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Chapter 40
Antibiotics Affecting Protein Synthesis
Chapter 40
Antibiotics Affecting Protein Synthesis
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Physiology Physiology
• In all cells, the process of protein synthesis is divided into two sections: transcription and translation.
• Initially, transcription occurs within the nucleus, producing messenger ribonucleic acid (mRNA).
• This mRNA migrates from the nucleus to the cytoplasm. During this step, mRNA goes through different types of maturation, including one called splicing, during which the noncoding sequences are eliminated.
• Translation occurs in the cytoplasm.
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Protein SynthesisProtein Synthesis
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Aminoglycosides Aminoglycosides
• The aminoglycosides have been in use since 1944.
• They are extremely effective antibiotics for treating severe infections.
• However, their general use is limited because of the potential for serious adverse effects.
• Prototype drug: gentamicin
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Gentamicin: Core Drug Knowledge Gentamicin: Core Drug Knowledge
• Pharmacotherapeutics
– Serious infections
• Pharmacokinetics
– Distribution: throughout the body except CS; higher concentration in kidneys than serum
• Pharmacodynamics
– Entering the bacterial cell and binding to the 30S ribosomal subunit
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Gentamicin: Core Drug Knowledge (cont.)Gentamicin: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitivity, pregnancy and lactation
• Adverse effects
– Neurotoxicity, nephrotoxicity, ototoxicity, and neuromuscular blockade
• Drug interactions
– Acyclovir, amphotericin B, cephalothin, cisplatin, cyclosporine, loop diuretics, prostaglandin synthetase inhibitors, and vancomycin
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Gentamicin: Core Patient Variables Gentamicin: Core Patient Variables
• Health status
– Past medical and any kidney problems
• Life span and gender
– Ototoxic to the fetus, assess pregnancy status.
• Lifestyle, diet, and habits
– Assess the nutritional status of the patient.
• Environment
– Assess the environment where the drug will be given.
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Gentamicin: Nursing Diagnoses and Outcomes Gentamicin: Nursing Diagnoses and Outcomes
• Risk for Injury related to potential drug-related allergic reactions or neuromuscular blockade or suppression of bone marrow function
– Desired outcome: The patient will remain free of injury and will contact the prescriber if unusual adverse effects occur.
• Diarrhea related to drug effects
– Desired outcome: The patient will avoid dehydration, maintain fluid intake, and contact the prescriber if diarrhea persists.
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Gentamicin: Nursing Diagnoses and Outcomes (cont.)Gentamicin: Nursing Diagnoses and Outcomes (cont.)
• Imbalanced Nutrition: Less than Body Requirements, related to drug-induced GI effects or superinfection
– Desired outcome: The patient will maintain body weight and report any persistent adverse effect.
• Risk for Injury related to CNS effects
– Desired outcome: The patient will remain free of injury and contact the provider if confusion, disorientation, or depression occurs.
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Gentamicin: Nursing Diagnoses and Outcomes (cont.)Gentamicin: Nursing Diagnoses and Outcomes (cont.)
• Disturbed Sensory Perception related to potential ototoxicity
– Desired outcome: The patient will report sensory or perceptual changes to the prescriber.
• Excess Fluid Volume related to potential nephrotoxicity
– Desired outcome: The patient will report any weight gain exceeding 3 lb to the health care prescriber.
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Gentamicin: Planning and InterventionsGentamicin: Planning and Interventions
• Maximizing therapeutic effects
– Make sure that patients receive the full course as prescribed at around-the-clock intervals.
– Do not give at the same time as extended penicillin.
• Minimizing adverse effects
– Maintain blood levels of gentamicin within a therapeutic margin that is very narrow.
– Monitor for signs of ototoxicity and nephrotoxicity.
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Gentamicin: Teaching, Assessment, and EvaluationsGentamicin: Teaching, Assessment, and Evaluations
• Patient and family education
– Patients should not take the drug if pregnant or breast-feeding.
