Download - DMS. K13. Antifungal + Antilepra
![Page 1: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/1.jpg)
Antifungal Drugs
Pharmacology & Therapeutics Dept .School of Medicine
Universitas Sumatera Utara
![Page 2: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/2.jpg)
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.
![Page 3: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/3.jpg)
Systemic Antifungal Agents
1. Griseofulvin
2. Oral Azole Derivatives
3. Terbinafine
4. Hidroksistilbamidin
5. Flucytosin
6. Amphoterisin B
ANTIFUNGAL
![Page 4: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/4.jpg)
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
![Page 5: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/5.jpg)
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
![Page 6: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/6.jpg)
2. Orally administered agents
- griseofulvin
- terbinafine
- ketoconazole
- fluconazole
- and itraconazole.
![Page 7: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/7.jpg)
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.
![Page 8: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/8.jpg)
Fig. 1 Mode action of antifungal drugs
![Page 9: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/9.jpg)
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 - - - -
![Page 10: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/10.jpg)
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
![Page 11: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/11.jpg)
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
![Page 12: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/12.jpg)
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
![Page 13: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/13.jpg)
• 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.
![Page 14: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/14.jpg)
• 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.
![Page 15: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/15.jpg)
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.
![Page 16: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/16.jpg)
• 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
![Page 17: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/17.jpg)
Medan, 28 Februari 2008
![Page 18: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/18.jpg)
ANTILEPROSY DRUGS
dr. Zulkarnain Rangkuty, MSi
Dept. Pharmacology & Therapeutic School of Medicine
Universitas Sumatera Utara
![Page 19: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/19.jpg)
Leprosy (Hansen's Disease)
Leprosy, or Hansen's disease, is a chronic infectious disease caused by the bacterium Mycobacterium leprae.
Incubation : ~ 5 years
![Page 20: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/20.jpg)
![Page 21: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/21.jpg)
Mycobacterium leprae
Mycobacterium leprae, the causative agent of leprosy. As acid-fast bacteria, M. leprae appear red when a Ziehl-Neelsen stain is used
![Page 22: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/22.jpg)
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.
![Page 23: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/23.jpg)
Cutaneous leprosy lesions on a patient's thigh.
The clinical symptoms of leprosy vary but primarily affect the skin, nerves, and mucous membranes.
![Page 24: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/24.jpg)
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.
![Page 25: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/25.jpg)
CLASSIFICATION
• Paucibacillary (tuberculoid leprosy)
• Multibacillary Hansen's disease (lepromatous leprosy)
• or borderline leprosy
![Page 26: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/26.jpg)
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.
![Page 27: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/27.jpg)
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.
![Page 28: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/28.jpg)
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.
![Page 29: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/29.jpg)
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 - - +
![Page 30: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/30.jpg)
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.
![Page 31: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/31.jpg)
THERAPY:
DAPSON RIFAMPICIN CLOFAZIMIN
![Page 32: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/32.jpg)
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.
![Page 33: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/33.jpg)
![Page 34: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/34.jpg)
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.
![Page 35: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/35.jpg)
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).
![Page 36: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/36.jpg)
In Patient reject Clofazimin, we can use:• Rifampicin 600 mg + Ofloxacin 400 mg + Minosiklin 100 mg
single dose/month (24 month)
![Page 37: DMS. K13. Antifungal + Antilepra](https://reader033.vdocuments.net/reader033/viewer/2022061608/55cf8c8a5503462b138d75b4/html5/thumbnails/37.jpg)
Medan, 26 Februari 2008