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DRUGS FOR BUGS ?? ANTIBIOTICS ANTIVIRALSA ANTIFUNGALS ANTI-TUBERCULAR ANTIMALARIAL ANTIHELMINTHIC ANTIMYCOBACTERIAL ANTIVIRALS ANTIBIOTICS COMMONLY.

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Presentation on theme: "DRUGS FOR BUGS ?? ANTIBIOTICS ANTIVIRALSA ANTIFUNGALS ANTI-TUBERCULAR ANTIMALARIAL ANTIHELMINTHIC ANTIMYCOBACTERIAL ANTIVIRALS ANTIBIOTICS COMMONLY."— Presentation transcript:

1 DRUGS FOR BUGS ?? ANTIBIOTICS ANTIVIRALSA ANTIFUNGALS ANTI-TUBERCULAR ANTIMALARIAL ANTIHELMINTHIC ANTIMYCOBACTERIAL ANTIVIRALS ANTIBIOTICS COMMONLY KNOWN AS ANTIMICROBIALS Winter 2013

2 WHAT IS AN INFECTION? A disease or condition caused by a microorganism that releases toxins or invade body tissues Localized infection Systemic infection Winter 2013

3 WHO IS MORE LIKELY TO GET AN INFECTION?
SKIN NOT INTACT BLOOD SUPPLY IMPAIRED NEUTROPENIA MALNUTRITION SUPPRESSION OF NORMAL BACTERIAL BALANCE SUPPRESSION OF THE IMMUNE SYSTEM DIABETES CHRONIC ILLNESS ADVANCED AGE Winter 2013

4 Infections: Sites of Origin
Community-associated infections An infection that is acquired by a person who has not been hospitalized or had a medical procedure (such as dialysis, surgery, catheterization) within the past year Winter 2013

5 Infections: Sites of Origin (cont’d)
Healthcare-associated infections Contracted in a hospital or institutional setting Were not present or incubating in the patient on admission to the facility More difficult to treat because causative microorganisms are often drug resistant and the most virulent One of top ten leading causes of death in the U.S. MRSA most common Previously known as nosocomial Winter 2013

6 Healthcare-Associated Infections: Prevention
Hand washing Antiseptics Disinfectants Winter 2013

7 Healthcare-Associated Infections: Prevention (cont’d)
Disinfectant Kills organisms Used only on nonliving objects Antiseptic Generally only inhibits the growth of microorganisms but does not necessarily kill them Applied exclusively to living tissue Winter 2013

8 FUNCTIONS OF ANTIBIOTICS
BACTERICIDAL – Kills or destroys microorganisms BACTERIOSTATIC – Retards the growth of microorganisms Winter 2013

9 IDENTIFICATION OF BACTERIA
GRAM TESTING CULTURE AND SENSITIVITY TESTING SEND SPECIMEN FIRST !!!!! START ANTIBIOTIC BEFORE CULTURE RESULTS ARE KNOWN (EMPIRIC THERAPY) RX MAY CHANGE WHEN CULTURE IS GROWN Winter 2013

10 Winter 2013

11 BACTERIAL RESISTANCE Bacterial resistance PENICILLINASE
USED BY BACTERIA TO DESTROY PCN BETA-LACTAMASE BREAKS DOWN THE STRUCTURE OF THE ABX INACTIVATING THE DRUG Winter 2013

12 ANTIMICROBIAL RESISTANCE
UNWISE USE OF ANTIBIOTICS ANTIBIOTICS ARE NOT EFFECTIVE AGAINST VIRAL INFECTIONS WHEN VIRAL SYMPTOMS PERSIST, ABX WILL BE USED FOR A SECONDARY BACTERIAL INFECTION ANTIBIOTICS MAY BE PRESCRIBED AS PROPHYLACTIC TO ANOTHER TREATMENT OR PROCEDURE Winter 2013

13 ANTIMICROBIAL RESISTANCE
METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS MRSA HAND WASHING AND GLOVING GOAL IS TO AVOID HEALTHCARE ASSOCIATED INFECTIONS “COLONIZED” MEANS HARBORS THE BACTERIA Winter 2013

14 ANTI-INFECTIVES / ANTIBIOTICS
PROPER DOSE AND DURATION OF THERAPY AVERAGE OF 7 – 10 DAYS OF THERAPY SPECIFY TIME OF DAY TO TAKE THE DRUGS TO MAINTAIN THERAPEUTIC LEVELS PATIENT MUST COMPLETE ENTIRE RX NEVER SAVE FOR USE AT ANOTHER TIME NEVER SHARE WITH ANOTHER PERSON Winter 2013

15 ADVERSE REACTIONS TO ABX
HYPERSENSITIVITY (allergy) Requires at least one exposure to the drug Mild – Rash, pruritus, urticaria Severe – Anaphylaxis Laryngospasms (wheezing) Dyspnea Decrease in blood pressure Winter 2013

