06 February 2010

Drugs for Viral Infections



Drugs for Viral Infections

Virus vs. Bacteria

* Compare and contrast structural components of bacteria and viruses
* Describe a viron.
* Identify indications for viral infection pharmacotherapy.

Challenges of Anti-Viral Therapy
* Rapid mutation
* Intracellular nature of virus
* Drugs have narrow spectrum of activity

HIV vs. AIDS
* Discuss the difference between a virus and a retrovirus.
* Differentiate between HIV infection and AIDS.
* Describe the replication of HIV.

Pharmacotherpy for HIV-AIDS
* Identify the therapeutic goals of therapy.
* Classifications:
o Nucleoside reverse transcriptase inhibitors (NRTI)
o Nonnucleoside reverse transcriptase inhibitors (NNRTI)
o Protease Inhibitors
o Neucleotide reverse transcriptase inhibitor (NtRTI)
o Fusion (entry) inhibitor

HIV-AIDS Pharmacotherapy
* Compare and contrast the mechanism of action of:
o Reverse transcriptase inhibitors
o Protease inhibitors
o Fusion inhibitors
* Identify reasons treatment failures occur.

Antiretrovirals: NCs
* Drug is not a cure
* Prior to RX: assess for sx of HIV, opportunistic infection, use of herbals
* Monitor viral load
* Verify ordered combination drugs
* Common side effects:
o Fatigue, headache, GI disturbances
* Other side effects dependent upon specific drug

Antiretrovirals: NCs

* Most contraindicated: pregnancy, lactation
* Side effects can influence ADLs
* NRTIs: cautiously: pancreatitis, PVD, neuropathy, kidney or liver disorders, cardiac disease, alcohol abuse
* NNRTIs: judiciously use in liver impairment, CNS disease
* PIs: potential risks if sensitive to sulfonamides, liver disorders, renal insufficiency

Antiretrovirals: NCs

* Variations in administration instructions:
o NRTIs: empty stomach, water only, no fruit juice
o Nevirapine (Viramune) and saquinavir (Invirase) – take with food to decrease GI upset
o Contact HCP before taking any OTC med or supplement

Antiretrovirals: Client Teaching

* NRTIs: report fever, skin rash, abd pain, n/v, numbness or burning of hands/feet
* NNRTIs: report fever, chills, rash, blistering or reddening of the skin, muscle or joint pain
* PIs: report rash, abd pain, headache, insomnia, fever, constipation, cough, fainting, visual changes

Antiretrovirals: Client Teaching

* Wash hands frequently; avoid crowds
* Increase fluid intake; empty bladder frequently
* Abstinence or barrier contraception
* Do not share needles
* Take medications as ordered
* Sufficient rest and sleep; healthy diet
* Keep all scheduled appts and lab visits

Perinatal HIV Transmission
Discuss pharmacotherapy for the prevention of perinatal transmission.

Occupation Exposure
* Identify risk factors for occupational exposure to HIV.
* Describe post HIV exposure prophylaxis.

Herpesvirus Infections
* HSV-1
* HSV-2
* CMV
* VZV
* EBV
* Herpesvirus 6
o Children: roseola
o Immunocompromised: hepatitis or encephalitis

Herpesvirus Infections
* Triggering events:
o Immunosuppression
o Physical challenges
o Emotional stress

* Pharmacologic goals:
o Relieve acute symptoms
o Prevent recurrences

Antivirals: NCs
* Baseline: VS, wt, CBC, viral cultures, LFTs, RFTs
* Cautiously: pre-exisiting renal or liver dysfunction
* Judiciously: pregnancy
* Routes: IV, oral, topical, inhalation
o instruct re: proper technique
o Emphasize compliance

Antivirals: NCs
* Generally well tolerated:
o Take with food if GI upset
* Severe adverse reactions:
o Renal Failure, Thrombocytopenia
* More frequently side effects:
o Headache
o Fatigue
o Dizziness

Antivirals: Client Teaching

* Meds do not prevent transmission
o avoid activities that may transmit
* Immediately report: hematuria, bruising, jaundice, fever, chills, confusion, nervousness, dizziness, nausea, vomiting
* Complete full course of treatment
* Keep scheduled appts and lab visits

Antivirals: Client Teaching

* Caution while performing hazardous activities
* No other prescription, OTC, herbals or supplements without HCP approval
* Apply topicals with applicator or glove
* No other creams, ointments, or lotions to infected sites

Influenza

* Describe the characteristics of influenza.
* Differentiate between primary and secondary pharmacotherapy for influenza infections.
* Differentiate between antiviral and neuroaminidase inhibitor therapy.

