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CHAPTER 40: ANTIBIOTICS AFFECTING PROTEIN SYNTHESIS

PHYSIOLOGY OF PROTEIN SYNTHESIS

  • The process of protein synthesis in all cells is divided into two main sections:

    • Transcription

    • Occurs within the nucleus.

    • Produces messenger ribonucleic acid (mRNA).

    • mRNA migrates from the nucleus to the cytoplasm.

    • mRNA undergoes maturation, including:

      • Splicing: elimination of noncoding sequences.

    • Translation

    • Occurs in the cytoplasm.

    • Involves ribosomes, tRNA, and mRNA to synthesize proteins based on the genetic code.

AMINOGLYCOSIDES

  • General Information:

    • Aminoglycosides have been in use since 1944.

    • Very effective against severe infections.

    • General use is limited due to potential for serious adverse effects.

    • Prototype drug: Gentamicin (Garamycin).

GENTAMICIN: CORE DRUG KNOWLEDGE

  • Pharmacotherapeutics

    • Indicated for treating serious infections.

  • Pharmacokinetics

    • Distribution: Throughout the body but not in CNS; usually given parenterally or topically; higher concentration in kidneys than in serum.

  • Pharmacodynamics

    • Mechanism involves entering the bacterial cell and binding to the 30S ribosomal subunit, disrupting protein synthesis.

GENTAMICIN: ADVERSE EFFECTS AND PRECAUTIONS

  • Contraindications and Precautions:

    • Hypersensitivity, pregnancy, and lactation.

  • Adverse Effects:

    • Neurotoxicity, nephrotoxicity, ototoxicity, and neuromuscular blockade.

  • Drug Interactions:

    • Interacts with medications such as Acyclovir, Amphotericin B, Cephalothin, Cisplatin, Cyclosporine, Loop diuretics, Prostaglandin synthetase inhibitors, and Vancomycin.

GENTAMICIN: CORE PATIENT VARIABLES

  • Health status: Check for past medical and any kidney problems.

  • Life span and gender: Consider that it is ototoxic to the fetus, assess pregnancy status.

  • Lifestyle, diet, and habits: Assess patient's nutritional status.

  • Environment: Consider the environment where the drug will be administered.

GENTAMICIN: PLANNING & INTERVENTIONS

  • Maximizing Therapeutic Effects:

    • Ensure complete course is taken and administered at specific intervals; do not administer with extended penicillins.

  • Minimizing Adverse Effects:

    • Maintain blood levels of gentamicin within a narrow therapeutic margin.

    • Monitor for signs of ototoxicity and nephrotoxicity.

GENTAMICIN: TEACHING, ASSESSMENT & EVALUATIONS

  • Patient and Family Education:

    • Advise against taking the drug during pregnancy or breastfeeding.

    • Teach how to identify and report signs of allergic reactions and adverse effects.

  • Ongoing Assessment and Evaluation:

    • Coordinate care to avoid addition of other potentially nephrotoxic or ototoxic drugs.

QUESTION

  • Gentamicin is effective against what organism(s)?

    • A. Pseudomonas aeruginosa

    • B. Proteus mirabilis

    • C. Klebsiella

    • D. Enterobacter

    • E. All of the above

    • Correct Answer: E. All of the above.

RATIONALE FOR GENTAMICIN

  • Gentamicin is effective against infections caused by gram-negative bacilli, including:

    • Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli, Klebsiella, Enterobacter, Serratia, Citrobacter species, and staphylococci.

    • Requires oxygen for transport across the cell membrane, ineffective against anaerobes.

LINCOSAMIDES

  • General Information:

    • Used cautiously due to high toxicity; limited to infections by sensitive bacteria.

    • Prototype drug: Clindamycin (Cleocin).

CLINDAMYCIN: CORE DRUG KNOWLEDGE

  • Pharmacotherapeutics:

    • Effective against aerobic gram-positive cocci and several anaerobic organisms.

  • Pharmacokinetics:

    • Varies with route of administration (oral, topical, IM, IV); metabolized in the liver, excreted via bile and urine.

  • Pharmacodynamics:

    • Enters the bacterial cell and binds to bacterial ribosomes, thus suppressing protein synthesis.

