Overview
Pharmacological properties of individual sulfonamides [edit | edit code]
According to the rate of absorption and excretion, sulfonamides for oral administration are divided into three groups: 1) rapidly absorbed and rapidly excreted (e.g. sulfafurazole and sulfadiazine), 2) very poorly absorbed - acting in the intestinal lumen (e.g. sulfasalazine), 3) rapidly absorbed, but slowly excreted - long-acting drugs (sulfadoxine). In addition, there are sulfonamides for topical use, such as sulfacetamide, mafenide and silver sulfadiazine.
Quickly absorbed and rapidly excreted sulfanilamides [edit | edit code]
Sulfafurazole. This drug has high antibacterial activity. Due to its good solubility, it practically does not have a damaging effect on the kidneys and therefore almost replaced older, less soluble preparations.
Sulfafurazole is significantly bound to plasma proteins. After taking the drug in a dose of 2–4 g, the maximum serum concentration — 110–250 µg / ml — is reached in 2–4 hours. The acetylated form accounts for 28 to 35% of the drug in the blood and about 30% in the urine. After 24 hours, approximately 95% of the dose is excreted by the kidneys. The concentration of sulfafurazole in urine is significantly higher than in serum, and can have a bactericidal effect. The concentration of the drug in CSF is approximately a third of serum.
Sulfafurazole diethanolamine used, in particular, for eye infections. Sulfafurazole acetate has no taste and therefore is used in children. Sulfafurazole is produced as a combined preparation with phenazopyridine (500 mg sulfafurazole and 50 mg phenazopyridine), which has the properties of a urinary antiseptic and analgesic. Phenazopyridine gives the urine an orange-red color. A combination drug containing sulfafurazole acetate and erythromycin ethyl succinate is https://zentherapycenter.com/let-n/naprelan.php to treat otitis media in children.
Quickly absorbed and rapidly excreted
Poorly absorbed (acting in the intestinal lumen)
For topical use
The side effect of sulfafurazole is the look as that of other sulfonamides (see below). Severe side effects occur in less than 0.1% of patients. Sulfafurazole is better soluble in urine than sulfadiazine, and therefore rarely causes hematuria and crystalluria (in 0.2-0.3% of cases). However, during treatment, the ballroom should consume a sufficient amount of fluid. In renal failure, sulfafurazole, like all sulfonamides for systemic use, is prescribed with caution. Sulfafurazole can cause allergic reactions, including fatal ones. If it is necessary to prescribe a rapidly absorbed and rapidly excreted sulfanilamide, most doctors prefer sulfafurazole.
Sulfamethoxazole. This drug is close to sulfafurazole, but is absorbed and excreted more slowly. Sulfamethoxazole is prescribed orally for both urinary tract infections and other infections. The acetylated metabolite of sulfamethoxazole is poorly soluble, and its content in the urine is quite large, so measures should be taken to prevent crystalluria. Sulfamethoxazole is used in the same situations as sulfafurazole. Sulfamethoxazole is also produced in the form of a combined preparation with phenazopyridine, which has the properties of a urinary antiseptic and analgesic, as well as a combination with trimethoprim (see below).
Sulfadiazine. The drug is rapidly absorbed when taken orally; its maximum serum concentration is reached after 3-6 hours. After ingestion of 3 g of the drug, it is 50 μg / ml. At a serum concentration of 100 μg / ml and a normal plasma albumin level, the proportion of the drug bound to plasma proteins is approximately 55%. After oral administration at a dose of 60 mg / kg, the therapeutic concentration in the CSF is reached after 4 hours.
Sulfadiazine is excreted by Bactipront kidneys, first quickly, and then, within 2-3 days, slower. In urine, it can be detected within 30 minutes after ingestion. From 15 to 40% sulfadiazine is excreted in acetylated form. Acetylated drug is excreted more easily than unchanged. Alkalization of urine accelerates the excretion of both forms of the drug by reducing their tubular reabsorption.
When treated with sulfadiazine, patients should consume a sufficient amount of fluid. In adults, diuresis must be maintained at least 1200 ml; in children, its value depends on weight. If it is impossible to ensure the required diuresis, sodium bicarbonate is prescribed to prevent crystalluria.
