Sulfonamide Type Antimicrobial - Report Example

Silver sulfadiazine Name Institution Date Silver Sulfadiazine Description of disease/condition (Burns) Burns are among the most frequent and devastating types of trauma (Herndon, 2007, pg 10). Patients who have serious thermal injury need immediate specialized management so as to reduce both morbidity and mortality (McCulloch & Kloth, 2010, pg 142). The intact skin surface of human is essential to thermoregulation, preservation of homeostasis of body fluid, and protection of the host against infection. Additionally, the skin has neurosensory, immunological and metabolic roles like metabolism of vitamin D. thermal injury brings about a break in the skin surface (McCulloch & Kloth, 2010, pg 152). A basic understanding regarding the physiology and anatomy of the skin is needed to comprehend emergency burn assessment as well as burn care approaches (McCulloch & Kloth, 2010, pg 152). The damage of tissue incurred is categorized into three groups: first, second and third-degree burns (Herndon, 2007, pg 15). Burns classified as first-degree entail only topmost layer damage of the skin (the epidermis). Burns of second-degree entail damage to both epidermis and dermis, which is the skin’s underlying layer (Herndon, 2007, pg 17). Burns of third-degree involve destruction or damage of the whole skin’s depth and tissues beneath the skin. These are considered 3-dimensional injuries with destruction or damage widening in every direction from the injury’s center (Herndon, 2007, pg 18). The burn’s region is frequently established by the “Rule of Nines,” which partitions the body into divisions that match with nearly 9 percent of the surface area of the body (McCulloch & Kloth, 2010, pg 162). For instance, the abdomen, an arm and the whole head each make up 9 percent. In case all the three body parts were injured or burned, estimation would be that the individual sustained injuries to 27 percent of his whole body (McCulloch & Kloth, 2010, pg 164). The skin is considered as one of the biggest organs within the body, with respect to both weight and overall size. Various essential physiological skin functions are altered through thermal injury. Patients who are severely burned need immediate hospitalization to the unit of burn care in order to increase their survival (Herndon, 2007, pg 30). The skin barrier that is breached is the foundation of thermal injury. When injury occurs, the body attempts to sustain homeostasis through initiation of a process of retraction, contraction, and coagulation of vessels of blood (McCulloch & Kloth, 2010, pg 172). Three different zones have actually been established in the burn wound. These are: the coagulation zone, which makes up the dead tissues that create burn eschar situated at the middle of the wound closer to the source of heat; the stasis zone, which encompasses tissues nearer to the region of the burn necrosis, which is still viable although at risk of continuous ischemic injury because of reduced perfusion; and the hyperemia zone, which encompasses usual skin with the least cellular damage that has major vasodilation as well as escalated flow of blood as a reaction to injury (McCulloch & Kloth, 2010, pg 182). Serious thermal damage brings about total skin surface loss over large regions of the whole body. Due to the significance of skin as a microbial host invasion’s barrier, it is not shocking that the possibility of subsequent infection of burn wound as well as systemic infection associate with the burn injury’s size (McCulloch & Kloth, 2010, pg 202). Widespread application of topical antimicrobial agent that is effective considerably decreases the load of microbial on the burn wound area that is open and decreases the possibility of infection (Lehne, 2007, pg 133) History of drug development Sulfonamide medicines were the initial antimicrobial drugs, and provided the way for revolution of antibiotics in medicine (Brenner & Stevens, 2010, pg 120). The primary sulfonamide, prontosil by trade-named was a prodrug. Prontosil experiments started in 1932 within the Bayer AG’s laboratories, at that moment a component of the enormous IG Farben which is a German chemical trust (Lesch, 2007, pg 29). The team of Bayer trusted that coal-tar dyes with the capacity of preferentially binding to parasites and bacteria may be applied in targeting organisms that are harmful within the