CLINDAMYCIN: ADVERSE EFFECTS AND PRECAUTIONS

  • Contraindications and Precautions:

    • Hypersensitivity, pregnancy, and lactation.

  • Adverse Effects:

    • Can cause pseudomembranous colitis, maculopapular rash, erythema, and pruritus.

  • Drug Interactions:

    • Interactions with neuromuscular blockers, aluminum salts, cyclosporine, benzoyl peroxide, tretinoin, and salicylic acid.

CLINDAMYCIN: CORE PATIENT VARIABLES

  • Health Status: Assess for medication allergies.

  • Life Span and Gender: Evaluate growth and development levels in children.

  • Lifestyle, Diet, and Habits: Ensure proper administration of the drug.

  • Environment: Evaluate the environment where the drug will be given.

CLINDAMYCIN: PLANNING & INTERVENTIONS

  • Maximizing Therapeutic Effects:

    • Ensure full course is taken as prescribed.

    • Coordinate administration to minimize adverse interactions.

  • Minimizing Adverse Effects:

    • Administer clindamycin on an empty stomach with a full glass of water.

    • Patients should report diarrhea to the provider immediately.

CLINDAMYCIN: TEACHING, ASSESSMENT & EVALUATIONS

  • Patient and Family Education:

    • Instruct to contact the prescriber immediately if diarrhea occurs.

    • Teach to recognize symptoms of allergic reactions and superinfection.

  • Ongoing Assessment and Evaluation:

    • Monitor for the onset of diarrhea.

QUESTION

  • What is the most serious adverse reaction of clindamycin administration?

    • A. Respiratory arrest

    • B. Pseudomembranous colitis

    • C. Ventricular tachycardia

    • D. Ototoxicity

    • Correct Answer: B. Pseudomembranous colitis.

RATIONALE FOR CLINDAMYCIN

  • Pseudomembranous colitis is the most serious side effect of clindamycin and carries a Black Box warning.

MACROLIDE ANTIBIOTICS

  • General Information:

    • In use since 1952; characterized by molecules with large-ring lactones.

    • May be bacteriostatic or bactericidal against susceptible bacteria.

    • Prototype drug: Erythromycin (E-mycin).

ERYTHROMYCIN: CORE DRUG KNOWLEDGE

  • Pharmacotherapeutics:

    • Treats Legionnaire disease, Mycoplasma pneumoniae, diphtheria, chlamydial infections, and chancroid.

  • Pharmacokinetics:

    • Easily inactivated by gastric acid; peak 1-4 hours post-administration; metabolized in the liver; excreted via urine and bile.

  • Pharmacodynamics:

    • Inhibits RNA-dependent protein synthesis at the chain elongation step.

ERYTHROMYCIN: ADVERSE EFFECTS AND PRECAUTIONS

  • Contraindications and Precautions:

    • Allergy to the medication.

  • Adverse Effects:

    • Can cause GI symptoms, urticaria, maculopapular rash, erythema, and interstitial nephritis.

  • Drug Interactions:

    • Notable interactions with Astemizole and Terfenadine.

ERYTHROMYCIN: CORE PATIENT VARIABLES

  • Health Status: Assess medical history and allergies.

  • Life Span and Gender: Consider pregnancy and lactation status.

  • Lifestyle, Diet, and Habits: Instruct how to take medication to avoid toxicity.

  • Environment: Assess the environment where the drug will be given.

ERYTHROMYCIN: PLANNING & INTERVENTIONS

  • Maximizing Therapeutic Effects:

    • Reconstitute with sterile water only; prepared infusion solutions at room temperature must be used within 8 hours.

  • Minimizing Adverse Effects:

    • Administer IV infusions over 30 to 60 minutes to prevent vein irritation.

ERYTHROMYCIN: TEACHING, ASSESSMENT & EVALUATIONS

  • Patient and Family Education:

    • Encourage completing the course of antibiotics; take on an empty stomach unless GI distress is unbearable.

  • Ongoing Assessment and Evaluation:

    • Monitor for signs of allergic reactions, symptom resolution from infection, and signs of superinfection.

QUESTION

  • Grapefruit juice will decrease the serum concentration of erythromycin.

