Our goal as doctors and pharmacists in the treatment of infections is to kill the microorganisms (bacteria, virus, fungi, parasite etc.…) or at least to inhibit their ability to proliferation, so that what the immune system can do best of these roles. The difficulties in practice are twofold. First, the chemotherapeutics must kill the microbes but protects and not exposed to the host; this is the principle of selective toxicity. Secondly, microorganisms tend to develop resistance to antimicrobial that are initially effective. The chemotherapeutics classified depends on types of microorganisms and some disease which is malignant such as antibacterial, antiviral, antifungal and anticancer.
Role of antibacterial in the treatment of infection.
Antibacterial drugs have the main two roles which are: kill and prevent replication of bacteria specifically.
There are many spectrums of antibacterial drugs which indicates the affinity and capacity of antibacterial drugs to kill bacteria. Broad spectrum antibacterial drugs have a high affinity than other spectrums against most groups of bacteria such as streptococcus, staphylococcus and negative bacteria than other spectrums. Narrow spectrum antibacterial drugs have a lower affinity than other spectrums against less only one class of bacteria. For example, only against negative bacteria. Extended spectrum antibacterial drugs have a higher affinity than other spectrums against most groups of bacteria such as streptococcus, staphylococcus and negative bacteria than other spectrums.
The most important classification of antibacterial drugs depends on the mechanism of action of a drug, which interfere with one of each mechanism, cell wall synthesis. Cell membrane integrity. Protein synthesis. Production of folic acid. Replication of DNA. But the 3 main groups: Inhibition of cell wall synthesis. Inhibition of protein synthesis. Inhibition of bacterial nucleic acid synthesis
Mechanism of action of antibacterial drugs.
1. Inhibition of bacterial nucleic acid synthesis.
Became it is the first synthetic antibacterial agent. produce more active derivatives against G+ve bacteria. They act as competitive dihydropteroate synthetase inhibitors and block the biosynthesis of Dihydrofolic acid in bacterial cells. They act as competitive inhibitors by their similarity to p-aminobenzoic acid(PABA) one of the normal substrate for dihydropteroate synthetase.
Indication of Sulphonamides:
1.Burn therapy infection by Pseudomonas aeruginosa
2. Intestinal infection
3. Ophthalmic infection
2. Inhibition of protein synthesis
They inhibit bacterial protein synthesis. They bind to the 30S ribosomal subunit and then prevent the binding of aminoacyl tRNA to the mRNA ribosome complex. Tetracyclines also inhibit protein synthesis in the host but are less likely to reach the concentration required because eukaryotic cells do not have a tetracycline uptake mechanism.
3. Inhibition of cell wall synthesis
Penicillin inhibits final crosslinking stage of cell wall synthesis. It reacts with the transpeptidase enzyme to form an irreversible covalent bond Inhibition of transpeptidase leads to a weakened cell wall. Cells swell due to water entering the cell, then burst (lysis).
Indication of penicillin’s
3. Listeria meningitis
2. Haemophilus influenzae infection
Role of antifungal in the treatment of infection.
Fungi are eukaryotic cells, like plants but, cannot make photosynthesis due to lack of chlorophyll. They have cell wall and filamentous structures.
Mycosis: fungal diseases caused by pathogenic fungi. Fungal infections involve the super facial invasion of skin and mucous membranes.
Most of antifungal drugs interfere with the biosynthesis of ergosterol.
When compared to antibacterial drugs, the range of antifungal drug classes available is limited, with most systemic treatment accomplished with the azole group of medications. Although therapeutic drug monitoring would improve treatment with the azole antifungals and 5-flucytosine, this is rarely done because of variable availability of clinical assays and uncertainty in interpretation of the measured concentrations.
Fungal infections often require prolonged treatment durations. This may be costly for some pet owners and can increase the risk of adverse effects to pets. Classification of antifungal drugs
(1) polyenes (amphotericin B)
(2) azoles, (fluconazole, itraconazole and voriconazole)
(3) Echinocandins (caspofungin, and anidulafungin)
(4) fluorinated pyrimidines (flucytosine)
(5) allylamines (terbinafine).
Mechanism of action
The drug acts by binding to ergosterol irreversibly in the cell membrane of susceptible fungi. This creates a transmembrane channel, and the resultant change in membrane permeability allowing leakage of intracellular components. Resulting in disruption of membrane integrity and then cell death.
It is the antifungal agent of choice for most serious infections and for empirical treatment of febrile neutropenia refractory to appropriate antibacterial treatment. Not used for minor fungal infections such as yeast and mouth infection. Used for aspergillosis, north American blastomycosis, coccidioido-mycosis.
Squalene epoxidase, which converts squalene to ergosterol. Inhibition of this enzyme which is the mechanism of allylamines causes squalene, a substance toxic to fungal cells, to accumulate intracellularly of fungal and leads to rapid cell death.
Topically and orally:
Cutaneous dermatomycoses, onychomycoses, molds, dimorphic fungi, and vulvovaginal candidiasis.
Topical treatment of tinea pedis, tinea cruris, and tinea corporis.
A class of semisynthetic antifungal lipopeptides that are structurally characterized by a cyclic hexapeptide core linked to variably configured lipid side chains. Inhibit glucan synthase, the enzyme responsible for synthesis of ?1-3 linked glucan, a major polysaccharide component of the cell wall of several pathogenic fungi, decreased ?-( 1,3)-glucan results in a loss of cell integrity and rigidity, which can result in cell lysis.
Invasive aspergillosis, Pneumocystis and Candida species.
At the end, the most important issue in the treatment of infections by chemotherapeutic agents that the pharmacists and doctors should consider is resistance of microorganisms which may lead to cancel the process of treatment or prophylaxis of infections.