sign in sign up
<<
Home , Antimycobacterial

UNIT 13 -II Chemotherapy-II

Structure

13.1 Introduction Objectives 13.2 Antimalarial Agents 13.3 Anti-tubercular and Anti-leprosy Agents Anti-tubercular Agents Anti-leprosy Agents 13.4 Agents 13.5 Antiviral Agents 13.6 Anticancer Agents 13.7 Summary 13.8 Terminal Questions 13.9 Answers

13.1 INTRODUCTION

In the last unit you studied about chemotherapeutic agents obtained from natural and synthetic sources that are used in the treatment of bacterial , protozoal and helmintic infestations. In this unit you will study about agents that are used in the treatment of Malaria, Mycobacterial diseases caused by Mycobacterium spp., Fungal and viral infections, and used in the treatment of neoplastic diseases.

Objectives After studying this unit, you should be able to:

• study the drugs used in the treatment of malaria; • enumerate the various drugs used in the treatment of tuberculosis and leprosy; • various drugs used in fungal and viral infections; and • know about the drugs used in various types of malignancies.

13.2 ANTIMALARIAL AGENTS

Human malaria is caused by four species of Plasmodium namely Plasmodium falciparum, P. vivax, P. malariae and P. ovale. P. vivax is mainly responsible for most of the infections (70%) which results in benign tertian malaria. In P. falciparum and P. vivax infections, the patient has fever with rigors every third day and termed as tertian. The other two, P. ovale and P. malariae are mild in nature in which fever develops every fourth day and termed as benign quartan. Symptoms and complications in P. falciparum malaria are more severe than P. vivax malaria. 157

Pharmacology on The important antimalarial drugs are discussed here. Various Body Systems-IV Chloroquine Chloroquine is a 4-aminoquinoline antimalarial agent used for the suppression and clinical cure of malaria. It is an excellent erythrocytic schizontocide. It does not prevent relapse in P. vivax and P. ovale malaria. It is a of choice for clinical cure and suppressive prophylaxis of acute malaria but not for the resistant cases of P. falciparum. It can be safely used in pregnancy. Apart from malaria, chloroquine in also used in: Rheumatoid arthritis. • Giardiasis. • Discoid lupus erythematosus. • Infectious mononucleosis. • Taeniasis. • Lepra reactions. • Hepatic amoebic abscess (used along with metronidazole).

Primaquine Primaquine is a poor erythrocytic schizontocide. It is highly effective against gametocytes and exoerythrocytic stages. It is effective in radical cure of P. vivax and P. ovale malaria. Mefloquine It is a highly effective erythrocytic schizonticide especially against mature trophozoite and schizont forms of malarial parasite. It is used in multiresistant P. falciparum malaria. It is not useful in complicated/cerebral malaria. Quinine Quinine is a natural alkaloid obtained from cinchona bark. It is used in the treatment of cerebral falciparum malaria and multidrug resistant strains of cerebral malaria. It is also used along with clindamycin in the treatment of babesiosis. It is also effective in myotonia congenita and nocturnal muscle cramps. Proguanil It is mainly used in prophylaxis of malaria in combination with chloroquine in areas with low chloroquine resistance among P. falciparum. It can be safely used in pregnancy. Pyrimethamine-Sulfonamide Combination Ultra long acting sulfonamides in combination with pyrimethamine are used. The effect is supra-additive due to sequential block. The combination is indicated in chloroquine resistant malaria and prophylaxis. Pyrimethamine- sulfadiazine combination is used for treatment of toxoplasmosis. 158

Artemisinin Derivatives Chemotherapy-II Artemisinin is the active plant principle isolated from plant Artemisia annua, active against P. falciparum resistant strains. Three derivatives obtained from artimisinin which are used in the treatment of multidrug resistant P. falciparum are Artesunate, Artether and Artemether. SAQ 1 a) P. falciparum and P. vivax infections are also known as______malaria. b) Mefloquine is used in ______P. falciparum malaria. c) ______is a natural anti-malarial alkaloid obtained from cinchona bark. d) ______is indicated in acute attack of multidrug resistant P. falciparum malaria.