body (Lesch, 2007, pg 39). Following years of trial-and-error fruitless work on numerous dyes, a group led by researcher/physician Gerhard Domagk (that worked under the universal direction of Farben management Heinrich Horlein) eventually established one that was able to work: a red dye produced by Bayer chemist Josef Klarer, which had substantial effects on preventing a number of bacterial infections within mice (Lesch, 2007, pg 35). The initial official communication regarding the breakthrough invention was not made public until 1935, not less than two years following the medicine that was unproved by his partner in research Fritz Mietzsch (Lesch, 2007, pg 39). Protosil, the new medicine named by Bayer, was the initial drug ever invented that might effectively treat various bacterial infections within the body (Finkel et al, 2009, pg 100). It had a powerful defending action against infections brought about by streptococci, such as childbed fever, erysipelas, and blood infections, and a minimal effect on other cocci infections. On the other hand, it had insignificant effect in the test tube, putting its action of antibacterial only in animals that are live (Lesch, 2007, pg 50). Afterward, it was established by Bovet Nitti and Th. Trefouel, a French team of researchers directed by Ernest Fourneau at the Pasteur Institute, that this medicine was actually metabolized into two parts within the body, discharging from the dye portion that is inactive a smaller, active, colorless compound termed as sulfanilamide (Lesch, 2007, pg 69). The invention assisted in the establishment of the bioactivation concept and rushed the German business dreams of huge profit; the active particle sulfanilamide (or sulfa) had initial been synthesized during 1906 and was broadly used in the industry of dye making; its rights had since ended and the medicine was accessible to anyone (Lesch, 2007, pg 85). The outcome was a sulfa trend. For many years during the closure of 1930s, numerous manufacturers produced countless of tons of numerous types of sulfa (Lesch, 2007, pg 129). The testing requirements resulted in the disaster of elixir sulfanilamide in the 1937’s fall, during which almost 100 individuals were poisoned by diethylene glycol. This resulted in the Federal Food, Drug and Cosmetic Act’s passge in 1938 in America (Lesch, 2007, pg 132). As the initial and merely effective antibiotic accessible within the years prior to penicillin, sulfa medicines continued to prosper through the initial World War II years (Lesch, 2007, pg 134). They are recognized for saving numerous lives of patients, including Winston Churchill and Franklin Delano Roosevelt, Jr (son of Franklin Delano Roosevelt, America’s president) (in 1936) (Lesch, 2007, pg 149). Sulfa had a major function in wound infections’ prevention during the period of war. American warriors were given a first-aid box that had sulfa powder and pills, and were instructed to sprinkle it on whichever open wound (Lesch, 2007, pg 150). The compound of sulfanilamide is very active in the form that is protonated (Brenner & Stevens, 2010, pg 150). The drug’s solubility is slow and occasionally may crystallize within the kidneys, because of its initial pK, of nearly 10. This is actually an experience that is painful; therefore patients are informed to take the drug with plentiful quantity of water. Latest related compounds prevent such complication since they contain a lower pK, nearly 5 to 6, facilitating them to remain within a soluble form. Numerous molecules that contain the structure of sulfanilamide have been formed since its invention, producing formulations that are improved with less toxicity and greater effectiveness. Sulfa medicines are still broadly applicable for conditions like urinary tract infections and acne, and are getting improved interest for the management of infections brought about by bacteria that are resistant to other types of antibiotics (Finkel et al, 2009, pg 190). Mechanism of action of sulfonamides particularly silver sulfadiazine Sulfonamide is regarded an organic sulfur compound that contains the radical –SO2NH2 (the sulfonic acids’ amides) (Cairns, 2012, pg 12). Its molecular structure resembles p-Aminobenzoic acid (PABA) which is required in organisms of bacteria as an enzyme substrate dihydropteroate synthetase for tetrahydrofolic acid (THF) synthesis (Brenner & Stevens, 2010, pg 293). Sulfonamides, chiefly