Download Amphotericin B

Alterations in Skin Function/Integrity and
Antiviral/Antifungal therapy
Wanda Lovitz, APRN
Objectives: Skin Disorders
Describe the etiology, clinical manifestations, and pharmacological treatment of the
skin conditions listed below:
Pigmented lesions
1.
•
•
•
•
Melasma
Albinism
Vitiligo
Sun damage
Fungal skin conditions
2.
•
•
•
•
•
•
•
•
•
Impetigo
Abcesses
Furuncles and carbuncles
Cellulitus
MRSA skin infections
Stasis dermatitis
Viral skin infections
•
•
•
6.
•
•
7.
Verrucae vulgaris
Herpes Zoster
HSV1 and HSV2
Misc skin conditions
•
Tinea pedis
Candidiasis
Tinea versicolor
Bacterial skin infections
3.
5.
Drug Reactions
Urticaria
Angioedema
Skin Cancers
•
•
•
Basal Cell
Squamous Cell
Melanoma
Objectives: Antifungal and Antiviral Agents
• Explain why we have very few antiviral agents.
• Describe the MOA and major side effects of the following antiviral
agents:
• acyclovir/Zovirax
• oseltamvir/Tamiflu
• Identify the mode of transmission of suprficial and systemic
fungal infections.
• Identify common drugs, MOA, and side effect profiles for the
following classes of antifungal agents:
• Polyenes
• Azoles
• Miscellaneous agent: griseofulvin/Fulvicin
Drugs to Know
Antiviral
Antifungal
Antibacterial
acyclovir (Zovirax)
amphotericin B
(Amphotec)
Mupirocin (Bactroban)
oseltamvir (Tamiflu)
nystatin (Mycostatin)
fluconazole (Diflucan)
griseofulvin (Fulvicin)
Introduction to the Antiviral Agents
Antiviral Therapy
for Non-HIV infections
• Viruses have no cell wall
• Antivirals kill viruses by inhibiting their ability to replicate
• This then allows the body’s immune system to destroy the virus.
Why so few antivirals?
1. Often the virus has
time S & S develop
2.
finished replicating by the
Antivirals only work during cell replication
1. Viruses live inside the body’s cells, so drugs that kill
a virus could also kill healthy cells
Antivirals
• Current antivirals only effective against a FEW
viruses:
• Examples:
• Herpes Simplex Virus (HSV)
• Herpes Zoster Virus (HZV)
• Influenza A & B
Human immunodeficiency virus
 HIV) (drugs to treat HIV will not be discussed in this lecture)
Antivirals
•
MOA: (work in 3 different ways)
1.
Interferes with viral nucleic acid synthesis, its
regulation or both (DNA & RNA)
2.
Prevents virus from binding to cells so VIRUS
CANNOT GET INTO CELLS thus preventing viral
replication
3.
Stimulates the body’s IMMUNE SYSTEM to kill
the virus
Antiviral agent for Herpes virus:
acyclovir (Zovirax)
•
*acyclovir (Zovirax)
• Used to suppress replication of
HSV 1(oral) & 2 (genital) & VZV
(herpes zoster and
varicella/chickenpox)
•  Sx severity and frequency of
outbreaks, NOT a cure!
• Used for BOTH initial and recurrent
infection
• May require multiple treatments!
• Reduces viral shedding and
decreases local sx
•  severity and duration of
illness
• Disease can reoccur, again,
NOT a cure
• Available po, IV, and
topical
• SE: GI distress, renal
impairment, seizures, ITP
Drug for “the flu”:
oseltamivir/Tamiflu
Tamiflu
• Oseltamivir/
• Mostly active against
• Used for
influenza A
prophylaxis and to treat active disease (48H of
sx onset)
• Most often giv
• en to elderly and immunocompromised after known exposure
to influenza A
• CDC approved April 2009 for treatment of H1N1 (swine flu)
• Available po only
• SE: nausea and vomiting; seizures, renal impairment
Moving on . . .
Fungal Infections
Systemic Fungal
Infections

Affecting:




Blastomycosis
Histoplasmosis
Affecting lungs &
meninges



Intestines
urinary tract
Affecting lungs


Superficial Fungal
Skin Infections
Cryptococcosis
Nail mycoses
Candidiasis
Oral, topical, and vaginal
(75% of women will be
infected over their lifetime)