13.3 ANTI-TUBERCULAR AND ANTI-LEPROSY AGENTS

13.3.1 Anti-tubercular Agents Tuberculosis is a chronic infectious disease caused by various species of mycobacteria. The important human mycobacterium pathogens are Mycobacterium tuberculosis and Mycobacterium bovis. According to WHO, about one third of the world’s population is infected with tuberculosis. The chemotherapeutic agents used in the treatment of tuberculosis are classified into first line and second line drugs. First Line Drugs It is the most active drug used in the treatment of tuberculosis. It is a hydrazide of isonicotinic acid. It inhibits the synthesis of which is an important component of mycobacterial cell wall. As a result it kills the tubercle bacilli. It is a semisynthetic derivative of isolated from Streptomyces mediterranei. It is bactericidal against Mycobacterium tuberculosis. Apart from its main use in tuberculosis, it is also used in leprosy. The , obtained from Streptomyces griseus was the first antitubercular drug. It is the first line drug administered only through the parenteral route. It is used in all forms of tuberculosis along with other antitubercular drugs. 159

Pharmacology on Various Body Systems-IV Pyrazinamide is also a bacteriocidal drug that has similar mechanism of action as isoniazid. It also inhibits the synthesis of mycolic acid which is an important component of mycobacterial cell wall. As a result it kills the tubercle bacilli. It is tuberculostatic drug effective against many atypical mycobacteria also. It acts mainly against rapidly multiplying organisms in the cavities walls.

Second Line Drugs It is a tuberulostatic drug of moderate efficacy. This drug produces many side effects and therefore its use is limited to patients in whom resistance to better tolerated drugs is present. It is used for treatment of multidrug resistant tuberculosis with other primary drugs. It is also used in acute urinary tract infections caused by susceptible microorganisms. It is a peptide protein synthesis inhibitor antibiotic isolated from Streptomyces capreolus. It is second line antimycobacterial drug which exhibits activity against human strains of Mycobacterium tuberculosis. Kanamycin It is used in the treatment of tuberculosis caused by streptomycin resistant strains but since agents with lesser toxicity e.g. capreomycin and are available, its use is obsolete. It is similar to rifampicin and shows significant activity against M. tuberculosis, M. avium complex. Because it is less potent inducer, rifabutin is used (in place of rifampicin) for the treatment of tuberculosis in HIV-infected patients, who are on concurrent antiretroviral therapy with a protease inhibitor. It is used alone or in combination with pyrazinamide.

13.3.2 Anti-Leprosy Agents Leprosy is caused by Mycobacterium leprae. The various drugs used in the treatment of leprosy are described here. It is chemically related to sulfonamides, have been used effectively in the long term treatment of leprosy. Its mechanism of action is same as that of 160

sulfonamides i.e. inhibition of para-amino benzoic acid (PABA) incorporation Chemotherapy-II into folic acid (inhibition of folate synthesis). It is also used with pyrimethamine in chloroquine resistant malaria. Rifampicin It is bactericidal and highly effective in leprosy. Clofazimine is phenazine dye and used as alternative to dapsone in dapsone intolerant/resistant cases and in combination with dapsone and rifampicin in the multidrug treatment of leprosy. Ethionamide It is antitubercular drug used as an alternative to clofazimine in the treatment of leprosy. But due to its hepatotoxicity, its use in leprosy is very limited. Other Agents Among fluoroquinolones, ofloxacin, pefloxacin and sparfloxacin can be used in alternative regimen, when drugs like rifampicin can not be used. Detailed pharmacology of quinolones is discussed in chapter ‘Sulfonamides, nitrofurans and quinolones’. Among macrolide , clarithromycin is effective against M. leprae as an alternative multidrug therapy (MDT) regimen (detailed pharmacology is discussed in ‘Macrolide antibiotics’). SAQ 2 a) ______is the most active drug used in the treatment of tuberculosis. b) ______is the only bacteriostatic first line anti-tubercular drug. c) ______is a first line drug in the treatment of tuberculosis and leprosy. d) ______is a leprostatic dye that is used in the multidrug treatment of leprosy.