Viral Hepatitis
* Caused by several different viruses with unique clinical features
* All cause inflammation and necrosis of liver cells
* Acute
o Fever, chills, fatigue, anorexia, nausea, vomiting
* Chronic
o Prolonged fatigue, jaundice, liver cirrhosis, hepatic failure

Viral Hepatitis

* Differentiate between Hepatitis A, Hepatitis B, and Hepatitis C.
* Compare and contrast pharmacotherapy for Hepatitis A, Hepatitis B, and Hepatitis C.

Viral Hepatitis Exposure
Compare and contrast post-exposure prophylaxis for Hepatitis A, Hepatitis B, and Hepatitis C.

Drugs for Viral Infections.ppt

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Board review - Viral infections



Rubeola (nine-day or red measles)

* Prodromal symptoms - fever, malaise, dry (occasional croupy) cough, coryza, conjunctivitis c clear d/c, marked photophobia
* 1-2 days p prodromal symptoms - Koplik spots on the buccal mucosa
* Koplik spots - tiny, bluish-white dots surrounded by red halos

rubeola (nine-day or red measles)

* Day 3 or 4 - blotchy, erythematous, blanching, maculopapular exanthem appears
* Rash begins at the hairline and spreads cephalocaudally and involves palms and soles
* Rash typically lasts 5 - 6 days
* Can see desquimation in severe cases

rubeola (nine-day or red measles)

* Patients can be systemically ill
* Incubation period 9-10 days
* Patients contagious from 4 days prior to the rash until 4 days after the resolution of the rash
* Highly contagious - 90% for susceptible people

rubeola (nine-day or red measles)

* High morbidity and mortality common in children in underdeveloped countries
* Peak season is late winter to early spring
* Potential complications - OM, PNA, obstructive laryngotracheitis, acute encephalitis
* Vaccination is highly effective in preventing disease

rubeola (nine-day or red measles)

Rubella (german measles)

* Little or no prodrome in children
* In adolescents - 1-5 days of low-grade fever, malaise, headache, adenopathy, sore throat, coryza
* Exanthem - discrete, pinkish red, fine maculopapular eruption - begins on the face and spreads cephalocaudally
* Rash becomes generalized in 24 hours and clears by 72 hours

rubella (german measles)

* Forchheimer spots - small reddish spots on the soft palate - can sometimes be seen on day 1 of the rash
* Arthritis and arthralgias - frequent in adolescents and young women - beginning on day 2 or 3 lasting 5-10 days
* Up to 25% of patients are asymptomatic - serology testing may be necessary to establish the diagnosis

rubella (german Measles)

* Important in establishing the diagnosis if the patient is pregnant or has been in contact c a pregnant woman
* Peaks in late winter to early spring
* Contagious from a few days before the rash to a few days after the rash
* Incubation period 14-21 days
* Complications - rare in childhood - arthritis, purpura c or s thrombocytopenia, mild encephalitis

rubella (german Measles)

Varicella (chickenpox)

* Caused by varicella-zoster virus
* Highly contagious
* Brief prodrome of low-grade fever, URI symptoms, and mild malaise may occur
* Rapid appearance of puritic exanthem

varicella (chickenpox)

* Lesions appear in crops - typically have 3 crops
* Crops begin in trunk and scalp, then spread peripherally
* Lesions begin as tiny erythematous papules, then become vesicles surrounded by red halos
* Lesions began to dry - umbilicated appearance, then surrounding erythema fades and a scab forms

varicella (chickenpox)

