Antifungal Agents

Infectious diseases are leading cause of death all over the world(Bobbarala 13). They are caused by microbial organisms which infest the body leading to the host manifesting undesirable symptoms that can be life-threatening(Allen 2). They interfere with the normal physiological processes of the body. The infectious diseases have caused numerous deaths until the discovery and use of antimicrobial agents (Chopra and Marilyn 224). Research indicates that people in the ancient times used plant extracts to control the diseases caused by the microbes(Bobbarala 4). Scientists have since identified efficient methods to extract the antimicrobial-active components of the plants. This has led to the development of numerous natural and synthetic molecules which significantly reduced the mortality and morbidity rates caused by the infectious diseases.
The treatment of these conditions have, however, encountered challenges, the major one being the resistance of the microbes to the antimicrobial agents(Chemother 256). This has been occasioned by the ease to access the antimicrobial agents which have resulted into misuse of the products. The misuse has led to the microorganisms devising ways to escape the activity of the drugs( Sfetcu 143). Additionally, the antimicrobial agents have been used in industries to produce food substances(Bobbarala 18). This has resulted in increased exposure of human beings to the antimicrobial substances even when their activity is not required. The microorganisms have mutated to adapt to the presence of the antimicrobial agents which means that when the host becomes ill, the antimicrobial agents fail to work against the condition(Hahn 318).

Antimicrobial Agents

Antimicrobial agents are substances that kill or stops the growth of microorganisms(Hayashi, Bizerra, and Da Silva 34). The agents are acquired from both natural and synthetic sources. They are classified according to the microorganisms they kill. There are three major categories of the antimicrobial agents including anti-bacterial, antifungal, antiviral and antiparasitic agents(Maalanda, Papichb and Guardabassia 3548). Each of the class acts against specific groups of microbes as follows: antibacterials act against bacteria, anti-virals act against viruses, the anti-fungals act on fungi and the antiparasitics act against the parasites in the host.

Antibacterials

Antibacterials are used in the treatment of bacterial infections(Chopra and Marilyn 236). This group of antimicrobial agents has low drug toxicity to human beings since most of the molecules selectively target the bacterial cell. The discovery and use of the antibacterial have been applied for various therapeutic conditions which have led to reduced mortality rates(Chopra and Marilyn 241). Some of the antibacterial agents have side effects on human beings, and proper mechanisms for managing the side effects should be applied. Additionally, prolonged use of the antibacterial in human being beings destroys the normal flora in the gut which can result in chronic diarrhea(Maalanda, Papichb and Guardabassia 3552). This is, however, managed by the intake of probiotics to restore the normal flora in the gut and thus restoring its normal.
The antibacterials discovery and development began with the pneumatic application of nitroglycerine drugs(Bobbarala 8). Extensive research was conducted between 1945 and 1970 that led to the discovery of various antibacterial molecules. Since then, the antibacterial products have widely been accepted for use in the treatment of bacterial infections(Hahn 322). The ease of acquiring the antibiotics has, however, been abused leading to misuse of the product which has resulted in antibacterial resistance of the products by various bacteria. This has led to a dilemma in the medical world since some conditions have become untreatable using the existing antibacterial agents(Hayashi, Bizerra, and Da Silva 121).

Antifungals

Antifungal molecules are used to kill or prevent the growth of fungi(Maalanda, Papichb and Guardabassia 3523). They are used in the treatment of conditions caused by fungi including thrush, ringworm and athlete's foot. The antifungal molecules has a simple mechanism of action since there exist a difference between the human cell and the fungal cell(Chopra and Marilyn 254). The agents exploit these differences to ensure that they eliminate the fungi without causing any harm to the human body, except in some cases(Allen 6). The structure of the cells, however, generates a challenge for the activity of the antifungal. Both the human and the fungal cells are eukaryotic, unlike the bacterial cell(Maalanda, Papichb and Guardabassia 3558). This makes it difficult for the antifungal agents to target specific fungal cells. As a result, some of the antifungal agents may have side effects, some of which are life-threatening especially if the drug is improperly used( Sfetcu 126). Apart from the therapeutic use, antifungals are used in homes to prevent the growth of mold in damp areas. It stops their growth and encapsulates the area to prevent the release of the spores thus preventing propagation(Hayashi, Bizerra, and Da Silva 112). Manufacturers have taken advantage of this feature to make paints with antifungal agents for use in bathrooms and other damp areas of the house(Bobbarala 12).

