Pharmacology of Anti-Infective and Immunomodulatory Agents

Posted on Jul 18, 2026 in Biotechnology

1. Malaria: Life Cycle and Anti-Malarial Pharmacology

Life Cycle of the Malarial Parasite (Plasmodium)

  • Infection: Female Anopheles mosquito injects sporozoites into the host during a blood meal.
  • Liver Stage (Exo-erythrocytic): Sporozoites travel to the liver, invading hepatocytes to mature and multiply into merozoites. In P. vivax and P. ovale, some remain dormant as hypnozoites.
  • Blood Stage (Erythrocytic): Merozoites are released into the bloodstream, invading erythrocytes (RBCs). They feed on hemoglobin, undergo schizogony (multiplication), and rupture the RBCs, causing cyclical fever and chills.
  • Sexual Stage (Gametogony): Some merozoites develop into male and female gametocytes. These are ingested by a mosquito, where they mature, fertilize, and form an oocyst, releasing sporozoites into the mosquito’s salivary glands.

Classification of Anti-Malarial Drugs

  • Arylamino Alcohols: Chloroquine, Amodiaquine, Quinine, Quinidine, Mefloquine, Lumefantrine.
  • Antifolates: Sulfadoxine, Pyrimethamine, Proguanil, Dapsone.
  • 8-Aminoquinolines: Primaquine, Tafenoquine.
  • Artemisinin Derivatives: Artemisinin, Artesunate, Artemether, Dihydroartemisinin.
  • Antibiotics: Doxycycline, Clindamycin (used adjunctive to Quinine).

Mechanism of Action (MOA)

  • Heme Polymerase Inhibitors (Chloroquine, Quinine): Prevent the polymerization of toxic heme into inert hemozoin in the parasite’s food vacuole, leading to parasite toxicity and death.
  • Artemisinins: Activated by the parasite’s iron-rich heme to produce reactive free radicals, which inflict severe oxidative damage to the parasite’s proteins and membranes.
  • Antifolates: Disrupt folate biosynthesis. Sulfonamides act as competitive inhibitors of dihydropteroate synthase (DHPS), while Pyrimethamine and Proguanil selectively inhibit dihydrofolate reductase (DHFR).
  • 8-Aminoquinolines (Primaquine): Disrupt the parasite’s mitochondrial function and electron transport, effectively clearing dormant liver hypnozoites and gametocytes.

2. Anti-Tubercular Drugs and DOTS Therapy

First-Line Anti-Tubercular Drugs (RIPE Therapy)

  • Isoniazid (INH): Prodrug activated by catalase-peroxidase (KatG). It inhibits the synthesis of mycolic acid, a critical component of the mycobacterial cell wall.
  • Rifampin (RIF): Binds to the β-subunit of the DNA-dependent RNA polymerase, blocking RNA transcription.
  • Pyrazinamide (PZA): Converted to pyrazinoic acid by mycobacterial pyrazinamidase. It lowers intracellular pH and disrupts membrane transport.
  • Ethambutol (EMB): Inhibits arabinosyl transferase, thereby disrupting the assembly of the mycobacterial cell wall.

Second-Line Anti-Tubercular Drugs

  • Injectable Aminoglycosides (Streptomycin, Kanamycin, Amikacin) and Polypeptides (Capreomycin): Bind to the 30S ribosomal subunit, inhibiting bacterial protein synthesis.
  • Fluoroquinolones (Moxifloxacin, Levofloxacin): Inhibit DNA gyrase and topoisomerase IV, thereby disrupting DNA replication and repair.

DOTS Therapy (Directly Observed Therapy, Short-course)

  • Definition: A highly effective, WHO-recommended strategy to control tuberculosis. It involves a healthcare worker or a designated observer physically watching the patient swallow their anti-TB medications on a daily or intermittent basis.
  • Objective: To ensure strict medication compliance, maximize treatment completion rates, prevent the development of multidrug-resistant TB (MDR-TB), and reduce disease transmission.

3. Antifungal Drugs and Classification

Antifungal agents are drugs used to treat mycoses (fungal infections). They act by selectively targeting fungal cell walls, membranes, or nucleic acid synthesis.

  • Polyenes: Bind to ergosterol in the fungal cell membrane, forming pores that cause leakage of intracellular contents (e.g., Amphotericin B, Nystatin).
  • Azoles: Inhibit the enzyme lanosterol 14-alpha-demethylase, which blocks ergosterol synthesis.
    • Imidazoles: Ketoconazole, Clotrimazole, Miconazole.
    • Triazoles: Fluconazole, Itraconazole.
  • Echinocandins: Inhibit β-glucan synthase, disrupting fungal cell wall synthesis (e.g., Caspofungin, Micafungin).
  • Allylamines: Inhibit squalene epoxidase, preventing ergosterol synthesis (e.g., Terbinafine).
  • Antimetabolites: Converted to 5-fluorouracil inside fungal cells, inhibiting DNA/RNA synthesis (e.g., Flucytosine).
  • Mitotic Inhibitors: Disrupts the mitotic spindle to halt fungal cell division (e.g., Griseofulvin).

4. Immunomodulators and Cyclophosphamide

Immunomodulators are agents that stimulate or suppress the immune system to treat autoimmune disorders, inflammatory conditions, and cancers.

Mechanism of Action of Cyclophosphamide

Cyclophosphamide is a prodrug converted by hepatic cytochrome P450 enzymes into active alkylating metabolites like phosphoramide mustard. This active metabolite causes DNA cross-linking, which prevents DNA replication and transcription. Because highly proliferative immune cells (such as T and B lymphocytes) require rapid division, cyclophosphamide severely impairs their function and reduces their numbers, providing an immunosuppressive effect.