* Hallmark - lesions in all stages of evolution
* All scabs slough off 10-14 days
* Scarring not typical unless superinfected
* Cluster in areas of previous skin irritation
* Puritic lesions on the skin
* Painful lesions along the oral, rectal, and vaginal mucosa, external auditory canal, tympanic membrane

varicella (chickenpox)

* Occurs year-round, peaks in late autumn and late winter through early spring
* Incubation period ranges from 10-20 days
* Contagious 1-2 days prior to rash until all lesions are crusted over
* Complications - secondary bacterial skin infections (GAS), pneumonia, hepatitis, encephalitis, Reye syndrome

varicella (chickenpox)

* Severe in the immunocompromised host - can be fatal
* Can have severe CNS, pulmonary, generalized visceral involvement (often hemorrhagic)
* Need to get varicella-zoster immunogloblin 96 hours post-exposure to possible varicella

varicella (chickenpox)

Adenovirus

* 30 distinct types
* Variety of infections including conjunctivitis, URIs, pharyngitis, croup, bronchitis, bronchiolitis, pneumonia (occ fulminant), gastroenteritis, myocarditis, cystitis, encephalitis
* Can be accompanied by a rash - variable in nature
* Typically can see - conjunctivitis, rhinitis, pharyngitis c or s exudate, discrete, blanching, maculopapular rash

adenovirus

* Can see anterior cervical and preauricular LAD, low-grade fever, malaise
* Peak season is late winter through early summer
* Contagious during first few days
* Incubation period 6-9 days

Coxsackie hand-foot-and-mouth disease

* Brief prodome - low-grade fever, malaise, sore mouth, anorexia
* 1-2 days later, rash appears
o Oral lesions - shallow, yellow ulcers surrounded by red halos
o Cutaneous lesions - begin as erythematous macules then evolve to small, thick-walled, grey vesicles on an erythematous base

Coxsackie hand-foot-and-mouth disease

* Highly contagious
* Incubation period 2-6 days
* Lasts 2-7 days
* Peak season summer through early fall
* If no cutaneous lesions - herpangina
o less painful and less intense than herpes gingivostomatitis

erythema infectiosum (fifth disease)

* Caused by Parvovirus B19
* Affects preschool and young school aged children
* Peak incidence in late winter and early spring, but it is seen year round
* Characterized by rash - large, bright red, erythematous patches over both cheeks - warm, but non-tender

erythema infectiosum (fifth disease)

* Facial rash fades, then see a symmetrical, macular, lacy, erythematous rash on the extremities
* Resolution occurs within 3-7 days of onset
* Transmitted by respiratory secretions, replicates in the RBC precursors in the bone marrow
* Can cause aplastic crisis in patients with sickle cell disease, other hemogloblinopathies, and other forms in hemolytic anemia

erythema infectiosum (fifth disease)

roseola infantum (exanthem subitum)

* Febrile illness affecting children 6-36 months
* Human herpesvirus 6 is causative agent
* Symptoms include:
o fever, usually >39
o anorexia
o irritability
o these symptoms subside in 72 hours

roseola infantum (exanthem subitum)

* As fever defervenscences, usually an erythematous, maculopapular rash that appear on the trunk and then spread to the extremities, face, scalp, and neck
* Occurs year-round
* More common in late fall and early spring
* Incubation period thought to be 10-15 days

roseola infantum (exanthem subitum)

Infectious mononucleosis

* Acute self-limiting illness of children and young adults
* Caused by EBV
* Transmission by oral contact, sharing eating utensils, transfusion, or transplantation
* Incubation period 30-50 days (shorter, 14-20 days, in transfusion-acquired infection)
* Don’t usually see “classic mono” in young children

Infectious mononucleosis

* Prodrome - fatigue, malaise, anorexia, HA, sweats, chills lasting 3-5 days
* Symptoms
o fever - can have wide daily fluctuations
o pharyngitis c tonsillar and adenoidal enlargement c or s exudate, halitosis, palatal petechiae
o LAD - anterior cervical and posterior cervical - in classic cases, generalized LAD toward end of wk 1

