It 16_teo Leprostatics (Farmakologi)

8/11/2019 It 16_teo Leprostatics (Farmakologi)

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Leprostatics

Leprosy (Morbus Hansen) is a chronic infectious diseasecaused by M Leprae

The disease mainly affects the skin, the peripheral nerves,mucosa of the upper respiratory tract and also the eye andthe testes

Leprosy can affect all ages (most often during two differentperiode of life: 10-14 and 35-44 years) and both sexes

It is estimated that 12 million patients worldwide

Most often the incubation periode is between 3 to 5 years

Is transmitted from one untreated person to another via therespiratory tract or skin

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1. DAPSONE (sulfones)

Dapsone (4,4 diaminodiphenylsulfone, DDS) isananalogue of p-aminobenzoic acid

It is white, odorless, crystalline powder

Insoluble in water and oil

Inexpensive and relatively non-toxic in thedoses used

Dapsone is bactericidal as well asbacteriostatic against M. Leprae

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dapsone

MECHANISM OF ACTION

- inhibits the synthesis of folic acid

PHARMACOKINETICS

- dapsone is rapidly and nearly completelyabsorbed from the GI tract

- Peak plasma concentrations are reach-

ed in 1 to 3 hours

- 70-90% of dapsone is plasma protein bound- Half-life ranges 10 to 50 hours

- Dapsone is acetylated in liver, the rate of acetylation is

genetically determined

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dapsone

Pharmacokinetics

- about 70-80% is excreted in urine as

conjugates and metabolites

INDICATIONS- Leprosy

- Dermatitis herpetiformis

- Prophylaxis malaria

- Pneumocystis carinii pneumonia

- Treatment of relapsing polychondritis

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dapsone

CONTRAINDICATIONS

- Hypersensitivity to dapsone or its

derivates

- NADPH

- Liver disease

- Lactation

ADVERSE REACTIONS

- GI tract: nausea, vomiting, anorexia and

abdominal pain

- Dematologic: drug induced-lupus erythema-

tosus, phototoxicity

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dapsone

Adverse reactions

- CNS: peripheral neuropathy, headache,

paresthesia, psychosis

- Hematologic: Dose-related hemolysis- Liver: Hyperbilirubinemia

- Sulfone syndrome (fever, exfoliative derma-

titis, jaundice and methemoglobinemia) may

develop 5 to 6 weeks after initiation of treat-

ment in malnourished patients

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dapsone

DRUG INTERACTION

- Probenicid decreases the urinary excre-

tion of dapsone

- Pyrimethamine may increases hematolo-

gic reaction

- Trimethoprim may increases serum level

of both drugs

PREPARATION AND DOSES

- Dapsone is available for oral administration in

tablets containing 25 or 100 mg

- Adult: 50100 mg daily

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2. CLOFAZIMINE

Clofazimine is a phenazine dye

It is a reddish brown powder

Fat and benzene soluble

Water insoluble Virtually non-toxic

Clofazimine exerts a slow bactericidal and

also have anti-inflammatory properties

Investigation: in combination with otherantimycobacterial drugs to treat M.Avium infectionin AIDS patients

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clofazimine

MECHANISM OF ACTION

- The mechanism of the antibacterial action

is uncertain. It preferentially binds to my

- cobacterial DNA and interferes with

growth

- Anti-inflammatory properties have been

suggested , but the mechanism is still poor

-ly understood

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clofazimine

PHARMACOKINETICS

- The absorption of this drug is quite varia-

ble, ranging from 45 to 62% after oral

administration

- Highly lipophilic and is deposited predominant-

ly in fatty tissues and in the reticuloendothelialsystem

- Has a long halflife (70 days) after re-

peated administration

- Slowly excreted, largely unmetabolized, less than 1%

appears in the urine- Small amount of this drug is eliminated in sputum,

sebum and sweat

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clofazimine

INDICATION

- Lepromatous leprosy including dapsone-

resistant lepromatous leprosy and lepro-

matous leprosy complicated by erythema

nodosum leprosum CONTRAINDICATION

- There are no known contraindication

Warning:

- Severe abdominal symptoms (pain or diarrhea)- Pregnancy women

- Nursing mothers

- Children: safety and efficacy have not been established

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clofazimine

DRUG INTERACTIONS

- No known

PREPARATION AND DOSES- Clofazimine (lamprene) is available for

oral administration in capsules

containing 50 mg and 100 mg- Dose: 50- 100 mg/daily

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3. RIFAMPIN

A semisynthetic derivative of rifamycin B

Rifampin is also effective in the treatment

of leprosy (rapid bactericidal)

To avoid resistance, this drug should begiven in combination with other leprostatics

The major side effect: hepatotoxicity

Dapsone concentration may be reduced, but it isgenerally considered unnecessary

Dose: 600 mg/daily or 12-15 mg/kg/daily

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4. ETHIONAMIDE

The use of this drug for the treatment of leprosy isinvestigational

It has been shown to be bactericidal for

M. Leprae, and its bactericidal effect is intermediatebetween that of dapsone and rifampin

It used as alternative for clofazimine (not acceptable)

The major side effect: hepatotoxicity

Dose: 250375 mg/daily

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5. OFLOXACIN

A synthetic fluoroquinolone, acts as a specificinhibitor of bacterial DNA gyrase and has showneffective in the treatment of M. Leprae

Ofloxacin is usually rapidly bactericidal forsusceptible bacteria

Adverse reaction have affected the gastrointestinaltract and the central nervous system most frequently

Should not be used for patients under 22 years Dose: 100-300 mg/daily

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6. MINOCYCLINE

Minocycline is a semisynthetic tetracycline

It achieves selective concentration insusceptible organism and induces bacterio

statics by inhibiting protein synthesis The most common adverse reaction is

esophagal irritation

Should not be used in pregnant or nursingwoman or children under 8 years

Dose: 100 mg, twice daily

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TREATMENT FOR MB LEPROSY

MB (multibacillary) Leprosy: if the number of basilmore than 10 per fields

Strain sensitive to dapsone:

- Dapsone: 100 mg/daily for 3 years, some-times for 10 years (tipe BL and LL)

- Rifampin: 600 mg/daily for 3 years

Strain resistance to dapsone:

- Clofazimine: 50-100 mg/daily, unlimited

- Rifampin: 600 mg/daily for 3 years

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It 16_teo Leprostatics (Farmakologi)

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