16 Winter 2013

17 Winter 2013

18 ADVERSE REACTIONS TO ABX
CROSS-SENSITIVITY REACTIONS If allergic to one antibiotic, allergic to antibiotics from same family EXAMPLE – ALLERGY TO PCN, ALSO MAY BE ALLERGIC TO CEPHALOSPORIN Winter 2013

19 STEVENS-JOHNSON SYNDROME
Severe (can be fatal) hypersensitivity reaction caused by reaction to a medication Typically involves the skin and mucous membranes developing severe inflammation progressing to necrosis of the tissues. Can also progress to the lining of internal organs. TABER’S – TOXIC EPIDERMAL NECROLYSIS Winter 2013

20 Winter 2013

21 Winter 2013

22 Winter 2013

23 SUPERINFECTION A secondary infection that occurs during antibiotic therapy in which normal flora are destroyed Winter 2013

24 Superinfection LOCATION OF INFECTION OFFENDING ORGANISM GROIN AXILLA
MOUTH UNDER BREAST TISSUE ANY WARM MOIST AREA OFFENDING ORGANISM YEAST BACTERIA Winter 2013

25 Candida Yeast / Thrush Winter 2013

26 NURSING RESPONSIBILITIES
PATIENT’S RESPONSE TO THERAPY EVALUATE TEMPERATURE, APPETITE AND GENERAL LEVEL OF WELLNESS FLUID INTAKE DRUGS ARE NEPHROTOXIC ADVISE PATIENT TO INCREASE PO INTAKE FULL GLASS OF WATER WITH MED WATER WILL DECREASE GI SYMPTOMS OTHER MEDS LOOK FOR CONTRAINDICATED MEDS LOOK FOR HERBAL INTERACTIONS Winter 2013

27 CHARACTERISTICS OF ANTIBACTERIALS
BROAD SPECTRUM NARROW SPECTRUM MECHANISM OF ACTION Winter 2013

28 BROAD SPECTRUM ANTIBIOTIC
AN ANTIBIOTIC THAT IS EFFECTIVE AGAINST BOTH GRAM-NEGATIVE AND GRAM-POSITIVE BACTERIAL SPECIES BROAD-SPECTRUM AGENTS INCLUDE CARBAPENEMS EXTENDED-SPECTRUM CEPHALOSPORINS BETA-LACTAM/BETA-LACTAMASE INHIBITOR COMBINATIONS FLUOROQUINOLONES Winter 2013

29 NARROW SPECTRUM ANTIBIOTIC
AN ANTIBIOTIC EFFECTIVE AGAINST A LIMITED NUMBER OF MICROORGANISMS. EXAMPLES OF NARROW-SPECTRUM AGENTS INCLUDE PENICILLIN G MACROLIDES NITROFURANTOIN METRONIDAZOLE AZTREONAM NALIDIXIC ACID Winter 2013

30 MECHANISMS OF ACTION Inhibition of bacterial cell wall synthesis
Inhibition of protein synthesis Disruption of cell membranes Inhibits cell reproduction Inhibits cell metabolism Winter 2013

31 Antibiotics: Sulfonamides
One of the first groups of antibiotics Sulfadiazine Sulfamethoxazole Sulfisoxazole Often combined with another antibiotic Sulfamethoxazole combined with trimethoprim (a nonsulfonamide antibiotic), known as Bactrim, Septra, or co-trimoxazole (SMX-TMP) This combination is used commonly Winter 2013

32 Sulfonamides: Mechanism of Action
Bacteriostatic action Prevent synthesis of folic acid required for synthesis of purines and nucleic acid Do not affect human cells or certain bacteria Only affect organisms that synthesize their own folic acid Winter 2013

33 Sulfonamides: Indications
Effective against both gram-positive and gram-negative bacteria Treatment of UTIs caused by susceptible strains of: Enterobacter , Escherichia coli, Klebsiella , Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus Winter 2013

34 Sulfonamides: Indications (cont’d)
Urinary tract infections Upper respiratory tract infections Winter 2013

35 Sulfonamides: Adverse Effects
Body System Adverse Effects Blood Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia Integumentary Photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis Winter 2013

36 Sulfonamides: Adverse Effects (cont’d)
Body System Adverse Effects GI Nausea, vomiting, diarrhea, pancreatitis Other Convulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria 1&list=PL27024F7449C9E999&feature=results_main Winter 2013

37 Beta-Lactam Antibiotics
Penicillins Cephalosporins Carbapenems Monobactams Winter 2013

38 Winter 2013

39 Penicillins First introduced in the 1940s
Bactericidal: inhibit cell wall synthesis Kill a wide variety of bacteria Bacteria produce enzymes capable of destroying penicillins These enzymes are known as beta- lactamases As a result, the medication is not effective Winter 2013

