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155
Anti-infective
Agents
13.2 ANTI-TUBERCULAR AGENTS
Tuberculosis (TB) is the disease caused by Mycobacteria species. Tuberculosis is caused by
either Mycobacterium tuberculosis in human beings or by M. bovis in animals.
Tuberculosis is a disease transmitted through air. A person gets infected when he comes in
contact with the environment contaminated with viable tubercle bacilli. These bacilli are expelled
while coughing, sneezing by infected person.When people with lung TB cough, sneeze or spit
they propel the TB germs into the air. Even an inhalation of only a few of these germs may cause
infection.
Tubercles are formed in the infected organs during the course of the disease. Hence the
disease is known as tuberculosis. The main symptoms are cough, tachycardia, cyanosis etc.
Depending upon the site of infection, the disease is known as:
(i) Pulmonary tuberculosis
(ii) Genitourinary tuberculosis
(iii) Tuberculous meningitis
(iv) Miliary tuberculosis
A wide variety of drugs are available for the treatment of tuberculosis. The major
breakthrough was given by Waksman and his co-workers by the introduction of streptomycin in
1944. This was followed by the introduction of p-amino salicylic acid, isoniazid, ethambutol and
rifampin.
Chemotherapy of tuberculosis faces some problems because of slow growth rate of
mycobacteria and their intracellular location. Therapy needs to be continued for at least two years.
In such a long treatment, if only single drug is used, there is a risk of drug resistance development
to that particular drug. To avoid resistance development a treatment comprises of combination of
two or more drugs.
About one-third of the world’s population has latent TB, which means people have been
infected by TB bacteria but are not ill with disease and cannot transmit the disease.
People infected with TB bacteria have a lifetime risk of falling ill with TB of 10%. However
persons with compromised immune systems, such as people living with HIV, malnutrition or
diabetes and people who use tobacco, have a much higher risk of falling ill.
When a person develops active TB, the symptoms (cough, fever, night sweats, weight loss
etc.) may be mild for many months. This can lead to delay in seeking care and results in
transmission of the bacteria to others.
Anti-tuberculosis drugs are medicines used to treat tuberculosis, an infectious disease that
can affect the lungs and other organs.
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First Line Therapy
A drug considered to be the first choice useful in initial stages of TB having high efficacy
and lesser toxicity.
Second Line Therapy
The second line drugs (WHO groups 2, 3 and 4) are only used to treat disease that is resistant
to first line therapy. These drugs have low efficacy and higher toxicity.
DOTS (Directly Observed Treatment of Short-Course)
It is known as TB-DOTS; the name given to the tuberculosis control strategy recommended
by the World Health Organization (WHO).
According to WHO, the most cost-effective way to stop the spread of TB in communities
with a high incidence is by curing it. The best curative method for TB is known as DOTS. DOTS
have five main components:
Government commitment (including political will at all levels, and establishment of a
centralized and prioritized system of TB monitoring, recording and training).
Case detection by sputum smear microscopy.
Standardized treatment regimen directly of six to nine months observed by a healthcare
worker or community health worker for at least the first two months.
A drug supply.
A standardized recording and reporting system that allows assessment of treatment results.
Antituberculosis agents are classified as follows:
(a) First Line Drugs
Isoniazid (INH)
Rifampin
Pyrazinamide
Ethambutol
Streptomycin
(b) Second Line Drugs
Ethionamide
Cycloserine
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Anti-infective
Agents
PAS (p-Amino salicylic acid)
Rifambutin
(c) Fluroquinolones
Ofloxacin
Levofloxacin
Ciprofloxacin, Moxifloxacin
Isoniazid
Structure:
O
NH
H
2
N
N
Chemical name: Pyridine-4-carbohydrazide.
Uses: It is used in the treatment of latent and active tuberculosis.
Isoniazid has been approved as prophylactic therapy for the following populations:
People with HIV infection and a purified protein derivative (PPD) reaction of at least
5mm indurations (It means person is getting infected with tuberculosis).
Contacts of people with tuberculosis and who havea PPDreaction at least5mm induration.
Formulation: Tablet.
Brand names: Isonex and Isokin.
Ethionamide
Structure:
NH
2
N
S
Chemical name: 2-Ethylpyridine-4-carbothioamide.
