4T), tenofovir (TDF), and
zidovudine (ZDV).
- Diagnostics & Monitoring for anthelmintics
Summary of Key Prescribing
Considerations
Anthelmintic Drugsa
Therapeutic Goal: To eradicate parasitic worm
infestation
Baseline Data: Confrmation of infestation. Pregnancy
test. Drugs requiring additional baseline data are
albendazole (liver function and complete blood count
[CBC] with differential); mebendazole (liver function, CBC
with differential, and renal function); praziquantel (liver
function); and ivermectin and moxidectin
(ophthalmologic exam for evidence of eye infestation).
Monitoring: Drugs requiring monitoring (other than
confrmation of a cure, if needed) are: albendazole (liver
function and CBC with differential); mebendazole (liver
function, CBC with differential, and renal function);
praziquantel (liver function); and ivermectin andmoxidectin (ophthalmologic exam if abnormal at
baseline).
Identifying High-Risk Patients:
o• Albendazole – Because bone marrow
suppression, impaired liver function, and possibly
renal function may occur, patients with liver or
kidney disease, anemia, bleeding disorders, and
infections are at increased risk.
o• Mebendazole – Because bone marrow
suppression and liver impairment may occur,
patients with liver disease, anemia, bleeding
disorders, and infections are at increased risk.
o• Pyrantel pamoate – Patients with liver
impairment are at a higher risk for adverse
effects. Neonates should not be prescribed
formulations containing benzyl alcohol or its
derivatives.
o• Praziquantel – Patients with cardiac disease,
liver impairment, or seizure disorders are at
increased risk for complications.
o• Ivermectin and Moxidectin – Patients with
hypotension or taking antihypertensive drugs
may be at risk for increased hypotension and
falls.
Evaluating Therapeutic Effects: Follow-up testing
confrms cure.
Minimizing Adverse Effects: For most of these drugs,
adverse reactions do not require special treatment.
Mazzoti reactions can be treated with antihistamines and
NSAIDs. Rarely, glucocorticoids are needed. Ensuring
adequate hydration is important.
- Identifying High-Risk Patients with the following drugs
o Albendazole:
Albendazole
o Target Organismso Albendazole (Albenza) is active against many cestode
and nematode parasites, including larval forms
of Taenia solium and Echinococcus granulosus. In the
United States, the drug is approved only for (1)
parenchymal neurocysticercosis caused by larval
forms of the pork tapeworm, T. solium; and (2) cystic
hydatid disease of the liver, lung, and peritoneum
caused by larval forms of the dog tapeworm, E.
granulosus. However, despite lack of FDA
approval, albendazole is considered a drug of choice
for infestation with hookworms, pinworms,
whipworms, Chinese liver flukes, giant roundworms,
and pork roundworms, the cause of trichinosis.
o Mechanism of Action
o Albendazole inhibits polymerization of tubulin and hence prevents
the formation of cytoplasmic microtubules. As a result,
microtubule-dependent uptake of glucose is prevented.
o Adverse Effects
o Albendazole is generally well tolerated. Mild to moderate liver
impairment has occurred in 16% of patients, as indicated by
elevation of liver transaminases in plasma. Liver function should be
assessed before each cycle of treatment and 14 days later.
o Albendazole suppresses bone marrow function and can, hence,
cause granulocytopenia, agranulocytosis, and even pancytopenia.
Liver impairment may increase risk. Blood cell counts should be
obtained before each cycle of treatment and 14 days later. In postmarketing studies, some patients developed renal failure. This
occurred rarely and the association with albendazole has not been
established.
o Albendazole is teratogenic in animals and hence should not be used
during pregnancy. If pregnancy occurs, the drug should be
discontinued immediately.
o Mebendazole:Mebendazole
Target Organisms
Mebendazole (Emverm and Vermox) is a drug of choice for most intestinal
roundworms. This agent clears infestation with pinworms, hookworms, and
giant roundworms. Because of its relatively broad spectrum of action,
mebendazole is especially useful for treatment of mixed infestations.