– Teach patients how to identify, report, and manage signs and symptoms of allergic reaction and adverse effects.
• Ongoing assessment and evaluation
– Coordinate the care of the patient to ensure that other potentially nephrotoxic or ototoxic drugs are not added to the treatment plan.
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QuestionQuestion
• Gentamicin is effective against which of the following organism(s)?
– A. Pseudomonas aeruginosa
– B. Proteus mirabilis
– C. Klebsiella
– D. Enterobacter
– E. All of the above
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AnswerAnswer
• E. All of the above
• Rationale: Gentamicin is effective in managing infections caused by gram-negative bacilli.
• Susceptible organisms include Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli; Klebsiella, Enterobacter, Serratia, and Citrobacter species; and staphylococci.
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Lincosamides Lincosamides
• They are very toxic drugs.
• Their use must be monitored and limited to situations with infections by bacteria with known sensitivity.
• Prototype drug: clindamycin (Cleocin)
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Clindamycin: Core Drug Knowledge Clindamycin: Core Drug Knowledge
• Pharmacotherapeutics
– Aerobic gram-positive cocci and several anaerobic gram-negative and gram-positive organisms
• Pharmacokinetics
– Varies with route of administration. Metabolized: liver. Excreted: bile and urine.
• Pharmacodynamics
– Enters the bacterial cell and binds to bacterial ribosomes, suppressing protein synthesis
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Clindamycin: Core Drug Knowledge (cont.)Clindamycin: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitivity, pregnancy, and lactation
• Adverse effects
– Pseudomembranous colitis, maculopapular rash, erythema, and pruritus
• Drug interactions
– Neuromuscular blockers, aluminum salts, cyclosporine, benzoyl peroxide, tretinoin, and salicylic acid
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Clindamycin: Core Patient Variables Clindamycin: Core Patient Variables
• Health status
– Assess for allergy to medication.
• Life span and gender
– Assess the growth and developmental level of the child or infant.
• Lifestyle, diet, and habits
– Assess lifestyle to ensure that the drug will be given properly.
• Environment
– Assess the environment where the drug will be given.
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Clindamycin: Nursing Diagnoses and Outcomes Clindamycin: Nursing Diagnoses and Outcomes
• Risk for Injury related to allergic reactions
– Desired outcome: The patient will stop drug therapy and immediately report symptoms of allergic reaction to the prescriber.
• Diarrhea related to drug effects
– Desired outcome: The patient will avoid dehydration and report persistent diarrhea to the provider.
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Clindamycin: Nursing Diagnoses and Outcomes (cont.)Clindamycin: Nursing Diagnoses and Outcomes (cont.)
• Imbalanced nutrition: Less than Body Requirements, related to drug-related GI effects, alteration in taste, superinfections
– Desired outcome: The patient will maintain body weight and report persistent symptoms affecting nutritional status.
• Risk for Injury related to possible blood dyscrasias
– Desired outcome: The patient will remain injury-free throughout drug therapy.
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Clindamycin: Planning and InterventionsClindamycin: Planning and Interventions
• Maximizing therapeutic effects
– Make sure that the patient receives the full course of clindamycin as prescribed.
– Coordinate the administration of drugs to decrease potential undesired interactions.
• Minimizing adverse effects
– Clindamycin should be administered on an empty stomach with a full glass of water.
– Report diarrhea to the provider immediately.
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Clindamycin: Teaching, Assessment, and EvaluationsClindamycin: Teaching, Assessment, and Evaluations
• Patient and family education
– Advise patients to contact the prescriber immediately if they experience diarrhea.
– Teach patients to recognize and report symptoms of allergic reaction and superinfection.
• Ongoing assessment and evaluation
– Monitor the patient for the onset of diarrhea.
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QuestionQuestion
• What is the most serious adverse reaction of clindamycin administration?
– A. Respiratory arrest
– B. Pseudomembranous colitis
– C. Ventricular tachycardia
– D. Ototoxicity
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AnswerAnswer
• B. Pseudomembranous colitis
• Rationale: Pseudomembranous colitis is the most serious side effect of clindamycin and carries a Black Box warning because of this side effect.