Antivirals

Antivirals are a class of antimicrobial used in the treatment of viral infections(Maalanda, Papichb and Guardabassia 3545). Specific antivirals are used to treat particular ailments caused by specific viruses. The antivirals are relatively harmless to the host and can be applied to treat viral infections with minimal side effects(Chemother 265). This class of antimicrobial is particularly crucial in the healthcare sector due to its ability to reduce the impact of the HIV which is a problem in the healthcare sector world over(Hahn 330). The World Health Organization (WHO) reported that HIV had infected approximately 36.7 million people in the world by 2016(Allen 10). Majority of these patients are put on antiviral therapy to control the effects of the virus. The data shows that more than 20 million people are under the lifesaving antiretroviral treatment therapy(Allen 8). As such, this class is crucial in the medical sector as it prevents the deaths of people suffering from the viral infections, and more precisely the HIV which is an epidemic in every part of the world. The most commonly used antivirals act by the inhibition of protease and neuraminidase(Maalanda, Papichb and Guardabassia 3540). The antiviral medicines used in the treatment of infections caused by herpes virus including cold sores and genital herpes are nucleoside analog acyclovir( Sfetcu 154). These products are useful in the treatment and control of most of the conditions resulting from viral infections.

Antiparasitics

Antiparasitic is a group of antimicrobials that acts against the parasites, some of which live within the human body(Hayashi, Bizerra, and Da Silva 76). These parasites include amoebae, cestodes, infectious protozoa, nematodes, and trematodes( Sfetcu 136). The parasite causes illnesses whose treatment can be achieved through the use of the antiparasitic medicine. Most of the parasites compete for nutrition with the host which can result in malnutrition in the host as well as other effects that are unpleasant to human beings such as dizziness, nausea, and diarrhea(Hayashi, Bizerra, and Da Silva 87). The antiparasitic agents kill the parasites without causing harm to the human cells.

Sources of Antimicrobial Agents

Antimicrobial agents are primarily obtained from natural sources. Extensive research has, however, established synthetic mechanisms to produce these antimicrobials in a laboratory(Hayashi, Bizerra, and Da Silva 98). The natural sources of the antimicrobials include;

Plants

The use of plants to cure infectious diseases is a traditional practice(Bobbarala 5). The use of plants with medicinal value was passed from one generation to the other. This knowledge has significantly contributed to the development of antimicrobial products through modern extraction methods(Hahn 327). It is crucial to note that the World Health Organization indicates that an estimated 80% of the world population still use the herbal medicines(Bobbarala 14). The drugs that are currently in the pharmaceutical are majorly extracted from plants or obtained as a result of artificial modification of the plants' medicinal components.
Plants are known to produce numerous secondary metabolites that have been proven to contain some antimicrobial activities(Bobbarala 10). These metabolites are classified into phenolic, terpenes and alkaloids depending on the source as well the mechanism of action(Hayashi, Bizerra, and Da Silva 49). The phenolics and polyphenols contribute the largest source of secondary metabolites that have been confirmed to contain antimicrobial properties. The subclasses in this group include coumarins, quinones, flavonoids, flavones, tannins and the flavonols(Hayashi, Bizerra, and Da Silva 65). The phenols consist of a hydroxyl functional group attached to an aromatic phenolic group(Bobbarala 32). Research indicates that the higher the number of hydroxyl and the phenolic groups in a compound, the higher its toxicity to microorganisms( Sfetcu 126). These compounds are primarily effective in the treatment of bacterial infections although a lower degree of effectiveness has been shown with parasites and fungi(Hahn 305).

