Brief description about chemotherapeutic agents - Definition Evolution Antibiotics Antiviral agents Antifungal agents Antiprotozoal agents Anihelminthic agents AIDS related parasitic diseases

1. CHEMOTHERAPEUTIC AGENTS

2.  Definition
 Evolution
 Antibiotics
 Antiviral agents
 Antifungal agents
 Antiprotozoal agents
 Anihelminthic agents
 AIDS related parasitic diseases

3. CHEMOTHERAPY:
Definition:
It is the use of chemical
compounds in the treatment of
diseases caused by microbial
organisms, so as to destroy the
organism, without damaging the host
tissues.

4. EVOLUTION
 Pre- Ehrlich era before 1891
 Era of Ehrlich
 Period after 1935

5. PRE-EHRLICH ERA:
Compounds were used empirically
(experimentation & observation).
E.g.:
Mercury in Syphilis Cinchona Bark for Malaria

6. Era of Ehrlich
Paul Ehrilich (1854-1915):
 German scientist
 Father of modern chemotherapy
 Nobel Prize in 1909
 Found that methylene blue killed and stained some
bacterial cells. He demonstrated that methylene blue is
useful in the treatment of malaria.
 He also discovered Salvarsan, an arsenical compond
(magic bullet) which was capable of destroying the
spirochete of syphilis.

7. Period after 1935
Gerhardt Domagk (1895-1964) :
He discovered Protosil, an azo dye which was
active against specific bacteria, Streptococcus.
Alexender Fleming:
In 1928 found that culture
of a fungus called Penicillium notatum
prevented the growth of staphylococci.
Penicillin : filtrate
Majority of antibiotics are obtained from fungi,
but some are obtained from bacteria like Bacitracin,
Colistin, Polymyxin.

8. Antibacterial Agents:
Grouped according to the site of action:
 Inhibitors of bacterial cell wall synthesis
 Inhibitors of bacterial protein synthesis
 Inhibitiors of nucleic acid synthesis

9. Inhibitors of bacterial cell wall
 β-Lactam agents
 Penicillins
 Narrow spectrum – penicillinase sensitive
 Narrow spectrum – penicillinase resistant
 Broad spectrum penicillins
 Extended-spectrum penicillins
 Cephalosporines
 Carbapenems
 Monobactams
 Vancomycin, Bacitracin

10. Inhibitor of bacterial protein
synthesis
 Tetracyclins
 Chloramphenicol
 Aminoglycosides
 Macrolides
 Lincosamides
 Fusidic acid

11. Inhibitors of nucleic acid
synthesis
Nucleic acids are ubiquitous in living cells and it is
perhaps surprising that a number of important antibacterial
agents act directly or indirectly on DNA or RNA synthesis.
• Sulphonamides and Diaminopyrimidines
• Quinolones
• Nitro-imidazoles
• Nitrofurans
• Novobiocin
• Rifamycins

13. ANTIVIRAL AGENTS
 Viruses are quite different from bacteria in their
structure, metabolic activity and multiplication.
 Virus is made of one nucleic acid core (either DNA
or RNA) enclosed in protein coat called capsid
composed of subunits called as capsomeres.
 There is no cell wall, no enzymes associated with it.

14. Antiviral compounds
 Interfering with Nucleic acid synthesis:
Idoxuridine, Alanine arabinoside, acyclovir,
ribavirin, azidothymidine
 Natural substances: Interferons
 Others: Amantadine, fomivirsen, gamma
globulin

15. Antiviral compounds:
Compound Mode of action Indication
Acyclovir Nucleoside analogue
( prevent replication)
Herpes simplex
Amantadine (and
rimantadine)
Viral uncoating and
assembly
Influenza A
Foscarnet Inhibiton of polymerase Cytomegalovirus retinitis
Ganciclovir Nucleoside analogue Cytomegalovirus
Idoxuridine Nucleoside analogue Herpes simples (topical)
Inosine pranobex Immunomodulator Herpes simplex
Tribavirin Nucleoside analogue Respiratory syncytial virus
Vidirabine Nucleoside analogue Herpes simplex virus
Zidovudine Nucleoside analogue Human immunodeficiency
virus

16. Drugs Route Indications
Idox uridine Topical HIV keratitis
Tirfluridine Topical HIV keratitis, dermatitis
Acyclovir Topical/ oral Herpeszoster, herpes
genitalis, encephalitis
Ganciclovir I.V. CMV infection
Forcarnet ” ”
Amantadine Oral Influenza A
Rimantadine Oral ”
Oseltamivir Influenza A and B
Adefovir ” HBV
Oseltamivir ” HIV

17. DRUGS USED IN HIV INFECTION
 Nucleoside Reverse transcriptase inhibitors ( NRTI):
Azidothymidine, didsnosine, stavudine, lamivudine
 Non NRTI: Nevirapine, Delaviridine
 Protease inhibitors: sanquinavir, ritonavir, indinavir
 Post exposure prophylaxis:
a. Mild to Moderate: Lamivudine 150mg bid + AZT 300mg
bid x 4 weeks
b. Severe exposure: above drugs plus, indinavir 800mg tid,
nelfinavir 750 mg tid, expanded regime.

18. ANTIFUNGAL AGENTS
Fungal Disease:
1. Superficial Mycoses: Strictly surface infection.
Skin, nail, hair & mucosa. Eg:- Pityrosporum
orbicularis by dermatophytes.
2. Subcutaneous Mycoses: Saprophytic fungi or
decaying vegetation, produces local disease with
tissue distruction and sinus formation. Eg:-
mycetoma, chromoblstomycosis, sporotricosis
and rhinosporidiosis.

