1. Chemotherapeutic Drugs
Chemotherapy is the term originally used to describe the use of drugs that are 'selectively toxic' to invading micro-
organisms while having minimal effects on the host. The term also embraces the use of drugs that target tumors.
Mechanism of action of chemotherapeutic drugs
Chemotherapeutic drugs can affect cells by disrupting the cell membrane, interfering with DNA synthesis, altering RNA,
or blocking the use of essential nutrients.
2. Chemotherapy includes:
1. Antimicrobial agents: e.g. antibacterial (antibiotics), antiviral and antifungal.
2. Antiparasitic agents: antihelminthic and antiprotozoal.
3. Anticancer chemotherapy.
bactericidal: substance that causes the death of bacteria.
bacteriostatic: substance that prevents the replication of bacteria.
spectrum: range of bacteria against which an antibiotic is effective (e.g., broad-spectrum antibiotics are effective against a
wide range of bacteria).
3. Classification of antibiotics
Antibiotics can be classified according to the mechanism of action into cell wall inhibitors,
inhibitors of protein synthesis, Quinolones, folic acid inhibitors and antimycobacterium.
Cell Wall Inhibitors
Cell wall inhibitors are antimicrobial drugs selectively interfere with synthesis of the bacterial
•Penicillin G (benzylpenicillin): Spectrum: gram-positive and gram-negative cocci, gram-
positive bacilli, and spirochetes.
•Penicillin V: has a spectrum similar to that of penicillin G and is more acid-stable than
•Antistaphylococcalpenicillins: Methicillin,nafcillin,oxacillin and dicloxacillin are
4. •Extended-spectrum penicillins: Ampicillin and amoxicillin have an
antibacterial spectrum similar to that of penicillin G.
•Antipseudomonalpenicillins:Carbenicillin,ticarcillin, and piperacillin are
called antipseudomonalpenicillins because of their activity against P.
Clinical uses :
• Bacterial meningitis (e.g. caused by Neisseria meningitidis,
Streptococcus pneumoniae): benzylpenicillin.
•Bone and joint infections (e.g. with Staphylococcus aureus): flucloxacillin.
5. Skin and soft tissue infections (e.g. with Strep. pyogenes or Staph. aureus): benzylpenicillin, flucloxacillin.
Pharyngitis (from Strep. pyogenes): phenoxylmethylpenicillin.
Otitis media (organisms commonly include Strep. pyogenes, Haemophilusinfluenzae): amoxicillin.
Bronchitis (mixed infections common): amoxicillin.
Urinary tract infections (e.g. with Escherichia coli): amoxicillin.
Syphilis: procaine benzylpenicillin.
Endocarditis (e.g. with Strep. viridans or Enterococcus faecalis).
Hypersensitivity, Diarrhea, Nephritis, Neurotoxicity.
Hematologic toxicities: Decreased coagulation may be observed with the antipseudomonal and, to some extent,
with penicillin G. Additional toxicities include eosinophilia.
Are β-lactam antibiotics that are closely related both structurally and functionally to the penicillins.
Clinical uses :
Pneumonia caused by susceptible organisms.
Biliary tract infection.
Urinary tract infection.
- Hypersensitivity reactions, very similar to those seen with penicillin.
- Nephrotoxicity, and diarrhea.
7. Antimicrobial agents that interfere
with the synthesis or action of folate
The action of a sulfonamide is to inhibit growth of the bacteria, not to kill them; that is to say, it is bacteriostatic rather than
Clinical uses of sulfonamides
Combined with trimethoprim (co-trimoxazole) for Pneumocystis carinii.
Combined with pyrimethamine for drug-resistant malaria and for toxoplasmosis.
In inflammatory bowel disease: sulfasalazine (sulfapyridine-aminosalicylate combination) is used.
For infected burns (silver sulfadiazine).
For some sexually transmitted infections (e.g. trachoma).
For respiratory infections.
For acute urinary tract infection.
8. Side effects:
- Mild to moderate side effects include nausea and vomiting, headache and mental depression. Cyanosis caused by
methaemoglobinaemia may occur.
- Serious adverse effects necessitating cessation of therapy include hepatitis, hypersensitivity reactions (rashes,
fever, anaphylactoid reactions), bone marrow depression and crystalluria. This last effect results from the
precipitation of acetylated metabolites in the urine.
Trimethoprim is active against most common bacterial pathogens, and it is bacteriostatic too. It is sometimes
given as a mixture with sulfamethoxazole in a combination called co-trimoxazole.
- Nausea, vomiting, blood disorders and skin rashes.
- Folate deficiency, with resultant megaloblasticanaemia.