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Macrolide Antibiotics Macrolide Antibiotics
• The macrolide antibiotics have been in use since 1952.
• They are characterized by molecules made up of large-ring lactones.
• Macrolides are bacteriostatic or bactericidal in susceptible bacteria.
• Prototype drug: erythromycin
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Erythromycin: Core Drug Knowledge Erythromycin: Core Drug Knowledge
• Pharmacotherapeutics
– Treating Legionnaire disease, Mycoplasma pneumoniae pneumonia, diphtheria, chlamydial infections, and chancroid
• Pharmacokinetics
– The drug is easily inactivated by gastric acid. Peak 1 to 4 hours. Metabolized: liver. Excreted: urine and bile.
• Pharmacodynamics
– Inhibiting RNA-dependent protein synthesis at the chain elongation step
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Erythromycin: Core Drug Knowledge (cont.)Erythromycin: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Allergy to medication
• Adverse effects
– GI symptoms, urticaria, maculopapular rash, erythema, and interstitial nephritis
• Drug interactions
– Astemizole and terfenadine
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Erythromycin: Core Patient Variables Erythromycin: Core Patient Variables
• Health status
– Assess medical history and allergies.
• Life span and gender
– Assess pregnancy and lactation status.
• Lifestyle, diet, and habits
– Instruct how to take the medication to avoid toxicity.
• Environment
– Assess the environment where the drug will be given.
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Erythromycin: Nursing Diagnoses and Outcomes Erythromycin: Nursing Diagnoses and Outcomes • Risk for Injury related to possible allergic reactions
– Desired outcome: The patient will stop drug therapy and report any signs of allergic reaction immediately to the prescriber.
• Diarrhea related to drug-induced GI upset
– Desired outcome: The patient will avoid dehydration, maintain fluid intake, and contact the prescriber if diarrhea persists.
• Risk for Infection related to potential for superinfection following drug therapy
– Desired outcome: The patient will contact the provider if any signs of superinfection occur, for example, sore throat or fever.
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Erythromycin: Planning and InterventionsErythromycin: Planning and Interventions
• Maximizing therapeutic effects
– Reconstitute erythromycin with sterile water only.
– Prepared infusion solutions that are stored at room temperature must be used within 8 hours.
• Minimizing adverse effects
– Because erythromycin can be very irritating to veins, it is important to administer IV infusions over 30 to 60 minutes.
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Erythromycin: Teaching, Assessment, and EvaluationsErythromycin: Teaching, Assessment, and Evaluations
• Patient and family education
– Encourage patients to take the complete course of antibiotics.
– Advise patients to take erythromycin on an empty stomach, unless GI distress is unbearable.
• Ongoing assessment and evaluation
– Monitor for signs of allergic reactions, resolution of presenting signs and symptoms of infection, and signs of superinfection.
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QuestionQuestion
• Grapefruit juice will decrease the serum concentration of erythromycin.
– A. True
– B. False
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AnswerAnswer
• B. False
• Rationale: Instruct the patient to avoid grapefruit or grapefruit juice because it increases the serum concentration of erythromycin and may cause adverse effects or toxicity.
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Oxazolidinones Oxazolidinones
• Oxazolidinones are the first new class of antibiotics developed specifically for treating methicillin-resistant Staphylococcus aureus (MRSA) infections.
• Prototype drug: linezolid (Zyvox)
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Linezolid: Core Drug Knowledge Linezolid: Core Drug Knowledge
• Pharmacotherapeutics
– Treatment of VRE and MRSA
• Pharmacokinetics
– Administered: oral or IV. Metabolism: liver. Excreted: kidneys.