40 Penicillins Natural penicillins Penicillinase-resistant penicillins
Aminopenicillins Extended-spectrum penicillins Winter 2013

41 Penicillins (cont’d) Natural penicillins Penicillinase-resistant drugs
penicillin G, penicillin V potassium Penicillinase-resistant drugs cloxacillin, dicloxacillin, nafcillin, oxacillin Winter 2013

42 Penicillins (cont’d) Aminopenicillins Extended-spectrum drugs
amoxicillin, ampicillin Extended-spectrum drugs piperacillin, ticarcillin, carbenicillin Usually used with other drugs; rarely used alone Winter 2013

43 Penicillins (cont’d) Chemicals have been developed to inhibit these enzymes: Clavulanic acid Tazobactam Sulbactam These chemicals bind with beta-lactamase and prevent the enzyme from breaking down the penicillin, thus making the drug more effective Winter 2013

44 Penicillins (cont’d) Penicillin–beta-lactamase inhibitor combination drugs Ampicillin + sulbactam = Unasyn Amoxicillin + clavulanic acid = Augmentin Ticarcillin + clavulanic acid = Timentin Piperacillin + tazobactam = Zosyn Winter 2013

45 Penicillins: Indications
Prevention and treatment of infections caused by susceptible bacteria, such as: Gram-positive bacteria Streptococcus, Enterococcus, Staphylococcus Winter 2013

46 Penicillins: Adverse Effects
Allergic reactions occur in 0.7% to 4% of cases Urticaria, pruritus, angioedema Those allergic to penicillins have a fourfold to sixfold increased risk of allergy to other beta-lactam antibiotics Cross-sensitivity between penicillins and cephalosporins is between 1% and 4% Winter 2013

47 Penicillins: Adverse Effects (cont’d)
Common adverse effects Nausea, vomiting, diarrhea, abdominal pain Other adverse effects are less common Winter 2013

48 Penicillins: Interactions
MANY interactions! NSAIDs Oral contraceptives – Decreases effectiveness Warfarin – Enhanced anticoagulant effect r/t decrease in intestinal flora producing vitamin K Others Winter 2013

49 MRSA METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS
Hand washing and gloving Goal is to avoid healthcare associated infections “Colonized” means harbors the bacterial infection Winter 2013

50 NURSING CONSIDERATIONS FOR PENICILLIN
Take with a full glass of water Do not skip doses Take all of the medication as prescribed Notify MD of adverse reactions Winter 2013

51 Winter 2013

52 Cephalosporins First generation Second generation Third generation
Fourth generation Fifth generation (not yet marketed) Winter 2013

53 Cephalosporins (cont’d)
Semisynthetic derivatives Structurally and pharmacologically related to penicillins Bactericidal action Broad spectrum Divided into groups according to their antimicrobial activity Winter 2013

54 Cephalosporins: First Generation
Good gram-positive coverage Poor gram-negative coverage Parenteral and PO forms Examples cefadroxil cephradine cefazolin cephalexin Winter 2013

55 Cephalosporins: First Generation (cont’d)
Used for surgical prophylaxis, and for susceptible staphylococcal infections cefazolin (Ancef and Kefzol): IV or IM cephalexin (Keflex): PO Winter 2013

56 Cephalosporins: Second Generation
Good gram-positive coverage Better gram-negative coverage than first generation Examples: cefaclor cefprozil cefoxitin cefuroxime loracarbef cefotetan Winter 2013

57 Cephalosporins: Second Generation (cont’d)
cefoxitin (Mefoxin): IV and IM Used prophylactically for abdominal or colorectal surgeries Also kills anaerobes cefuroxime Zinacef is parenteral form; Ceftin is PO Surgical prophylaxis Does not kill anaerobes Winter 2013

58 Cephalosporins: Third Generation
Most potent group against gram-negative bacteria Less active against gram-positive bacteria Examples ceftibuten cefotaxime ceftazidime cefdinir ceftizoxime ceftriaxone Winter 2013

59 Cephalosporins: Third Generation (cont’d)
ceftriaxone (Rocephin) IV and IM, long half-life, once-a-day dosing Elimination is primarily hepatic Easily passes meninges and diffused into CSF to treat CNS infections Winter 2013

60 Cephalosporins: Third Generation (cont’d)
ceftazidime (Ceptaz) IV and IM forms Excellent gram-negative coverage Used for difficult-to-treat organisms such as Pseudomonas Eliminated by renal instead of biliary route Excellent spectrum of coverage Resistance is limiting usefulness Winter 2013

