Antifungals

04/04/16Ayaz Ahmed Khaskheli M.Phil. Pharmacology 2016 1

Ayaz Ahmed Khaskheli
M.Phil. Pharmacology 20162
““Fungal Infections of theFungal Infections of the
Skin & Antifungals.”Skin & Antifungals.”
PHGY-804-Chemotherapy & Neuropharmacology- Sir Abdul Raheem
04/04/16

• Basics of Skin
• Mycology
• Fungal Infections
• Treatment
• Fungistatic and Fungicidal
• Mode of Action of antifungal
• Research StudiesTouch.
Ayaz Ahmed Khaskheli M.Phil. Pharmacology 2016 3
OBJECTIVE: after this session we will be able to understand
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SKIN:
04/04/16

Skin is the largest organ of the body. In adults it covers up to two square meters.
And all the skin is not same.
FUNCTIONS:
•Protects us against mechanical injury.
•Prevent the entry of micro-organism.
•Prevents dehydration.
•Control body temperature.
•Makes vitamin D.
•Protects against damage from uv radiation.
•Senses the outside world {heat/cold/pressure}
•Is important for social behavior.
Skin: Introduction
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2. Dermis 3. Hypodermis
1. Epidermis
SKIN: Types

##
The outer most layer
responsible for the
protective function of
the skin.
• Made up of three
main cell types.
•Keratinocytes More
than 90% of
epidermal.
•Melanocytes 5%
containing the dark
pigment .
•Melanin.
•Langerhans cells 4%
important for immune
response.
SKIN: Types
Epidermis

##
SKIN: Types
Dermis
• The thick layer beneath
epidermis.
• Strength and elasticity.
• Provide epidermis
nutrients and oxygen.
• Main cells are
fibroblast.
• Dermis contains
important structures.
{Hair,Blud
vessels,Nerves,Sweet
Glands,}

##
SKIN: Types
Hypodermis
• Consists mainly
Subcutaneous fat
(adipose tissue)
• Provides insulation
against cold and acts s
a store of energy.

FUNGAL INFECTION:
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• Some 250000 species are known
like mushrooms or yeast.
• Some of them harmful.
• The main component of their cell
membrane is ergo sterol.
• Parasite or Saprophyte.
Classified in three main classes.
• Dermatophytes.
• Mould.
• Yeasts.
MYCOLOGY: Fungus
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FUNGAL INFECTION:
Fungi are member of large group of organisms that include microorganisms such as
yeasts and molds, as well as the more familiar mushrooms. Fungi are classified as a
kingdom that is separate from plants, animals and bacteria.
FUNGAL INFECTIONS: can be itchy
and annoying, but they're rarely
serious. Common infections such as
athlete's foot, jock itch, and
ringworm are caused by fungus and
are easy to get and to pass around.
Mycology:
The study of pathogenic fungi is
referred to as medical mycology.
Tinea: Infections of the skin or nails
caused by fungi and appearing as
itching circular patches
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13
FUNGAL INFECTION: Classes
04/04/16Ayaz Ahmed Khaskheli M.Phil. Pharmacology 2016

• Tinea Pedis, more commonly known as
athlete's foot is an infection of the skin
and feet that can be caused by a variety
of different fungi
• Transmitted by spores present in
infected skin scales, which are
continually shed.
• It is often due toTrichophyton species.
• Although tinea pedis can affect any
portion of the foot, the infection most
often affects the space between the
toes.
• Athlete’s foot is typically characterized
by skin fissures or scales that can be red
and itchy.
FUNGAL INFECTION: Tinea Pedis

• Tinea pedis is spread through contact with
infected skin scales or contact with fungi in
damp areas (for example, showers, locker
rooms, swimming pools).
• Tinea pedis can be a chronic infection that
recurs frequently.
• Athlete's foot occurs when a certain fungus
grows on your skin in your feet. In addition to
the toes, it may also occur on the heels, palms,
and between the fingers.
• Athlete's foot is the most common type of tinea
fungal infections.The fungus thrives in warm,
moist areas
How is it spread

• The most common symptom is
cracked, flaking, peeling skin between
the toes or side of the foot. Other
symptoms can include:
• Red and itchy skin
• Burning or stinging pain
• Blisters that ooze or get crusty
• If the fungus spreads to your nails, they
can become discolored, thick, and even
crumble.
Signs and Symptoms

Interdigitalis
•In acute form, the lesion may include papules,
vesicles and blisters as a result of acute
inflammatory reaction.
•It can sometimes spread to the top of the foot, the
sole and the toenails, where it results in
onychomycosis.
•It normally resolves spontaneously, but relapse or re
infection can lead to chronic infection.
•This is severe if the skin on the foot is soft and damp
Plantar
•Known as “Moccasin foot”, more serious than
interdigitalT. Pedis.
•It is a chronic infection affecting the entire foot and
takes the form of erythematous, dry, scaly patches,
often extending to the back and side of the foot.

