COURSEWORK

Biology of Disease Coursework II



Biology of Disease Coursework II

Mode of Action & Mechanism of drugs

Meropenem

Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. There are several mechanisms of resistance to carbapenems: 1) decreased permeability of the outer membrane of Gram-negative bacteria (due to diminished production of porins) causing reduced bacterial uptake, 2) reduced affinity of the target penicillin binding proteins (PBP), 3) increased expression of efflux pump components, and 4) production of antibiotic-destroying enzymes (carbapenemases, metallo-(3-lactamases).

Gentamicin

The aminoglycosides are bactericidal. They act by binding essentially irreversibly to the 30S ribosomal subunit and inhibiting protein synthesis. There are two main ways that they can do this. First, they interfere with amino acid polymerization and elongation, which essentially halts protein biosynthesis. Second, they cause tRNA to misread amino acid codons, and they also impair proofreading mechanisms(Park, et al. 2009). This leads to the incorporation of incorrect amino acids into the protein chain, leading to faulty, inactive proteins. It appears that one of these mechanisms is more important than the other in some aminoglycosides. However, it is possible that the determination of which mechanism takes place is based on the concentration of the aminoglycoside inside the cell. It is postulated that the second mechanism occurs rapidly at low aminoglycoside concentrations, and the first mechanism provides the more extended antibacterial effects of this drug class.

Teicoplanin

Due to its reduced rate of side effects that does not require close monitoring, its longer serum half-life and a simplified mode or application, teicoplanin is a valuable alternative of Vancomycin and has become the glycopeplide or choice in many hospitals.

Teicoplanin is clinically and bacteriologically effective against a wide variety of Gram-positive infections such as septicaemia, endocarditis, skin and soft tissue infections and infections associated with venous catheters.

The exceptional long half-life allows once-daily intramuscular or intravenous administration. Oral teicoplanin has been demonstrated to be effective in the treatment of pseudomembranous colitis and Clostridium difficile-associated diarrhoea, with comparable efficacy to vancomycin.

Acyclovir

Acyclovir, an acyclic purine nucleoside analog, is a highly potent inhibitor of herpes simplex virus (HSV), types 1 and 2, and varicella zoster virus, and has extremely low toxicity for the normal host cells. This selectivity is due to the ability of these viruses to code for a viral thymidine kinase capable of phosphorylating acyclovir to a monophosphate; this capability is essentially absent in uninfected cells. The acyclovir monophosphate (acyclo-GMP) is subsequently converted to acyclovir triphosphate (acyclo-GTP) by cellular enzymes. Acyclo-GTP persists in HSV-infected cells for many hours after acyclovir is removed from the medium. The amounts of acyclo-GTP formed in HSV-infected cells are 40 to 100 times greater than in uninfected Vero cells. Acyclo-GTP acts as a more potent inhibitor of the viral DNA polymerases than of the cellular polymerases(Park, et al. 2009).

Amphotericin B

Amphotericin B, the active ingredient of AmBisome, acts by binding to the sterol component of a cell membrane, leading to alterations in cell permeability and cell ...