ANTI-INFECTIVE AGENTS Anti-infective agents are used to treat disorders caused by bacteria, viruses, protozoa, worms, fungi, and

yeast. These are drugs designed to act selectively on foreign organisms that have invaded and infected the body of a human host. Anti-infective agents include the following: antibiotics, antivirals, antifungals, antiprotozoals, antihelminthics, and antineoplastics. O Mechanisms of Action The main goal of anti-infective agents is to interfere with the normal function of the invading organism to prevent it from reproducing and to cause cell death without affecting the host cells (selective toxicity). Each drug class under anti-infectives have specific mechanisms of actions such as: Interference with biosynthesis of the bacterial cell wall. Prevent the cells of the invading organism from using substances essential to their growth and development, leading to an inability to divide and eventually to cell death. Interference with the steps involve in protein synthesis, an essential function to maintain the cell and permit cell division. Interference with DNA synthesis, leading to inability to divide and cell death. Alter the permeability of the cell membrane to allow essential cellular components to leak out, causing cell death. O Anti-infective Activity Broad-spectrum drugs that interfere with biochemical reactions in different kinds of microorganisms; used in the treatment of a wide variety of infections Narrow-spectrum drugs that are very selective in their action and effective against only a few microorganisms with a very specific metabolic pathway or enzyme. Bactericidal drugs that cause death to the cell they affect. Bacteriostatic durgs that inhibit the growth or the ability of the cells to reproduce and divide. ANTIBACTERIALS (ANTIBIOTICS) O Mechanisms of Actions of Antibacterial Drugs Inhibitions of cell wall Bactericidal effect Enzyme breakdown of the cell wall Inhibition of the enzyme in the synthesis of the cell wall Alteration in membrane permeability Bacteriostatic or bactericidal effect Membrane permeability is increased. The loss of cellular substances causes lysis of the cell. Inhibition of protein synthesis Bacteriostatic or bactericidal effect Interferes with protein synthesis without affecting normal cell. Inhibits the steps of protein synthesis. Inhibition of synthesis of bacterial RNA and DNA Inhibits synthesis of RNA and DNA in bacteria. It binds to the nucleic acid and to the enzymes, which are needed for nucleic acid synthesis. Interference with cellular metabolism Bacteriostatic effect Interferes with steps of metabolism within the cells. O Resistance to Antibacterials Natural and Acquired Resistance Natural resistance also called inherent resistance; occurs without previous exposure to the antibacterial drug; some microorganism have inherent resistance to a specific type of antibacterial drug Acquired resistance is caused by previous exposure to an antibacterial drug

Mechanisms of Microbial Resistance Microorganisms become resistant because of the alterations in their function or structure, such as: Microbes may elaborate drug-metabolizing enzyme through increase production of enzymes, some microorganisms are able to inactivate several different kinds of antibiotics. Microbes may cease active uptake of certain drugs since the site of action of many antibiotics is intracellular, reduced uptake will produce resistance Microbial drug receptors may undergo change, resulting in decreased antibiotic binding action the structural changes that occur in bacterial cell organelles, especially in organelles which are sites for synthesis causes diminished binding action of antibiotics Microbes may synthesize compounds that antagonize drug actions when microorganisms acquire the ability to synthesize increased amounts of certain chemicals that antagonize a microbial drug, this results to resistance O Selection of Antibiotics The therapeutic objective of antimicrobial therapy is to produce maximal antimicrobial effects while causing minimal harm to the host. To be able to achieve this goal, the most appropriate antimicrobial drug must be selected. Three principal factors to consider when choosing an antimicrobial drug: The identity of the infecting organism 1. The infecting organism should be identified prior to the initiation of therapy. 2. Gram-stained preparation a. The quickest, simplest and most versatile technique for identifying microorganisms through microscopic examination. b. Samples for examination may be obtained from pus, sputum, urine, blood, and other body fluids. Although, the most useful samples are direct aspirates from the site of infection. Drug sensitivity of the infecting organism 1. Testing for drug susceptibility is not always needed rather, this is only indicated when the infecting organism is one in which resistance is likely. 