SULFONAMIDES

Abstract
Sulfonamides are among one of the oldest drugs to be used as antibiotics. They were invented in 1930's. Nowadays doctors prefer to prescribe them as the traditional drug of choice for urinary tract infections and sexually transmitted diseases. Currently, the new development of antibiotics to combat illnesses caused by bacterial resistant strains and have limited the usefulness of Sulfa medications.

Objectives
Upon successful completion of this presentation you should be able to:
• Understand and communicate your knowledge of Sulfonamides mode of action and bacterial resistance
• Identify and understand the contra indications, common signs and symptoms of allergic reactions to Sulfonamides.
• Identify 3 common trade names for sulfonamides and select indication for use between different patient population.

Type and class of Pathogen
Sulfonamides have been in use since the 1930's , these drugs are effective against both gram- negative and gram - positive bacteria. Sulfonamides are know as broad spectrum antimicrobial drugs; they are effective against a wide variety of microorganisms most Enterobacteriaceae, Chlamydia trachomatis, Nisseria, Haemophilus influenzae,, Norcardia, E.Coli , P. mirabilis some staphylococci, and many streptococci (with exception of Enterococcus faecalis). They are used for treatment of Protozoan such as Toxoplasma gondii, and mycobacterial. Sulfonamides are use for treatment and prophylaxis of Pneumocytis carinii and Shigella small bowel infections.

Mode of Action Sulfonamides are bacteriostatic anti-invectives that "inhibit bacteria" growth but do not destroy it (Lilley, Collins, Harrington & Snyder, 2011). By preventing the bacterial synthesis of a water soluble vitamin B-complex known as folic acid, inhibiting the synthesis of purines and pyrimidines essential components precursors to RNA and DNA. As humans, We are unable to synthesize folic acid and must obtain it through our diet but bacteria are impermeable to folic acid and must synthesize it inside the cell nucleus (Karch, 2010). Sulfonamides act as antimetabolites competing with paraaminobenzoic acid (PABA) from folic acid for binding with the enzyme called Tetrahydropteroic acid synthetase and interrupt a crucial step in the biosynthetic pathway, Sulfonamides action of blocking a biosynthesis of folic acid components to slows the harmful bacterial growth inside our system.

Indication for Use
This widely known anti infective drug combination is mostly use as the traditional choice for acute uncomplicated cystitis or urinary tract infections . Trimethoprim-sulfamethoxazole (TMP-SMZ) is prescribed as a 3 day oral regimen, and infused IV pump over 60 -90 minutes this drug is never mixed with other medications nor ever given as an intravenous bolus is readily absorbed and widely distributed to all the body fluids, including cerebral spinal fluid CSF; crosses placenta is secreted in breast milk, protein binding is 70%(SMZ) and 44% (TMP) It is metabolized in the liver and excreted through the kidneys. the onset action PO is 1-4 hours duration half life of 8-10 hours (TMP) and 10-13 hours (SMZ) It has been used for the treatment of uropathogens such as Escheria coli, Staphyllacoccus saprophyticus, Klebsiella, Proteus mirabilis Enterobacter (Lilley, Collins, Harrington & Snyder, 2011). However, the widespread use of Sulfonamides over 80 years produced resistant strains where mutant enzymes continue the process of folic acid synthesis binding with PABA and no longer binding to sulfonamides.
Most common trade names Bactrim, Septra (Trimetrhoprim- Sulfamethoxazole) TMP-SMZ for treatment of otitis media, bronchitis, UTI and pneumonitis caused by pneumocystis carinii. Gantrisin (Sulfisoxazole) treatment of wide range of infections including STDs. Azulfidine (Sulfasalazine) treatment of ulcerative colitis , Crohn's disease, rheumatoid arthritis