Infectious mononucleosis

* Symptoms cont:
o splenomegaly - develops in 50% of patients in 2nd-3rd wk
o hepatomegaly in 10% of patients
o exanthem - erythematous, maculopapular, rubelliform rash in 5-10% of patients

Infectious mononucleosis

* Complications:
o pneumonia
o hemolytic anemia and thrombocytopenia
o icteric hepatitis
o acute cerebellar ataxia, encephalitis, aseptic meningitis, myletis, Guillain-Barre
o rarely myocarditis and pericarditis

Infectious mononucleosis

* Complications cont:
o upper airway obstruction from tonsillar and adenoidal enlargement
# seen more often in younger patients
# children < 5 yrs of age c obstruction are more likely to have secondary OM, recurrent bouts of OM, tonsillitis, and sinusitis
o splenic rupture

Infectious mononucleosis

* Diagnosis:
o classic finding - lymphocytosis (50% or more) c 10% atypical lymphocytes
o 80% or more of patients c elevated liver enzymes
o Monospot - detects heterophil antibodies - specific, not as sensitive - 85% of adolescents + and fewer younger patients
o specific EBV antibody titers and PCR

Infectious mononucleosis

* DDx
o If fever and exudative tonsillitis predominate
# GAS, diphtheria, viral pharyngitis
o If LAD and splenomegaly predominate
# CMV, toxo, malignancy, drug-induced mono
o If severe hepatic involvement
# viral hepatitis, leptospirosis

herpes simplex infections

* Primarily involve the skin and mucous surfaces
* Can be disseminated in neonates and immunocompromised hosts
* Produces primary infection - enters a latent or dormant stage, residing in the sensory ganglia - can be reactivated at any time

herpes simplex infections

* HSV-1
+ >90% of primary infections caused by HSV-1 are subclinical
+ more common
* HSV-2
+ usually the genital pathogen
+ usual pathogen of neonatal herpes

herpes simplex infection

* Diagnosis
o usually made clinically
o can scrap base of vesicle and a special stain - Giemsa-stained (Tzanck)
# ballooned epithelial cells c intranuclear inclusions and multinucleated giant
o viral cultures take 24-72 hours

Primary herpes simplex infections

* Herpetic gingivostomatitis
o high fever, irritability, anorexia, mouth pain, drooling in infants and toddlers
o gingivae becomes intensely erythematous, edematous, friable and tends to bleed
o small yellow ulcerations c red halos seen on buccal and labial mucosa, tongue, gingivae, palate, tonsils

primary herpes simplex infections

* Herpetic gingivostomatitis
o yellowish white debris builds on the mucosal surfaces causing halitosis
o vesiculopustular lesions on perioral surfaces
o anterior cervical and tonsillar LAD
o symptoms last 5-14 days, but virus can be shed for weeks following resolution

primary herpes simplex infections

* Skin infections
o fever, malaise, localized lesions, regional LAD
o direct inoculation (usually cold sores)
o lesions are deep, thick-walled, painful vesicles on an erythematous base - usually grouped, but may be single
o lesions evolve over several days - pustular, coalesce, ulcerate, then crust over

primary herpes simplex infections

* Skin infections
o most common sites are lips and fingers or thumbs (herpes whitlow)
o eyelids and periorbital tissue infection can lead to keratoconjunctivitis - dx by dendritic ulcerations on slit lamp exam
# can lead to visual impairment - consult ophtho

Eczema herpeticum (kaposi varicelliform eruption)

* Onset of high fever, irritability, and discomfort
* Lesions appear in crops in areas of currently or recently affected skin (for those with atopic eczema or chronic dermatitis)
* Lesions begin as pustules, then rupture and crust over the course of a couple of days
* Lesions can become hemorrhagic

Eczema herpeticum (kaposi varicelliform eruption)

* Multiple crops can appear over 7-10 days (like varicella)
* Can be mild or fulminant, depending (in part) on the underlying dermatitis
* If area of involvement is large, can be lots of fluid loss and potentially fatal
* Treat promptly c acyclovir
* Risk of secondary bacterial infections

