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.

Systemic Antifungal Agents

1. Griseofulvin

2. Oral Azole Derivatives

3. Terbinafine

4. Hidroksistilbamidin

5. Flucytosin

6. Amphoterisin B

ANTIFUNGAL

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

1. Topical antifungal agents

- clotrimazole

- miconazole

- econazole

- ketoconazole

- oxiconazole

- sulconazole

- ciclopirox olamine

- naftitine

- terbinafine

- and tolnaftate

The treatment of superficial fungal infections caused by dermatophytic fungi may be accomplished

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 DrugsNo Drugs Absorp

tionDistribution 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

Obat pilihan untuk infeksi jamur sistemik yang berat

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 sum-sum tulang

-Gagal Ginjal

-Kehamilan dan Laktasi

+ Amfoterisin B =

Aktifitasnya

4. Ketoconazole -Blastomikosis

-Histo

plasmosis-Kandidiasis-Dermatomikosis

-Mual

-Ginekomastia

-Hepatitis Kolestatik

-Hipersensitivitas

-Kehamilan dan Laktasi

-Penyakit hepar akut

Ketokonazol merupakan obat pilihan untuk Blastomikosis

Pharmacodynamic con’t…

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 ApplicationsNo. Disease Therapy

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

2. Vaginal Candidiasis Ovula: Clotrimazole 200 mg during 3 days or single dose 500 mg

Oral: Fluconazole tablet 150 mg single dose

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

6. Tinea Pedis Myconazole ointment 2% 1-2 dd during 3-5 week

Ung.Whitfield (Benzoic Acid 5 %, Salisilyc acid 5% in lanolin-vaselin ana)

7. Tinea Unguium (Onicomycosis)

Terbinafine tablet 250 mg/days6 weeks for finger hand, 12 weeks for finger foot

8. Tinea capitis Griseofulvin 500mg/day [tidak lebih dari 10 mg/kgBB/hari]hingga sembuh [6-8 weeks].

9. Ptyriasis versicolor 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 MIC Dosis Rasio serum Lamanya konsentrasi Aktivitas

Ug/ml mg puncak MIC serum lampaui MIC (hari) bakterisidal

Rifampicin 0.3 600 30 1 +++DDS 0.003 100 500 10 +Acedapson 0.003 225 15 200 -Etionamid 0.05 375 60 1 ++Protionamid 0.05 375 460 1 ++Clofazimin - 50/100 - - +

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