2. Disk-Diffusion (Kirby-Bauer)Test a. The most widely used method for assessing drug sensitivity. b. This test is done by inoculating agar plate with the infecting organism and then placing on that plate several small disks, each of which is saturated with a different antibiotic. c. The sensitivity is known when the growth of bacteria is inhibited around a specific disk. The degree of drug sensitivity is proportional to the size of the bacteria-free zone. d. Determination of drug susceptibility and resistance is done by measuring the diameter of the bacteria free zones. 3. Broth Dilution Procedure a. Useful for guiding therapy of infections that are unusually difficult to treat. b. This procedure is done by growing bacteria in a series of tubes containing different concentrations of an antibiotic. c. This method has an advantage over the disk-diffusion test since it provides a more precise measure of drug sensitivity. d. Using this procedure, two clinically useful values can be estimated: i. Minimum Inhibitory Concentration (MIC) the lowest concentration of antibiotic that produces complete inhibition of bacterial growth ii. Minimum Bactericidal Concentration (MBC) the lowest concentration of drug that produces a 99.9% decline in the number of bacterial colonies Host factors Host factors must be considered when prescribing antimicrobial drug, which are the host defenses, site of infection, age, pregnancy, and previous drug reactions. For most infections, there is usually one drug that is superior to the other alternatives. The drug of first-choice may be preferred over others because of its greater efficacy, lower toxicity, or narrower spectrum. Alternative agents should only be used when the first choice drug is inappropriate. The following are conditions that may rule-out a first-choice agent inappropriate for use: Allergy to the drug of choice Inability of the drug of choice to penetrate to the site of infection Unusual susceptibility of the client to toxicity of the first-choice drug GENERAL NURSING CONSIDERATIONS RELATED TO ANTIBIOTIC THERAPY O Assessment

Screen for possible contraindications and cautions for the use of drug. Assessment (complete physical examination and nursing health history) should be performed to establish baseline data for assessing effectiveness of the drug and the occurrence of any adverse effect associated with drug therapy. O Interventions Check culture and sensitivity reports to ensure that this is the drug of choice for the client. Check laboratory results, especially those that indicate renal and liver function (e.g., BUN, serum creatinine, aspartate aminotransferase, alanine aminotransferase, and bilirubin. Ensure that the client receives the full course of antibiotic therapy as prescribed, divided round the clock, to increase effectiveness and decrease the risk of development of resistant strains of bacteria. Monitor the site of infection and presenting signs and symptoms throughout the course of drug therapy. Failure of these signs and symptoms to resolve may indicate the need to reculture the site. In coordination with the client physician, arrange to continue drug therapy for at least 2 days after all signs and symptoms resolve. Monitor the client regularly for signs of nephrotoxicity, neurotoxicity, and bone marrow suppression to effectively arrange for discontinuation of the drug or decreased dosage, if appropriate, and if any of these toxicities occur. Implement safety measures, including adequate lighting, use of siderails and assistance with ambulation to protect client from injury if CNS effects occur. Provide small, frequent meals as tolerated; frequent mouth care and ice chips or sugarless candy to suck if stomatitis and sore mouth are problems to relieve discomfort. Provide adequate fluids to replace fluid loss with diarrhea, if appropriate. Ensure that the client is hydrated at all times during drug therapy to minimize renal toxicity from drug exposure. Ensure that the client is instructed about the appropriate dosage regimen and possible adverse effects to enhance client knowledge about drug therapy and to promote compliance. Instruct the client to: Take safety precautions like changing positions slowly, temporary stop driving or other hazardous activities, if CNS effects occur. Try to drink a lot of fluids and to maintain nutrition even though nausea, vomiting and diarrhea may occur. Avoid exposure to other infections. Use sunblock and protective clothing during sun exposure. Photosensitivity may occur during antibiotic therapy. Promptly report difficulty breathing, severe headache, loss of hearing or ringing in the ears, loss of balance, or changes in the urine output while undergoing therapy. CHEMICAL CLASSIFICATIONS OF ANTIBIOTICS O Aminoglycosides Therapeutic Actions Bactericidal Inhibits protein synthesis of most of the aerobic gram-negative bacilli, like E. coli, K. pneumonia, S. marcescens, P. mirabilis, and P. aerigunosa. Indications Parenteral Therapy use for treatment of serious infections; aminoglycosides most commonly used for parenteral therapy are gentamycin, tobramycin and amikacin. Oral Therapy can be administered to clients anticipating elective colorectal surgery as prophylaxis to suppress bacterial growth in the bowel Topical Therapy neomycin in topical formulations can be applied to the eyes, ears and skin; gentamycin and tobramycin are used to treat conjunctivitis caused by gram-negative bacilli. Pharmacokinetics Absorption 1. Cross membranes poorly, thus they are poorly absorbed in the GI tract. 