Antimicrobial Drugs- Interfere with DNA function

Name of the Antimicrobial Drugs that interfere with DNA function

1.Rifampin

Mechanism of Action

Inhibits bacterial and mycobacterial RNA synthesis by binding to DNA-dependent RNA polymerase, thereby blocking RNA transcription. Exhibits dose-dependent bactericidal or bacteriostatic action. Rifampin is highly effective against rapidly dividing bacilli in extracellular cavitary lesions, such as those found in the nasopharynx.

Pharmacokinetics

• Peak plasma time: PO, 2-4 hr
• Protein bound: 80%
• Metabolized by liver; undergoes enterohepatic recirculation
• Half-life: 3-4 hr (prolonged in hepatic impairment); in end-stage renal disease, 1.8-11 hr
• Excretion: Feces (60-65%) and urine (~30%) as unchanged drug
• Distribution:Highly lipophilic; crosses blood-brain barrier well, and relative diffusion from blood into CSF is adequate, with or without inflammation (exceeds usual MICs)

Administration

• Add 10 ml of sterile water to vial to yield a 60-mg/ml solution for I.V. infusion.
• Further dilute in 100 ml of dextrose 5% in water (D5W) and infuse over 30 minutes, or add to 500 ml of D5W and infuse over 3 hours.
• Give oral doses with a full glass of water 1 hour before or 2 hours after a meal.
• For an adult who can’t swallow capsules or for a young child, mix capsule contents with syrup, shake well, and administer.
• If patient can’t receive dextrose, use normal saline solution to dilute. Don’t use other I.V. solutions.

Contraindications

Hypersensitivity to drug or other rifamycin derivatives

Precautions:

• Porphyria
• History of hepatic disease
• Concurrent use of other hepatotoxic drugs
• Pregnant or breastfeeding patients.

Adverse reactions

• CNS: ataxia, confusion, drowsiness, fatigue, headache, asthenia, psychosis, generalized numbness
• EENT: conjunctivitis; discolored tears, saliva, and sputum
• GI: nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, epigastric distress, flatulence, discolored feces, anorexia, sore mouth and tongue, pseudomembranous colitis
• GU: discolored urine
• Hematologic: eosinophilia, transient leukopenia, hemolytic anemia, hemolysis, disseminated intravascular coagulation (DIC), thrombocytopenia
• Hepatic: jaundice
• Metabolic: hyperuricemia
• Musculoskeletal: myalgia, joint pain
• Respiratory: dyspnea, wheezing
• Skin: flushing, rash, pruritus, discolored sweat, erythema multiforme, toxic epidermal necrolysis, StevensJohnson syndrome
• Other: flulike symptoms, hypersensitivity reactions including vasculitis

Patient monitoring

• Monitor kidney and liver function tests, CBC, and uric acid level.
• Watch for signs and symptoms of bleeding tendency, especially DIC.
• Assess for signs and symptoms of hepatic impairment.
• Monitor bowel movements for diarrhea, which may signal pseudomembranous colitis.

Patient teaching

• Advise patient to take oral dose 1 hour before or 2 hours after meals. If drug causes significant GI upset, instruct him to take it with meals. To further minimize GI upset, teach him to eat small, frequent servings of food and drink plenty of fluids.
• Instruct patient to immediately report easy bruising or bleeding, fever, malaise, appetite loss, nausea, vomiting, or yellowing of skin or eyes.
• Tell patient drug may color his tears, urine, and other body fluids reddish or brownish orange. Instruct him not to wear contact lenses during therapy, because drug may stain them permanently.
• Instruct patient not to drink alcohol.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

Nursing Considerations

• Obtain blood samples or other specimens for culture and sensitivity testing, as ordered, before giving rifampin and throughout therapy to monitor response to drug.
• Expect to monitor liver function test results before and every 2 to 4 weeks during therapy. Immediately report abnormalities.
• For I.V. infusion, reconstitute by adding 10 ml sterile water for injection to 600-mg vial of rifampin. Swirl gently to dissolve. Withdraw appropriate dose and add to 500 ml D5W (preferred solution) or normal saline solution and infuse over 3 hours. Or, withdraw appropriate dose and add to 100 ml D5W (preferred solution) or normal saline solution and infuse over 30 minutes. Use reconstituted drug promptly because rifampin may precipitate out of D5W solution after 4 hours. In normal saline solution, drug is stable up to 24 hours at room temperature.
• Be aware that patient receiving intermittent therapy (once or twice weekly) is at increased risk for adverse reactions.
• Expect drug to discolor skin and body fluids reddish orange to reddish brown.
• Be aware that rifampin can cause myelosuppression and increase risk of infection. Notify prescriber immediately if signs of infection, such as fever, develop

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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