61 Cephalosporins: Fourth Generation
Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria Uncomplicated and complicated UTI cefepime (Maxipime) Winter 2013

62 Cephalosporins: Fifth Generation
Ceftobipriole (not available) Broader spectrum of antibacterial activity Effective against a wide variety of organisms MRSA Pseudomonas Winter 2013

63 Cephalosporins: Adverse Effects
Similar to penicillins Mild diarrhea, abdominal cramps, rash, pruritus, redness, edema Potential cross-sensitivity with penicillins if allergies exist Winter 2013

64 Carbapenems Very broad-spectrum antibacterial action
Reserved for complicated body cavity and connective tissue infections May cause drug-induced seizure activity This risk can be reduced with proper dosage All given parenterally Winter 2013

65 Carbapenems imipenem/cilastatin (Primaxin) meropenem (Merrem)
Used for treatment of bone, joint, skin, and soft-tissue infections; many other uses Cilastatin inhibits an enzyme that breaks down imipenem meropenem (Merrem) ertapenem (Invanz) doripenem (Doribax) Winter 2013

66 Monobactams Aztreonem (Azactam) Only drug in this catagory
Beta-lactam antibiotic Gram negative bacteria Inhibits cell wall synthesis Common adverse effects Winter 2013

67 Macrolides erythromycin (E-mycin, E.E.S, others)
azithromycin (Zithromax) “Z-Pack” 3 – 5 day dose pack clarithromycin (Biaxin) dirithromycin Winter 2013

68 Macrolides: Mechanism of Action
Prevent protein synthesis within bacterial cells Considered bacteriostatic Bacteria will eventually die In high enough concentrations, may also be bactericidal Winter 2013

69 Macrolides: Indications
Strep infections Streptococcus pyogenes (group A beta-hemolytic streptococci) Mild to moderate URI and LRI Haemophilus influenzae Spirochetal infections Syphilis and Lyme disease Gonorrhea, Chlamydia, Mycoplasma Winter 2013

70 Macrolides: Indications (cont’d)
azithromycin and clarithromycin Recently approved for mycobacterium avium- intracellular complex infection (opportunistic infection associated with HIV/AIDS) clarithromycin Recently approved for use in combination with omeprazole for treatment of active ulcer disease associated with Helicobacter pylori infection Winter 2013

71 Macrolides: Indications (cont’d)
Fidaxomicin (Dificid) Treatment of Clostridium difficile-associated diarrhea in adults ≥18 years of age. Following oral administration, only minimal systemic absorption occurs; remains mainly confined to and acts locally in the GI tract. Winter 2013

72 Macrolides: Adverse Effects
GI effects, primarily with erythromycin Nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia Newer drugs, azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration Winter 2013

73 Ketolide telithromycin (Ketek) Only drug in this class
Better antibacterial coverage than macrolides Active against gram-positive bacteria, including multi–drug-resistant strains of S. pneumoniae Associated with severe liver disease Use is limited Winter 2013

74 Tetracyclines demeclocycline (Declomycin) oxytetracycline tetracycline
doxycycline (Doryx, Vibramycin) minocycline tigecycline (Tygacil) Winter 2013

75 Tetracyclines (cont’d)
Natural and semisynthetic Obtained from cultures of Streptomyces Bacteriostatic—inhibit bacterial growth Inhibit protein synthesis Stop many essential functions of the bacteria Winter 2013

76 Tetracyclines: Indications
Broad spectrum Gram-negative and gram-positive organisms, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease, acne, others Demeclocycline is also used to treat SIADH by inhibiting the action of ADH Winter 2013

77 Tetracyclines (cont’d)
Bind (chelate) to Ca2+ and Mg2+ and Al3+ ions to form insoluble complexes Thus, dairy products, antacids, and iron salts reduce oral absorption of tetracyclines Should not be used in children under age 8 or in pregnant/lactating women because tooth discoloration will occur if the drug binds to the calcium in the teeth Winter 2013

78 Tetracyclines: Adverse Effects
Strong affinity for calcium Discoloration of permanent teeth and tooth enamel in fetuses and children, or nursing infants if taken by the mother May retard fetal skeletal development if taken during pregnancy Winter 2013

79 Tetracyclines: Adverse Effects (cont’d)
Alteration in intestinal flora may result in: Superinfection (overgrowth of nonsusceptible organisms such as Candida) Diarrhea Pseudomembranous colitis Winter 2013

80 Tetracyclines: Adverse Effects (cont’d)
May also cause: Vaginal candidiasis Gastric upset Enterocolitis Maculopapular rash Other effects Winter 2013

81 Winter 2013

82 Antibiotic Therapy: Toxicities
Ototoxicity Temporary or permanent hearing loss, balance problems Nephrotoxicity Varying degrees of reduced renal function Rising serum creatinine may indicate reduced creatinine clearance Monitor trough levels every 5 to 7 days while on therapy or as ordered Monitor serum creatinine levels at least every 3 days as an index of renal function Winter 2013