Tineas



Corporois
(ringworm)
Pedis (athlete’s
foot)
Tinea Versicolor
(skin)
How do we get a fungal infections?
• Implantation under the skin after injury
• tineas
• Inhalation from airborne fungi
• crytococcal meningitis
• pneumocystis pneumonia
• From taking antibiotics which wipe out normal flora
and allow fungi to proliferate
• candidiasis
• More common in elderly and immuno-compromised
persons
• Also may occur in patients with vascular indwelling
catheters, organ transplant recipients, and patients
receiving chemotherapy
Systemic fungal infection: Histoplasmosis
•
• Histoplasmosis is a fungal infection that mostly
affects the LUNGS
• Histoplasmosis lives in the soil
• Especially soil that is enriched with bat or bird droppings
• People get histoplasmosis when they breathe in the dust
that contains the fungi
Systemic fungal infection:
Blastomycosis
• Blastomycosis is a fungal infection acquired
through contact with rotting debris or wood
• Endemic southeastern US along the Ohio and Mississippi Rivers
• Affects lungs, skin, bones, and genitourinary tract
Four major classes of Antifungals
very few agents available: fungi are difficult to kill
1. Polyenes

nystatin/Mycostatin

amphotericin B/
Amphotec
3. Azoles
fluconazole/Diflucan
4. Pyrimidine
Flucytosine/Ancobon
2. Misc Agent
grisefulvin /Fulvicin
Antifungals: Drug Profile:
Amphotericin B: polyene
• amphotericin B/Amphotec
A polyene antifungal
MOA:
 Binds to
ergosterol in fungal cell membrane and
causes leakage of K and Mg
Available as topical or parenteral
Agent
of choice for most SYSTEMIC mycoses
A HIGH ALERT DRUG!!
Amphotericin B
SE: “Awful B”
• The most effective antifungal, also the most toxic!
• SE occur in MOST people receiving amphotericin!
• Most dangerous is renal damage and low K levels which can cause
cardiac irritability
• Some selective toxicity, but may also injure host cell membrane by
binding to cholesterol
• Infusion reactions and renal damage occur in almost
all patients
Amphotericin B – IV only!
• Administration:
• Must be diluted
• Infuse via an IV pump
• Patient must be on a cardiac monitor with frequent
monitoring of vital signs
• Given every other day for several months!
• Takes up to 7 weeks to be eliminated from the body
•
Pretreatment with benadryl, tylenol, or aspirin may decrease
infusion sx of fever, pain, nausea, and h/a
• Synergistic effect when given with flucytosine/Ancobon
•
thereby allowing a reduction in Amphotericin B dose
Antifungal: Pyrmidine
• flucytosine/
Ancobon
• MOA
• Inhibits fungal DNA synthesis
• Allows a lower dose of Amphotercin to be used
• this decreases SE r/t Amphtocerin use
Polyene: nystatin/Mycostatin
Advantage: available in
many formulations:
• Creams, powder, topical,
lozenges, vaginal tablets
• Useful for candidial infections
of mouth, oral mucosa,
vagina, skin, and intestine
•
Disadvantage:
• Too toxic for parenteral
administration
• Common oral form is a
suspension: “swish & swallow
or swish & spit”
• SE:
• few, mild skin irritation
• N-V-D when taken orally. Poor GI
absorption
Imidazoles
• azoles”
includes several
drugs. Available po, topical, and
some IV)
• Used for superficial and less
serious systemic fungal
infections
• Advantage over amphotericin B
 Less side effects!
• “Available po, IV, and topically
• SE:
• vaginal: burning and rash
• Anorexia, N- V, diarrhea, stomach
cramps, H/A
• miconazole/Monistat)=
• itraconazole/Sporonox
• clotrimazole/
• Lotrimin OTC
• fluconazol/Diflucan
• Prototype drug
• can cross into CSF
• Used po for simple fungal
infections
• Used IV to tx crytococcal
meningitis
Imidazole: fluconazole/Diflucan
• MOA:
Interferes with synthesis of ergosterol to inhibit
fungal growth
•
Advantage:
•
Disadvantage:
• Rapidly and completely absorbed when given orally
• Penetrates most body membranes to reach
• infections in CNS, bone, eyes, respiratory and urinary tracts
• Narrow spectrum of activity