Mechanism of Action
Mebendazole prevents uptake of glucose by susceptible intestinal worms.
Glucose deprivation results in immobilization followed by slow death. Because
the worms die slowly, up to 3 days may elapse between treatment onset and
complete clearance of parasites. Mebendazole does not influence glucose uptake
or utilization by humans.
Adverse Effects
Systemic effects are rare at usual doses, perhaps because the
drug is so poorly absorbed. The most concerning are bone
marrow suppression and liver impairment; however, these are
typically only a problem with high doses or prolonged
treatment. In patients with massive parasitic infestations,
transient abdominal pain and diarrhea may occur.
o Pyrantel pamoate:
Pyrantel Pamoate
Target Organisms
Pyrantel pamoate (Reese's Pinworm Medicine, Combantrin ) is active against
intestinal nematodes. The drug is an alternative to mebendazole or albendazole
for infestations with hookworms or pinworms.
Mechanism of Action
Pyrantel is a depolarizing neuromuscular blocking agent that causes spastic
paralysis of intestinal parasites. The paralyzed worms are cleared in the feces.Adverse Effects
Neonates given formulations with benzyl alcohol or its derivatives had
developed a potentially fatal “gasping syndrome” with complications that
include respiratory distress, cardiovascular collapse, seizures, and metabolic
acidosis. Otherwise, serious reactions are rare. The most common effects are GI
reactions (nausea, vomiting, diarrhea, stomach pain, and cramps). Possible
central nervous system effects include dizziness, drowsiness, headache, and
insomnia.
o Ivermectin:
Ivermectin
o Target Organisms
o Ivermectin (Stromectol) is active against many nematodes.
Currently, the drug has two approved indications:
onchocerciasis (a major cause of blindness worldwide) and
intestinal strongyloidiasis. Ivermectin is active against the
tissue microfilariae of O. volvulus (the cause of
onchocerciasis), but not against the adult form. However,
because adults are unable to produce microfilariae that
remain viable, they are not replaced. Ivermectin can also be
used to kill mites and lice, although these parasites are not
approved targets. In addition to its use in
humans, ivermectin is used widely in veterinary medicine.
o Mechanism of Action
o Ivermectin disrupts nerve traffic and muscle function in target
parasites by opening chloride channels on the cell surface,
which allows chloride ions to rush into nerve and muscle
cells. The resultant hyperpolarization of these cells causes
paralysis followed by death. Host cells are not affected,
because ivermectin is selective for chloride channels in
parasites.
o Adverse Effects
o Patients treated for onchocerciasis commonly develop
pruritus, rash, fever, lymph node tenderness, and bone and
joint pain. This reaction, known as a Mazotti reaction, is an
allergic and inflammatory response to the death of O.volvulus rather than a reaction to the drug. (Mazotti-type
reactions do not occur in patients treated for strongyloidiasis.)
Abdominal pain and headache are seen in less than 5% of
patients. Hypotension develops rarely.
o Ivermectin is teratogenic in mice, rats, and rabbits. Cleft
palate is the most common effect. There are no adequate data
on teratogenesis in humans. Until more is
known, ivermectin should be avoided during pregnancy.
o Moxidectin:
Moxidectin
Target Organisms
Moxidectin (Moxidectin) received the FDA approval for treatment of
onchocerciasis due to O. volvulus in 2018. Activity against other helminths is
unknown at this time.
Mechanism of Action
The exact mechanism of moxidectin is unknown, but the end result,
like ivermectin, is increased cellular permeability followed by influx of calcium.
Also, like ivermectin, the resultant hyperpolarization leads to paralysis.