• Tinea corporis is a skin infection due to fungi. It is also called
ringworm of the body.
• Tinea corporis is a common skin disorder among children.
However, it may occur in people of all ages. It is caused by mold-
like fungi called dermatophytes.
• Fungi thrive in warm, moist areas.The following raise your risk for
a fungal infection:
• Long-term wetness of the skin (such as from sweating)
• Minor skin and nail injuries
• Poor hygiene
• Tinea corporis can spread easily to other people.You can catch the
condition if you come into direct contact with an area of ringworm
on someone's body, or if you touch contaminated items such as:
• Clothing
• Combs
• Pool surfaces
• Shower floors and walls
• The fungi can also be spread by pets (cats are common carriers).
FUNGAL INFECTION: Tinea Corporis

• Symptoms may include itching.
• The rash begins as a small area of red, raised
spots and pimples.The rash slowly becomes
ring-shaped, with a red-colored, raised border
and a clearer center.The border may look scaly.
• The rash may occur on the arms, legs, face, or
other exposed body areas.
Signs andTests:
• The health care provider can often diagnose
tinea corporis by how the skin looks.
• In some cases, the following tests may be done:
• Looking at a skin scraping of the rash under
the microscope using a KOH (potassium
hydroxide) test
• Skin lesion biopsy
Signs and Symptoms

• Ringworm usually responds to topical
medications within 4 weeks. Severe
or resistant cases usually respond
quickly to antifungal medicines taken
by mouth.
Complications
• Bacterial skin infections,
cellulitis
• Skin disorders such as pyoderma
or dermatophytid
• Spread of tinea to feet, scalp,
groin, or nails
• Whole-body (systemic) side
effects of medications

• Tinea cruris or ringworm of the groin, is an infection
of the groin area caused by fungus.
• Jock itch occurs when a particular type of fungus
grows and spreads in the groin area.
• Jock itch occurs mostly in adult men and adolescent
boys. It can sometimes accompany athlete's foot and
ringworm.The fungus that causes jock itch thrives in
warm, moist areas.
• Jock itch can be triggered by friction from clothes
and prolonged wetness in the groin area, such as
from sweating.
• Jock itch may be contagious. It can be passed from
one person to the next by direct skin-to-skin contact
or contact with unwashed clothing.
FUNGAL INFECTION: Tinea Cruris

Causes, incidence, and risk factors
•Jock itch occurs when a particular type of fungus grows and spreads in
the groin area.
•Jock itch occurs mostly in adult men and adolescent boys. It can
sometimes accompany athlete's foot and ringworm.The fungus that
causes jock itch thrives in warm, moist areas.
•Jock itch can be triggered by friction from clothes and prolonged
wetness in the groin area, such as from sweating.
•Jock itch may be contagious. It can be passed from one person to the
next by direct skin-to-skin contact or contact with unwashed clothing.
Symptoms
•Itching in groin, thigh skin folds, or anus
•Red, raised, scaly patches that may blister and ooze --The patches
often have sharply-defined edges and are often redder around the
outside with normal skin tone in the center
•Abnormally dark or light skin
FUNGAL INFECTION: Tinea Cruris

FUNGAL INFECTION: Other Fungal Infections
04/04/16

• Tinea Pedis, more commonly known
as athlete's foot is an infection of the
skin and feet that can be caused by a
variety of different fungi
• Transmitted by spores present in
infected skin scales, which are
continually shed.
• It is often due toTrichophyton
species.
• Although tinea pedis can affect any
portion of the foot, the infection
most often affects the space between
the toes.
• Athlete’s foot is typically
characterized by skin fissures or
scales that can be red and itchy.
 Localized form of T.corporis,
affecting the groin. Most often
seen in men
 Occurs worldwide but is
specially common in hot,
humid countries
 Appears in skin folds, around
genitalia and in the perianal
region
 May be associated with poor
personal hygiene
 The lesions are itchy, red,
ring-shaped, scaly patches
with an exaggerated edge.
The edges of the lesions may
have pustules or papules
 A dermatophytes infection of
the trunk and limbs. Common
specially in warm climates
 Affects all age groups
 Transmitted by direct
contact with infected
animals, humans of soil
 The condition might be seen
in infants in parts of the body
covered by nappies and may
confused with cutaneous
cadidiasis ( and hence
incorrectly treated )
 T. Corporis presents
most commonly as
characteristic ring-shaped
erythematous lesions that
spread out from their centers
( and which gave rise to the
older name “ringworm”).
These may appear in
inflammatory or non-
Tinea Pedis Tinea Corporis Tinea Cruris
MAJOR FUNGAL INFECTION: Summary