13.4 ANTIFUNGAL AGENTS

Antifungal agents are used in the treatment of topical and systemic fungal . They can be classified as systemic or topical antifungal agents and some are used both systemically as well as topically in the form of powder, ointment and vaginal tablets etc. The important drugs and infungal infections are described as under. Amphotericin B It is an antifungal antibiotic obtained from Streptomyces nodosus and chemically it is an amphoteric polyene macrolide. Amphotericin B has a wide 161

Pharmacology on spectrum of antifungal activity. It is active against Histoplasma capsulatum, Various Body Cryptococcus neoformans, Candida albicans, Sporotrichum schenkii, Systems-IV Blastomyces brasiliensis, Coccidioides immitis, Rhodotorula, Aspergillus etc. It is fungicidal at high and fungistatic at low concentration. It is used orally for intestinal candidiasis, topically for oral, vaginal and cutaneous candi-diasis and hospital treatment of progressive and potentially fatal systemic fungal infections. It is the gold standard of antifungal therapy. Nystatin It is obtained from Streptomyces noursei. It has similar antifungal action as amphotericin but is highly toxic and used topically only. It is effective against Candida, Histoplasma, Trichophyton, Blastomyces, Microsporum audouini etc. It is indicated in Candida albicans especially oral moniliasis, monilial vaginitis, conjunctival, cutaneous and corneal candidiasis. Griseofulvin It is isolated from Penicillium griseofulvium. It is active against Epidermophyton, Trichophyton and Microsporum causing superficial infection or dermatophytosis. It is indicated in fungal infections of skin, scalp and nails, tinea of hand and beard and athlete’s foot. Flucytosine It is effective against Cryptococcus neoformans and some Candida strains and dermatiaceous moulds which cause chromoblastomycosis. It is mainly used as an adjuvant drug to amphotericin. Clotrimazole It is useful as topical application. It is indicated in infections of the genital region (vaginitis) caused by fungi (mostly Candida) and superinfections caused by clotrimazole sensitive bacteria; infectious leucorrhoea caused by yeast fungi. All imidazoles and triazoles produce antifungal action by inhibiting ergosterol biosynthesis. Ketoconazole It is orally effective broad spectrum imidazole antifungal drug. It is useful in both dermatophytosis and deep mycosis. Its spectrum is similar to that of miconazole and is more active against Coccidioides. Terbinafine Terbinafine is used in the treatment of dermatophytoses especially onchomycosis by oral therapy. Also useful in tinea and pityriasis versicolor. It exerts its mechanism by inhibiting squalene epoxidase.

Miscellaneous Agents Tolnaftate is effective in tinea cruris and tinea corporis. Used in the form of 162 solution and cream used topically. Not useful in candidiasis and other types of

superficial mycoses. Selenium sulfide is used as shampoo and used in the Chemotherapy-II treatment of scalp fungal infection. Quinindochlor is found effective against dermatophytosis, infected eczema and seborrhoea. SAQ 3 a) ______and ______act by inhibiting ergosterol synthesis. b) ______exerts its antifungal effect by inhibiting squalene epoxidase. c) ______is indicated only in fungal infections of skin, scalp and nails.

13.5 ANTIVIRAL AGENTS

Viruses have no cell wall and made up of nucleic acid core enclosed in a protein coat which consists of identical subunits. Viruses are of two types, DNA (deoxyribonucleic acid) viruses and RNA (ribonucleic acid) viruses. DNA viruses are herpes simplex, small pox, hepatitis B, varicella-zoster etc. and RNA viruses are rabies, measles, dengue, rubella, yellow fever, poliomyelitis and HIV etc. In viral infections, replication of viruses is at peak, at or before the manifestation of clinical symptoms. So, the treatment generally depends either on early initiation of therapy or prevention of infection i.e. chemoprophylaxis. The various antiviral agents are described here. Idoxuridine It is chemically related to thymidine and acts by competing with it in the synthesis of DNA and ultimately preventing the utilization of thymidine. It prevents the replication of DNA viruses and its clinical use is limited to herpes simplex keratitis. It is used in herpes simplex keratoconjunctivitis in 0.1 to 0.5% solution/eye ointment applied one to two hourly. Acyclovir Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses. It is used in the treatment of:

• Herpes simplex virus infection of the skin and mucous membrane, including initial and recurrent genital herpes.

• Prevention of recurrences of herpes simplex infection in immunocompetent patients.

• Prophylaxis of herpes simplex infection in immunocompromised patients.