Contraindication and cross sensitivity reactions
TPM-SMZ are contra indicated to pregnant patients due to its teratogenic effect during the first trimester (category C ) " potential for birth defects" (Karch, 2010). There is a high incidence of cross sensitivity of this drug during lactation due to the permeability of this medication secreted through milk producing glands. This will most likely affect the infant with kernicterus diarrhea and rash .
Allergic reactions and adverse effects Adverse effects of anti-invectives are associated with nephrotoxicity, crystalluria, hematuria and protenuiria; all of which can lead to nephrotic syndrome, upper gastrointestinal effects, diarrhea and death of normal flora. Non therapeutic reactions to this medication may cause hepatic injury and neurotoxic effects including bone marrow depression, dizziness, headache, ataxia, depression and convulsion. dermatological effects include rash and photosensitivity (Lilley, Collins, Harrington & Snyder, 2011). Unfortunately once resistance to one sulfonamide is created the patient acquires resistance to all members of this drug class causing an allergic reaction. Sulfa allergies includes: sulfonamide, thiazide diuretics, sulfonylureas. Special caution must be taken when patient are prescribed sulfonamides and they are taking the following drugs that potentiate a drug on drug interaction. acetohexamide, chlorpropamide, glypizide, glyburide, tolazamide and tolbutamide with the risk of increasing hypoglycemic episodes. It is known that if sulfonamides and cyclosporine taken together can cause nephrotoxicity. If any of these medications are given a close monitoring of the patient's renal function must be done to avoid kidney damage (Karch, 2010).
Herbal, dietary OTC for Urinary tract infections
Despite its growing popularity, research indicates that patients often do not discuss the use of Complementary and Alternative Medicine (CAM) with their primary health care provider. Only about one-third of CAM users reported their use of complementary therapies with their clinicians (Jackson & Taubenburger, 2012). Cranberry juice has been used since early 1900 Native Americans, who used the berry to treat digestive problems noting the change in their urinary system due to its consumption. Later it became known that the cranberry was able to lower the pH of the of the consumer's urine, thereby making it more acidic (Adams & Koch, 2010) . Cranberry contains antioxidants and vitamin C, many studies have been made about the effectiveness of cranberry products to ward of UTIs However, not specific proof has been obtained about this claims. It was previously thought that cranberry juice changes the pH of urine discouraging bacteria growth. A more recent study proved that cranberry chemical properties prevent bacteria from attaching to the walls of the bladder thereby obstructing bacteria reproduction.
Cranberry Juice must be 100% juice and not mixed with alcohol or with added sugar, this may not be recommended for diabetic patients. However, they may benefit from cranberry extract available in capsules. The study of Complementary and Alternative Therapies for Urinary Symptoms brings about a diverse range of remedies used to treat urinary symptoms and how patients use such remedies in relation to allopathic care (Jackson & Taubenburger, 2012).
Nurses can use these findings to enhance their education to patients, The use of remedies more commonly recognized, such as cranberry juice and saw palmetto," it is more frequently seen among Caucasian men and women", while African-American and Hispanic men and women rely on a broader range of remedies, including flaxseeds, ginseng, barley, cinnamon, and moabi, and other herbs, juices, and substances (Jackson & Taubenburger, 2012). Special Nursing considerations
When nurses have patients with urinary tract infections is useful to differentiate and understand the different modalities of pharmacotherapy use for each population group. Uncomplicated urinary tract infections is often seen in "women of reproductive age, the highest incidence from 18 -24 years" of age due to frequent sexual activity, use of spermicides for contraception, use of diaphragm or Estrogen deficiency (Adams & Koch, 2010) . Patients of this category are able to recognize their symptoms and seek medical attention starting drug therapy immediately prior to receive the results from the urinalysis that confirms the uropathogen involve. Young women drug treatment usually is a single dose or short course therapy .Women over the age of 60 usually have no symptoms of bacteriuria however, they will seek help only when they become symptomatic. Thus, the case of this infection is of most concern to pregnant patients, patients that are immunosuppressed or undergoing urologic procedures.

Complicated urinary tract infections are usually occurring in male patients with underlying co morbid conditions that will increases the risk of treatment failure. this type of UTI will require prolonged treatment time and higher doses of more toxic drugs. The most common co morbid conditions are neurogenic bladder, abnormalities of the genitourinary tract, renal tumor, urinary stones and Benign prostatic Hyperplasia (BPH) (Adams & Koch, 2010). Indwelling catheters, recurring UTIs with resistant uropathogens, patients with poor periurethral hygiene, all UTI in males are usually caused by an obstruction such an enlarged prostate a urinary stone or a medical procedure utilizing an indwelling catheters. Complicated UTI require urine culture and sensitivity test (C&S) to identify the specific microbe and tailor the most effective drug therapy treatment usually lasting 14 days (Adams & Koch, 2010). Treatment starts by giving them a broad spectrum anti-infective with confirmed diagnoses and then adjusted based on culture and sensitivity test results. once drug therapy is finished several weeks after another C&S test is taken to confirm the elimination of infective pathogens

Infants and children
Recurring UTI's in infants and children pose the risk of scarring of the kidneys resulting in hypertension during their adult life treatments with TPM-SMZ and nitrofurantoin are effective however, "the use of fluroquinolones is found to affect cartilage development in children" (Adams & Koch, 2010).

Older adults The elderly population with co morbid conditions and institutionalize must undergo a very aggressive form of pharmacotherapy due to the high prevalence of resistant strains in hospitals and nursing homes, their treatment for UTI must have a C&S test and monitor for hypersensitivity reactions in the first 2 -30 minutes and delay reaction from 1-72 hours. Due to polypharmacy in the elderly population, fluid intake is essential from 2000 up to 3000ml of fluid to prevent crytalluria, monitor severe diarrhea as it could be sign of superinfection due to the elimination of natural flora or adverse effect to antibiotic, take precautions for photosensitivity and administer medication as prescribed to maintain therapeutic blood levels. Up to 25% of hospitalized patients have urinary catheters inserted; of these individuals, 10-27% develop UTIs. In fact, UTI accounts for approximately 40% of all nosocomial infections; 15% of these infections occur in clusters and often involve highly resistant organisms. (Brusch MD, 2012)

In Summation
The study of Sulfonamides have clarified and deepened my understanding to why this type of medication is mainly used for urinary tract infections. Sulfonamides were once considered a miracle drug against all type of ailments; unfortunately the long spread use of this drug over the course of 80 years have resulted in the growth of great number of resistant strains deactivating the effectiveness of this antibacterial against respiratory, digestive and ear infections a careful consideration about signs and symptoms of adverse effects is very useful to educate our patients about their safety while on this class of bacteria inhibiting medication.

References Lilley, L. L., Collins, S. R., Harrington, S., & Snyder, J. S. (2011). Pharmacology and the nursing process. (6 ed., p. 589). St. Louis, MO: Mosby-Elsevier.

Karch, A. M. (2010). Focus on nursing pharmacology. (p. 114). Philadelphia, PA: Lippincott Williams & Wlkins.

Adams, M., & Koch, R. W. (2010). Pharmacology, connections to nursing practice. (p. 845). Upper Saddle River, NJ: Prentice Hall.
Brusch MD, J. (2012). Prevention of urinary tract infections . doi: 2040239

Jackson, C., & Taubenburger, S. (2012). Complementary and alternative therapies for urinary symptoms. use in a diverse population, doi: PMID:22860393