Adverse Effects
Patients typically experience the flu-like symptoms of the
Mazotti-response associated with death of the microflariae
during the frst week. Adverse effects mirror those
of ivermectin. Early studies suggest that a major advantage
over ivermectin is moxidectin's apparent decreased risk for
teratogenesis. In animal studies with rats (at 15 times the
human dose) and rabbits (at 24 times the human dose), there
were no signifcant effects on the embryo or fetus. Human
studies are lacking, though, and we do not yet know what postmarketing studies may reveal.
o Didanosine:Patient-Centered Care Across the Life
Span
Nucleoside Reverse Transcriptase Inhibitors
Life Stage Considerations or Concerns
Children Both stavudine and zidovudine are approved for neonates. Abacavir
and lamivudine are approved for infants as young as 3 months.
Tenofovir is approved for children age 2 and
older. Didanosine is approved for children 6 years and older
weighing at least 20 kg.
Pregnant
women
Antiretroviral therapy is recommended for all HIV-infected
pregnant women to lower the viral load and decrease the risk of
perinatal transmission. The choice of antiretroviral drug for the
pregnant woman must consider not only the risk for harm to the
fetus from the drug but also the risk for harm to the fetus from
the adverse effects tied to the drug. Didanosine, emtricitabine,
and tenofovir are associated with less risk than lamivudine,
stavudine, and zidovudine. Less is known about abacavir, but
there are currently no known long-term adverse effects to the
fetus despite a high level of placental transfer. Combined NRTIs
during pregnancy increase the risk for lactic acidosis, which can
be life threatening.
Breastfeeding
women
Breastfeeding should be avoided by women with HIV because
there is a danger of transmitting the virus.
Older adults Older patients taking didanosine have a higher risk for developing
pancreatitis than younger patients. Peripheral neuropathy mayLife Stage Considerations or Concerns
be increased for older patients taking stavudine.
o Zidovudine:
Zidovudine
Instruct patients to report new or worsening symptoms of
anemia (e.g., pallor, weakness) or neutropenia (evidence of
infection). To prevent exposure to illness, patients should be
cautioned to avoid contact with people who are ill and to avoid
areas where people may congregate in large numbers.
o Lopinavir:
Lopinavir/ritonavir oral solution is contraindicated for fullterm infants (until 14 days after birth) and preterm infants
(until 14 days after their predicted due date).
• Use atazanavir, saquinavir, and lopinavir/ritonavir with
caution in patients with structural heart disease, cardiac
conduction disturbances, and ischemic heart disease, and
in those taking other drugs that prolong the PR interval.
• Avoid lopinavir/ritonavir and saquinavir in patients with
congenital long QT syndrome, and in those taking drugs
that prolong the QT interval.
- Adverse Effects
o Albendazole
o Pyrantelpamoate:
o Mebendazole
o Ivermectin
o Moxidectino Lopinavir/ritonavir
see above!!
o Saquinavir:
Use atazanavir, saquinavir, and lopinavir/ritonavir with
caution in patients with structural heart disease, cardiac
conduction disturbances, and ischemic heart disease, and
in those taking other drugs that prolong the PR interval.
• Avoid lopinavir/ritonavir and saquinavir in patients with
congenital long QT syndrome, and in those taking drugs
that prolong the QT interval.
o Enfuvirtide
Adverse effects
Injection-site reactions.
In clinical trials, ISRs developed in 98% of patients, usually
within the frst week of treatment. Principal manifestations are
pain and tenderness, erythema and induration, nodules or
cysts, pruritus, and ecchymosis (small hemorrhagic spots).
Although generally mild to moderate, symptoms can also be
severe. In 17% of patients, individual ISRs persisted more than
7 days. Because ISRs are both common and long lasting, 23%
of patients had six or more ongoing ISRs at any given time. The
intensity of ISRs can be reduced by rotating the injection site,
avoiding sites with an active ISR, and avoiding unnecessarily
deep injections. If a severe ISR occurs, or if local infection
develops, patients should seek immediate medical attention.
Pneumonia.