Secondary Metabolites from Microorganisms

Various secondary metabolites produced by different species of microorganism has been used in the production of antimicrobial agents(Hayashi, Bizerra, and Da Silva 38). These organisms includes the soil actinomycetes such as Streptomyces spp and some fungi species. The metabolites were exploited by Alexander Fleming when he discovered penicillin in 1929(Chopra and Marilyn 238). The discovery revolutionized the search for antimicrobial components in living organisms.Many related bacteria and fungi produce similar secondary metabolites which are used in the large-scale production of the antimicrobial agents(Bobbarala 29). Some of the common molecules obtained from the secondary metabolites of the soil actinomycetes include streptothricin, streptomycin, tetracycline, and actinomycin(Hayashi, Bizerra, and Da Silva 26).

Synthetic Production

The modern technology has allowed the production of antimicrobial agents in the laboratories(Chopra and Marilyn 268). The synthetic molecules are produced to mimic the natural molecules. There are, however, some improvements that have been made in various molecules to increase its efficacy. Addition of various groups in the molecules such as phenol and hydroxyl has resulted to more stable compounds that overcome the bacterial resistance mechanisms(Maalanda, Papichb and Guardabassia 3533). Also, the synthetic production has targeted the improvement of the drug pharmacokinetics through devising methods that improve the half-life, onset of action as well as a consistent therapeutic window to ensure constant availability of the product thus enhances the drug's efficacy(Chopra and Marilyn 229).

Mechanism of Action of Tetracycline

The discussion of the action of tetracycline requires concentration on the pharmacodynamics and the pharmacokinetics of the molecule.

Pharmacodynamics

Tetracycline belongs to a family of antibiotics that act by inhibiting the process of protein synthesis(Chopra and Marilyn 250). The inhibition is achieved through interruption the transport of tRNA necessary in the synthesis of amino acids. The antibiotic prevent the attachment of aminoacyl- tRNA to the ribosomal acceptor site(Hahn 320). It is classified as broad-spectrum antibiotic due to its ability to act against a wide range of both Gram-positive and Gram-Negative bacteria as well as atypical organisms such as Mycoplasmas, Chlamydiae, Rickettsiae and a range of protozoan parasites(Maalanda, Papichb and Guardabassia 3549). The antibiotics are also used in prophylaxis to prevent malaria caused by mefloquine-resistant Plasmodium falciparum.
The mechanism of action of tetracycline involves the interaction of the ribosomes which requires the molecules to transverse membrane systems depending on whether the microbe is Gram-positive or Gram-negative(Bobbarala 15). Tetracycline molecules traverse the outer membrane of Gram-negative enteric bacteria. They diffuse through the OmpF and OmpC porin channels since they are highly concentrated on the outer membrane than the inside of the microbes(Hahn 325). They form a complex with cations such as magnesium which has a higher potential to cross the outer layer into the periplasm. The complex then dissociates to free the uncharged tetracycline which is a lipophilic molecule with the ability to diffuse through the lipid bilayer of the cytoplasmic membrane(Maalanda, Papichb and Guardabassia 3550).
The absorption of tetracycline is an energy-dependent process facilitated by the change in pH component of the proton motive force( Sfetcu 140). The tetracycline molecules within the cytoplasm are chelated due to the higher internal pH relative to that of the outer membrane. It is probable that the active drug component attaches to the ribosome as a magnesium-tetracycline complex(Hayashi, Bizerra, and Da Silva 98).Different studies conducted to establish the binding mechanism of the tetracycline molecules shows a single, high-affinity binding site in the ribosomal A site of the 30S subunit(Chopra and Marilyn 242). The binding hinders the attachment of the tRNA carrying the amino acids necessary for protein synthesis. This prevents the synthesis of proteins which are vital for the survival of the bacteria. The lack of the proteins hinders the normal functioning of resulting into a reversible bacteriostatic effect(Hahn 324).

