Question

Damilola Anderson is a 62-year-old woman. She was travelling with her husband to see their children...

Damilola Anderson is a 62-year-old woman. She was travelling with her husband to see their children and grandchildren following Queensland’s eased COVID-19 restrictions. Damilola developed generalised abdominal pain, fever, and vomiting and was admitted to the CQUniversity Hospital (CQUH). After being assessed in the emergency department (ED), Damilola was diagnosed with acute appendicitis. A broad-spectrum antimicrobial, ceftriaxone was commenced immediately and she underwent a non-elective appendectomy. As part of the treatment plan, paracetamol is charted as regular analgesia, oxycodone as prn analgesia and ondansetron as a once only order for nausea/vomiting. Damilola has a history of severe anaphylaxis to penicillins. On day 2 post-op care on a surgical ward, the medical team reviewed Damilola and ceased ceftriaxone. They commenced Damilola on ampicillin. Nurse B administered ampicillin as per the medication order and Damilola developed anaphylaxis. Nurse B activated a medical emergency team (MET) call and the MET moved Damilola to the intensive care unit for further care.

The medical team at the hospital changed the antimicrobial to a broad-spectrum (ampicillin) for Damilola as part of the appendicitis treatment plan.

1. Discuss the pharmacokinetics (absorption, distribution, metabolism, excretion) of penicillins.

Include in your response:

a) Absorption: • Clarify how penicillins can be absorbed, i.e. routes of administration. • Explain the difference in the onset of action between administering penicillins via oral and intravenous routes. • Discuss which is the most appropriate route to administer this antimicrobial to Mrs Anderson and provide an evidence-based rationale for your decision.

b) Distribution: After absorption, some of the penicillins, binds to plasma proteins. • Discuss your understanding of ‘protein binding’.

c) Metabolism: • Describe the half-life of penicillins

d) Excretion: • Briefly discuss the organ responsible for the excretion of penicillins and the importance of monitoring its function. • Identify the renal clearance of penicillins and your understanding of this phrase.

2. Discuss the pharmacodynamics (mechanism of action) of penicillins.

• Discuss how penicillins work to manifest its pharmacological effects.

• Discuss two (2) major side effects and/or adverse reactions of penicillins specifically relating these effects to Mrs Anderson.

Homework Answers

Answer #1

1. Pencillin is a group of antibiotics derived originally from common moulds known as pencillium moulds which includes pencillin G( intravenous use), pencillin V ( use by mouth) procaine pencillin and benzathine pencillin( intramuscular use)

Pencillin antibiotics are the first medications to be effective against many bacterial infections caused by staphylococci and streptococci.

ABSORPTION:

  • Pencillin V has greater acid stability and is absorbed more completely than pencillin G after oral administration.
  • About 60% to 75% of oral dose of pencillin V absorbed.
  • Serum levels peak at 60 minutes in fasting subjects, food has no significant effect.
  • Pencillin ,once it is taken orally, spreads throughout the body. It is absorbed from the gastrointestinal tract to the plasma( the bloodstream). Once it has reached the plasma, it is distributed throughout the body. Pencillin can be inactivated in 3 ways: protein binding, metabolism or excretion.
  • It is generally accepted that IV antibiotics are better than oral. They are stronger and work faster.
  • Route of administration: Intravenous, intramuscular, oral . Its onset of action is slow with prolonged duration of action( oral)

DISTRIBUTION

  • Distributed widely into synovial,pleural,pericardial, and ascitic fluids and into bile,liver,skin,lungs, kidneys, muscle, intestines, tonsils, maxillary sinuses, saliva, and erythrocytes.
  • CSF penetration is poor but enhanced in patients with inflammed meninges.
  • Pencillin V crosses the placental barrier and is 75% to 89% protein bound.
  • Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficacy may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can tranverse cell membrane or diffuse.

METABOLISM

  • Between 35% and 70% is metabolized to inactive compounds.
  • Elimination half life of pencillin in adults is half hour. Severe renal impairmennt prolongs halflife

EXCREATION

  • Organ responsible for excretion of pencillin is kidney.
  • Excreted primarily in urine by tubular secretion, 26% to 65% of dose recovered in 6 hours.
  • Some drugs appears in breast milk.
  • Renal clearance of a substance refers to the how quickly a particular substance is removed from the plasma by the kidney and excreted in urine
  • Filtration-10%
  • Tubular secretion- 90%
  • Glomerular filtration rate-127ml/min
  • Renal clearance- 480ml/min

2. MECHANISM OF ACTION OF PENCILLINS

  • Bactericidal. Adheres to pencillin-binding proteins, thus inhibiting bacterial cellwall synthesis. Spectrum of activity includes most non- pencillinase producing strains of gram positive and gram negative aerobic and anaerobic bacilli.
  • Pencillin inhibits activity of enzymes that are needed for the cross linking of peptidoglycan in bacterial cell walls, which is the final step in cell wall biosynthesis

ADVERSE EFFECTS

  • CNS: Neuropathy
  • GI : Epigastric distress, vomiting, diarrhea, nausea, black hairy tongue
  • GU: Nephropathy
  • HEMATOLOGIC: Eosinophilia, hemolytic anemia, leukemia, thrombocytopenia
  • OTHER: Hypersensitivity reactions
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