Enfuvirtide appears to increase the risk for bacterial pneumonia. Patients should
be informed about signs of pneumonia (cough, fever, breathing difficulties), and
instructed to report them immediately. Enfuvirtide should be used with caution
in patients who have pneumonia risk factors: low initial CD4 cell counts, high
initial viral load, IV drug use, smoking, and a history of lung disease.Hypersensitivity reactions.
Because enfuvirtide is a foreign peptide, it can trigger hypersensitivity reactions.
Typical symptoms, which may occur individually and in combination, are rash,
fever, nausea, vomiting, chills, rigors, hypotension, and elevated serum
transaminases. Enfuvirtide has also been associated with respiratory distress,
glomerulonephritis, Guillain-Barré syndrome, and primary immune complex
reaction, all of which may be immune mediated. If a systemic hypersensitivity
reaction occurs, enfuvirtide should be discontinued immediately and never used
again.
- Lifespan Considerations
o Which medications are safe during pregnancy or childhood
Patient-Centered Care Across the Life
Span
Antifungal Agents
Life Stage Patient Care Concerns
Infants Nystatin is used to treat oral candidiasis in premature
and full-term infants. Fluconazole is also used
safely to treat systemic candidiasis in newborn
infants.
Children/adolescents Many antifungal agents are used safely in children, in
lower doses. Side-effect profiles are similar to those
of adults.
Pregnant women Risks and benefits must be considered forLife Stage Patient Care Concerns
administration during pregnancy.
Breastfeeding
women
Data are lacking regarding most antifungals and
breastfeeding. Most antifungals are considered safe
in lower doses. The exception to this is
ketoconazole. Because it has high potential for
hepatotoxicity, it should be avoided in
breastfeeding women.
Older adults Older adults have a higher risk for achlorhydria than
do younger individuals and may not predictably
absorb some antifungal agents. In addition,
common drugs prescribed to older adults, including
warfarin, phenytoin, and oral hypoglycemic agents,
are increased by azoles.
Patient-Centered Care Across the Life Span
Nonnucleoside Reverse Transcriptase Inhibitors
Life Stage Considerations or Concerns
Children Nevirapine may be given to infants as young as 15 days.
Efavirenz is approved for children older than 3 months
and weighing at least 3.5 kg. Etravirine may be given to
children who are 3 years and older. Safety and efficacy
have not been established for rilpivirine and, for
delavirdine, safety has not been established for patientsLife Stage Considerations or Concerns
younger than 16 years.
Pregnant
women
Antiretroviral therapy is recommended for all HIV-infected
pregnant women to lower the viral load and decrease the
risk of perinatal transmission. Etravirine, nevirapine, and
rilpivirine are among the safest drugs in this category.
Delavirdine carries a slightly higher risk for
complications. Efavirenz is teratogenic. Pregnancy must
be ruled out before efavirenz is used. For women capable
of becoming pregnant, two forms of contraception are
recommended during treatment and for 3 months after
treatment is discontinued.
Breastfeeding
women
Breastfeeding should be avoided by women with HIV
because there is a danger of transmitting the virus.
Older adults Each drug in this category identified insufficient numbers of
older adults in clinical trials. Consider individual patient
status regarding cardiac, hepatic, and renal status or
comorbidities that may necessitate alternate regimens.
Patient-Cenetered Care Across The Life
Span
AnthelminticsaLife Stage Considerations or Concerns
Children There are inadequate studies in children taking most of these
drugs. Pyrantel pamoate formulations containing benzyl
alcohol or its derivatives should not be prescribed for
neonates. As with all drugs the benefits of treatment must
be weighed against the risk of adverse effects.
Pregnant
Women
Praziquantel appears to be the safest of the anthelmintics. No
abnormalities occurred in animal studies. Moxidectin has
also demonstrated apparent safety; however, it was only
approved in June 2018 and post-marketing studies are
unavailable. Animal reproduction studies have
demonstrated abnormalities for mebendazole, albendazole,
and ivermectin; however, the risk to humans has not been
established. The World Health Organization (WHO) allows
use of mebendazole, albendazole, and pyrantel pamoate in
the second and third trimesters, but not the first trimester,
and does not recommend the use of ivermectin and
diethylcarbamazine as treatment for women who are
pregnant.