Poorly absorbed sulfonamides [edit | edit code]
Sulfasalazine. This drug is almost not absorbed in the digestive tract. Sulfasalazine is used for ulcerative colitis and Crohn's disease, although relapse occurs in about a third of cases. With exacerbations of ulcerative colitis, glucocorticoids are more effective, but in mild or moderate cases, sulfasalazine is preferred. In mild cases of Crohn's disease, treatment also begins with this drug. In the intestine, sulfasalazine is broken down by bacteria to form sulfapyridine and 5-aminosalicylic acid. The latter remains in the lumen of the intestine and has an anti-inflammatory effect. Sulfapyridine is an active sulfanilamide that is absorbed and then excreted by the kidneys; it causes side effects. Sulfasalazine does not disturb the normal intestinal microflora. Side effects include anemia with Heinz bodies and agranulocytosis. With G-6-FD deficiency, acute hemolysis is possible. 20% of patients experience nausea, fever, and arthralgia; in these cases desensitization is effective. In men, sulfasalazine can cause reversible infertility due to a decrease in the number of sperm and a violation of their morphology.
Long-acting sulfanilamides [edit | edit code]
Sulfadoxine - N-1 - (5 dimethoxy-4-pyrimidinyl) sulfanilamide - is very slowly eliminated (T1 / 2 7–9 days). In the form of a combined preparation (sulfadoxine / pyrimethamine; 500 mg sulfadoxine and 25 mg pyrimethamine), it is used for the prevention and treatment of malaria caused by mefloquine-resistant strains of Plasmodium falciparum (Ch. 40). Since sulfadoxine can cause very serious, even fatal side effects, including Stevens-Johnson syndrome, it is prescribed for prophylactic purposes only at high risk of malaria resistant to other drugs.
Sulfanilamides for topical use [edit | edit code]
Sulfacetamide. This drug is N-1-acetylsulfanilamide. Its solubility is about 90 times higher than that of sulfadiazine. Sulfacetamide sodium salt solutions are widely used in ophthalmology. Topical sulfonamides are rarely used due to their low Bactipront and high risk of sensitization, but sulfacetamide is an exception to this rule. It is quite effective and even in high concentrations does not irritate the mucous membrane of the eye. Solutions of sodium salts of sulfonamides usually have a strong alkaline reaction, and the pH of a 30% solution of sodium salt of sulfacetamide is 7.4. Sulfacetamide penetrates the tissues of the eye and accumulates there in high concentrations. Although allergic reactions to sulfacetamide are rare, they are not prescribed for sulfonamides with allergies.
Silver sulfadiazine. In vitro, this drug inhibits the growth of almost all pathogenic bacteria and fungi, including those resistant to other sulfonamides. It is used for burns to reduce bacterial colonization of wounds and reduce the risk of wound infection. Silver sulfadiazine is not used to treat deep infections. Slowly released from the drug, silver has a toxic effect on microorganisms. Resistance to silver sulfadiazine may develop. Unlike silver, which is hardly absorbed from the wound surface, sulfadiazine can reach a therapeutic concentration in the blood if the wound surface is sufficiently extensive. Side effects therapy rare and include burning, rash, and itching. Silver sulfadiazine is additionally of the generally recognized drugs of choice for the prevention of infection of burn wounds.
Mafenide. This medication is paraaminomethylbenzol sulfamide. Available in the form of acetate. When applied topically, it prevents the colonization of wounds by most gram-negative and gram-positive bacteria. With deep infections, mafenide is not used. Sometimes, against the background of treatment, superinfection caused by Candida spp occurs. Cream with mafenide is applied to the wound surface 1-2 times a day with a layer of 1-2 mm. Before each application Bactipront the drug, the wound is cleaned of necrotic tissue. Treatment is continued until a skin transplant is possible. Mafenide is rapidly absorbed, enters the systemic circulation and turns into paracarboxybenzenesulfamide. The maximum serum concentration is achieved after 2-4 hours after applying the drug to the burn surface. Side effects include severe pain at the site of application and allergic reactions. Since there is no dressing applied with mafenide, fluid loss from the burn surface is possible. The drug and its metabolites inhibit carbonic anhydrase, causing alkalization of urine. Due to the risk of metabolic acidosis with compensatory tachypnea and hyperventilation, the use of mafenide is limited.
Side Effects [edit | edit code]
Sulfanilamides cause a wide variety of side effects, the overall frequency of which is approximately 5%. Some of the side effects are due to individual differences in the metabolism of sulfonamides (Shear et al., 1986).