• Varicella (chickenpox) and herpes zoster (shingles) infections. Early treatment of shingles with acyclovir can reduce the incidence of post- herpetic neuralgia (zoster-associated pain). 163

Pharmacology on Zidovudine Various Body Systems-IV It is a thymidine analogue. It is used in asymptomatic and symptomatic HIV disease. Lamivudine Lamivudine may be used prophylactically in health care workers at risk of acquiring HIV infection after occupational exposure to the virus and in combination with zidovudine for treatment of HIV infection. Nevirapine It is also been shown to be effective in the prevention of transmission of HIV from mother to new born. Efavirenz It is used in combination with other retroviral drugs for the treatment of HIV infection in a dose of 600 mg once daily. Indinavir It is indicated in treatment of HIV infection and is used in combination with other anti-retroviral agents in a dose 800 mg every eight hourly. Ritonavir It is inhibitor of HIV-1 and 2 proteases. The common adverse effects include GIT disturbances, hypertriglyceridemia and elevation of serum aminotransferase. Amantadine and its Derivative It is used in prophylaxis of influenza A virus, idiopathic parkinsonism and drug-induced extrapyramidal reactions. Rimanditine is a more potent and longer acting congener of amantadine. Ribavirin It is active against influenza A and B, measles, paramyxoviruses, respiratory syncytial virus, HCV and HIV-1. Interferons Interferons are cellular glycoproteins produced by the host cells which exert complex antiviral, immunoregulatory and antiproliferative activities. There are three types of interferons – alpha, beta and gamma. Interferons are indicated in chronic hepatitis B and C. Alpha interferon is also effective in the treatment of hairy cell leukaemia, condyloma acuminata (caused by papilloma virus), chronic myelogenous leukaemia and AIDS related Kaposi’s sarcoma. SAQ 4 1. a) Acyclovir is a synthetic ______analogue with inhibitory activity 164 against human herpes viruses.

b) The active form of zidovudine is ______. Chemotherapy-II c) ______is used in prophylaxis of influenza A virus, idiopathic parkinsonism and drug-induced extrapyramidal reactions. d) Zidovudine selectively inhibits the enzyme ______.

13.6 ANTICANCER AGENTS

Cancer is a disease of cells characterized by a shift in the control mechanism which govern cell proliferation and differentiation and the anticancer agents either kill cancer cells or modify their growth. The various anticancer agents are discussed as under. i) Alkylating Agents Alkylating agents react with nucleic acid and inhibit DNA synthesis and also interfere with cell replication. Alkylating agents has got cytotoxic action and damage the nuclei of growing and multiplying cells. They have got immunosuppressant action also and suppress antibody production. They also have radiomimetic (like ionizing radiation) actions. Cyclophosphamide is a prodrug. In the body it gets converted into the active cytotoxic forms, aldophosphosphamide and phosphoramide mustard. It is indicated in leukaemias, lymphogranulomatosis, lymphosarcoma, reticulum cell sarcoma, Hodgkin’s disease and multiple myeloma, retinoblastoma, carcinoma of the breast, adenocarcinoma of the ovary. It is used in combination with surgery, radiation and other therapeutic measures. Chlomabucil is indicated in chronic lymphocytic leukaemia (drug of choice), advanced ovarian adenocarcinoma, breast cancer, certain forms of non-Hodgkin’s lymphoma and Hodgkin’s disease. Lomustine is indicated in Hodgkin’s disease, brain tumour, lung carcinoma. ii) Antimetabolites are analogues of normal DNA components or of coenzymes involved in nucleic acid synthesis. They get incorporated or competitively inhibit utilization of normal substrate to form dysfunctional nucleic acid molecules. Methotrexate is a broad spectrum antineoplastic drug which act as an of folic acid. It is indicated in lymphoblastic leukemia and choriocarcinoma, and to reduce requirement in patients with severe steroid dependent asthma. It is also used as ‘disease modifying drug’ in rheumatoid arthritis as it reduces lymphocyte proliferation, rheumatoid factor production and interferes with the release of inflammatory cytokines. 6- Metrcaptopurine is used in acute leukaemia, choriocarcinoma and chronic granulocytic leukaemia. Fluorouracil is used in the treatment of carcinoma of breast, colon, urinary bladder, stomach liver, rectum and ovaries. Cytarabine is indicated in acute myelocytic leukaemia, acute 165

Pharmacology on lymphocytic leukaemia, chronic myeloid leukaemia (blast phase), non- Various Body Hodgkin’s lymphoma in children, treatment and maintenance of Systems-IV meningeal neoplasms.