BreastFeeding
Women
The WHO advises women taking mebendazole and pyrantel
pamoate to continue breastfeeding but advises caution with
albendazole and ivermectin. The manufacturer of pyrantel
pamoate, however, does not recommend breastfeeding
when taking this drug. The manufacturer of praziquantel
notes that significant amounts of the drug are excreted into
breast milk and advises that women not nurse on the day of
praziquantel treatment and during the subsequent 72 hours.
Data are lacking for moxidectin.Life Stage Considerations or Concerns
Older Adults There are no current contraindications for older adults taking
these drugs; however, because there are relatively few
studies on the effects of these drugs on older adults,
insufficient data are available to determine safety.
- How to measure therapeutic effect of HIV therapy
Summary of Key Prescribing Considerations
Drugs for Human Immunodeficiency Virus Infection
Therapeutic Goal: Treatment has five goals: (1) maximal and long-lasting
suppression of viral load, (2) restoration and preservation of immune function,
(3) improved quality of life, (4) reduction of HIV-related morbidity and
mortality, and (5) prevention of HIV transmission.
Baseline Data: In addition to a complete history and physical exam: CD4
count, HIV viral load, resistance testing, HBsAb, HBsAg, HBcAb total, HCV
antibody, serum Na, K, HCO3, Cl, BUN, creatinine, estimated glomerular
filtration rate, ALT, AST, total bilirubin, CBC with differential, fasting lipid
profile, fasting glucose or hemoglobin A1c, urinalysis, pregnancy test if capable
of becoming pregnant, HLA-B*5701 testing if considering abacavir, tropism
testing if considering maraviroc, and serum phosphorus if considering tenofovir
for patients with chronic kidney disease.
Monitoring: See Box 81.2.
Identifying High-Risk Patients:
• Didanosine's risk for pancreatitis is increased by a history of alcoholism
or pancreatitis and by use of IV pentamidine.
• Zidovudine's risk for hematologic toxicity is increased by a low
granulocyte count; low levels of hemoglobin, vitamin B12, or folic acid;
and concurrent use of drugs that are myelosuppressive, nephrotoxic, or
toxic to circulating blood cells. • Lopinavir/ritonavir oral solution is contraindicated for full-term infants
(until 14 days after birth) and preterm infants (until 14 days after their
predicted due date).
• Use atazanavir, saquinavir, and lopinavir/ritonavir with caution in
patients with structural heart disease, cardiac conduction disturbances,
and ischemic heart disease, and in those taking other drugs that prolong
the PR interval.
• Avoid lopinavir/ritonavir and saquinavir in patients with congenital long
QT syndrome, and in those taking drugs that prolong the QT interval.
• Use enfuvirtide with caution in patients who have pneumonia risk
factors: low initial CD4 cell counts, high initial viral load, IV drug use,
smoking, and a history of lung disease.
• Patients with elevated liver function and cardiovascular disease who
take maraviroc must be monitored carefully.
Evaluating Therapeutic Effects:
HIV RNA
Success is indicated by a reduction in plasma HIV RNA. With ART, plasma
HIV RNA should decline to 10% of baseline within 2 to 8 weeks. After 16 to 20
weeks of treatment, plasma HIV RNA should reach its minimum. Ideally, the
minimum will be undetectable with sensitive assays.
CD4 T-Cell Counts
As viral load decreases, CD4 T-cell counts may rise, indicating some
restoration of immune function.
Additional Notes:
- Drugs that decrease gastric acid should be administered at least 2 hours apart from
other drugs due to decreased drug absorption.
- Prompt recognition of liver injury is essential with oral antifungal drugs. AST, ALT,
alkaline phosphatase, and bilirubin should be monitored prior to initiation of therapy,
monthly for 3 to 4 months, and frequently thereafter during treatment. [Show Less]