2. Rapidly absorbed when administered parenterally (IM or IV), reaching peak levels within one hour. 3. Absorption following application to the intact skin is minimal. Distribution 1. Distribution of this drug is limited to extracellular fluid. 2. Cannot readily enter the cerebrospinal fluid in adults. 3. These drugs bind tightly in renal tissue and penetrate the perilymph and endolymph of the inner ear readily. 4. Can cross the placenta and can enter breast milk. Elimination excreted unchanged in the urine and have an average half life of 2 to 3 hours. Contraindications and Cautions

Known allergy to any of the aminoglycosides renal or hepatic disease that could be aggravated by the toxic effects of aminoglycosides, and that could interfere with drug metabolism and excretion leading to higher toxicity. Pre-existing hearing loss that could be intensified by toxic drug effects on the auditory nerve. Active infection with herpes or mycobacterial infections that could be worsened by the effects of an aminoglycoside on normal defense mechanim. Myasthenia gravis or Parkinsonism, which could be exacerbated by a specific animoglycoside on the nervous sytem. Lactation, since the drug can be excreted in breast milk and potentially can cause serious effects in the baby. Caution during pregnancy and carefully weigh potential adverse effects of the drug on the fetus. Adverse Effects Ototoxicity 1. An ireversible adverse effect of aminoglycoside use. 2. Impaired hearing due to damage to sensory hair cells in the cochlea 3. Disruption of balance due to damage to sensory hair cells of the vestibular apparatus 4. May initially be manifested by dizziness, tinnitus and progressive hearing loss. 5. Risk for ototoxicity increases if aminoglycoside is combined with ethacrynic acid, torsemide, bumetanide, and furosimide. Nephrotoxicity 1. This is usually manifested by acute tubular necrosis, which is reversible following cessation of aminoglycoside use. 2. Prominent symptoms of this adverse effect are proteinuria, casts in the urine, production of dilute urine, and elevations in the serum creatinine and blood urea nitrogen (BUN). 3. Risk for nephrotoxicity increases if drug is combined with cephalosporins and diuretics. Nueromuscular Blockade 1. Rare adverse effect but may occur at high doses of aminoglycoside and may result to respiratory paralysis. 2. Increase risk for this when drugis combined with skeletal muscle relaxants, which could also result in repiratory depression. 3. Usually reversible by treatment with calcium and neostigmine, although mechanical ventilation may also be required. Other adverse effects include hypersensitivity reactions (e.g.,pruritus, rash, and urticaria), blood dsycrasia, neurologic disorders, contact dermatitis, suprainfection of the bowel, and intestina lmalabsorption although these rarely occur. O Cephalosporins Therapeutic Actions Bactericidal These drugs bind to penicillin-binding proteins (PBPs), which disrupt cell wall synthesis and activate enzymes that slice bonds in the cell wall. This result to damage to the cell wall and eventually cell death by lysis. Most effective against cells undergoing active growth and division. Indications First Generation Cephalosporin 1. Highly active against gram-positive bacteria. 2. The most active of all cephalosporins against staphylococci and nonenterococcal streptococci. 3. Has only moderate activity against gram-negative bacteria. 4. Does not effectively reach the CSF. 5. Coud also be used as surgical prophylaxis. Second Generation Cephalosporin 1. Usually have less activity against gram-positive bacteria but have enhanced activity against gram-negative bacteria which is caused by the following factors: a. Increased affinity to PBPs of gram-negative bacteria b. Increased ability to penetrate the gram-negative cell envelope c. Increased resistance to beta-lactamase produced by gram negative organisms 2. Is not active against P. aeruginosa, and does not effectively reach the CSF. Third Generation Cephalosporin 1. Has a broad spectrum of antimicrobial activity. 2. Has increased resistance to beta-lactamase, thus these drugs are considered more active than the latter generations of cephalosporins. 3. Some have important activity against P. aeruginosa, though others lack such activity. 4. Able to cross the blood-brain barrier, thus reaching clinically effective concentrations in the CSF.