Pharmacokinetics

Approximately 60-70% of tetracycline taken orally is absorbed in the stomach and the upper part of the small intestine(Chopra and Marilyn 234). The absorption is higher when the individual using the product is in a fasting state. Its absorption is compromised by alkaline pH and ingestion of divalent and trivalent cations such magnesium, calcium and zinc since they form complex compounds that are not absorbable(Chemother 260). Once absorbed, tetracycline distributes to the body fluids including synovial fluids, urine, maxillary sinus, and prostate. The peak plasma concentration is achieved after 2-4 hours after consumption(Allen 12). The product has a half-life of 6-10 hours which means that to maintain the product at the therapeutic window, it should be taken after every six hours. Tetracycline crosses the placenta membrane to reach the fetus and can be excreted in milk(Maalanda, Papichb and Guardabassia 3542).
The elimination process of tetracycline is primarily through the kidney although it is highly concentrated in the liver and is equally excreted through bile. The biliary excretion may lead to reabsorption of a portion of the product through enterohepatic recirculation( Sfetcu 146). It can also be excreted in the urine 24 hours after oral administration.

Resistance Mechanisms

The resistance of bacteria to antibiotics can be natural or acquired(Hahn 343). The natural mechanism of resistance is achieved when the bacterium undergoes spontaneous gene mutation. The mutation makes the bacteria to develop a gene that is resistant to a specific antibiotic(Chopra and Marilyn 228). This gene is transferred to other bacteria in the lineage which can result in a problematic resistance against the molecule. The acquired resistance results from a frequent contact of the bacteria with the antibiotic. The constant contact results into the bacteria adapting to the environment which significantly reduces the efficacy of the antibiotic against the specific species of bacteria. In this background, the antibiotic acts only on the sensitive bacteria while the resistant bacteria survive the presence of the antibiotic(Maalanda, Papichb and Guardabassia 3548). This leads to the dominance of the resistant species. There exist different mechanisms through which bacteria can develop resistance. First, there can be a modification of the binding site of the antibiotics which impairs its binding ability. As such, the antibiotic is prevented from penetrating the inside of the bacterium which reduces its efficacy(Bobbarala 30). Secondly, the bacteria can produce enzymes that directly destroys the antibiotic. The bacteria can also devise ways to modify the antibiotic make it impossible to bind on the active centers of the bacterium. Lastly, resistance can be developed through efflux of the antibacterial agent from the bacterial cell(Bobbarala 7). The evolution of the resistance mechanisms has made it easier for the bacteria to spread the resistance to other individuals of the same or different species. Extrachromosomal DNA materials, also known as plasmids, can horizontally transfer the resistant gene to other bacteria which makes the issue a big problem in the healthcare sector(Chopra and Marilyn 244).

Bacterial Resistance to Tetracycline

Various studies have been conducted to determine the resistance of different bacterial species to tetracycline(Maalanda, Papichb and Guardabassia 3554). The study of tetracycline resistance began in the 1980s when the genetic heterogeneity of tetracycline resistant genes from the plasmids of Enterobacteriaceae and Pseudomonadaceae were examined using restriction enzyme analysis, analogs and DNA-DNA hybridization( Sfetcu 156).
Since then, twenty-nine different genes responsible for tetracycline resistance has been characterized(Hahn 336). Eighteen of the genes have been shown to code for efflux pumps which are responsible for the tetracycline resistance. Seven of the characterized genes code for ribosomal protection enzymes(Chemother 262). Once these enzymes are produced, they destroy the antibiotics leading to reduced efficacy. The presence of the resistant genes makes it possible for them to be transferred to other species such as the Streptomyces among others. This has caused the widespread resistance of microorganisms to tetracycline molecules which pose a threat to human lives(Maalanda, Papichb and Guardabassia 3542). Management of bacterial infections is increasingly becoming difficult due to this resistance.

Does it have a Bactericidal or Bacteriostatic Effect?

Tetracycline has a bacteriostatic effect on the bacteria(Chopra and Marilyn 232). This is achieved through the inhibition of the protein synthesis of the microorganisms which significantly affects its cellular metabolism.