• Pharmacodynamics
– Blocking the early stages of the process bacteria use to make proteins
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Linezolid: Core Drug Knowledge (cont.)Linezolid: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitivity
• Adverse effects
– Diarrhea, headache, nausea, and vomiting
• Drug interactions
– Adrenergic and serotonergic agents
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Linezolid: Core Patient Variables Linezolid: Core Patient Variables
• Health status
– Assess medical history.
• Life span and gender
– Pregnancy Category C drug
• Lifestyle, diet, and habits
– Evaluate diet and alcohol use.
• Environment
– Assess the environment where the drug will be given.
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Linezolid: Nursing Diagnoses and Outcomes Linezolid: Nursing Diagnoses and Outcomes
• Deficient Fluid Volume related to nausea, vomiting, and diarrhea from linezolid therapy
– Desired outcome: The patient will remain well hydrated throughout therapy.
• Risk for Injury related to thrombocytopenia and pseudomembranous colitis
– Desired outcome: The patient will remain free from injury and contact the health care provider immediately if any signs of bleeding or abdominal pain occur.
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Linezolid: Nursing Diagnoses and Outcomes (cont.)Linezolid: Nursing Diagnoses and Outcomes (cont.)
• Risk for Injury related to hypertensive crisis
– Desired outcome: The patient will remain normotensive by adhering to antihypertensive therapy and limiting foods or beverages with tyramine, caffeine, or alcohol.
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Linezolid: Planning and InterventionsLinezolid: Planning and Interventions
• Maximizing therapeutic effects
– Administer at evenly spaced intervals.
• Minimizing adverse effects
– To avoid hypertensive crisis, monitor the patient’s intake of food or beverages containing tyramine, caffeine, or alcohol.
– Serial blood pressure readings should be obtained throughout therapy.
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Linezolid: Teaching, Assessment, and EvaluationsLinezolid: Teaching, Assessment, and Evaluations
• Patient and family education
– Explain dietary restrictions, focusing on food or beverages containing tyramine, caffeine, or alcohol.
– Teach patients the signs and symptoms of thrombocytopenia and pseudomembranous colitis.
• Ongoing assessment and evaluation
– Monitor for efficacy of treatment and resolution of the presenting infection.
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QuestionQuestion
• Linezolid is classified as a Pregnancy Category ___ drug.
– A. A
– B. B
– C. C
– D. D
– E. X
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AnswerAnswer
• C. C
• Rationale: Linezolid is classified as a pregnancy category C drug.
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Streptogramins Streptogramins
• Streptogramins are the newest class of antibiotics.
• Designed to eradicate “superbugs” resistant to other antibiotics.
• Prototype drug: quinupristin/dalfopristin (Synercid)
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Quinupristin/Dalfopristin: Core Drug Knowledge Quinupristin/Dalfopristin: Core Drug Knowledge
• Pharmacotherapeutics
– Serious or life-threatening infections associated with VRE
• Pharmacokinetics
– Administered: IV. T½: 1 hour.
• Pharmacodynamics
– Inhibits bacterial protein synthesis by irreversibly blocking ribosome functioning
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Quinupristin/Dalfopristin: Core Drug Knowledge (cont.)Quinupristin/Dalfopristin: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitivity
• Adverse effects
– Pseudomembranous colitis, superinfection, and hepatotoxicity
• Drug interactions
– Drugs that are metabolized by CYP3A4, a cytochrome of P-450
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Quinupristin/Dalfopristin: Core Patient Variables Quinupristin/Dalfopristin: Core Patient Variables
• Health status
– Assess health history and contraindications to medication use.
• Life span and gender
– Pregnancy Category B drug
• Environment
– Assess the environment where the drug will be given.
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Quinupristin/Dalfopristin: Nursing Diagnoses and Outcomes Quinupristin/Dalfopristin: Nursing Diagnoses and Outcomes
• Pain related to IV administration
– Desired outcome: The patient will inform you immediately should pain at the injection site occur.
• Diarrhea related to potential pseudomembranous colitis
– Desired outcome: The patient will remain well hydrated throughout therapy and report any diarrhea immediately.