Fourth Generation Cephalosporin 1. Have a very broad antibacterial spectrum and a very high resistance to beta-lactamase. 2. Has activity against P. aeruginosaand good penetration in the CSF. Pharmacokinetics Absorption 1. Must be administered parenterally (IM or IV) due to poor absorption from the GI tract. 2. There is only a minimum number of cephalosphorins that could be administered by mouth (e.g., cephalexin, cefuroxime, cefdinir, cefepime). Distribution 1. This drug class distribute well to most body fluids and tissues. 2. Therapeutic concentrations can be achieved in pleural, pericardial, and peritoneal fluids, while concentrations in ocular fluids are generally low. 3. Penetration by first- and second-generation drugs in the CSF is unreliable, while third- and fourth-generation drugs achieve CSF levels generally sufficient for bactericidal effects. Elimination almost all cephalosporins are eliminated unchanged by the kidney through the combination of glomerula filtration and active tubular secretion. Contraindications and Cautions Should not be used in clients with known allergies to cephalosporins or penicillins because cross sensitivity to one of these drugs is common. Caution must be used in clients with renal failure. Adverse Effects Cephalosporins are generally well tolerated and are one of the safest groups of antimicrobial drugs. Serious adverse effects, which include the following: Allergic Reaction 1. Hypersensitivity reactions are the most frequent adverse effects. 2. Maculopopular rash most common reaction that develops several days after the onset of treatment 3. Severe, immediate reactions, such as anaphylaxis or bronchospasm, are rare. In case of anaphylactic reaction, respiratory support and parenteral epinephrine should be administered. 4. If signs of allergy appear during the course of treatment, the cephalosporin should be discontinued immediately. Bleeding 1. Bleeding tendecies are caused by three cephalosporins cefmetazole, cefoperazone and cefotetan that interferes with vitamin K metabolism, which reduces prothrombin levels. 2. Monitor clients prothrombin time or bleeding time during prolonged treatment. Observe for signs of bleeding, the drug should be stopped if bleeding occurs. Parenteral administration of vitamin K can correct abnormal prothrombin time. Thrombophlebitis this may develop during IV infusion of the drug, and can be minimize by rotating the infusion site, using small needles, large veins, and by administering the drug slowly, in dilute solution. Electrolyte Imbalance most cephalosporins have high electrolyte content, watch out for the development of hyperkalemia or hypernatremia Other Adverse Effects 1. May cause pain at the site of IM injection. 2. Diarrhea, which is caused by the alteration on the bacterial flora of the GI tract. Encourage client not to discontinue therapy without consulting the physician. 3. Nephrotoxocity for individuals with a preexisting renal disorder. 4. Secondary infections, such as oral thrush, genital and anal pruritus, vaginitis, and vaginal discharge may occur prompt because these infections are resistant to the original antibiotic used. O Fluoroquinolones Therapeutic Actions

Bactericidal Interfere with the action of DNA enzymes necessary for the growth and reproduction of the bacteria. Indications These drugs have broad antimicrobial spectrum and is well tolerated in oral form. Could be used as therapy for a wide variety of infections, which include infections of the respiratory tract, urinary tract, GI tract, bones, joints, skin, and soft tissues. Indicated for treating infections caused by susceptible strains of gram-negative bacteria, such as E. coli, P. mirabilis, Enterobactercoacae, P. vulgaris, P. rettgeri, M. morganii, H. influenza, H. parainfluenza, P. aerigunosa, S. aureus, S. epidermidis. Pharmacokinetics Absorption 1. May be administered orally or through IV. 2. With oral administration, the drug is rapidly but incompletely absorbed. Distribution 1. High concentrations of these drugs are achieved in urine, stool, bile, saliva, bone, and prostate tissue. 