CHEMOTHERAPEUTIC AGENTS: A TEACHER’S COMPREHENSIVE GUIDE
Welcome, future pharmacologists and healthcare professionals!
The word chemotherapy usually refers to cancer treatment. In the simplest sense, chemotherapy is the treatment of an ailment by chemicals, especially by killing micro-organisms. As such, the term has been used for non-oncological use, such as the use of antibiotics (antibacterial chemotherapy).
The first modern chemotherapeutic agent was arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis. This was later followed by sulphonamides (sulpha drugs) and penicillin. As a pharmacology educator with years of experience teaching chemotherapy, I have observed that students often find this topic challenging due to the vast number of drugs and their mechanisms. Let me tell you: Understanding chemotherapeutic agents is essential for treating infectious diseases and cancer.
In this comprehensive guide, I will walk you through the major classes of chemotherapeutic agents—antibiotics, penicillins, cephalosporins, aminoglycosides, fluoroquinolones, macrolides, tetracyclines, chloramphenicol, sulphonamides, anti-tubercular drugs, anti-fungal drugs, anti-viral drugs, anti-amoebic agents, anthelmintic drugs, anti-malarial agents, and anti-neoplastic agents. By the end of this article, you will have a thorough understanding of these essential pharmacological agents. Let us begin!
Dpharmguru’s exam insights:
Chemotherapeutic agents are frequently tested in pharmacology exams. Remember: Chemotherapy principles include selectivity, therapeutic index, and combination therapy. Antibiotics are classified by chemical structure, mechanism of action, and spectrum of activity. Penicillins inhibit cell wall synthesis. Aminoglycosides cause misreading of mRNA. Fluoroquinolones inhibit DNA gyrase. Sulphonamides inhibit folic acid synthesis. These are classic exam questions!
PRINCIPLES OF CHEMOTHERAPY
- Selectivity: All clinically effective antimicrobial agents show selective toxicity for the bacterium rather than the host
- Therapeutic Index: Ratio of toxic dose to effective therapeutic dose; higher TI = better antibiotic effect
- Categories of Antibiotics: Bactericidal (kill bacteria) vs Bacteriostatic (inhibit growth)
- Antibiotic Susceptibility Testing:
- MBC: Minimum Bactericidal Concentration—kills 99.9% of original inoculum
- MIC: Minimum Inhibitory Concentration—inhibits visible growth of bacteria
- Combination Therapy: Used in emergency cases, to prevent emergence of resistant strains
- Antibiotic Synergism: Effects of combination > sum of individual effects
NEOPLASTIC DISEASES
- Carcinomas: Originate from epithelial tissue (skin, breast, prostate, lung, colon)
- Sarcomas: Originate from connective tissues (bones, cartilage, muscle)
- Myelomas: Originate from plasma cells of bone marrow
- Leukemias: Blood cancers of bone marrow—overproduction of immature blood cells
- Lymphomas: Develop in lymphatic system (Hodgkin’s and Non-Hodgkin’s)
PENICILLINS
Penicillin is the first antibiotic clinically used in 1941. The nucleus of penicillin consists of fused rings of thiazolidine and β-lactam.
Classification
- Acid-Resistant Penicillins: Penicillin V, Phenethicillin
- Beta-Lactamase Resistant Penicillins: Methicillin, Cloxacillin, Dicloxacillin
- Broad Spectrum (Gram +ve & -ve): Ampicillin, Amoxycillin
- Extended Spectrum: Carbenicillin, Clavulanic acid
Ampicillin
Indications: H. influenzae, Strep. viridans, Proteus mirabilis, Neisseria gonorrhoeae, Salmonella, E. coli, Shigella, Meningitis, Subacute bacterial endocarditis.
Clavulanic Acid
Pharmacological Action: Potent and irreversible inhibitor of many β-lactamases; protects β-lactam antibiotics from inactivation.
Indications: Used in combination with amoxycillin (Co-amoxiclav) to widen antibacterial spectrum to include β-lactamase producing strains.
