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Platinum-based agents: Nursing Pharmacology

Notes

Notes

PLATINUM-BASED AGENTS
DRUG NAME
cisplatin
*High Alert medication*

carboplatin (Paraplatin)
*High Alert medication*

oxaliplatin
*High Alert medication*

CLASS
Platins (Alkylating-like agents)
MECHANISM of ACTION
DNA damage in all phases of cell-cycle → cancer cell death  (cell cycle non-specific)
  1. Attaches alkyl groups to DNA bases → repair enzymes attempt to replace alkylated bases → DNA fragmentation 
  2. Causes two DNA bases to link together → formation of cross-bridges → DNA cross-linking → inhibition of essential cell processes (e.g., replication)
  3. Inhibits enzymes involved in replication and division

  1. Causes two DNA bases to link together → formation of cross-bridges → DNA cross-linking → inhibition of essential cell processes (e.g., replication)
  2. Causes two DNA bases to link together → formation of cross-bridges → DNA cross-linking → inhibition of essential cell processes (e.g., replication)
  3. Inhibits enzymes involved in replication and division
  1. Causes two DNA bases to link together → formation of cross-bridges → DNA cross-linking → inhibition of essential cell processes (e.g., replication)
INDICATIONS
Cancer treatment 
  • Hematologic malignancies (e.g., leukemia, lymphoma, multiple myeloma)
  • Solid tumours (e.g., breast, ovarian, uterus, lung, bladder cancers)
ROUTE(S) of ADMIN
  • IV
SIDE EFFECTS
Common side effects
  • Bone marrow suppression
  • Alopecia, skin rashes, photosensitivity
  • Gastrointestinal disturbances (nausea, vomiting)
  • Infertility 
  • Vesicants (damage to surrounding tissues if agent leaks out of vein)
  • Bone marrow suppression (boxed warning)
  • Nausea / vomiting (boxed warning)
  • Nephrotoxicity (boxed warning)
  • Peripheral neuropathy (boxed warning)
  • Hypersensitivity reactions
  • Ototoxicity
  • Vesicant
  • Bone marrow suppression (boxed warning)
  • Nausea / vomiting (boxed warning)
  • Hypersensitivity reactions (boxed warning)
  • Nephrotoxicity
  • Ototoxicity
  • Vesicant
  • Hypersensitivity reactions (boxed warning)
  • Bone marrow suppression
  • Neurotoxicity (peripheral neuropathy)
  • Vesicant

CONTRA-INDICATIONS & CAUTIONS
  • Pregnancy 
  • Breastfeeding
  • Liver disease
  • Renal disease
  • Carboplatin: contraindicated in severe bone marrow suppression or significant bleeding
NURSING CONSIDERATIONS for
PLATINUM-BASED AGENTS
ASSESSMENT & MONITORING
Assessment and monitoring: cisplatin

Assessment
  • Current symptoms: pelvic or abdominal pain, vaginal bleeding, fatigue, early satiety, bloating
  • Weight 
  • Vital signs
  • Laboratory test results: CBC, renal and liver function tests, electrolytes; negative pregnancy test as needed
  • Diagnostic tests: CA 125, transvaginal ultrasound 

Administration
  • Patent IV, port-a-cath, PICC line
  • Verify dose 
  • Hydrate with intravenous fluids
  • Premedicate antiemetic 30–60 minutes before infusion
  • Wear gloves when handling medication 

Monitoring
  • Vital signs
  • I & O 
  • IV site for extravasation
    • Stop the infusion immediately, elevate the extremity, administer sodium thiosulfate 
  • Hypersensitivity reaction
    • Administer emergency medications
  • Side effects
  • Therapeutic response: decrease in symptoms associated with ovarian cancer 
CLIENT EDUCATION
  • Purpose of medication: treat ovarian cancer 
  • IV administration every 3-4 weeks 
  • Side effects 
    • Severe nausea and vomiting
      • Increase fluid intake
      • Antiemetics
    • Increased risk for infection 
      • Frequent hand hygiene, avoiding large crowds, people with infections, and live attenuated vaccines
      • Notify healthcare provider for fever, sore throat, flu-like symptoms 
    • Bleeding
    • Renal impairment
    • Neurotoxicity
Transcript

Platinum-based agents, sometimes called platins, are medications that are mainly used to treat cancer.