83 Aminoglycosides gentamicin (Garamycin) neomycin (Neo-fradin)
tobramycin (Nebcin) amikacin (Amikin) kanamycin streptomycin Winter 2013

84 Aminoglycosides (cont’d)
Natural and semisynthetic Produced from Streptomyces Poor oral absorption; no PO forms Very potent antibiotics with serious toxicities Bactericidal; prevent protein synthesis Kill mostly gram-negative bacteria; some gram-positive also Winter 2013

85 Aminoglycosides: Indications
Used to kill gram-negative bacteria such as Pseudomonas, E. coli, Proteus, Klebsiella, Serratia Often used in combination with other antibiotics for synergistic effects Used for certain gram-positive infections that are resistant to other antibiotics Winter 2013

86 Aminoglycosides: Indications (cont’d)
Aminoglycosides are poorly absorbed through the GI tract, and given parenterally Exception: neomycin Given orally to decontaminate the GI tract before surgical procedures Also used as an enema for this purpose Winter 2013

87 Aminoglycosides: Adverse Effects
Cause serious toxicities Nephrotoxicity (renal damage) Ototoxicity (auditory impairment and vestibular impairment [eighth cranial nerve]) Must monitor drug levels to prevent toxicities Winter 2013

88 Winter 2013

89 Aminoglycosides: Adverse Effects (cont’d)
Ototoxicity and nephrotoxicity are the most significant Headache Paresthesia Fever Superinfections Vertigo Skin rash Dizziness Winter 2013

90 Quinolones ciprofloxacin (Cipro) norfloxacin (Noroxin)
levofloxacin (Levaquin) moxifloxacin (Avelox) Winter 2013

91 Quinolones (cont’d) Also called “fluoroquinolones”
Excellent oral absorption Absorption reduced by antacids Effective against gram-negative organisms and some gram-positive organisms Winter 2013

92 Quinolones: Mechanism of Action
Bactericidal Alter DNA of bacteria, causing death Do not affect human DNA Winter 2013

93 Quinolones: Indications
Gram-negative bacteria such as pseudomonas Respiratory infections Bone and joint infections GI infections Skin infections Sexually transmitted diseases Anthrax Winter 2013

94 Fluoroquinolones: Adverse Effects
Body System Adverse Effects CNS Headache, dizziness, fatigue, depression, restlessness, insomnia GI Nausea, vomiting, diarrhea, constipation, thrush, increased liver function studies, others Cardiac Prolonged QT interval Winter 2013

95 Fluoroquinolones: Adverse Effects (cont’d)
Body System Adverse Effects Integumentary Rash, pruritus, urticaria, flushing, photosensitivity (with lomefloxacin) Other Fever, chills, blurred vision, tinnitus Black box warning: increased risk of tendonitis and tendon rupture Winter 2013

96 Other Antibiotics clindamycin (Cleocin) linezolid (Zyvox)
metronidazole (Flagyl) nitrofurantoin (Macrodantin) quinupristin and Dalfopristin (Synercid) daptomycin (Cubicin) vancomycin (Vancocin) colistimethate (Coly-mycin) Winter 2013

97 Other Antibiotics (cont’d)
clindamycin (Cleocin) Used for chronic bone infections, GU infections, intra-abdominal infections, other serious infections May cause pseudomembranous colitis Winter 2013

98 Other Antibiotics (cont’d)
linezolid (Zyvox) New class: oxazolidinones Used to treat vancomycin-resistant Enterococcus faecium (VREF, VRE), hospital- acquired skin and skin structure infections, including those with MRSA May cause hypotension, serotonin syndrome if taken with SSRIs, and reactions if taken with tyramine-containing foods Winter 2013

99 Other Antibiotics (cont’d)
metronidazole (Flagyl) Used for anaerobic organisms Intra-abdominal and gynecologic infections Protozoal infections Several drug interactions Winter 2013

100 Other Antibiotics (cont’d)
nitrofurantoin (Macrodantin) Primarily used for UTIs (E. coli, S. aureus, Klebsiella , Enterobacter) Use carefully if renal function is impaired Drug concentrates in the urine May cause fatal hepatotoxicity Usually well-tolerated if patient is kept well- hydrated Winter 2013

101 Other Antibiotics (cont’d)
quinupristin and dalfopristin (Synercid) 30:70 combination, work synergistically Used for bacteremia and infections caused by vancomycin-resistant Enterococcus (VRE) and other complicated skin infections May cause arthralgias, myalgias Winter 2013

102 Other Antibiotics (cont’d)
daptomycin (Cubicin) New class: lipopeptide Used to treat complicated skin and soft-tissue infections Winter 2013