• MANY DRUG INTERACTIONS
•
•
•
•
•
Nursing alert:
Do not mix IV fluconazole/Diflucan with other drugs.
Monitor PT/INR levels for patients on Coumadin
Watch for hypoglycemia for patients on sulfonylureas
Increases dilantin and haldol levels
grisefulvin/Fulvicin: Misc agent
an inexpensive older agent
• MOA
• Inhibits fungal mitosis, binds
to keratin
• Has no effect on cell wall or
membrane
• SE
• Bone marrow
suppression, rash, CNS
changes, N-V-D, anorexia
• Therapeutic Uses:
• Tx of resistant
dermatophyte infections
of scalp, skin, and nails
Ringworm of
scalp
• Ex.
Skin Infections
Manifestations of Skin Disorders
• Skin disorders or sx may present as a primary skin
disease or as evidence of DISEASE to other
organ systems
• Examples
• Candidiasis  diabetes
• Malar rash (butterfly) systemic lupus erythematous (SLE)
• Pruritus  renal disease
• Jaundice  liver or biliary disease
• Oral candidiasis  HIV
Malar rash from
SLE
Assessment of the Skin
• Primary vs. Secondary
Lesions
• Primary Lesions-Original
appearance of rash/lesions
• Ex. Wheal, macule, papule, putsule
• Secondary Lesions-
Appearance modified by
time, scratching, topicals
• Ex. excoriation
Can you describe these primary skin
lesions?
Assessment of Skin Lesions-Descriptors:
Color
Hypopigmented
Hyperpigmented
Erythematous
Jaundiced
Assessment of Skin Lesions-Descriptors: Size
12 cm
2 cm
Assessment of Skin Lesions-Descriptors: Shape
maculopapular
pustular
Generalized/patchy
nodular
Assessment of Skin Lesions-Descriptors:
Symmetry
Left anterior upper thorax
Assessment of Skin Lesions-Descriptors:
Distribution
Where is/are the rash/lesions distributed?
Causes of Skin Disorders
• Vague, generalized
symptoms vs specific
and easily identifiable
causes
•
General categories
1. Infectious
2. Inflammatory
3. Allergic
4. Neoplastic
• Pruritus
• Erythema
• Bleeding
• Bruises
Symptom: Pruritus
• The sensation of itch
• May be severe
• Is a sx not a disease
• May indicate systemic disorders
• Chronic renal failure
• Diabetes
• Biliary disease
What nursing interventions relieve
pruritus?
• Treatment measures
• Moisturizing lotions
• Humidification
• Cold applications
• Topical corticosteroids
• Non-sedating antihistamines
Symptom: Dry Skin (Xerosis)
• Xerosis occurs naturally with aging
• May signal underlying disorder
• Often caused by
corneum
dehydration of stratum
• Appears rough & scaly
• c/o pruritus common
• Tx is moisturizing agents
Treatment of Xerosis
• Rx options
• Emollients (fatty acid derivatives)
• Vaseline or Aquaphor
(OTC)
• Humectants (contain alpha-hydroxy & urea)
• LacHydrin
(RX)
corticosteroids or mild
anesthetics to lotions or creams
• Addition of
Pigmented Skin Disorder: Melasma
• Melasma
• Characterized by dark
macules on the face
• Most common in brown-
skinned persons
• More common in women
(mask of pregnancy)
• Rx: avoid sun, bleaching
creams with
hydroquinone
(a
bleaching agent) and
tretinoin/Retin-A
(vitamin A derivative)
Pigment Skin Disorder: Albinism
• Partial or complete lack of
pigmentation
• Eye involvement-varying
levels of visual impairment
• Genetically transmitted
• Increased risk for dz related to
sun exposure-basal/squamous
cell carcinoma, solar keratoses
• Education targeted toward UV
protection
Pigment Disorder: Vitiligo
• Pigment disappears from
•
•
•
•
a patch of skin
Sudden onset
Usually occurs before
age of 21
Affected areas spread
May be associated with
pernicious anemia,
hyperthryoidism, and
diabetes melliuts
(autoimmune disorders)
Where are the rash/lesions distributed?
What color are the lesions?
Are the lesions symmetrical?
Can you name any famous people/characters with
vitiligo?
Ultraviolet Rays (UVR) & skin damage
• UVR can
directly
damage skin cells
(sunburn)
accelerates aging
increases risk of
skin cancer
• Photosensitive drugs
• UVR
• UVR
exaggerate UVR
response
• Examples:
• Tetracycline
• Sulfonamides
• Diuretics
Infectious Process: fungal infections