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Quinupristin/Dalfopristin: Nursing Diagnoses and Outcomes (cont.)Quinupristin/Dalfopristin: Nursing Diagnoses and Outcomes (cont.)
• Risk for Injury related to potential superinfection or hepatotoxicity
– Desired outcome: The patient will remain free of injury throughout therapy.
• Risk for Impaired Skin Integrity related to rash or pruritus.
– Desired outcome: The patient will report itching or rash immediately to minimize potential for infection.
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Quinupristin/Dalfopristin: Planning and InterventionsQuinupristin/Dalfopristin: Planning and Interventions
• Maximizing therapeutic effects
– The medication should not be administered with any other medications through a Y-site infusion.
– Flush the line before and after administration with 5% dextrose and water.
• Minimizing adverse effects
– Administer these drugs in a peripherally inserted central catheter (PICC) or a central line whenever possible.
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Quinupristin/Dalfopristin: Teaching, Assessment, and EvaluationsQuinupristin/Dalfopristin: Teaching, Assessment, and Evaluations
• Patient and family education
– Teach patients the potential adverse effects.
– Advise patients to report any diarrhea immediately.
• Ongoing assessment and evaluation
– During infusion, monitor the IV site for signs of infiltration, edema, or phlebitis.
– Question the patient regarding pain at the injection site.
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QuestionQuestion
• Quinupristin/dalfopristin is best administrated via
– A. Oral route
– B. PICC line
– C. Peripheral IV
– D. Z-track IM
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AnswerAnswer
• B. PICC line
• Rationale: Because injection site problems are very common with the administration of quinupristin/dalfopristin, administer these drugs in a peripherally inserted central catheter (PICC) line whenever possible.
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Tetracyclines Tetracyclines
• The tetracyclines were developed as semisynthetic antibiotics based on the structure of a common soil mold.
• They are broad-spectrum antibiotics that affect both gram-positive and gram-negative bacteria.
• Over the years, major resistance has developed to tetracyclines.
• Prototype drug: tetracycline
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Tetracycline: Core Drug Knowledge Tetracycline: Core Drug Knowledge
• Pharmacotherapeutics
– Rickettsia species, Mycoplasma pneumoniae, and Chlamydia trachomatis
• Pharmacokinetics
– Administered: oral. Excreted: kidneys.
• Pharmacodynamics
– Inhibits or retards the growth of bacteria but does not kill them
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Tetracycline: Core Drug Knowledge (cont.)Tetracycline: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Allergy, pregnancy, or lactation
• Adverse effects
– GI upset, photosensitivity, and rash
• Drug interactions
– Penicillin G, aluminum, bismuth, calcium, iron, magnesium, and zinc salts
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Tetracycline: Core Patient Variables Tetracycline: Core Patient Variables
• Health status
– Assess medical status.
• Life span and gender
– Pregnancy Category D drug
• Lifestyle, diet, and habits
– Assess dietary intake.
• Environment
– Assess for exposure to sun.
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Tetracycline: Nursing Diagnoses and Outcomes Tetracycline: Nursing Diagnoses and Outcomes
• Risk for Injury related to potential superinfection or allergic drug reaction
– Desired outcome: The patient will experience no new infection and no preventable allergic reaction related to tetracycline.
• Diarrhea related to drug-induced GI effects
– Desired outcome: The patient will report any incidence of diarrhea and follow the prescriber’s recommendation.
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Tetracycline: Nursing Diagnoses and Outcomes (cont.)Tetracycline: Nursing Diagnoses and Outcomes (cont.)
• Imbalanced nutrition: Less than Body Requirements, related to adverse GI effects of nausea, vomiting, diarrhea, and altered taste
– Desired outcome: The patient will maintain dietary intake to provide adequate nutrition.
• Risk for Impaired Skin Integrity related to drug-induced photosensitivity
– Desired outcome: The patient will dress appropriately and take adequate precautionary measures while outdoors to avoid unnecessary sunburn.