FUNGAL INFECTION: Treatment-Classes of Antifungal

Mevalonic Acid
Squalene
Lanosterol
Allylamines
C14-Demethyl-Lanosterol
Azoles
Fecosterol
Episterol
ERGOSTEROL
FUNGAL INFECTION: How Anti-Fungal Acts!

FUNGAL INFECTION: How Anti-Fungal Acts!

• They are predominantly fungi static, not fungicidal, but are still often
effective
• They have longer treatment times and are associated with relapse
• They do not have serious side effects when used topically.
• They include:
• Clotrimazole
• Ketoconazole
• Miconazole
Azole derivatives
FUNGAL INFECTION: Traement

Allylamine antifungals are FUNGICIDALS rather than fugistatic.This new group
includes:
•Naftifine (Exoderil) the parent compound which has no oral activity
•Terbinafine (Lamisil), the leading drug in this class which is also used
systemically
Allylamine antifungals
FUNGAL INFECTION: Treatment

They are mainly used orally for systemic infection but are also available in
topical forms.They include:
• Nystatin (Nystan)
• Amphotericin B (Fungilin, Amphocil) and
• Natamycin (Pimafucin, Synogil,Tymasil, Natacyn)
They are predominantly active against Candida infections where they are fungi
static.
They have no serious adverse effects in topical use.
Polyene antifungals

FUNGAL INFECTION: Comparative Studies- For Research Touch

• Studies show thatTerbinafine has a much higher
rate of cure after week 1 as opposed to
Clotrimazole
• The proportion of patients effectively treated by
terbinafine was higher at each visit compared
with clotrimazole.
• At four weeks 90% (96) of patients were
effectively treated by terbinafine compared with
only 59% (61) by clotrimazole (p=0.0001).
• At week 6 the proportion of patients effectively
treated by terbinafine remained unchanged but
was still significantly higher than the 73% (76) of
patients effectively treated by clotrimazole (p=0
002)
Terbinafine vs Clotrimazole
Results of a double blind study comparing twice daily application for one week of terbinafine 1% cream with twice daily
application for four weeks of clotrimazole
E G V Evans, B Dodman, D MWilliamson, GJ Brown, R G Bowen. BMJ VOLUME 307 1 1 SEPTEMBER 1993
FUNGAL INFECTION: Comparative Studies- For Research Touch

• Studies show that rates of mycological
cure were 94% for terbinafine emulsion-gel
and 69% for ketoconazole cream (p =
0.027).
• A clinical and mycological overall
evaluation was obtained for 72% of
patients receiving terbinafine emulsion gel
and 31% of patients receiving ketoconazole
cream (p = 0.002)
• As per the study, a 1-week course of
terbinafine 1% emulsion-gel is significantly
more effective than ketoconazole 2%
cream in the treatment of tinea corporis
and tinea cruris as regards clinical and
mycological cure and treatment safety.
Terbinafine vs Ketoconazole
Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and tinea
corporis.
Eur J Dermatol. 2000 Mar;10(2):107-9

• Studies have been conducted to compare the
efficacy of terbinafine cream during 1 week with
the efficacy of miconazole cream during 4 weeks
in the treatment of tinea pedis
• A similar patient profile with an equal
distribution as to age, sex, race, duration and
seriousness of the fungal infection and previous
treatment was kept
• Patients were treated with terbinafine cream for
1 week and placebo for 3 weeks, or with
miconazole cream for 4 weeks. Evaluation was
done 1, 2, 3, 4 and 10 weeks after the start of the
treatment.
• In the treatment of tinea pedis local application
of terbinafine cream during 1 week is as good as
treatment with miconazole cream during 4
weeks.
Terbinafine vs Miconazole
Double-blind study of the efficacy of 1 week topical terbinafine cream compared to 4 weeks miconazole cream in
patients with tinea pedis..
Vermeer BJ, Staats CC, van Houwelingen JC. J Med Assoc Thai. 1999 Oct;82(10):1006-10.
Effectivecure(weeks)

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