derived from sulfanilamide, are able to interfere with the process of metabolism in bacteria that need PABA. They are antimicrobial agents that act through inhibition of bacterial growth and activity. Their application involves treatment and prevention of bacterial infections. One of the topical sulfonamides used in the treatment of burns is silver sulfadiazine (Brenner & Stevens, 2010, pg 295). Silver sulfadiazine involves a combination of sulfadiazine and micronized silver. Micronized silver is an antibiotic material that is natural, and sulfadiazine is basically a sulfonamide antibiotic (Brenner & Stevens, 2010, pg 297). These compounds are generally effective against infections of yeast on the skin. The drug combination is accessible in liquid and cream formulations for topical application. Basically it is used in the treatment of third and second-degree burns. Through controlling infection, silver sulfonamide which is an effective therapy for topical antimicrobial reduces the conversion of fractional-thickness to whole-thickness wounds, although its application is adjunctive to immediate excision therapy (Brenner & Stevens, 2010, pg 300). Topical antimicrobial remedy’s selection should be grounded on the ability of the agent to inhibit the recovered microorganisms from the surveillance cultures of the burn wound and monitoring the nosocomial infections that are acquired within the burn unit. Prescription should be grounded on the topical agent’s preparation (for instance cream or ointment versus dressing or solution) as well as its properties of pharmacokinetics (Goodman et al, 2011, pg 127). Topical antimicrobial agents should be applied first directly to the dressings of the patient prior to application to the burn wound in order to prevent agent’s container contamination through burn wound flora (Cairns, 2012, pg 152). As stated earlier, silver sulfadiazine contains silver nitrate and sodium sulfadiazine, the silver ion attaches to the nucleic acid of the microorganism, sulfadiazine is then released, which then interrupts the microbe’s metabolism (Brenner & Stevens, 2010, pg 350). It is not difficult to use and it is painless during application and may be used together with a dressing or without. Some degree of systemic toxicity with frequent application of daily or twice-daily has taken place aside from leucopenia development (Brenner & Stevens, 2010, pg 352). Silver sulfadiazine has effective broad-spectrum coverage of antibacterial against Pseudomonas aeruginosa as well as other enteric bacteria that are gram-negative, even though resistance has presently been reported (Edmunds, 2013, pg 97). This agent has some activity against Candida albicans, even though enhanced activity of antifungal can be accomplished through nystatin use when mixed with silver sulfadiazine (Cairns, 2012, pg 42). Even though silver sulfadiazine has slow dissociation than silver nitrate, the penetration of the wound is still poor (Cairns, 2012, pg 28). Silver sulfadiazine is just absorbed in the surface layer of the epidermis, which restricts its effectiveness in a number of patients who have severe injuries. Silver sulfadiazine should not be applied on newborns or premature babies in the course of the initial 2 months of their life due to the possibility of serious unwanted effects (Cairns, D, 2012, pg 37). There are various advantages of silver sulfadiazine use as compared to the other preparations of topical antibiotic. It is quite effective against a broad variety of pathogenic bacteria, such as methicillin-resistant Staphylococcus aureus, also referred to as MRSA (Edmunds, 2013, pg 27). Serious unwanted effects are not common. The medicine has low possibility of toxicity when applied to wide regions of the burned skin. Most unwanted effects linked to silver sulfadiazine are actually superficial. In the compound the micronized silver can lead to dark or blue-colored scars (Edmunds, 2013, pg 37). The skin’s darkening or bluing from silver exposure is referred to as argyria. A slight burning or stinging sensation might take place following application of the liquid or the cream. Patients who are allergic to either sulfa- or silver based compounds may experience serious reactions, thus should not be allowed to use this drug. In general, sulfonamide’s mechanism of action is that it is a competitive inhibitor of enzymes; bacteriostatic agent; not