19. 3. Systemic Mycoses:
 Through fungi of soil, by inhalation.
 Dissemination to CNS, bones and other internal
organs
 . Eg:- Blastomycosis, paracoccidioidomycosis,
coccidioidomycosis, histoplasmosi and
cryptococcosis.

21. Antifungal Drugs
 Applied topically:
1. Nystatin: Increases cell membrane permiability
Indication – localised candidiasis of mouth,
skin, vagina
2. Pimaricin : Aspergillus, trichophyton,
trichomonas, candida
3. Hamycin : Systemic mycoses ( cryptococcosis,
blastomycosis, histoplasmosis, candidiasis)

22.  Agents used systemically:
A. Griseofulvin (cytotoxic activity) : Trichophyton,
microsporum, epidermophyton, onychomycosis
(nails). 500mg/day in 2 to 4 divided doses.
B. Amphoterecin B: It increases cell membrane
permeability and causes oxidative damage. It has
wide antifungal activity. Eg:- Blastomycosis,
Histoplasma, Cryptococcosis, coccidides,
sporotirchum species
Contd…….

23. C. Flucytosine : It inhibit DNA synthesis. Its for
systemic infection due to yeasts. Dose: 100-
200mg/kg in 4 divided doses.
1. Azole derivatives: Inhibit synthesis of ergosterol
in fungal cell.
a) Imidazole: clotrimazole, micanazole, ketoconazole.
b) Triazoles: Fluconazole, Itraconazole
Broad spectrum: Dermatophytes, cryptococcus,
blastomyces, coccidiodes, Madurella, Nocardia
Azoles: avoided during pregnancy and lactation as they are
embryotoxic and teratogenic.

24. Treatment of Parasitic diseases
 Treatment for disease caused by Nematodes.
 Treatment for disease caused by Cestodes.
 Treatment for disease caused by Trematodes.

25. Treatment for disease caused by
Nematodes
Parasites Drug of choice Alternatives
Ascaris Pyrental pamoate Mebendazole, albendazol
Hookworm Pyrental pamoate Mebendazole, albendazol
Trichuris trichura Mebendazole Pyrental pamoate,
albendazole
E. Vermicularis Mebendazole Pyrental pamoate,
albendazole
Strongyloides Thiabendazole Albendazole,
mebendazole
Trichinella Thiabendazole Albendazole,
mmebendazole
Cutaneous larra migrans Thiabenazole, Alb Mebendazole, ivermectin
W. Bancrofti Diethyl carbamazine Ivermectin
D. Medinensis Metronidazole Thiabendazole

26. Treatment for disease caused by
Cestodes
Parasites Drug of choice Alternatives
T. Saginata Praziquantel,
Niclosamide
Mebendazole
T. Solium Niclosamide Proziquantel
Echinococcus Albendazole Mebendazole
D. Latum Praziquantel,
Niclosamide
Dichlorophen
H. Nana Praziquantel Niclosamide

27. Treatment for disease caused by
Trematodes
Parasites Drugs
Schistosomes Praziquantel
Clonorchis Praziquantel
Paragonimus Praziquantel
F. Buski Praziquantel
F. hepatica Praziquantel/ Bithionol/
Emetine

28. AIDS Related Parasitic Diseases
A wide range of bacterial, viral, fungal and parasitic
diseases occur as secondary infections in AIDS disease
and other immuno deficiency diseases.
Parasitic opportunistic diseases:
A.Protozoal infection: P carinii, T. gondi (CNS
involvement), Isospora (diarrhoea >1month duration),
cryptosporidium (diarrhoea >1month duration)
B.Helminthic infection: S. stercoralis (disseminated
infection)

29. Drugs in t/t of Parasitic Diseases
Parasite Drug of Choice Alternative drugs
1. E histolytica
Asymptomatic amoeba Diloxanide furoate Iodoquinol
Acute dysentery Metronidazole + diloxanide
followed by chloroquine or
tetracycline
Dihydroemetine
Hepatic abscess Metronidazole + diloxamide
followed by chloroquine
Dihydroemetine +
chloroquine + iodoquinol
Free living amoebae Nifuratel
2. Plasmodium species
Chloroquine Sensitive
strains
Chloroquine Amodiquine
Chloroquine Resistant
strains
Quinine Pyrimethamine+
sulfadoximes
Radical treatment Chloroquine Pyrimethamine or Proguanil
Prophylactic treatment Chloroquine Pyrimethamine or Proguanil

30. 3) Bebesia Quinine + clindam ---
Toxoplasma Pyrimethamine+sulfa
diazine
Spiramycin
Leishmania Stibogluconate sod. Pentamidine + Am B
Giardia Metronidazole Furasolidine
Isospora Trimetho + sulpham
Pneumocysits Trimetho + sulpham Pentamidins

31. References:
 O. H. P. sheet presentation slides provided by
Department of Microbiology, MGM School of
Biomedical Science, Kamothe, Navi Mumbai.
 Medical Microbiology Guide to Microbial Infections
Pathogenesis, Immunity Laboratory Diagnosis and
Control , Greenwood D.
 Essentials of Medical Pharmacology, K.D. Tripathi.
 Medical Parasitology, Dr. Arora & Brij Bala Arora
 www.google.com