Uses: It is used in the treatment of latent and active TB.
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Chemistry
Formulation: Tablet.
Brand names: Trecator, Myobid, and Ethide.
Ethambutol
Structure:
HN
NH
HO
HO
Chemical name: (2S, 2’S)-2,2’-(Ethane-1,2-diyldiimino)-dibutan-1-ol.
Uses: It is used in the treatment of latent and active TB.
Formulation: Tablet.
Brand names: Mycobutol, Combutol, and Servambutol.
Pyrazinamide
Structure:
N
N
O
H
2
N
Chemical name: Pyrazine-2-carboxamide.
Uses: It is used in the treatment of latent and active TB.
Formulation: Tablet.
Brand names: Pyzina and Rizap.
PAS (p-Amino Salicyclic Acid)
Structure:
HO
O
H
O
NH
2
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Anti-infective
Agents
Chemical name: 4-Amino-2-hydroxy benzoic acid.
Uses: It is used in the treatment of latent and active TB.
Formulations: Tablet and Granules.
Brand names: Sodium-PAS and Mesalazine.
Rifampicin
Uses: It is used in the treatment of latent and active TB. It is an antibiotic used to treat a
several types of bacterial infections. This includes tuberculosis, leprosy and Legionnaire's disease
(form of atypical pneumonia caused by any type of Legionella bacteria).
Formulation: Capsule.
Brand names: Rimpin and RCIN.
Approved New Drugs (End TB Strategy Drugs as per WHO)
Delamanid
Mechanism of action: Delamanid is a dihydro-nitroimidazooxazole derivative and a pro-
drug which gets activated by the enzyme deazaflavin dependent nitroreductase. It acts by
inhibiting the synthesis of mycobacterial cell wall components, methoxymycolic acid and
ketomycolic acid.
Pretomanid (Linezolid and Meropenem Clavulanate)
Mechanism of action: It prevents the initiation of protein synthesis. It is also called as
repurposing drug because it is a new way of approaching drug compounds and targets that have
been derisked during the development stages.
13.3 ANTILEPROTIC AGENTS
Leprosy is another disease caused by mycobacteria. It is also called as a Hansen’s disease
and is a chronic disease caused due to an acid fast bacillus which producesnodules in the skin and
loss of sensation in the affected region. This dermatological infection is caused by
Mycobacterium leprae or Mycobacterium lepromatosis. M. leprae multiplies slowly and the
incubation period of the disease is about five years. Symptoms can take as long as twenty years to
appear.The disease mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory
tract and eyes.
Based upon the area under infection and intensity of reactions, leprosy can be classified in to
following:
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1. Tuberculoid Leprosy
It is characterized by the presence of infection in restricted area and less pronounced lepra
reaction. The latter indicates that very few numbers of micro-organisms present in the affected
areas.
2. Lepromatous Leprosy
It is characterized by disseminated disease with a high number of infecting micro-organisms.
Hence it requires more prolonged treatment.
3. Borderline Leprosy
Tuberculoid and lepromatous leprosy are the two extremities of the active form of the
disease. All the forms that lie in between these two extremities are known as borderline leprosy.
4. Indeterminate Leprosy
In very early stages of the disease, bacteria are not multiplied to the extent to induce lepra
reaction. This early form of the disease is known as indeterminate leprosy.
Leprosy is curable with multidrug therapy (MDT).
MDT (Multi Drug Therapy)
Since 1995, WHO has supplied MDT free of cost to leprosy patients in all endemic countries.
The drugs used in WHO-MDT are a combination of rifampicin, clofazimine and dapsone for
multibacillary (MB) leprosy patients and rifampicin and dapsone for paucibacillary (PB) leprosy
patients. Among these rifampicin is the most important antileprosy drug and therefore is included
in the treatment of both types of leprosy. Treatment of leprosy with only one antileprosy drug will
always result in development of drug resistance to that drug. Treatment with dapsone or any other
antileprosy drug used as monotherapy is considered as unethical practice.