suitable for patients who have immune systems that is weakened; mimic the PABA, which is the enzyme substrate; attach to active site and obstruct access to PABA; reversible inhibition; and its resistant strains produce extra PABA (Cairns, 2012, pg 32). Quantitative structure-activity relationships of sulfonamides Relationships involving sulfonamides’ antimicrobial activities and physicochemical characteristics including the hydrophobicity constant (pi) and the acid dissociation constant (pKa) were determined (Warshakoon et al, 2009, pg 25). The sulfonamides’ least inhibitory concentrations (MIC) against Actinobacillus pleuropneumoniae, a veterinary pathogen that is gram-negative, were used. Liquid chromatography of high performance was used to determine the hydrophobic and electronic parameters. Empirically established relationships indicated the dominant function of the ionization’s degree on the antimicrobial action (Warshakoon et al, 2009, pg 35). The data reveal that sulfonamides’ hydrophobic properties, determined by pi, are of minimal significance for the antibacterial activity in vitro. Due to the limited range of pKa (4.9-7.7) it may possibly not be recognized whether the connection between activity and pKa was bilinear or linear. Every time o,m-disubstituted sulfonamides were involved correlations reduced considerably (Warshakoon et al, 2009, pg 37). Relationships grounded on models of multicompartment equilibrium were derived and showed a bilinear connection between MIC and pKa. Equations that were model-based indicated that the activity of antibacterial was controlled by the sulfonamides’ extracellular ionic concentration every time different extra and intracellular values of pH were assumed within the model of equilibrium. The sulfonamides’ antimicrobial activities against organisms that are gram-positive were also connected to the sulfonamides’ ionization degree within the agar medium (Warshakoon et al, 2009, pg 45). A lot of work has been carried out to clarify the relation involving bacteriostatic activity and physicochemical properties of sulfonamides drugs. Robin and Bell established that the bacteriostatic activities’ logarithmic plot of a sequence of sulfonamides against their constants of dissociation display a parabolic relationship (Warshakoon et al, 2009, pg 55). Bearing in mind that the action raises with the SO2 group’s negative character, they hypothesized that the N substituent electron-attracting capacity should be within a maximum range for the optimal activity so that the SO2NH group’s ionization constant is around 10’6 to 10’7 (Warshakoon et al, 2009, pg 58). A different justification for the parabolic connection was suggested by Cowles who indicated that the –ve ion responsible for bacteriostatic activity penetrates with hardship to the action’s site within the cell so that there can be an optimal constant of dissociation where the equilibrium between the penetration and intrinsic activity is optimal to the process of bacteriostatic (Warshakoon et al, 2009, pg 65). Analysis of quantitative structure activity relationship (QSAR) facilitates the rational molecules’ exploration that is found active biologically. QSAR analysis has made it simple to estimate the characteristics of new chemical compounds without their synthesis as well as testing (Warshakoon et al, 2009, pg 75). Structure-activity relationships of sulfonamide (Cairns, 2012, pg 34) The first part of the structure is the para-Amino group, the second part is the aromatic part and the last part is the sulfonamide part. Reference Brenner, GM & Stevens CW, 2010, Pharmacology, Philadelphia, PA: Saunders/Elsevier. Cairns, D, 2012, Essentials of pharmaceutical chemistry, London: Pharmaceutical Press. Edmunds, MW, 2013, Introduction to clinical pharmacology, St. Louis, Mo: Elsevier/Mosby. Finkel, R, Clark, MA & Cubeddu LX, 2009, Pharmacology, Philadelphia: Lippincott Williams & Wilkins. Goodman, LS, Brunton, LL, Chabner, B & Knollmann BC, 2011, Goodman & Gilman's pharmacological basis of therapeutics, New York: McGraw-Hill. Herndon, DN, 2007, Total burn care, Edinburgh: Saunders Elsevier. Lehne, RA, 2007, Pharmacology for nursing care, St. Louis, Mo: Saunders Elsevier. Lesch, JE, 2007, The first miracle drugs: How the sulfa drugs transformed medicine, New York [u.a.: Oxford Univ. Pr. McCulloch, JM & Kloth L, 2010, Wound healing: Evidence-based management, Philadelphia: F.A. Davis. Warshakoon, HJ, Burns, MR & David SA, 2009, Structure-activity relationships of antimicrobial and lipoteichoic acid-sequestering properties in polyamine sulfonamides, Antimicrobial Agents and Chemotherapy, 53, 1, 57-62. Read More