2. Drug levels in the CSF are low. 3. Can cross the placent and enter the breast milk. Elimination the drug is metabolized in the liver and is excreted unchanged in the urine. Contraindications and Cautions Contraindicated to clients with known allergy to fluoroquinolones Contraindicated to pregnant and lactating women since the drugs have unknown effects to fetuses and infants Caution should be used in clients with: 1. Renal dysfunction that could interfere with drug excretion 2. Seizures that could be aggravated by the drugs effects on cell membrane channels. Adverse Effects Photoxicity sensation of skin burning, redness, swelling, blisters, rash, itching, or dermatitis may develop when exposed to direct and indirect sunlight during course of therapy. Tendon rupture although a rare adverse effect, this occurs due to the disturbance in the extracellular matrix of cartilage by fluoroquinolone. First sign is tendon pain or inflammation. O Macrolides Therapeutic Actions Broad-spectrum antibiotics which have both bacteriostatic and bactericidal effects. Exert their effect by binding to the bacterial cell membrane and changing protein function. This action can prevent the cell from dividing or cause cell death, depending on the sensitivity of the bacteria and the concentration of the drug. Indications Indicated for treatment for the following: 1. Acute infections caused by susceptible strains of S. pneumonia, M. pneumonia, L. monocytogenes, and L. pneumophilia 2. Infections caused by group A beta-hemolytic streptococci 3. Pelvic inflammatory infection caused by N. gonorrhoeae 4. Upper respiratory tract infections 5. Intestinal amebiasis Can also be used for prophylaxis before dental procedures to client with valvular heart disease and endocariditis, who are allergic to penicillin. Topical macrolides are indicated for treatment of ocular infections and for acne vulgaris. Pharmacokinetics Absorption

1. The drugs are readily absorbed in the GI tract, more specifically in the duodenum of the small intestine. 2. IV administration of these drugs produce plasma drug levels higher than those achieved with oral therapy. Distribution 1. The drugs are readily distributed to most tissues and body fluids. 2. Has poor penetration to the CSF. 3. Can cross the placenta and enter breast milk. Elimination these drugs are eliminated primarily by hepatic mechanism; the drug is concentrated in the liver and excreted in the bile. Contraindications and Cautions Contraindicated in clients with known allergy to macrolides since cross-sensitivity can occur. Ocular preparations of this drug is contraindicated for viral, fungal or mycobacterial infections of the eye, which could be aggravated by loss of bacteria of the normal flora. Caution should be used with the following clients: 1. Those with hepatic dysfunction that could alter the metabolism of the drug. 2. Those with renal disease that could interfere with the excretion of the drug. 3. Lactating women because macrolides secreted in breast milk can cause diarrhea and superinfections in the infant. 4. Pregnant women because of potential adverse effects on the developing fetus. Adverse Effects there are only very few adverse effects related to the use of macrolides, such as neurologic symptoms, hypersensitivity reactions, and superinfections related to loss of normal flora. O Lincosamides Therapeutic Actions Have almost the same actions to that of the macrolides (though they are not chemically related) but are more toxic. These drugs inhibit bacterial protein synthesis and have both bacteriostatic and bactericidal effects. Indications Clindamycin and lincomycin are the most common macrolides though clindamycin is more widely prescribed because it is active against most gram-positive and anaerobic organisms. Clindamycin is considered more effective than lincomycin and has fewer toxic effects. These drugs could be administered orally or through IM and IV injections. Pharmacokinetics Absorption rapidly absorbed from the GI tract and from IM or IV injections; absorption in the GI tract is nearly complete and is not affected by food. Distribution widely distributed to most body fluids and tissues, including synovial fluid and bone; penetration to the CSF is poor; can cross the placenta and enter breast milk Elimination metabolized in the liver and is excreted in the urine or feces Contraindications and Cautions Caution should be used in clients with hepatic or renal impairment which could interfere with them metaobolism and the excretion of the drug. Caution should also be used with pregnant or lactating clients. Adverse Effects Antibiotic-associated Pseudomembranous colitis 1. Most severe form of toxicity associated with the use of clindamycin caused by suprainfection of the bowel with C. difficile. 2. Charaterized by profuse, watery diarrhea (10-20 stools per day), abdominal pain, fever, and leukocytosis. The stools often contain mucus and blood. 3. May develop during the first week of treatment and as long as 4 to 6 weeks after treatment withdrawal. Could be fatal if left untreated. 4. Occurs with oral and parenteral therapy. 5. If this condition is diagnose, clindamycin should be discontinued, the client should be given oral vancomycin or metronidazole, and there should be vigorous replacement of fluids and electrolytes.