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Tetracycline: Planning and InterventionsTetracycline: Planning and Interventions
• Maximizing therapeutic effects
– To maximize absorption, oral preparations should be administered on an empty stomach either 1 hour before or 2 hours after any meals or other drugs.
• Minimizing adverse effects
– Monitor the patient to ensure that adequate fluids are given to replace fluid lost with diarrhea.
– Wear protective clothing and sunscreen when outdoors.
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Tetracycline: Teaching, Assessment, and EvaluationsTetracycline: Teaching, Assessment, and Evaluations
• Patient and family education
– Advise women of childbearing age that tetracycline should not be taken during pregnancy or breast-feeding.
– Advise patients to take tetracycline on an empty stomach.
• Ongoing assessment and evaluation
– Monitor renal status to detect and prevent hepatotoxicity and to observe for any signs of superinfection.
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QuestionQuestion
• Tetracycline should not be administered with antacids.
– A. True
– B. False
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AnswerAnswer
• A. True
• Rationale: Tetracycline forms an insoluble chelate with aluminum, bismuth, calcium, iron, magnesium, and zinc salts, which are frequently an ingredient in antacids.
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Miscellaneous Antibiotics that Affect Protein Synthesis Miscellaneous Antibiotics that Affect Protein Synthesis
• Miscellaneous antibiotics include chloramphenicol and spectinomycin.
• Used to treat large outbreaks of typhus
• Prototype: chloramphenicol
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Chloramphenicol: Core Drug Knowledge Chloramphenicol: Core Drug Knowledge
• Pharmacotherapeutics
– True broad-spectrum antibiotic
• Pharmacokinetics
– Administered: oral and IV. Peak 1 to 3 hours.
• Pharmacodynamics
– Inhibiting the protein synthesis of bacterial cells
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Chloramphenicol: Core Drug Knowledge (cont.)Chloramphenicol: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Toxic reaction to the medication
• Adverse effects
– Aplastic anemia, hypoplastic anemia, thrombocytopenia, pancytopenia, and granulocytopenia
• Drug interactions
– Many different types of drugs
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Chloramphenicol: Core Patient Variables Chloramphenicol: Core Patient Variables
• Health status
– Assess medical history.
• Life span and gender
– Assess pregnancy status.
• Environment
– Assess the environment where the drug will be given.
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Chloramphenicol: Nursing Diagnoses and Outcomes Chloramphenicol: Nursing Diagnoses and Outcomes
• Risk for Injury related to drug-induced adverse effects, such as blood dyscrasias, gray baby syndrome, and CNS effects, including optic or peripheral neuritis, headache, depression, confusion, or delirium
– Desired outcome: Regular and careful monitoring will protect the patient from permanent drug-related adverse effects.
• Risk for Impaired Skin Integrity, rash and pruritus, related to topical drug use
– Desired outcome: The nurse and patient will observe for and report signs of unusual skin reaction and contact the prescriber.
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Chloramphenicol: Planning and InterventionsChloramphenicol: Planning and Interventions
• Maximizing therapeutic effects
– Oral chloramphenicol should be administered on an empty stomach 1 hour before or 2 hours after meals.
• Minimizing adverse effects
– Monitor plasma concentrations at least weekly or more often in patients with hepatic or renal impairment.
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Chloramphenicol: Teaching, Assessment, and EvaluationsChloramphenicol: Teaching, Assessment, and Evaluations
• Patient and family education
– Explain the importance of completing therapy.
– Teach patients the importance of measuring fluid intake and output accurately.
• Ongoing assessment and evaluation
– For patients receiving systemic therapy, coordinate serial monitoring of chloramphenicol plasma concentrations.
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QuestionQuestion
• A serious and potentially life-threatening adverse effect of chloramphenicol is “gray baby” syndrome.
– A. True
– B. False
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AnswerAnswer
• A. True
• Rationale: “Gray baby” syndrome is most common in premature infants or newborns receiving chloramphenicol, whose hepatic systems have difficulty conjugating or excreting chloramphenicol.
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