Transcript ภาพนิ่ง 1

Case 22
Kongkrapun Pajeenboorawun, sec.c
Phramacology A
Case:
• Paolo, 17y/o, male, single who loves to play
basketball, came to the clinic because of irregular
whitish spots spread over his back and chest.
• He described the spots to be slightly itchy and
some of the lesions have round, reddish borders.
• He suspected that he got this condition by using
towels from his barkadas during and after
basketball games.
• Working diagnosis: TINEA CORPORIS
Tinea corporis
• Tinea corporis, on the other hand, is a common
superficial fungal infection of the body surface that
affects persons of all ages, but particularly children.
• Predisposing factors include exessive heat and
humidity, exposure to infected animals, and chronic
dermatophytosis of the feet or nail.
• The most common type of tinea corporis is an
expanding, round, slightly erythematous plaque with
an elevated scaling border.
Tinea. A, Characteristic plague of tinea corporis.
Routine histology (B) shows the picture of mild
eczematous (spongiotic) dermatitis, and periodic
acid-Schiff stain reveals deep red hyphae and
yeast form (c) within the stratum corneum.
Tinea corporis
• Tinea corporis (ringworm) is the name used for
infection of the trunk, legs or arms with a
dermatophyte fungus.
• In different parts of the world, different species cause
tinea corporis. In New Zealand, Trichophyton rubrum
(T. rubrum) is the most common cause. Infection
often comes from the feet (tinea pedis) or nails (tinea
unguium) originally.
• Microsporum canis (M. canis) from cats and dogs,
and T. verrucosum, from farm cattle, are also
common.
Inflammatory tinea
corporis
1.Give the 2 antifungal agent to
the condition.
treat
• Topical antifungal agent.
Topical azoles
Econazole, Ketoconazole, Clotrimazole,
Miconazole, Oxiconazole, Sulconazole
Topical Allylamines
Naftitine, terbinafine, and the related
benzylamine butenafine
• Systemic antifungal agent.
Systemic azoles
Fluconazole, Itraconazole,Ketoconazole
2. Discuss the mechanism of
action of these drug.
Azoles :
(Topical azoles and systemic azoles)
• Inhibit the enzyme lanosterol 14-alpha-demethylase, a
cytochrome P-450–dependent enzyme that converts
lanosterol to ergosterol.
• Inhibition of this enzyme results in unstable fungal cell
membranes and causes membrane leakage.
• The organism is unable to reproduce and is slowly killed
by fungistatic action.
Azoles (cont.)
• Adult Dose: Gently massage into affected and
surrounding skin areas bid for 2-6 wk
• Pediatric Dose: Apply as in adults
• Contraindications: Documented hypersensitivity
• Pregnancy: C - Safety for use during pregnancy has
not been established.
• Precautions: Not for treatment of systemic fungal
infections; avoid contact with the eyes; if irritation or
sensitivity develops, discontinue use and institute
appropriate therapy
Azoles (cont.)
• Clotrimazole, is a broad-spectrum, antifungal agent
used for the treatment of superficial infections
caused by species of pathogenic dermatophytes.
• The mechanism of action involves inhibition of the
synthesis of ergosterol, a major sterol in the fungal
cell membrane.
• This leads to instability of the cell membrane and
eventual death of the fungus
Azoles (cont.)
• Miconazole, a potent antifungal agent, labilizes rat liver
lysosomes. The effect of miconazole depends on the
drug/lysosome ratio and is influenced by the pH of the
incubation media, being minimal at alkaline pH. The effect of
miconazole on the lysosomal
• Ketoconazole 2% cream (Nizoral) -- Imidazole, broad-spectrum
antifungal agent indicated for topical treatment of tinea corporis.
Inhibits synthesis of ergosterol (main sterol of fungal cell
membranes), causing cellular components to leak; result is cell
death.
Azoles (cont.)
• Fluconazole (Diflucan) -- Synthetic oral antifungal (broadspectrum bistriazole) that selectively inhibits fungal cytochrome
P-450 and sterol C-14 alpha-demethylation, which prevents
conversion of lanosterol to ergosterol, thereby disrupting cellular
membranes.
• Has little affinity for mammalian cytochromes, which is believed
to explain its low toxicity.
• Available as tab for oral administration, as powder for oral susp,
and as a sterile solution for IV use.
• Has fewer adverse effects and better tissue distribution than
older systemic imidazoles.
Allyamines
• Inhibit squalene epoxidase that converts squalene to ergosterol.
• This causes squalene, a substance toxic to fungal cells, to
accumulate intracellularly and leads to rapid cell death.
• Allylamines bind effectively to the stratum corneum because of
their lipophilic nature.
• They also penetrate deeply into hair follicles.