10. Antimicrobial agents affecting bacterial protein synthesis
- Tetracyclines are broad-spectrum antibiotics against Gram-positive and Gram-negative bacteria, Mycoplasma,
Rickettsia, Chlamydia spp., spirochaetes and some protozoa (e.g. amoebae).
- Examples: tetracycline, doxycycline and minocycline.
Rickettsial and chlamydial infections, brucellosis, anthrax, mycoplasma and leptospira, mixed respiratory tract infections ,
chronic bronchitis and acne.
11. Adverse effects:
- Gastrointestinal caused initially by direct irritation and later by modification of the gut flora.
- Yellow discoloration of teeth in children.
- They should not be given to children, pregnant women or nursing mothers.
- Phototoxicity (sensitization to sunlight).
- High doses of tetracyclines may result in renal damage and disturbances of the bone marrow.
12. II. Chloramphenicol
Chloramphenicol has a wide spectrum of antimicrobial activity, including Gram-negative and Gram-positive
organisms and rickettsiae. It is bacteriostatic for most organisms but kills H. influenzae.
Infections caused by Haemophilus influenzae resistant to other drugs.
Meningitis in patients in whom penicillin cannot be used.
It is also safe and effective in bacterial conjunctivitis (given topically).
It is effective in typhoid fever.
13. Adverse effects:
Depression of the bone marrow.
Chloramphenicol should also be used with great care in newborns, it can result in the 'grey baby syndrome'-
vomiting, diarrhoea, flaccidity, low temperature and an ashen-grey colour-which carries 40% mortality.
Gastrointestinal disturbances secondary to alteration of the intestinal microbial flora.
The main agents are gentamicin, streptomycin, amikacin, tobramycin and neomycin.
The aminoglycosides are effective against many aerobic Gram-negative and some Gram-positive organisms they are most
widely used against Gram-negative enteric organisms and in sepsis.
Ototoxicity and nephrotoxicity .
A rare but serious toxic reaction is paralysis caused by neuromuscular blockade.
Examples: Azithromycin,erythromycin and Clarithromycin
Spectrum: Narrow spectrum (like penicillin G).
Replace penicillin in case of penicillin allergy.
Syphilis and gonorrhoeae.
Toxoplasmosis and chlamydial infection in pregnancy.
The fluoroquinolones include the broad-spectrum agents ciprofloxacin, levofloxacin, ofloxacin, norfloxacin and moxifloxacin, as
well as a narrow-spectrum drug used in urinary tract infections-nalidixic acid.
Mechanism of action: Bactericidal through inhibition of nucleic acid synthesis.
Spectrum: Broad spectrum.
Complicated urinary tract infections.
Respiratory infections in patients with cystic fibrosis.
Invasive external otitis ('malignant otitis') caused by P.aeruginosa.
Chronic Gram-negative bacillary osteomyelitis.
Eradication of Salmonella typhi in carriers.
Cervicitis Anthrax .
17. Adverse effects
- Gastrointestinal disorders and skin rashes.
- Arthropathy has been reported in young individuals.
- Central nervous system symptoms-headache and dizziness-have occurred, convulsions associated with central
nervous system pathology or concurrent use of theophylline or a non-steroidal anti-inflammatory drug.
- There is a clinically important interaction between ciprofloxacin and theophylline may lead to theophylline
toxicity in asthmatics treated with the fluoroquinolones.
- Not used in pregnancy, lactation and children less than 18 years.
18. Drugs used to treat T.B. (Tuberculosis)
- First-line drugs: isoniazid, rifampicin, rifabutin,, ethambutol and pyrazinamide.
- Some second-line drugs available are: capreomycin, cycloserine, streptomycin (rarely used now in the
UK), clarithromycin, and ciprofloxacin.
- These are used to treat infections likely to be resistant to first-line drugs, or when the first-line agents
have to be abandoned because of adverse reactions.
- Treatment begins by using three drugs of the first line for 3 months, then two antituberculous drugs for
6 months (may reach up to 1-5 years).