    • A. True

    • B. False

    • Correct Answer: B. False. Grapefruit juice increases the serum concentration, leading to potential adverse effects.

OXAZOLIDINONES

  • General Information:

    • The first new class of antibiotics specifically developed for treating methicillin-resistant Staphylococcus aureus (MRSA) infections.

    • Prototype drug: Linezolid (ZYVOX).

LINEZOLID: CORE DRUG KNOWLEDGE

  • Pharmacotherapeutics:

    • Effective for treating VRE and MRSA infections.

  • Pharmacokinetics:

    • Administered orally or via IV; metabolites primarily in the liver; excreted via kidneys.

  • Pharmacodynamics:

    • Blocks early stages of proteins used by bacteria for protein synthesis.

LINEZOLID: ADVERSE EFFECTS AND PRECAUTIONS

  • Contraindications and Precautions:

    • Hypersensitivity.

  • Adverse Effects:

    • Possible diarrhea, headache, nausea, and vomiting.

  • Drug Interactions:

    • Interacts with adrenergic and serotonergic agents.

LINEZOLID: CORE PATIENT VARIABLES

  • Health Status: Assess medical history.

  • Life Span and Gender: Pregnancy category C.

  • Lifestyle, Diet, and Habits: Evaluate dietary habits, particularly alcohol use.

  • Environment: Assess environment for drug administration.

LINEZOLID: PLANNING & INTERVENTIONS

  • Maximizing Therapeutic Effects:

    • Administer at evenly spaced intervals.

  • Minimizing Adverse Effects:

    • Monitor for hypertensive crisis; limit intake of tyramine, caffeine, or alcohol; obtain serial blood pressure readings throughout therapy.

LINEZOLID: TEACHING, ASSESSMENT & EVALUATIONS

  • Patient and Family Education:

    • Explain dietary restrictions regarding tyramine, caffeine, and alcohol.

    • Educate signs of thrombocytopenia and pseudomembranous colitis.

  • Ongoing Assessment and Evaluation:

    • Monitor treatment efficacy and infection resolution.

STREPTOGRAMINS

  • General Information:

    • The newest class of antibiotics designed to eradicate superbugs resistant to other antibiotics.

    • Prototype drug: Quinupristin/Dalfopristin (Synercid).

QUINUPRISTIN/DALFOPRISTIN: CORE DRUG KNOWLEDGE

  • Pharmacotherapeutics:

    • Indicated for serious or life-threatening infections, particularly associated with VRE.

  • Pharmacokinetics:

    • Administered via IV; half-life of about 1 hour.

  • Pharmacodynamics:

    • Inhibits bacterial protein synthesis by irreversibly blocking ribosome functioning.

QUINUPRISTIN/DALFOPRISTIN: ADVERSE EFFECTS AND PRECAUTIONS

  • Contraindications and Precautions:

    • Hypersensitivity.

  • Adverse Effects:

    • Risks include pseudomembranous colitis, superinfection, and hepatotoxicity.

  • Drug Interactions:

    • Interacts with drugs metabolized by CYP3A4, a cytochrome of the P-450 system.

QUINUPRISTIN/DALFOPRISTIN: CORE PATIENT VARIABLES

  • Health Status: Assess health history and contra-indications.

  • Life Span and Gender: Pregnancy category B.

  • Environment: Assess administration environment.

QUINUPRISTIN/DALFOPRISTIN: PLANNING & INTERVENTIONS

  • Maximizing Therapeutic Effects:

    • Avoid co-administration with other medications through a Y-site infusion; flush with 5% dextrose and water before and after administration.

  • Minimizing Adverse Effects:

    • Administer via peripherally inserted central catheter (PICC) or central line whenever possible.

QUINUPRISTIN/DALFOPRISTIN: TEACHING, ASSESSMENT & EVALUATIONS

  • Patient and Family Education:

    • Teach patients of potential adverse effects; advise immediate reporting of any diarrhea.

  • Ongoing Assessment and Evaluation:

    • Monitor IV site for infiltration, edema, or phlebitis; question patient regarding injection site pain.

TETRACYCLINES

  • General Information:

    • Developed as semisynthetic antibiotics based on common soil mold structure.

