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Antifungal Drugs

Pharmacology & Therapeutics Dept .


School of Medicine
Universitas Sumatera Utara

The antifungal drugs presently available fall


into several categories:
systemic drugs (oral or parenteral) for
systemic infections,
oral drugs for mucocutaneous infections, and
topical drugs for mucocutaneous infections.

ANTIFUNGAL
Systemic Antifungal Agents
1. Griseofulvin
2. Oral Azole Derivatives
3. Terbinafine
4. Hidroksistilbamidin
5. Flucytosin
6. Amphoterisin B

TOPICAL ANTIFUNGAL AGENTS


1. Topical Azole Derivatives
2. Ciclopirox Olamine
3. Naftitine
4. Terbinafine
5. Butenafine
6. Tolnaftate
7. Nystatin
8. Natamisin
9. Asam lemak
10. Haloprogin

The treatment of superficial fungal infections caused


by dermatophytic fungi may be accomplished
1. Topical antifungal agents
- clotrimazole
- miconazole
- econazole
- ketoconazole
- oxiconazole
- sulconazole
- ciclopirox olamine
- naftitine
- terbinafine
- and tolnaftate

2. Orally administered agents


- griseofulvin
- terbinafine
- ketoconazole
- fluconazole
- and itraconazole.

3. Superficial infections caused by candida species


may
be treated with topical applications of
- clotrimazole
- miconazole
- econazole
- ketoconazole
- oxiconazole
- ciclopirox olamine
- nystatin
4. Chronic generalized mucocutaneous candidiasis is
responsive to long-term therapy with oral
ketoconazole.

Fig. 1

Mode action of antifungal drugs

Pharmacokinetic Antifungal Drugs


No

Drugs

Absorp
tion

Distribution

Meta
bolism

Excretion

1.

Amphoterisin
B

Urine
Billier

2.

Fluconazole

Urine

3.

Fluciytosin

CNS fluid

Urine

4.

Ketoconazole

Urine
Billier

5.

Griseofulvin

Tissue
keratin

Urine
Faeces

6.

Nystatin

Fungal
Sterol

Faeces

7.

Salicylic Acid

Pharmacodynamic Antifungal Drugs


No

Drugs

Indications

Side effects

Contraindications

Exp.

1.

Amphoterisin B

-Sinusitis
-Meningitis kronis
-Kandidiasis

-Menggigil
-Demam
-Muntah
-Sakit Kepala
-Hipotensi

-Muntah
-Diare
-Gangguan fungsi hati

2.

Fluconazole

-Kandidiasis oral
dan esophagus
-Kandidiasis
sistemik
-Meningitis

-Muntah
-Diare
-Gangguan
fungsi hati

-Gangguan fungsi hati


-Kehamilan dan laktasi
-Hipersensitivitas

3.

Flucytosine

-Kandidiasis
-Meningitis
kriptokokal

-Mual,Muntah
-Rash
-Depresi sumsum tulang

-Gagal Ginjal
-Kehamilan dan Laktasi

+ Amfoterisin B =
Aktifitasnya

4.

Ketoconazole

-Blastomikosis
-Histo
plasmosis
-Kandidiasis
-Dermato
mikosis

-Mual
-Ginekomastia
-Hepatitis
Kolestatik

-Hipersensitivitas
-Kehamilan dan Laktasi
-Penyakit hepar akut

Ketokonazol merupakan
obat pilihan untuk
Blastomikosis

Obat pilihan untuk


infeksi jamur sistemik
yang berat

Pharmacodynamic cont
No

Drugs

Indications

Side Effects

Contraindication

Explanation

5.

Griseofulvin

Infeksi
dermatofitosis
berat pd kulit,
rambut, kuku
disebabkan
Trycophyton
rubrum.

-Infections
-Serum
Sickness
-Leukopenia

Kehamilan

Obat pilihan untuk


infeksi
dermatofitosis yang
berat

6.

Nystatin

-Skin Candidiasis
,selaput
Lendir, GIT
-Stomatitis

-Muntah
-Diarrhae

Hyper
sensitivitas

(-) Superinfeksi
pada wanita hamil

7.

Salisilyc acid

-Ptyriasis
versicolor
-Tinea Pedis

-Alergi

Hiper
sensitivitas

Asam salisilat
bekerja keratolitis,
yaitu dapat
melarutkan lapisan
tanduk

Antifungal Clinical Applications


No.

Disease

Therapy

1.

Oral Candidiasis

2.

Vaginal Candidiasis

3.

Aspergilosis

Parenteral: Amphotericin B IV 0,5-1,0 mg/kgbw daily

4.

Criptoccosis

Parenteral: Amphoterisin B IV 0,4-0,5 mg/kgbw

5.

Blastomicocys

6.

Tinea Pedis

7.

Tinea Unguium
(Onicomycosis)

8.

Tinea capitis

9.

Ptyriasis versicolor

Oral : Fluconazole tablet 1 dd 50-100 mg during 1-2 week


Ovula: Clotrimazole 200 mg during 3 days or single dose 500
mg
Oral: Fluconazole tablet 150 mg single dose

Oral : Ketoconazole tablet 1 dd 400 mg during 6-12 month


Myconazole ointment 2% 1-2 dd during 3-5 week
Ung.Whitfield (Benzoic Acid 5 %, Salisilyc acid 5% in lanolinvaselin ana)
Terbinafine tablet 250 mg/days
6 weeks for finger hand, 12 weeks for finger foot
Griseofulvin 500mg/day [tidak lebih dari 10 mg/kgBB/hari]
hingga sembuh [6-8 weeks].
Salisilat acid 5-10% (used in ruam)
Ketoconazole cream during 2-3 weeks

As with all topical products, selection of


the dosage form may be as important as
proper drug selection.
Thin liquids may preferable for application
to hairy areas, creams for the hands and
face, and ointments may be preferable for
the trunk and legs. Other dosage forms
available include shampoos and sprays.