Eczema herpeticum (kaposi varicelliform eruption)

Recurrent herpes simplex infection

* Triggers include fever, sunlight, local trauma, menses, emotional stress
* Seen most commonly as cold sores
* Prodrome of localized burning, itching or stinging before eruption of grouped vesicles

recurrent herpes simplex infection

* Vesicles contain yellow, serous fluid and are often smaller and less thick-walled than the primary lesions
* Vesicular fluid becomes cloudy after 2-3 days, then crusts over
* Regional, tender LAD

herpes zoster (shingles)

* Caused by varicella-zoster virus
* After primary infection, virus lies dormant in genome of sensory nerve root cell
* Postulated triggers include mechanical and thermal trauma, infection, debilitation as well as immunosuppression
* Lesions are grouped, thin-walled vesicles on an erythematous base distributed along the course of a spinal or cranial nerve root (dermatome)

herpes zoster (shingles)

* Lesions evolve from macule to papule to vesicle then crusted over a few days
* May have associated nerve root pain - not common in pediatrics - usually short-lived unless it involves a cranial nerve root dermatome
* +/- fever or constitutional symptoms
* Regional LAD common

herpes zoster (shingles)

* Thoracic, cervical, trigeminal, lumbar, facial nerve dermatomes (order of frequency)
* If cranial nerve involvement - prodrome of severe HA, facial pain, or auricular pain prior to the eruption
* Affected patients can transmit varicella, but less of a problem b/c lesions are often covered by clothing and the o/p is not involved in most cases

herpes zoster (shingles)

gianotti-crosti syndrome

* Papular acrodermatitis
* Associated c amicteric hepatitis B, EBV, echovirus, coxasckievirus, parainfluenza virus, CMV, and RSV
* Most patients between 1-6 years old (range 3 months to 15 years)
* Prodrome of low-grade fever and malaise
* May be associated c generalized LAD, hepatomegaly, URI symptoms, and diarrhea

gianotti-crosti syndrome

* Lesions appear within a few days - discrete, firm, lichenois papules c flat tops ranging from 1-10 mm (larger in infants and smaller in older children)
* Papules can be flesh colored, pink, red, dusky, coppery, or purpuric
* Distributed symmetrically over extremities (including palms and soles), buttocks, and face - relative sparing of the trunk and scalp
* No mucosal involvement and non-purtitic

gianotti-crosti syndrome

* Usually clears in 2-3 weeks, but can last for 8 weeks or more
* Lab studies are generally non-specific, but liver enzymes should be obtained and if abnormal - hepatitis B or EBV serology should be done
* Treatment is supportive
* Steroid creams contraindicated b/c they can make the rash worse

gianotti-crosti syndrome

Board review - Viral infections.ppt

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25 January 2010

How to Access The Cochrane Library



How to Access The Cochrane Library

All residents of India can access the full contents of The Cochrane Library for free, thanks to sponsorship provided by the Indian Council of Medical Research (ICMR).



All residents of Australia can access The Cochrane Library for free, thanks to funding provided by the Australian Government

All residents of Denmark can access The Cochrane Library for free

All residents of the Republic of Ireland can access The Cochrane Library for free

All countries in Latin America and the Caribbean can access The Cochrane Library for free via the Virtual Health Library BIREME interface (in English, Spanish or Portuguese), thanks to funding by BIREME, the Pan American Health Organisation (PAHO) and the World Health Organisation (WHO).

Low-Income Countries:The Cochrane Library (www.thecochranelibrary.com) is available with free one-click access to all residents of countries in the World Bank's list of low-income economies (countries with a gross national income (GNI) per capita of less that $1000).

All residents of Norway can access The Cochrane Library for free,

All residents of Spain can access for free the Biblioteca Cochrane Plus, that includes the Spanish version of all Cochrane reviews

All residents of Sweden can access The Cochrane Library for free,

All residents of England can access The Cochrane Library for free

All residents of Scotland can access The Cochrane Library for free

All residents of Wales can access The Cochrane Library for free

http://www.cochrane.org/index.htm
http://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/HOME

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