    • Broad-spectrum, affecting both gram-positive and gram-negative bacteria.

    • Significant resistance has developed over the years.

    • Prototype drug: Tetracycline (Sumycin).

TETRACYCLINE: CORE DRUG KNOWLEDGE

  • Pharmacotherapeutics:

    • Effective against Rickettsia species, Mycoplasma pneumoniae, and Chlamydia trachomatis.

  • Pharmacokinetics:

    • Administered orally, excreted via kidneys.

  • Pharmacodynamics:

    • Inhibits or retards bacterial growth, but does not kill them.

TETRACYCLINE: ADVERSE EFFECTS AND PRECAUTIONS

  • Contraindications and Precautions:

    • Allergy, pregnancy, or lactation.

  • Adverse Effects:

    • GI upset, photosensitivity, and rash.

  • Drug Interactions:

    • Interactions with Penicillin G, aluminum, bismuth, calcium, iron, magnesium, and zinc salts.

TETRACYCLINE: CORE PATIENT VARIABLES

  • Health Status: Assess medical status.

  • Life Span and Gender: Pregnancy category D.

  • Lifestyle, Diet, and Habits: Assess dietary intake.

  • Environment: Assess for sun exposure.

TETRACYCLINE: PLANNING & INTERVENTIONS

  • Maximizing Therapeutic Effects:

    • Administer on an empty stomach, 1 hour before or 2 hours after meals or other drugs.

  • Minimizing Adverse Effects:

    • Ensure adequate fluids to replace losses from diarrhea; use protective clothing and sunscreen outdoors.

TETRACYCLINE: TEACHING, ASSESSMENT & EVALUATIONS

  • Patient and Family Education:

    • Advise women of childbearing age to avoid use during pregnancy or breastfeeding.

    • Instruct to take tetracycline on an empty stomach.

  • Ongoing Assessment and Evaluation:

    • Monitor renal status to prevent hepatotoxicity and observe for signs of superinfection.

QUESTION

  • Tetracycline should not be administered with antacids.

    • A. True

    • B. False

    • Correct Answer: A. True.

    • Rationale: Tetracycline forms insoluble chelates with aluminum, bismuth, calcium, iron, magnesium, and zinc salts, common in antacids.

MISCELLANEOUS ANTIBIOTICS AFFECTING PROTEIN SYNTHESIS

  • General Information:

    • Examples include Chloramphenicol and Spectinomycin.

    • Used to treat large outbreaks of typhus.

    • Prototype: Chloramphenicol.

CHLORAMPHENICOL: CORE DRUG KNOWLEDGE

  • Pharmacotherapeutics:

    • A true broad-spectrum antibiotic.

  • Pharmacokinetics:

    • Administered orally and via IV; peak concentrations in 1-3 hours.

  • Pharmacodynamics:

    • Works by inhibiting the protein synthesis of bacterial cells.

CHLORAMPHENICOL: ADVERSE EFFECTS AND PRECAUTIONS

  • Contraindications and Precautions:

    • Monitor for toxic reactions to medication.

  • Adverse Effects:

    • Risks include aplastic anemia, hypoplastic anemia, thrombocytopenia, pancytopenia, and granulocytopenia.

  • Drug Interactions:

    • Interacts with many different types of drugs.

CHLORAMPHENICOL: CORE PATIENT VARIABLES

  • Health Status: Assess medical history.

  • Life Span and Gender: Assess pregnancy status.

  • Environment: Assess where the drug will be administered.

CHLORAMPHENICOL: PLANNING & INTERVENTIONS

  • Maximizing Therapeutic Effects:

    • Administer oral chloramphenicol on an empty stomach (1 hour before or 2 hours after meals).

  • Minimizing Adverse Effects:

    • Monitor plasma concentrations at least weekly, especially in patients with liver or renal impairment.

CHLORAMPHENICOL: TEACHING, ASSESSMENT & EVALUATIONS

  • Patient and Family Education:

    • Explain the importance of completing the full course of therapy.

    • Instruct on accurately measuring fluid intake and output.

  • Ongoing Assessment and Evaluation:

    • For patients on systemic therapy, coordinate serial monitoring of chloramphenicol plasma concentrations.