Tinea pedis
Associated with sneaker use
and ↑’d sweating of feet
Red, scaly, itchy
 May only effect web spaces
between toes or larger areas of
feet
Contagious
person→person
 Prevention: Use of shower
shoes, cleaning tub/shower
after each use may minimize
transmission
Fungal Infection:
Candidiasis: “Thrush, Yeast Infection”
• Risk Factors:
• Immunosuppression-
iatrogenic/acquired (HIV)
• Antibiotic use
• Appearance:
• May appear as white lesions in
mouth (thrush)
• Beefy red with satellite lesions in
intertriginous areas
• Tx:
•
usually with topical anti-fungal
agents
Fungal infection: Tinea versicolor
Tinea versicolor is caused by a overgrowth
of the yeast type skin fungus.
Treated with
topical antifungals or oral agents.
(Also , Selsum blue shampoo has been shown to be
helpful.)
Treatment of fungal skin infections
• Most fungal infections of the skin
are treated with topical antifungal
agents
• Oral agents used for more resistant and serious fungal
infections
• Intravenous antifungals available
for systemic infections
Tinea capitis
Bacterial Infection:
Impetigo
• Organisms carried in the
NOSE. Causative agents:
1.Staphylococci
2.Streptococci
• Acute,
contagious
• Appearance:
• Vesicles, pustules, honeycolored crust on red base
• Tx is topical antibacterials
(Bactroban ointment)
Bacterial Infection:
Abscesses
• Skin inflamed and red
• Area often raised with
palpable borders
• Tender
• May drain purulent
discharge or feel
fluctuant (fluid-filled)
Bacterial infections: Furnucles
• Furuncle is a bacterial
infection of a HAIR
FOLLICLE
& Carbuncles
• Carbuncle is a painful
deep swelling of the
skin caused by bacteria
Bacterial Infection: Cellulitis
• Non-contagious
•
• Infection of skin and
surrounding tissue
• (Staph, Strep)
• May be an initial injury or
wound that becomes
infected and spreads to
surrounding healthy tissue
• Appearance:
• Skin is red, swollen, tender
and warm
• Blisters may form on skin
Treatment of Cellulitus
Rx with oral antibiotics (severe cases may require IV
antibiotics)
Methicillin Resistant Staph Infection (MRSA)
MRSA Infections
•Hospital acquired MRSA is usually
sensitive to IV Vancomycin or Zyvox
•Community acquired MRSA is usually
sensitive to Bactrim or dicloxacillin
•Note: MRSA infections may also occur in the
urine, lungs, & sputum
Prophylaxis: Bactroban nasal ointment prior to surgery.
Stasis dermatitis (chronic venous insufficiency)
• Condition found primarily in the lower extremities
• Results from poor venous circulation
• Redness and scaling present
• Ulcerations may develop and a secondary
bacterial infection may occur
Viral Infections
HPV/human papilloma virus
• Viruses
are
intracellular
pathogens that must
GET INSIDE the cell
to use the host cell’s
DNA to reproduce
causes anal and gential
warts
Viral Infection: Verrucae
• Benign lesions caused by
papilloma virus
• The “common wart”
• Appearance:
• varies depending on location
• Usually painless, except for
plantar warts
• Tan base
• Irregularly thickened stratum
corneum
• May have central pinpoint
black flecks (plantar)
Vulgaris
Viral infection: Herpes Zoster
(shingles)
• An acute LOCALIZED
vesicular eruption over a
dermatomal segment of
the skin
• Believed to be a re-
activation of the varicellazoster virus (VZV) that
causes chicken-pox
• Can be transmitted to non-
immune persons
Tx: anti-viral agents
Prurituc erythematous vesicles
following a thoracic dermatone
Viral Infection
Herpes Zoster aka “Shingles”
• Varicella zoster virus (VZV) lies dormant on a
dermatomal segment after
infection with chickenpox
• Reactivated by immunosuppression, stress, illness
• Prodrome: burning/tingling along dermatome
• Appearance and Distribution:
• Vesicles on red base that follow along dermatomal distribution-asymmetric (Does
not cross midline)
• Usually extremely painful!
• Clears in 2-3 weeks
• Post-herpetic neuralgia and chronic pain may persist for years