Rapid IV administration can cause electrocardiographic changes, hypotensionand cardiac arrest. Hepatotoxicity and blood dyscrasiadevelop rarely. O Monobactam Antibiotic (Aztreonam) Therapeutic Actions This is a new class of beta-lactam antibiotics that inhibits bacterial cell wall synthesis, ultimately causing the cell to rupture and die. Has a narrow antimicrobial spectrum. Has no activity against gram-positive microorganisms. Has a high degree of activity against beta-lactamase producing, bacteria, including P. aerigunosa. Indications Used to treat urinary tract, lower respiratory tract, skin, intra abdominal, gynecologic, septicemic infections, and meningitides. It is recommended that this drug be combined with a broad spectrum antibiotic in the initial treatment of infection of unknown\ cause to treat susceptible anaerobes or gram-positive organisms. Pharmacokinetics Absorption not absorbed in the GI tract, thus it must be administeredparenterally (IM or IV). Distribution the drug distributes widely to most body fluids and tissues; concentration can be achieved in the CSF. Elimination the drug is eliminated by the kidneys, primarily as the unchanged drug. Contraindications and Cautions Contraindicated to clients with any known allergy to aztreonam. Caution should be used in clients with history of acute allergic reaction to penicillins or cephalosporins because of the possibility of cross-reactivity. Caution should also be applied to pregnant and lactating women. Adverse Effects is the same with other beta-lactam antibiotics. O Penicillins Therapeutic Actions Bactericidal These drugs act by interfering with the synthesis of bacterial cell walls. The cell wall is weakened because of the defective structure, and the bacteria are consequently destroyed by osmoticlysis (the cell takes up excessive amounts of water and then rupture). Penicillins are most effective with bacteria that multiply rapidly. Indications Used to treat middle ear infections (otitis media), pneumonia, meningitis, urinary tract infections, syphilis, and gonorrhea. Used as prophylaxis before surgery or dental procedures for clients with history of rheumatic heart disease. Pharmacokinetics Absorption 1. Penicillins (except Penicillin G) are rapidly absorbed from the GI tract, reaching peak levels in an hour. 2. These drugs are sensitive to the gastric levels in the stomach and should be taken on an empty stomach to ensure absorption. Distribution 1. These drugs distribute well to most tissues and body fluids. 2. In the presence of inflammation, entry into CSF, joints and eyes are enhanced, permitting treatment of infections caused by susceptible organisms. Elimination eliminated by the kidneys, primarily as unchanged drug in the urine. Contraindications and Cautions Contraindicated in clients with allergies to penicillin or cephalosphorins or other allergens. Caution should be exercised in clients with renal disease, in those who are pregnant, and in lactating women. O Penicillinase-Resistant Antibiotics (AntistaphylococcalPenicillins)

 This is a group of penicillins that are highly resistant to inactivation by beta-lactamase. Agents in this group have a very narrow antimicrobial spectrum and are used only against penicillinase-producing strains of staphylococcus. O Sulfonamides Therapeutic Actions Generally bacteriostatic but are not true antibiotics because they are not synthesized by microorganism. Suppresses bacterial growth by inhibiting synthesis of folic acid (folate), a compound required by all cells for biosynthesis of DNA, RNA, and proteins. These drugs are active against gram-positive and gram-negative organisms. Indications The clinical usefulness of sulfonamides has decreased because of the availability and effectiveness of penicillin and other antibiotics, plus resistance to some sulfonamides can develop. This drug can be an alternative for clients allergic to penicillin. Still used to treat urinary tract and ear infections, and may be used as prophylaxis for newborn. Also useful in the treatment of meningococcal meningitis and against the organisms Chlamydia and Toxoplasma gondii. Pharmacokinetics Absorption 1. Well absorbed following oral administration. 