103 Other Antibiotics (cont’d)
vancomycin (Vancocin) Natural, bactericidal antibiotic Destroys cell wall Treatment of choice for MRSA and other gram-positive infections Must monitor blood levels to ensure therapeutic levels and prevent toxicity May cause ototoxicity and nephrotoxicity Should be infused over 60 minutes Rapid infusions may cause hypotension Winter 2013

104 Other Antibiotics (cont’d)
vancomycin (Vancocin) (cont’d) Monitor IV site closely Red man syndrome may occur Flushing/itching of head, neck, face, upper trunk Antihistamine may be ordered to reduce these effects Ensure adequate hydration (2 L fluids/24 hr) if not contraindicated to prevent nephrotoxicity Monitor trough levels carefully Winter 2013

105 Nursing Implications It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy Instruct patients to take antibiotics exactly as prescribed and for the length of time prescribed; they should not stop taking the medication early when they feel better Winter 2013

106 Nursing Implications (cont’d)
Aminoglycosides Monitor peak and trough blood levels of these drugs to prevent nephrotoxicity and ototoxicity Symptoms of ototoxicity include dizziness, tinnitus, and hearing loss Symptoms of nephrotoxicity include urinary casts, proteinuria, and increased BUN and serum creatinine levels Winter 2013

107 ANTIVIRAL MEDICATIONS
Winter 2013

108 Understanding Viruses
Viral replication A virus cannot replicate on its own It must attach to and enter a host cell It then uses the host cell’s energy to synthesize protein, DNA, and RNA Winter 2013

109 Understanding Viruses (cont’d)
Viruses are difficult to kill because they live inside the cells Any drug that kills a virus may also kill cells Winter 2013

110 Viral Illnesses Most viral illnesses are bothersome, but survivable
Effective vaccines have prevented some illnesses Effective drug therapy is available for a small number of viral infections Winter 2013

111 Antiviral Drugs Antiviral drugs kill or suppress the virus by destroying virions or inhibiting ability to replicate viruses controlled by current antiviral therapy Winter 2013

112 Antiviral Drugs (cont’d)
Viruses controlled by current antiviral therapy Cytomegalovirus (CMV) Hepatitis viruses Herpes viruses Human immunodeficiency virus (HIV) Influenza viruses (the “flu”) Respiratory syncytial virus (RSV) Winter 2013

113 Antiviral Drugs (cont’d)
Key characteristics of antiviral drugs Able to enter the cells infected with virus Interfere with viral nucleic acid synthesis and/or regulation Some drugs interfere with ability of virus to bind to cells Some drugs stimulate the body’s immune system Winter 2013

114 Antiviral Drugs (cont’d)
Opportunistic infections Occur in immunocompromised patients Would not normally harm an immunocompetent person Require long-term prophylaxis and antiinfective drug therapy Can be other viruses, fungi, bacteria, or protozoa Winter 2013

115 Antiviral Drugs (cont’d)
Used to treat infections caused by viruses other than HIV Antiretroviral drugs Used to treat infections caused by HIV, the virus that causes AIDS Winter 2013

116 Virus Infections Herpes-simplex viruses Human herpesvirus/VZV
HSV-1 (oral herpes) HSV-2 (genital herpes) Human herpesvirus/VZV Chickenpox and shingles (HHV-3 or VZV) Shingles Epstein-Barr (HHV-4) Cytomegalovirus (HHV-5) Kaposi’s sarcoma (HHV-8) Winter 2013

117 Winter 2013

118 Winter 2013

119 Winter 2013

120 Antiviral Drugs (non-HIV)
Mechanism of action Inhibit viral replication Used to treat non-HIV viral infections Influenza viruses HSV, VZV CMV Hepatitis A, B, C (HAV, HBV, HCV) Winter 2013

121 Antiviral Drugs (non-HIV) (cont’d)
Adverse effects Vary with each drug Healthy cells are often killed also, resulting in serious toxicities Winter 2013

122 Antiviral Drugs (non-HIV) (cont’d)
amantadine (Symmetrel) Narrow antiviral spectrum; active only against influenza A 2008 CDC guidelines do not recommend use for treatment or prevention of flu CNS effects: insomnia, nervousness, lightheadedness GI effects: anorexia, nausea, others Winter 2013

123 Antiviral Drugs (non-HIV) (cont’d)
rimantadine (Flumadine) Same spectrum of activity, mechanism of action, and indications as amantadine Fewer CNS adverse effects Causes GI upset Winter 2013

124 Antiviral Drugs (non-HIV) (cont’d)
acyclovir (Zovirax) Synthetic nucleoside analog Used to suppress replication of: HSV-1, HSV-2, VZV Drug of choice for treatment of initial and recurrent episodes of these infections Oral, topical, parenteral forms Winter 2013