Indications of Penicillins
- Streptococcal infections (pharyngitis, otitis media, scarlet fever, endocarditis)
- Pneumococcal infections (pneumonia, pericarditis, meningitis)
- Meningococcal infections
- Syphilis (drug of choice)
- Diphtheria (adjuvant to antitoxin therapy)
- Tetanus and Gas gangrene
Adverse Effects
- Diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, super-infection
- Fever, vomiting, erythema, dermatitis, angioedema, seizures
CEPHALOSPORINS
| Generation | Parenteral | Oral |
|---|---|---|
| First | Cephalothin, Cefazolin | Cephalexin, Cefadroxil |
| Second | Cefuroxime, Cefoxitin | Cefaclor, Cefuroxime axetil |
| Third | Cefotaxime, Ceftriaxone, Ceftazidime | Cefixime, Cefpodoxime |
| Fourth | Cefepime, Cefpirome | – |
Adverse Effects: Allergic manifestations, Disulfiram-like effect (with alcohol), Bleeding (anti-vitamin K effects).
AMINOGLYCOSIDES
Classification: Systemic—Streptomycin, Gentamicin, Kanamycin, Tobramycin. Topical—Neomycin, Framycetin.
Indications
- Acute conjunctivitis, blepharitis, bacterial keratitis
- Amikacin for gram-negative bacterial endophthalmitis
- Tobramycin and neomycin for prophylaxis after ocular surgery
Adverse Effects
- Neuromuscular Paralysis: Risk in myasthenia gravis
- Ototoxicity: Damage to eighth cranial nerve—hearing loss, ataxia, vertigo
- Nephrotoxicity: Renal irritation, albuminuria, pyuria
- Curaremimetic: Skeletal muscle relaxant effect—respiratory arrest
- Superinfection: Candida or Staphylococcal infection
FLUOROQUINOLONES
| Generation | Examples | Spectrum |
|---|---|---|
| First | Nalidixic acid, Cinoxacin | Gram-negative (not Pseudomonas) |
| Second | Ciprofloxacin, Norfloxacin, Ofloxacin | Gram-negative (including Pseudomonas), some Gram-positive |
| Third | Levofloxacin, Moxifloxacin, Gatifloxacin | Expanded Gram-positive (including S. pneumoniae) |
| Fourth | Trovafloxacin | Broad anaerobic coverage |
Contraindications
Contraindicated in children, adolescents, and pregnant/breast-feeding women because they may affect cartilage development.
Adverse Effects
- Nausea, headache, dizziness, abdominal discomfort, photosensitivity, skin rash
- Ciprofloxacin causes ventricular ectopy, palpitations, hypertension, angina
MACROLIDES
Examples: Erythromycin, Clarithromycin, Azithromycin
Indications
- Orodental infections, periapical abscesses
- Legionnaire’s Pneumonia, whooping cough, pharyngitis, tonsillitis, scarlet fever
- Diphtheria (acute and carrier stage)
- Skin infections, acne vulgaris
Adverse Effects
- Gastrointestinal: Anorexia, nausea, vomiting, diarrhoea (most common reason for discontinuation)
- Liver Toxicity: Cholestatic hepatitis with erythromycin estolate
- Allergic Reactions: Eosinophilia, rashes
TETRACYCLINES
- Short Acting (6 hrs): Chlortetracycline, Oxytetracycline
- Intermediate (16 hrs): Demeclocycline
- Long Acting (18-24 hrs): Doxycycline, Minocycline
Indications
- Chlamydia (trachoma, psittacosis), Mycoplasma pneumonia, Rickettsia
- Intestinal amoebiasis, Actinomycosis, P. falciparum malaria
- Minocycline for meningococcal carrier state
- Demeclocycline for chronic hyponatraemia
- H. pylori eradication (combination therapy)
Adverse Effects
- Bone and Teeth: Chelate with calcium—deposit in bones and teeth; yellow/brown discolouration and enamel dysplasia of milk teeth
- Hepatotoxicity: Impair hepatic function in pregnant women
- Renal Toxicity: Renal tubular necrosis
- Photosensitisation: Demeclocycline
- Vestibular Disturbances: Minocycline and doxycycline (high doses)
CHLORAMPHENICOL
Indications: Enteric fever, topical ear/eye infections, meningitis (H. influenzae), brain abscess, severe anaerobic infections.