• The substituted pyridone ciclopirox is another topical antifungal
agent that causes membrane instability by accumulating inside
fungal cells and interfering with amino acid transport across the
fungal cell membrane.
Allyamines (cont)
• Naftifine 1% cream or gel (Naftin) -- Broad-spectrum
antifungal agent that appears to interfere with sterol
biosynthesis by inhibiting the enzyme squalene 2,3epoxidase.
• This inhibition results in decreased amounts of
sterols, causing cell death.
• If no clinical improvement occurs after 4 wk,
reevaluate patient.
Allyamines (cont.)
• Terbinafine 1% cream (Lamisil) -- Fungicidal activity;
synthetic allylamine derivative that inhibits squalene
epoxidase, a key enzyme in sterol biosynthesis of
fungi, resulting in deficiency in ergosterol that causes
fungal cell death.
• Use until symptoms significantly improve
3.What lab procedures would you need
to confirm your diagnosis & guide your
treatment?
• A potassium hydroxide (KOH) examination of skin scrapings
may be diagnostic.
• A KOH test is a microscopic preparation to visualize fungal
elements removed from the skin's stratum corneum.
• The sample should be taken from the active border of a
lesion because this region provides the highest yield of
fungal elements. A KOH preparation from a vesicular lesion
should be made from the roof of the vesicle.
• The KOH helps dissolve the keratin and leaves fungal
elements intact, revealing numerous septate, branching
hyphae amongst epithelial cells. A counterstain, such as
chlorazol black E or Parker blue-black ink, may help
visualize
Lab Studies (cont.)
• A fungal culture is often used as an adjunct to KOH
for diagnosis.
• Fungal culture is more specific than KOH for
detecting a dermatophyte infection; therefore, if the
clinical suspicion is high yet the KOH result is
negative
Lab Studies (cont.)
• A few culture mediums are available for
dermatophyte growth.
• Sabouraud agar containing neopeptone or polypeptone agar
and glucose is often used for fungal culture. However, it
does not contain antibiotics and may allow overgrowth of
fungal and bacterial contaminants.
• Mycosel, a commonly used agar, is similar to Sabouraud
agar but has antibiotics.
• Commonly, dermatophyte test medium (DTM) is used. It
contains antibacterial (ie, gentamicin, chlortetracycline) and
antifungal (ie, cycloheximide) solutions in a nutrient agar
base.
• This combination isolates dermatophytes while suppressing
other fungal and bacterial species that may contaminate the
culture.
Lab Studies (cont.)
• Following culture inoculation, potential fungal growth
is monitored for 2 weeks.
• Positive culture results vary depending on the
medium used.
• DTM contains phenol red solution, which causes a color
change from straw-yellow to bright-red under alkaline
conditions, indicating a positive dermatophyte culture result.
However, the color makes identification of culture
morphology (particularly pigmentation) difficult.
• Sabouraud or Mycosel agar should be used to
assess gross and microscopic colony characteristic
4. Side effects to watch out when
giving the drugs.
• Systemic therapy may be indicated for cases of
tinea corporis that are extensive, those that
involve patients who are immunocompromised, or
those that are not responsive to topical therapy.
• Most of the topical agents are safe as long as
they are used properly and the only side effect
may be hypersensitivity.
Side effects (cont.)
• Clotrimazole & Miconazole
• SIDE EFFECTS: The most commonly noted
side effects associated with clotrimazole and
miconazole are local redness, stinging,
blistering, peeling, swelling, itching, hives, or
burning at the area of application.
Side effects (cont.)
• Oral ketoconazole: has a risk of hepatitis in
less than 1 in 10,000 cases.
• Oral Itraconazole: cytochrome P-450 activity
allows for the potential of interactions with
other commonly prescribed drugs.
• Oral terbinafine: the potential for cytochrome
P-450 drug interactions with this agent is less.
Side effects (cont.)
• Itraconazole (Sporanox)
• Rare cases of reversible idiosyncratic
hepatitis reported; monitor hepatic enzyme
test values in preexisting hepatic function
abnormalities; concomitant administration of
antacids or gastric acid secretion suppressors
may decrease absorption
Side effects (cont.)
• Fluconazole (Diflucan)
• Associated with rare cases of hepatotoxicity,
anaphylaxis, and exfoliative skin disorders;
concomitant cisapride administration may
cause torsade de pointes.
Side effects (cont.)
• Terbinafine (Lamisil)
• Rare cases of hepatobiliary dysfunction,
including cholestatic hepatitis, may occur;
changes in ocular lens and retina have been
reported, but significance is unknown;
transient decreases in absolute lymphocyte
count have been observed in controlled clinical
trials; isolated cases of reversible severe
neutropenia have been reported.