125 Antiviral Drugs (non-HIV) (cont’d)
ganciclovir (Cytovene) Synthetic nucleoside analog Used to treat infection with cytomegalovirus (CMV) Oral, parenteral forms CMV retinitis Ophthalmic form surgically implanted Ocular injection (fomivirsen) Winter 2013

126 Antiviral Drugs (non-HIV): Dose-Limiting Toxicities
ganciclovir Bone marrow toxicity foscarnet and cidofovir Renal toxicity Winter 2013

127 Antiviral Drugs (non-HIV): Neuraminidase Inhibitors
oseltamivir (Tamiflu) and zanamivir (Relenza) Active against influenza types A and B Reduce duration of illness Oseltamivir: causes nausea and vomiting Zanamivir: causes diarrhea, nausea, sinusitis Treatment should begin within 2 days of influenza symptom onset Winter 2013

128 Antiviral Drugs (non-HIV): Ribavirin
Synthetic nucleoside analog Given orally, or oral or nasal inhalation Inhalation form (Virazole) used for hospitalized infants with RSV infections Winter 2013

129 HIV and AIDS Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) ELISA (enzyme-linked immunosorbent assay) Detects HIV exposure based on presence of human antibodies to the virus in the blood Retrovirus Transmitted by sexual activity, intravenous drug use, perinatally from mother to child Winter 2013

130 Four Stages of HIV Infection*
Stage 1: asymptomatic infection Stage 2: early, general symptoms of disease Stage 3: moderate symptoms Stage 4: severe symptoms, often leading to death *WHO model Winter 2013

131 Opportunistic Infections
Protozoal Toxoplasmosis of the brain, others Fungal Candidiasis of the lungs, esophagus, trachea Pneumocystis jirovecii pneumonia, others Viral CMV disease, HSV infection, others Winter 2013

132 Opportunistic Infections (cont’d)
Bacterial Various mycobacterial infections Extrapulmonary TB Opportunistic neoplasias Kaposi’s sarcoma, others HIV wasting syndrome Major weight loss, chronic diarrhea, chronic fever Winter 2013

133 Antiretroviral Drugs HAART Highly active antiretroviral therapy
Includes at least three medications “Cocktails” These medications work in different ways to reduce the viral load Winter 2013

134 Antiretroviral Drugs (cont’d)
Reverse transcriptase inhibitors (RTIs) Block activity of the enzyme reverse transcriptase, preventing production of new viral DNA Protease inhibitors (PIs) Inhibit the protease retroviral enzyme, preventing viral replication Fusion inhibitors Inhibit viral fusion, preventing viral replication Entry inhibitor-CCR5 coreceptor antagonists HIV integrase strand transfer inhibitors Winter 2013

135 Antiretroviral Drugs (cont’d)
Reverse transcriptase inhibitors (RTIs) Nucleoside RTIs (NRTIs) Nonnucleoside RTIs (NNRTIs) Examples abacavir (Ziagen) delavirdine (Rescriptor) didanosine (Videx) lefavirenze (Sustiva) Winter 2013

136 Antiretroviral Drugs (cont’d)
zidovudine (Retrovir) First anti-HIV medication Nucleoside reverse transcriptase inhibitor Can be given to pregnant HIV-positive women and newborn babies to prevent maternal transmission of HIV Major dose-limiting adverse effect: bone marrow suppression Winter 2013

137 Antiretroviral Drugs (cont’d)
Protease inhibitors (PIs) Inhibit the protease retroviral enzyme, preventing viral replication amprenavir (Agenerase) indinavir (Crixivan) nelfinavir (Viracept) ritonavir (Norvir) Winter 2013

138 Antiretroviral Drugs (cont’d)
Fusion inhibitors Inhibit viral fusion, preventing viral replication A newer class of antiretroviral drugs Example: enfuvirtide (Fuzeon) Winter 2013

139 Antiretroviral Drugs (cont’d)
CCR5 antagonist maraviroc (Selzentry) HIV integrase strand transfer inhibitor raltegravir (Isentress) Winter 2013

140 Antiretroviral Drugs (cont’d)
Combinations of multiple antiretroviral medications are common Adverse effects vary with each drug and may be severe; monitor for dose-limiting toxicities Monitor for signs of opportunistic diseases Winter 2013

141 Nursing Implications Be sure to teach proper application technique for ointments, aerosol powders, and so on Emphasize hand washing before and after administration of medications to prevent site contamination and spread of infection Instruct patients to wear a glove or finger cot when applying ointments or solutions to affected areas Winter 2013

142 Antitubercular Drugs Winter 2013

143 Antitubercular Drugs Tuberculosis (TB)
Caused by Mycobacterium tuberculosis Antitubercular drugs treat all forms of Mycobacterium Winter 2013