• Usually occurs in people > 50 years old, but can occur in anyone who has had
chickenpox
• Person with Herpes Zoster CAN transmit it to someone who has never had
chickenpox!
Viral Infection: Herpes Simplex
• Caused by:
• HSV1/HSV2
• No cure!
• Tx:
• with anti-viral agents may decrease severity of outbreak
• Appearance:
• Prodrome-local burning or tingling
• Clusters of vesicles on red base, may progress to pustules and ulcerations
• Crust and shed after 10-14 days
• Distribution:
•
Usually seen on face, lips, mouth (HSV1) or genitalia (HSV2)
• Recurrent-precipitated by stress, illness, sun exposure
• Virus may shed and client may be contagious without visible lesions
Urticaria/Hives: a manifestation of an
allergic reaction
• Characterized by edematous plaques that
cause intense itching
• Lesions are raised pink or red areas
surrounded by a paler halo that blanch
with pressure
swelling of the tongue or
pharynx, larynx usually spared
• May see
Urticaria
• Histamine is mediator in most cases, causing
hyperpermeabilty of the microvessels in the skin
and allowing fluid to leak into the tissues causing
edema and wheal formation
• Common causes: food or drinks, medications,
insect stings, viral infections, dust mites,
exposure to pollen or chemicals
Drug-Induced Skin Eruptions
• Most drugs can cause a local
or generalized skin eruption
• Topicals usually cause a local
reaction vs systemic reaction
with systemic drugs
• May mimic
disorder
any other skin
• Urticaric lesions
Amoxicillin rash –generalized erythematous fine maculo-papular pruritic rash
on posterior thorax
Drug Reactions
Appearnace:
• Maculo-papular rash
• Bright red
• Distribution:
• Starts on trunk, spreads to limbs-
usually spares face
• Itches and burns
• May start at any time during course
of drug therapy on through 2-3
weeks after course is finished
• Penicillins and
cephalosporins are common
causes
Urticaria/Angioedema
•
Angioedema is a severe
form of urticaria
• Will see thicker lesions from
massive transudation of fluid
into the dermis or
subcutaneous tissue
• Typically affects the lips,
periorbital area, hands, feet,
penis, or scrotum
• Potential Complication:
airway obstruction d/t
laryngeal edema
Skin Cancer
Why is the incidence increasing?
• Directly related to sun
exposure
• More common in fair-
skinned people
• Tanning bed exposure
• Radiation exposure
Neoplastic lesions: Skin Cancer
•
Three major types
of skin cancer
1. Basal cell
• Basal Cell carcinoma-most
common, but least often
malignant
2. Squamous cell
• Squamous cell carcinoma2nd most common-can
metastasize to remote areas
3. Malignant
• Melanoma- Rare but high
rates of metastasis
melanoma
Basal Cell Carcinoma
• The
most common skin
cancer in white-skinned people
• Usually a non-metastasizing
tumor
• Appearance:
• Nodular form begins as small, flesh-
colored or pink, smooth,
translucent pearly nodule
• Telangiectatic vessels
may be seen
• Eventually will form an ulcer
surrounded by a shiny border
Squamous Cell Carcinoma
• Second most
frequent skin cancer
• A red,
scaling,
keratotic, slightly
elevated lesion with
an irregular border
usually with a shallow
chronic ulcer
Melanoma: the most deadly form of
skin cancer
•
Malignant Melanoma
• Risk factors
• Family h/o of melanoma
• Blond or red hair
• Presence of freckling on the upper back
• H/o 3 or more blistering sunburns before age 20
• H/o 3 or more years of an outdoor job as a teenager
Malignant Melanoma
•
Most deadly form of
skin cancer
• Rapidly spreading and
metastatic
• Lesions vary in size and
shape
• Appearance:
• Typically raised, black or
brown, with irregular
borders, and uneven
surfaces
Skin Cancer-Know the ABCs of Melanoma
Screening
Summary of Dermatologic Agents
Topical Antiinfectives
2. Oral Agents and
Parenteral Agents
• Antibacterial agents
• Antifungal agents
• Antiviral agents
1.
• Vehicles
• Creams
• Ointments
• Powders
• Suppositories