2. May be absorbed in amounts sufficient to cause systemic effects when applied topically to the skin or mucous membrane. Distribution 1. Well distributed to all tissues. 2. Readily cross the placenta, and levels achieved in the fetus are sufficient to produce both antimicrobial effects and toxicity. Excretion excreted primarily by the kidneys Contraindications and Cautions Contraindicated: 1. To clients with any known allergy to sulfonamide, sulfonylureas, or thiazide diuretics because cross-sensitivity occur. 2. During pregnancy, because these drugs can cause birth defects and kernicterus. 3. During lactation because of a risk of kernicterus, diarrhea, and rash in the infant. Caution should be used in clients with renal disease or history of kidney stones because of the possibility of increased toxic effects of the drugs. Adverse Effects Steven-Johnson Syndrome 1. Most severe hypersensitivity reaction to sulfonamides but is rare. 2. Symptoms include widespread lesions of the skin and mucous membranes, together with fever, malaise and toxemia. 3. This reaction occurs most likely with long term acting sulfonamides. Hematologic Effects 1. These drugs can cause hemolytic anemia in clients whose red blood cells have a genetically determined deficiency in glucose-6-phosphate dehydrogenase (G6PD). 2. In addition to hemolytic anemia, sulfonamides can also cause agranulocytosis, leucopenia, thrombocytopenia, and very rarely, aplastic anemia. Kernicterus sulfonamides promote this effect by displacing bilirubin from plasma proteins, and because the blood-brain barrier of infants is not yet fully developed, the newly freed bilirubin has easy access to sites within the brain. O Tetracyclines Therapeutic Actions Broad-spectrum antibiotics and are bacteriostatic. Suppress bacterial growth by inhibiting protein synthesis. Active against a wide variety of gram-positive and gram-negative bacteria.

Indications The use of tetracyclines has declined at present due to the increasing bacterial resistance. These drugs are rarely used nowadays as the first drug of choice. Disorders where tetracyclines are the first drug of choice include rickettsial diseases, infections caused by C. trachomatis, brucellosis, cholera, pneumonia caused by M. pneumonia, Lyme disease, anthrax, and gastric infection with H. pylori. Used orally or topically for the treatment of severe acne vulgaris caused by Propionibacterium acnes. Used orally and topically for the treatment of periodontal disease. Pharmacokinetics Absorption 1. All tetracyclines are orally effective, although the extent of absorption differs among individual agents. 2. Short-acting and immediate-acting tetracyclines are reduced in the presence of food while the long-acting ones are not. 3. Should not be administered together with calcium supplements, milk products, iron supplements, magnesium containing laxatives, and most antacids because these decreases absorption of the drug. Distribution 1. Widely distributed to most tissues and body fluids. 2. Penetration in the CSF is poor. 3. Can readily cross the placenta and enter fetal circulation.