144 Mycobacterium Infections
Common infection sites Lung (primary site) Brain Bone Liver Kidney Winter 2013

145 Mycobacterium Infections (cont’d)
Aerobic bacillus Passed from infected: Humans Cows (bovine) and birds (avian) Much less common Winter 2013

146 Mycobacterium Infections (cont’d)
Tubercle bacilli are conveyed by droplets Droplets are expelled by coughing or sneezing, and then gain entry into the body by inhalation Tubercle bacilli then spread to other body organs via blood and lymphatic systems Tubercle bacilli may become dormant, or walled off by calcified or fibrous tissue Winter 2013

147 Antitubercular Drugs First-line drugs isoniazid (INH)* ethambutol
rifampin rifabutin pyrazinamide (PZA) Rifapentine streptomycin *Primary drug used Winter 2013

148 Antitubercular Drugs (cont’d)
Second-line drugs capreomycin amikacin cycloserine levofloxacin ethionamide ofloxacin kanamycin para-aminosalicyclic acid (PAS) Winter 2013

149 Antitubercular Drug Therapy Considerations
Perform drug-susceptibility testing on the first Mycobacterium that is isolated from a patient specimen to prevent the development of MDR-TB Even before the results of susceptibility tests are known, begin a regimen with multiple antitubercular drugs (to reduce chances of development of resistance) Winter 2013

150 Antitubercular Drug Therapy Considerations (cont’d)
Adjust drug regimen once the results of susceptibility testing are known Monitor patient compliance closely during therapy Problems with successful therapy occur because of patient nonadherence to drug therapy and the increased incidence of drug-resistant organisms Winter 2013

151 Antitubercular Therapy
Effectiveness depends upon: Type of infection Adequate dosing Sufficient duration of treatment Adherence to drug regimen Selection of an effective drug combination Winter 2013

152 Antitubercular Therapy (cont’d)
Problems Drug-resistant organisms Drug toxicity Patient nonadherence Multidrug-resistant TB (MDR-TB) Winter 2013

153 Isoniazid (INH) Drug of choice for TB
Resistant strains of Mycobacterium emerging Metabolized in the liver through acetylation—watch for “slow acetylators” Used alone or in combination with other drugs Contraindicated with liver disease Winter 2013

154 Adverse Effects INH Peripheral neuropathy, hepatotoxicity ethambutol
Retrobulbar neuritis, blindness rifampin Hepatitis; discoloration of urine, stools, and other body fluids Winter 2013

155 Nursing Implications Perform liver function studies in patients who are to receive isoniazid or rifampin (especially in elderly patients or those who use alcohol daily) Winter 2013

156 Nursing Implications (cont’d)
Patient education is critical Therapy may last for up to 24 months Take medications exactly as ordered, at the same time every day Emphasize the importance of strict adherence to regimen for improvement of condition or cure Winter 2013

157 Nursing Implications (cont’d)
Remind patients that they are contagious during the initial period of their illness— instruct in proper hygiene and prevention of the spread of infected droplets Teach patients to take care of themselves, including adequate nutrition and rest Winter 2013

158 Nursing Implications (cont’d)
Patients should not consume alcohol while on these medications or take other medications, including over-the-counter medications, unless they check with their physician Rifampin causes oral contraceptives to become ineffective; another form of birth control will be needed Winter 2013

159 Nursing Implications (cont’d)
Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish orange; even contact lenses may be stained Pyridoxine may be needed to combat neurologic adverse effects associated with INH therapy Oral preparations may be given with meals to reduce GI upset, even though recommendations are to take them 1 hour before or 2 hours after meals Winter 2013

160 Nursing Implications (cont’d)
COMPLIANCE AND DOT THERAPY Because of the length of treatment, it is difficult to be sure patient will comply Family education may improve compliance DOT = DIRECT OBSERVATION THERAPY Winter 2013

161 Antifungal Drugs Winter 2013

162 Indications Systemic and topical fungal infections
Drug of choice for the treatment of many severe systemic fungal infections is amphotericin B Choice of drug depends on type and location of infection Winter 2013

163 Adverse Effects: Amphotericin B
Fever Chills Cardiac dysrhythmias Nausea and GI upset Renal toxicity Headache Malaise Hypotension Tingling, numbness in hands and feet Lowered potassium and magnesium levels Winter 2013

164 Adverse Effects: Amphotericin B (cont’d)
Main concerns: *Renal toxicity *Neurotoxicity: seizures and paresthesias Many other adverse effects Winter 2013

165 Nursing Implications (cont’d)
amphotericin B To reduce the severity of the infusion- related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, antiemetics, and corticosteroids may be given Use an IV infusion pump Winter 2013


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