iii) Cytotoxic Antibiotics

These drugs are obtained from various micro-organisms and have antitumor activity. They act by binding to double stranded DNA and interfere with its functions. Actinomycin-D is a potent antitumor antibiotic isolated from Streptomyces organism. It is used in choriocarcinoma, Hodgkin’s disease and Wilm’s tumour in combination with irradiation. Doxorubicin is indicated in gastro-intestinal tract carcinoma, acute myeloblastic leukaemia, breast and ovarian carcinoma, soft tissue and sarcomas, malignant lymphoma; primary management of nonmetastatic bladder carcinoma and neuroblastoma. Bleomycin is used as palliative and adjuvant to surgery and radiation therapy in testicular tumour, squamous cell carcinoma of skin, neck and head, genitourinary tract and oesophagus neoplasm, malignancy of cervix, Hodgkin’s and non Hodgkin’s lymphoma, embryonal cell carcinoma of testis and brain tumour.

iv) Vinca Alkaloids

The vinca alkaloids are isolated from plant Vinca rosea. They are cell cycle specific and mitotic inhibitors. They exert their cytotoxic action by binding to the protein tubulin and preventing the formation of the mitotic spindle. Vincristine is indicated in acute leukaemias, lymphomas, Ewing’s sarcoma, neuroblastoma, and thrombocytopenic purpura. Vinblastine is indicated in Hodgkin’s and non Hodgkin’s lymphoma and testicular carcinoma. Vinorelbine is used for the treatment of non small cell lung carcinoma, breast carcinoma, Hodgkin’s disease, ovarian carcinoma, squamous cell carcinoma of the head and neck, cervical squamous cell carcinoma and renal cell cancer.

v) Texanes

Paclitaxel and docetaxel are related drugs derived from the western yew tree (Taxus brevifolia). They are indicated in metastatic ovarian and breast cancer.

vi) Topoisomerase-I Inhibitors

Irinotecan and Topotecan belong to the chemical group Camptothecin analogues. They are used in the treatment of metastatic carcinoma of colon or rectum. vii) Hormone and Hormone Antagonists

These are not cytotoxic drugs. They act by modifying the growth of hormone dependent tumours. Fosfestrol is a synthetic non-steroidal estrogen which is activated by the enzyme acid phosphatase to produce 166

stilboestrol. It is used as palliative treatment of disseminated mammary Chemotherapy-II or prostatic carcinoma. Ethinylestradiol is also indicated in palliative treatment of disseminated mammary or prostatic carcinoma. Tamoxifen is used as palliative treatment of estrogen receptor positive advanced or metastatic carcinoma of breast. viii) Miscellaneous Agents

Hydroxyurea is indicated in treatment of chronic granulocytic leukaemia, polycythemia vera, metastatic or inoperable carcinoma of ovary. In combination with radiotherapy in carcinoma of cervix, head, neck and lung. Procarbazine is found to be effective in Hodgkin’s disease and carcinoma of lungs. L-Asparginase is used in the treatment of malignant lymphoma and acute leukaemia. Cisplatin is effective in metastatic testicular and ovarian carcinoma and advanced bladder carcinoma. ix) Immunosuppressants

The drugs like azathioprine and cyclosporine A are used chiefly to prevent transplant rejection and in the treatment of autoimmune diseases. They are used to prevent graft rejection after kidney, liver, lung, pancreas transplant or bone marrow transplantation. Azathioprine is used primarily as immunosuppressant in organ transplantation, progressive rheumatoid arthritis and some other autoimmune diseases. Cyclosporine is the most effective drug for prevention and treatment of graft rejection reaction. It is used in cardiac, hepatic, renal, bone marrow transplantation and as second line drug in rheumatoid arthritis, inflammatory bowel disease, dermatomyositis, bronchial asthma and certain other autoimmune diseases.

SAQ 5 a) Aldophosphamide is the active form of ______. b) Vinca alkaloids inhibit mitosis by binding to the protein ______. c) ______is used as palliative treatment of estrogen receptor positive carcinoma of breast.

13.7 SUMMARY

• Human malaria is caused by four species of Plasmodium namely Plasmodium falciparum, P. vivax, P. malariae and P. ovale.

• Chloroquine is the drug of choice for clinical cure and suppressive prophylaxis of drug sensitive acute malaria.