Most topical antifungal drugs require four


weeks of treatment. Infections in some
areas, particularly the spaces between
toes, may take up to six weeks for cure.

Precautions
Most topical antifungal agents are well tolerated.
The most common adverse effects are localized
irritation caused by the vehicle or its
components. This may include redness, itch,
and a burning sensation. Some direct allergic
reactions are possible.
Topical antifungal drugs should only be applied
in accordance with labeled uses. They are not
intended or ophthalmic (eye) or otic (ear) use.
Application to mucous membranes should be
limited to appropriate formulations.

The antifungal drugs have not been


evaluated for safety in pregnancy and
lactation on topical application under the
pregnancy risk category system. Although
systemic absorption is probably low,
review specific references.
Interactions
Could be reduced metabolism of several
drugs

Medan, 28 Februari 2008

ANTILEPROSY DRUGS

dr. Zulkarnain Rangkuty, MSi

Dept. Pharmacology & Therapeutic


School of Medicine
Universitas Sumatera Utara

Leprosy (Hansen's Disease)

Leprosy, or Hansen's disease,


is a chronic infectious disease
caused by the bacterium
Mycobacterium leprae.
Incubation : ~ 5 years

Mycobacterium leprae

Mycobacterium leprae, the causative agent of


leprosy. As acid-fast bacteria, M. leprae
appear red when a Ziehl-Neelsen stain is used

Leprosy is primarily a granulomatous


disease of the peripheral nerves and
mucosa of the upper respiratory tract; skin
lesions are the primary external symptom.
Left untreated, leprosy can be progressive,
causing permanent damage to the skin,
nerves, limbs, and eyes.

Cutaneous leprosy
lesions on a patient's
thigh.

The clinical symptoms of leprosy vary but


primarily affect the skin, nerves, and
mucous membranes.

Effective treatment for leprosy appeared in


the late 1940s with the introduction of
dapsone and its derivatives. However, leprosy
bacilli resistant to dapsone gradually evolved
and became widespread, and it was not until
the introduction of multidrug therapy (MDT) in
the early 1980s that the disease could be
diagnosed and treated successfully within the
community.

CLASSIFICATION
Paucibacillary (tuberculoid leprosy)
Multibacillary Hansen's disease
(lepromatous leprosy)
or borderline leprosy

PAUCIBACILLARY
Paucibacillary Hansen's disease is
characterized by one or more
hypopigmented skin macules and
anaesthetic patches, i.e., damaged
peripheral nerves that have been attacked
by the human host's immune cells.

MULTIBACILLARY
Multibacillary Hansen's disease is
associated with symmetric skin lesions,
nodules, plaques, thickened dermis, and
frequent involvement of the nasal mucosa
resulting in nasal congestion and epistaxis
(nose bleeds) but typically detectable
nerve damage is late.

BORDERLINE
Borderline leprosy (also termed multibacillary),
of intermediate severity, is the most common
form. Skin lesions resemble tuberculoid leprosy
but are more numerous and irregular; large
patches may affect a whole limb, and peripheral
nerve involvement with weakness and loss of
sensation is common. This type is unstable and
may become more like lepromatous leprosy or
may undergo a reversal reaction, becoming
more like the tuberculoid form.

Tabel MIC ANTILEPROSY DRUGS


Obat

Rifampicin
DDS
Acedapson
Etionamid
Protionamid
Clofazimin

MIC

Dosis

Rasio serum

Ug/ml

mg

puncak MIC

0.3
0.003
0.003
0.05
0.05
-

600
100
225
375
375
50/100

30
500
15
60
460
-

Lamanya konsentrasi
serum lampaui MIC (hari)

1
10
200
1
1
-

Aktivitas
bakterisidal

+++
+
++
++
+

TREATMENT of LEPROSY
Multidrug therapy (MDT) and combining all
three drugs was first recommended by a
WHO Expert Committee in 1981. These
three anti-leprosy drugs are still used in
the standard MDT regimens. None of
them are used alone because of the risk
of developing resistance.

THERAPY:
DAPSON
RIFAMPICIN
CLOFAZIMIN

The WHO Study Group's report on the


Chemotherapy of Leprosy in 1993
recommended two types of standard MDT
regimen be adapted.
The first was a 24-month treatment for
multibacillary (MB or lepromatous) cases using
rifampicin, clofazimine, and dapsone.
The second was a six-month treatment for
paucibacillary (PB or tuberculoid) cases, using
rifampicin and dapsone.

Until the development of dapsone, rifampin,


and clofazimine in the 1940s, there was no
effective cure for leprosy. However, dapsone
is only weakly bactericidal against M. leprae
and it was considered necessary for patients
to take the drug indefinitely. Moreover, when
dapsone was used alone, the M. leprae
population quickly evolved antibiotic
resistance; by the 1960s, the world's only
known anti-leprosy drug became virtually
useless.

WHO (1998)
MB (12-18 month)
PB with 2-5 lesion (6-9 month)
PB only 1 lesion :
Rifampicin 600 mg + Ofloxacin 400 mg + Minosiklin 100 mg
single dose
Or
MB resistance to Rifampicin and DDS CLOFAZIMIN:
Clofazimin 50 mg + Ofloxacin 400 mg + Minosiklin 100 mg
during 18 month (everyday).

In Patient reject Clofazimin, we can use:


Rifampicin 600 mg + Ofloxacin 400 mg + Minosiklin 100 mg
single dose/month (24 month)

Medan, 26 Februari 2008