19. Precautions during antibiotic therapy:
1. Sensitivity test should be done before each injection of pencillin.
2. If there is drug allergy, treat it with H1 blockers (antihistaminic), cortisone IV and adrenaline IM.
3. Oral penicillins must be given 1 hour before or after meals.
4. Don’t give cephalosporine to penicillin sensitive patients.
5. Culture and sensitivity test is an accurate guide for successful treatment.
6. Don’t give tetracycline during pregnancy, lactation and in early years of life.
7. Don’t give sulphonamide during 1st months of life.
8. Kidney function tests should be done during aminoglycosides treatment to avoid nephrotoxicity.
9. Total and deferential leucocytic count is important during chloramphenicol therapy to avoid bone marrow depression.
10. Highly nutritious diet is important during treatment of T.B.
20. Antiviral Drugs
Viruses are small (usually in the range 20-30 nm) infective agents that are incapable of reproduction outside their host
cells. Viruses are generally characterized either as DNA or RNA viruses depending on the nature of their nucleic acid
I.Nucleoside reverse transcriptase inhibitors
Example: Zidovudine, lamivudine
Treatment of reterovirus infection, mainly HIV.
- Gastrointestinal disturbances including nausea, vomiting, abdominal pain and diarrhea.
- Central nervous system and related effects including headache, insomnia and dizziness, and neuropathy,
musculoskeletal and dermatological effects including fatigue, myalgia, arthralgia, rash, urticaria and fever.
- Blood disorders including anemia, neutropenia and thrombocytopenia metabolic effects.
21. II. Non-nucleoside reverse transcriptase inhibitors
nevirapine and efavirenz.
Treatment of HIV, generally in combination.
- Dermatological effects including rash and urticaria.
- Central nervous system and related effects including fatigue, headache, sleep disturbances, depression and
- Gastrointestinal disturbances including nausea, vomiting, abdominal pain and diarrhea.
- Blood disorders including anemia, neutropenia and thrombocytopenia.
- Metabolic effects including pancreatitis, raised cholesterol, liver dysfunction and lipodystrophy.
22. III.Protease inhibitors
Protease inhibitors: amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir.
Treatment of HIV, generally and other retrovirals.
IV.DNA polymerase inhibitors: aciclovir ,cidofovir, famciclovir, foscarnet ,ganciclovir, idoxuridine, penciclovir.
Therapeutic uses :
Herpes (genital herpes, mucocutaneous herpes and herpes encephalitis), cytomegalovirus,Varicella zoster infections
(chickenpox, shingles), or hepatitis C and respiratory syncitial virus infections.
Patients who are to be treated with immunosuppressant drugs or radiotherapy and who are at risk of herpesvirus infection owing
to reactivation of a latent virus.
Individuals who suffer from frequent recurrences of genital infection with herpes simplex virus.
23. Adverse effects
Acyclovir: minimal local inflammation can occur during intravenous injection if there is extravasation of the
solution. Renal dysfunction, nausea and headache can occur and, rarely, encephalopathy .
Ganciclovir: has serious side actions, including bone marrow depression and potential carcinogenicity, and is
consequently used only for life- or sight-threatening cytomegalovirus infections in patients who are
immunocompromised. Oral administration can be used for maintenance therapy in AIDS patients.
24. V.Inhibitors of HIV fusion with host cells: enfurvitide
Treatment of HIV and other retrovirals.
VI.Inhibitors of viral coat disassembly and neuraminidase inhibitors: amantadine, oseltamivir, zanamivir,
Influenza A or A and B.
VII. Immunomodulators: interferon-α
Treatment of he`patitis B and C, herpes and respiratory syncitial virus.
25. Antifungal Drugs
Amphotericin B, ketoconazole, fluconazole and terbinafine are systemic antifungal drugs
used for treatment of local and systemic fungal infections and for prophylaxis of fungal
infection during immunosuppression. All systemic antifungal drugs are contraindicated
in liver diseases.
26. Antiparasitic Agents
The substituted benzimidazoles.
This group of broad-spectrum agents includes mebendazole, tiabendazole and albendazole.
It is generally given as a single dose for threadworm, and twice daily for 3 days for hookworm
and roundworm infestations.
Spectrum: Ascaris, Ancylostoma, Enterobius.
Side effects: are few with albendazole, or mebendazole,, although gastrointestinal
disturbances can occasionally occur.
28. Antiprotozoal drugs
Amoebiasis is caused by infection with Entamoebahistolytica, which causes dysentery and liver abscesses. The
organism may be present in motile invasive form or as a cyst. The main drugs are as follow:
Given orally.Active against the invasive form in gut and liver but not the cysts.
Side effects: The drug has a metallic, bitter taste in the mouth gastrointestinal disturbances, central nervous system
(CNS) symptoms (dizziness, headache, sensory neuropathies). Metronidazole, should not be used in pregnancy.
- Trichmonas vaginalis.
29. Diloxanide is given orally with no serious side effects. It is active, while
unabsorbed, against the non-invasive form in the gastrointestinal tract.
Hepatic amebiasis: Metronidazole + chloroquine.
Cystic amebiasis: Diloxanide furate.