• Quinine is the drug of choice for the treatment of cerebral falciparum malaria and multidrug resistant strains of cerebral malaria. 167

Pharmacology on • Tuberculosis is a chronic infectious granulomatous disease caused by Various Body various species of mycobacteria. Systems-IV • First line drugs used in the treatment of tuberculosis are isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin.

• The second line drugs are only employed when the organism is resistant to isoniazid or rifampicin or both.

• Leprosy is caused by Mycobacterium leprae. The most commonly used drugs in the treatment of leprosy are dapsone, clofazimine and rifampicin.

• Antifungal agents are used in the treatment of topical and systemic fungal infection.

• It is orally effective broad spectrum imidazole antifungal drug. It is useful in both dermatophytosis and deep mycosis.

• Acyclovir is used in the treatment of herpes simplex and herpes zoster infections.

• The main mechanism of alkylating agents is the alkylation of DNA, shich leads to cell death.

• Methotrexate is a broad spectrum antineoplastic drug which acts as an antimetabolite of folic acid.

• Hormone antagonists are generally used in the treatment of hormone dependent neoplasms.

13.8 TERMINAL QUESTIONS

1. What are the different organisms that cause malaria in humans? 2. Classify the drugs used in the treatment of Tuberculosis? 3. Write briefly about the first line anti-mycobacterial agents. 4. Explain the mechanism of action and therapeutic uses of Amphoterecin B.

13.8 ANSWERS

1. a) Tertian b) Multiresistant c) Quinine d) Artesunate 2. a) Isoniazid b) Ethambutol c) Rifampicin d) Clofazimine 168

3. a) Imidazoles & triazoles Chemotherapy-II b) Terbinafine c) Griseofulvin 4. a) Purine nucleoside b) Zidovudine triphosphate c) Amantadine d) Reverse transcriptase 5. a) Cyclophosphamide b) Tubulin c) Tamoxifen Terminal Questions 1. Malaria is a parasitic infection caused by four species of Plasmodium namely Plasmodium falciparum, P. vivax, P. malariae and P. ovale. P. vivax is mainly responsible for most of the infections (70%) in India. In P. falciparum and P. vivax infections, the patient has fever with rigors. Symptoms and complications in P. falciparum malaria are more severe than P. vivax malaria. The other two, P. ovale and P. malariae are mild in nature. 2. Based on the duration of onset of action, the adverse effects and the susceptibility of M. tuberculosis, the drugs used in the treatment of tuberculosis are classified into the following groups: I. First line or standard drugs: Isoniazid, Rifampicin, Streptomycin, Pyrazinamide, Ethambutol II. Second line or reserved drugs: Ethionamide, Para-amino salicylic acid, Thiacetazone etc. III. Newer drugs: Rifabutin, 3. First line agents are those agents that are used in the treatment of tuberculosis. If therapy with these agents does not improve the prognosis, the second line drugs are added to the regimen. Isoniazid is the most active drug used in the treatment of tuberculosis. It is a hydrazide of isonicotinic acid. It is a bactericidal drug, effective against mycobacterium tuberculosis and ineffective against atypical mycobacteria. Rifampicin is a semisynthetic derivative of rifamycin isolated from streptomyces mediterranei. It is bactericidal against mycobacterium tuberculosis. Apart from its main use in tuberculosis, it is also used in leprosy. Streptomycin was the first antitubercular drug. After oral administration it is not absorbed. After injection the absorption is rapid. It is used in all forms of tuberculosis along with other antitubercular drugs. 169

Pharmacology on Pyrazinamide is chemically related to nicotinamide and Various Body thiosemicarbazone used in tuberculosis. Systems-IV Ethambutol it is tuberculostatic drug effective against many atypical mycobacteria also. It acts mainly against rapidly multiplying organisms in the cavities walls. 4. Amphoterecin B is an antifungal antibiotic obtained from Streptomyces nodosus. It has a wide spectrum of antifungal activity. It is active against Histoplasma capsulatum, Cryptococcus neoformans, Candida albicans, Sporotrichum schenkii, Blastomyces brasiliensis, Coccidioides immitis, Rhodotorula, Aspergillus etc. It is fungicidal at high and fungistatic at low concentration. It is used orally for intestinal candidiasis, topically for oral, vaginal and cutaneous candi-diasis and hospital treatment of progressive and potentially fatal systemic fungal infections. It is the gold standard of antifungal therapy.

170