Patients who are severely burned need immediate hospitalization to the unit of burn care in order to increase their survival (Herndon, 2007, pg 30). The skin barrier that is breached is the foundation of thermal injury. When injury occurs, the body attempts to sustain homeostasis through initiation of a process of retraction, contraction, and coagulation of vessels of blood (McCulloch & Kloth, 2010, pg 172). Three different zones have actually been established in the burn wound. These are: the coagulation zone, which makes up the dead tissues that create burn eschar situated at the middle of the wound closer to the source of heat; the stasis zone, which encompasses tissues nearer to the region of the burn necrosis, which is still viable although at risk of continuous ischemic injury because of reduced perfusion; and the hyperemia zone, which encompasses usual skin with the least cellular damage that has major vasodilation as well as escalated flow of blood as a reaction to injury (McCulloch & Kloth, 2010, pg 182).

Serious thermal damage brings about total skin surface loss over large regions of the whole body. Due to the significance of skin as a microbial host invasion’s barrier, it is not shocking that the possibility of subsequent infection of burn wound as well as systemic infection associate with the burn injury’s size (McCulloch & Kloth, 2010, pg 202). Widespread application of topical antimicrobial agent that is effective considerably decreases the load of microbial on the burn wound area that is open and decreases the possibility of infection (Lehne, 2007, pg 133) History of drug development Sulfonamide medicines were the initial antimicrobial drugs, and provided the way for revolution of antibiotics in medicine (Brenner & Stevens, 2010, pg 120).

The primary sulfonamide, prontosil by trade-named was a prodrug. Prontosil experiments started in 1932 within the Bayer AG’s laboratories, at that moment a component of the enormous IG Farben which is a German chemical trust (Lesch, 2007, pg 29). The team of Bayer trusted that coal-tar dyes with the capacity of preferentially binding to parasites and bacteria may be applied in targeting organisms that are harmful within the body (Lesch, 2007, pg 39). Following years of trial-and-error fruitless work on numerous dyes, a group led by researcher/physician Gerhard Domagk (that worked under the universal direction of Farben management Heinrich Horlein) eventually established one that was able to work: a red dye produced by Bayer chemist Josef Klarer, which had substantial effects on preventing a number of bacterial infections within mice (Lesch, 2007, pg 35).

The initial official communication regarding the breakthrough invention was not made public until 1935, not less than two years following the medicine that was unproved by his partner in research Fritz Mietzsch (Lesch, 2007, pg 39). Protosil, the new medicine named by Bayer, was the initial drug ever invented that might effectively treat various bacterial infections within the body (Finkel et al, 2009, pg 100). It had a powerful defending action against infections brought about by streptococci, such as childbed fever, erysipelas, and blood infections, and a minimal effect on other cocci infections.

On the other hand, it had insignificant effect in the test tube, putting its action of antibacterial only in animals that are live (Lesch, 2007, pg 50). Afterward, it was established by Bovet Nitti and Th. Trefouel, a French team of researchers directed by Ernest Fourneau at the Pasteur Institute, that this medicine was actually metabolized into two parts within the body, discharging from the dye portion that is inactive a smaller, active, colorless compound termed as sulfanilamide (Lesch, 2007, pg 69).

The invention assisted in the establishment of the bioactivation concept and rushed the German business dreams of huge profit; the active particle sulfanilamide (or sulfa) had initial been synthesized during 1906 and was broadly used in the industry of dye making; its rights had since ended and the medicine was accessible to anyone (Lesch, 2007, pg 85).

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