Antileprotic Drugs are Classifies as:
(a) Sulfone
Dapsone
(b) Phenazine derivatives
Clofazimine
(c) Antibiotics
Rifampin
Ofloxacin
Moxifloxacin
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Anti-infective
Agents
Minocycline
Clarithromycin
13.4 ANTIVIRAL AGENTS
Viruses are essentially intracellular parasites. Unlike bacteria, viral replication is dependent
upon the energy, proteins, and enzymatic machinery of the host cell. Bacteria have self-
biosynthetic machinery therefore the drug in bacterial chemotherapy enjoys the advantage of
selective attack on bacteria due to many metabolic differences. But viruses take over the
metabolic system of the infected host cell. Virus replication is dependent upon the host cell
metabolism. This fact limits the scope to design the antiviral agents.
Antiviral agents have been failed due to the following demerits in their development.
Lack of satisfactory experimental models.
Use of the wrong virus in the lab.
Narrow spectrum of activity.
Difficulties in clinical assessment.
DNA Viruses
Adenoviruses (URT and eye infection)
Hepadnaviruses (Hepatitis-B)
Herpes viruses
Herpes Simplex Virus type‐1 (It causes oral herpes, ocular herpes, viral encephalitis, herpes
keratitis).
Herpes Simplex Virus type‐2 (Genital herpes)
Varicella-Zoster Virus (Chickenpox, zoster, or shingles)
Cytomegalovirus (Infectious mononucleosis)
Epstein Barr virus (Inf. mono, B‐cell lymphoma)
Papillomavirus (Warts, Skin growth)
Poxvirus (Smallpox virus)
RNA Viruses
Picornaviruses (Poliovirus causing polio)
Hepatovirus (It causes hepatitis‐A)
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Chemistry
Orthomyxovirus (Influenza A,B,C – influenza H1B1 causes swine flu)
Paramyxoviruses
Rubella virus (It causes mumps)
RSV Viruses (Respiratory Syncytial Virus)
It causes LRTI (Lower Respiratory Tract Infections)
Rhabdoviruses (It causes rabies)
Other RNA viruses are Arbovirus, rotavirus, retrovirus, arenavirus, and coronavirus.
Antiviral drugs are used to treat viral infections. Most antiviral agents are used for specific
viral infections while a broad-spectrum antiviral agent is effective against a wide range of viruses.
Antiviral agents are classified as follows:
(a) Anti-herpes Virus Drugs
Idoxuridine
Acyclovir
Famciclovir
Ganciclovir
Foscarnet
(b) Anti-influenza Drugs
Amantadine
Rimantidine
Oseltamivir
Zanamivir
(c) Anti-retroviral Drugs
(i) Nucleoside reverse transcriptase inhibitors (NRTIs)
Zidovudine
Stavudine
Lamivudine
Abacavir
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Anti-infective
Agents
(ii) Non-Nucleoside reverse transcriptase inhibitors (NNRTIs)
Nevirapine
Efavirenz
(iii) Protease inhibitors
Ritonavir
Indinavir
Lopinavir
Amantadine Drug Profile
Structure:
NH
2
Chemical name: Adamantan-1-amine.
Uses: It is useful in the treatment of influenza, Parkinson’s disease.
Formulations: Tablet and Injectable.
Brand names: Symmetral, Amantrel and Neamah.
Idoxuridine drug Profile
Structure:
N
HN
O
O
I
O
H
O
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Chemistry
Chemical name: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodo-1,2,3,4-
tetrahydropyrimidine-2,4-dione.
Uses: It is useful in the treatment of viral infections.
Formulations: Tablet, Eyedrops and Ointment (0.5% ophthalmic ointment or as a 0.1%
ophthalmic solution).
Brand names: Toxil and Idurin.
Antiretroviral therapy (ART) is a treatment for people infected with human
immunodeficiency virus (HIV) using anti-HIV drugs. The standard treatment consists of a
combination of at least three drugs that suppress HIV replication.
HAART (Highly Active Anti-Retroviral Therapy) refers to the use of combinations of
various antiretroviral drugs with different mechanisms of action to treat HIV.
Acyclovir (ACV)
Structure:
N
NH
N
N
O
NH2
O
H
O
Chemical name: 2-Amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one.
Uses: It is used in the treatment of
Genital herpes simplex
Neonatal herpes simplex
Herpes simplex labialis (cold sores)
Shingles
Acute chickenpox in immuno compromised patients
Herpes simplex encephalitis
Formulations: Tablet and Ointment.
Brand names: Zovirax, Acivir, and Ocuvir.
NH
2
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