Therapeutic Effect of Tetracycline

Tetracycline is active against various Gram-positive and Gram Negative bacteria(Chopra and Marilyn 260). It shows more activity against Gram Positive bacteria. It is not effective against fungi. The product has a therapeutic effect on conditions caused by specific bacteria. It has been shown to have therapeutic activity against Mycoplasma pneumoniae, Chlamydia pneumoniae, Actinomyces spp, Rickettsia, Legionella spp, Treponema pertenue, Treponema Pallidum, Coxiella burnetti and spirochetes spp like Borrelia recurrentis.
Tetracycline is used in the treatment of conditions including atypical pneumonia, brucellosis, syphilis, rickettsial infections, relapsing fever, bartonellosis, trachoma, uncomplicated gonorrhea, anthrax and diseases caused by clostridia spp. The dosage is 500mg twice a day or four times a day depending on the severity of the infection(Allen 6). It has a fast onset of action since it is absorbed immediately into the body fluids. It can be administered parentally, orally or intravenously( Sfetcu 122). The product should not be taken with dairy products since they contain calcium and other cations that chelate the product thus impairing the absorption process(Allen 4).

Side Effects

Human beings have been shown to have tolerance to tetracycline(Chopra and Marilyn 264). The products may, however, have some side effects majorly mild. If the side effects are severe, it is recommended that the user discontinue the dose and seek medical help(Allen 14). Signs that suggest severe side effects include;

• Blistering, red skin rash and peeling of the skin. This may indicate a severe case of allergic reaction.
• Flu symptoms including fever and chills
• Yellowing of the skin with compromised integrity which may result to easy bruising and breeding.

These side effects should not be ignored because they are life-threatening. They primarily indicate a severe allergic reaction that interferes with the normal functioning of the body( Sfetcu 162). The patient using the product is advised to seek emergency medical services.
Other common side effects of tetracycline include;

• Nausea and vomiting. The patients should ensure that they take a lot of fluids if they are vomiting to help in rehydrating the body.
• Loss of appetite, stomach discomfort, and diarrhea. The symptoms may include mild lower abdominal pains characterized by spasms(Allen 6). The patients are advised to consume a lot of water to restore the electrolyte balance that may be upset by diarrhea. The antibiotics are not selective and may destroy the normal flora of the gut which leads to diarrhea. The patient can, therefore, take a probiotic to restore the damaged flora which stops diarrhea(Chemother 263).
• Vaginal itching or discharge
• Swelling around the rectal and the genital areas
• Sores around the lips and white patches inside the mouth

Tetracycline is contraindicated in individuals who are allergic to tetracyclines, pregnant women, individuals with impaired renal activity and children below eight years( Sfetcu 152).

Conclusion

Tetracycline is one of the most important antibiotics in the pharmaceutical industry. It has a relatively broad spectrum and offers treatment to varied medical conditions. It should be noted that there is a growing resistance of the microbes to tetracycline. This is majorly contributed by self-medication and frequent exposure of the body to antibiotics. As such, people should avoid taking the medicines when there are not needed in the body. The product has a quick onset of action against different bacteria which gives fast relief from the symptoms associated with the bacterial infection.
Further studies should be conducted on microbial resistance mechanism to allow structural modification of tetracycline to curb the resistance. Additionally, research from plants and other natural sources should be enhanced to allow the discovery of new molecules that would aid in curing people suffering from conditions caused by resistant bacterial strains.

Works Cited

Sfetcu, Nicolae. Health & Drugs: Disease, Prescription & Medication. Nicolae Sfetcu, 2014. Document.
Allen, Hellen. Patient info. 29 November 2016. https://patient.info/medicine/tetracycline-tablets. 3 November 2017.
Bobbarala, Varaprasad . Antimicrobial Agents. Rijeka: InTech Press, 2014. Document.
Chemother, Antimicrob J. ""Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines."" NCBI Resources (2012): 256-265. Document.
Chopra, Ian and Roberts Marilyn . ""Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance."" Microbiology and Molecular Biology Review (2012): 224-269.
Hahn, Fred E. Mechanism of Action of Antibacterial Agents. Springer Science & Business Media, 2012. Document.
Hayashi, Mirian A., Fernando C. Bizerra, and Pedro Ishmael Da Silva. ""Antimicrobial compounds from natural sources."" NCBI Resources (2013): 20-121.
Maalanda, Gaastra Marit, et al. ""Pharmacodynamics of Doxycycline and Tetracycline against Staphylococcus pseudintermedius: Proposal of Canine-Specific Breakpoints for Doxycycline."" Journal of Clinical Microbiology
(2013): 3547-3558.