Adverse Effects
- Bone Marrow Depression: Depresses RBC, WBC, and platelet formation
- Grey Baby Syndrome: Vomiting, lethargy, anorexia, hypothermia, grey cyanosis, death
- GI: Irritation, stomatitis, glossitis
- Neurological: Headache, mental confusion, depression
SULPHONAMIDES
Pharmacological Action: Competitive inhibitors of Para-Aminobenzoic Acid (PABA)—inhibit folic acid synthesis.
Classification
- Short Acting (4-8 hrs): Sulfadiazine
- Intermediate (8-12 hrs): Sulfamethoxazole
- Long Acting (~7 days): Sulfadoxine
- Special Purpose: Sulfacetamide, Sulfasalazine, Mafenide, Silver sulfadiazine
Adverse Effects
- Fever, rash, exfoliative dermatitis, photosensitivity, urticaria
- Stevens-Johnson syndrome (<1% frequency)
- Renal irritation, crystalluria, albuminuria, haematuria
- Haemopoietic toxicity: agranulocytosis, thrombocytopenia, aplastic anaemia
- CNS: confusion, depression, ataxia, tinnitus, fatigue, acute psychotic episodes
ANTI-TUBERCULAR DRUGS
First Line Drugs
- Isoniazid (H): Inhibits mycolic acid synthesis—most effective; 300 mg/day
- Rifampin (R): Inhibits DNA-dependent RNA polymerase—10 mg/kg/day
- Pyrazinamide (Z): Bactericidal in acidic environment
- Ethambutol (E): Inhibits arabinosyl transferase—25-30 mg/kg/day
- Streptomycin (S): Bactericidal—15 mg/kg IM
Second Line Drugs
- Thiacetazone, Paraaminosalicylic acid (PAS), Ethionamide, Cycloserine, Kanamycin, Amikacin, Capreomycin
Newer Drugs
- Ciprofloxacin, Ofloxacin, Clarithromycin, Azithromycin, Rifabutin, Bedaquiline
ANTI-FUNGAL DRUGS
Classification
- Polyenes: Amphotericin B, Nystatin, Hamycin, Natamycin
- Echinocandins: Caspofungin, Micafungin
- Heterocyclic Benzofuran: Griseofulvin
- Antimetabolite: Flucytosine (5-FC)
- Azoles: Imidazoles (Clotrimazole, Ketoconazole), Triazoles (Fluconazole, Itraconazole)
- Allylamine: Terbinafine
Amphotericin B
Pharmacological Action: Binds to ergosterol in fungal cell membrane—forms pores, ion leakage, fungal cell death.
Indications: Systemic fungal infections (Candida, Cryptococcus, Histoplasma, Blastomyces, Aspergillus).
Adverse Effects: Renal toxicity, chill, fever, headache, vomiting, shock-like hypotension, anaemia, hypokalaemia, hepatic impairment.
ANTI-VIRAL DRUGS
Acyclovir
Pharmacological Action: Specific inhibitor of herpesvirus DNA polymerase.
Indications: HSV-1, HSV-2, VZV infections; herpes simplex encephalitis; neonatal HSV infection.
Adverse Effects: Nausea, headache, encephalopathy (rare).
Anti-retrovirus Drugs
- NRTIs: Zidovudine (AZT), Lamivudine, Didanosine, Stavudine
- NNRTIs: Nevirapine, Efavirenz, Delavirdine
- Protease Inhibitors: Ritonavir, Indinavir, Nelfinavir, Saquinavir
ANTI-AMOEBIC AGENTS
Metronidazole
Pharmacological Action: Inhibits protein synthesis by interacting with DNA—loss of helical DNA structure, strand breakage, cell death.
Indications: Amoebiasis, giardiasis, trichomoniasis, pseudomembranous colitis.
Adverse Effects: Nausea, vomiting, diarrhoea, metallic taste, headache, dizziness, ataxia, vertigo, peripheral neuropathy.
ANTHELMINTIC DRUGS
Albendazole
Pharmacological Action: Binds to β-tubulin—prevents microtubule formation and glucose uptake—paralysis and death of helminth.
Indications: Neurocysticercosis (Taenia solium), Hydatid disease (Echinococcus granulosus).
Ivermectin
Pharmacological Action: Paralyses nematodes by GABA-ergic activation.
Indications: Strongyloidiasis, onchocerciasis, filariasis.
ANTI-MALARIAL AGENTS
Chloroquine