Excretion 1. All tetracyclines are excreted by the liver into the bile. After the bile enters the intestine, most tetracyclines are reabsorbed. 2. Ultimate elimination of short-acting and immediate-acting tetracyclines in the urine, as an unchanged drug. 3. Long acting Contraindications and Cautions Contraindicated in clients: 1. with known allergies to tetracycline 2. who are pregnant and lactating Caution use in: 1. children younger than 8 years of age because these drugs can potentially damage the bone and teeth 2. clients with hepatic or renal dysfunction O Anti-Mycobacterial Antibiotics Antituberculosis Drugs Isoniazid 1. Primary agent for treatment and prophylaxis of tuberculosis. 2. Highly selective for mycobacteria. 3. Bactericidal to mycobacteria that are actively dividing, but are only bacteriostatic to resting organisms. 4. Studies suggest that the action of this drug is to suppress bacterial growth by inhibiting protein synthesis of mycolic acid (an acid produce only by mycobacteria), a component of mycobacterial cell wall. 5. Administered orally and via IM; absorption is good in both routes. 6. Inactivated in the liver; excreted in the urine as inactive metabolites. 7. Adverse effects a. Peripheral neuropathy i. Most common adverse effect ii. Principal symptoms are symmetric parethesias (tingling, numbness, burning, pain) of the hands and feet; clumsiness and muscle aches may also develop iii. This results from isoniazid-induced deficiency in pyridoxine (vitamin B6) b. Hepatotoxity i. Isoniazid can cause hepatocellular injury and multilobular necrosis ii. Liver injury is thought to result from production of toxic isoniazid metabolite Rifampin 1. A broad-spectrum antibiotic; active against most grampositive bacteria and a number of gram-negative organisms. 2. Bactericidal to M. tuberculosis and M. leprae. 3. This drug inhibits bacterial DNA-dependent RNA polymerase, thus suppressing RNA synthesis, and consequently protein synthesis.

4. Well absorbed if taken in empty stomach. 5. Widely distributed to tissues and body fluids, including the CSF; eliminated primarily by hepatic metabolism. 6. Drug of choice for the treatment of pulmonary tuberculosis and disseminated disease, as well as an important agent in the treatment of leprosy. 7. Adverse effect the drug is generally well tolerated, thus significant toxicity are rare a. Hepatotoxity toxic to the liver and may cause jaundice and even hepatitis; this effect is most likely in alcoholics and clients with preexisting liver disease b. Discoloration of body fluids frequently, the drug imparts a red-orange color to urine, sweat, saliva, and tears, which is actually harmless Pyrazinamide 1. Bactericidal to M. tuberculosis although its specific mechanism of action is unknown. 2. Well absorbed following oral administration and is widely distributed to tissue and body fluids. 3. Converted in the liver to be an active metabolite; excreted in the urine as an inactive metabolite. 4. The principal adverse effect of this drug is hepatotoxicity. Ethambutol 1. Active only against mycobacteria and is bacteriostatic. 2. Usually active against tubercle bacilli that are resistant to isoniazid and rifampin. 3. Known to suppress incorporation of mycolic acid in the cell wall but the precise mechanism by which the drug suppresses bacterial growth has not been established. 4. Optic neuritis is the only significant adverse effect of the drug. Ethambutol can produce dose-related optic neuritis, resulting to blurred vision, constriction of the visual field, and disturbance of color discrimination, reasons for these are still unknown. Streptomycin 1. An aminoglycoside antibiotic. 2. Bactericidal to tubercle bacilli. 3. Toxicity to this drug causes injury to the 8 (vestibulocochlear) cranial nerve, which results in hearing loss and disturbance of balance. This incidence is increased by advance age and kidney dysfunction. 4. This drug is administered via IM injection. Drugs for Leprosy (Hansens Disease)
th

Rifampin Dapsone 1. The drug is weakly bactericidal to M. leprae. 2. It is safe, inexpensive and moderately effective. 3. Dapsone is chemically related to sulfonamides and shares their mechanism of action inhibition of folic acid synthesis. 4. Absorbed rapidly and nearly completely from the GI tract. 5. Once in the blood, the drug is widely distributed to tissues and body fluids. 6. Undergoes hepatic metabolism followed by excretion in the urine. 7. Dapsone is generally well tolerated, and the drug has been taken in years without untoward effects. Clofamazine 1. Slowly bactericidal to M. leprae. 2. Its mechanism of action is unknown. 3. In addition to its antibacterial action it also has anti-inflammatory effects. 4. Oral route is the only means of administration; undergoes partial absorption in the GI tract. The absorbed drug is retained in fatty issues and skin.