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Chemotherapy-II

UNIT 13 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 Antifungal 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
infections, 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 drugs 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 drug 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
Isoniazid
It is the most active drug used in the treatment of tuberculosis. It is a hydrazide
of isonicotinic acid. It inhibits the synthesis of mycolic acid which is an
important component of mycobacterial cell wall. As a result it kills the tubercle
bacilli.
Rifampicin
It 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

The aminoglycoside antibiotic, 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 Pyrazinamide
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.

Ethambutol

It is tuberculostatic drug effective against many atypical mycobacteria also. It


acts mainly against rapidly multiplying organisms in the cavities walls.

Second Line Drugs


Ethionamide
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.

Cycloserine

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.

Capreomycin

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 amikacin are
available, its use is obsolete.

Rifabutin

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.

Dapsone

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

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 Antimicrobial 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 antibiotics, 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
infection. 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
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 antimetabolite of folic acid. It is indicated in
lymphoblastic leukemia and choriocarcinoma, psoriasis and to reduce
corticosteroid 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 bone 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
168
d) Clofazimine
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, Rifapentine

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