Broadly speaking, they are part of the bigger “alkylating-like agents” category, and they are primarily used in the treatment of solid tumors, like colon, rectum, lung, ovarian, uterus, testicular, and bladder cancer.

Now, the most commonly used platins include cisplatin, carboplatin and oxaliplatin, which are administered intravenously.

Once administered, platins act as cell-cycle phase nonspecific agents, which means they work by causing damage to the DNA of rapidly dividing cancer cells in all phases of the cell-cycle, ultimately causing their death.

There are three ways they do this. First, they can attach an alkyl group to one of the DNA bases of cancer cells.

Repair enzymes recognize there’s something wrong, so they jump in to replace the alkylated bases and cause DNA fragmentation, which eventually results in DNA damage and cancer cell death.

The second mechanism is the crosslinking of DNA, which means the alkylating agent links two DNA bases together, forming cross-bridges.

Cross-linking prevents DNA from being separated for essential cell processes, like replication or transcription, eventually resulting in cancer cell death and stopping the multiplication of cancer cells.

Cisplatin and carboplatin employ both these mechanisms to exert their antineoplastic effect, while oxaliplatin only seems to act through crosslinking of DNA.

Additionally, cisplatin and carboplatin also act through a third mechanism, which is to inhibit the enzymes involved in cell replication and multiplication.

Unfortunately, platinum-based agents also act on healthy rapidly dividing cells, including those in the skin, bone marrow, and gastrointestinal tract.

As a result, these medications can often cause several side effects, such as alopecia, skin rash, and photosensitivity, as well as nausea, vomiting. Vomiting is actually a boxed warning for cisplatin and carboplatin.

In addition, these medications can cause bone marrow suppression, which is yet another boxed warning for cisplatin and carboplatin, and can manifest as anemia, thrombocytopenia and increased risk of bleeding, and leukopenia, which increases the risk of infections.

Also remember that all platins are vesicants, so another side effect is that they can all cause the formation of blisters and tissue necrosis if the drug leaks out of the vein into surrounding tissues.

Two more boxed warnings for cisplatin include neurotoxicity, specifically peripheral neuropathy, as well as nephrotoxicity.

Remember that peripheral neuropathy is another common side effect for oxaliplatin, and carboplatin can also cause nephrotoxicity.

For more specifics, cisplatin and carboplatin can cause ototoxicity, which can present as tinnitus, or ringing in the ears, or even hearing loss, and both carboplatin and oxaliplatin have boxed warnings for potentially fatal hypersensitivity reactions.

As far as contraindications go, platinum-based agents shouldn’t be used during pregnancy and breastfeeding because they are teratogens, meaning they disrupt fetal development, which can lead to birth defects.

They should also be used with caution in clients with renal disease, and can cause temporary elevation of liver function tests.

Carboplatin is also contraindicated in clients with significant bone marrow suppression or bleeding.

Now, when a client with ovarian cancer is prescribed cisplatin, start by performing a baseline assessment, including weight, vital signs, and their current symptoms, such as pelvic or abdominal pain, vaginal bleeding, fatigue, early satiety, and bloating.

Then, review their most recent laboratory test results such as CBC, renal and liver function tests, electrolytes, and confirm a negative pregnancy test as needed.

Sources
  1. "Focus on Nursing Pharmacology" LWW (2019)
  2. "Pharmacology: Edition A Patient-Centered Nursing Process Approach (8e)" Elsevier Health Sciences (2014)
  3. "Mosby's 2021 Nursing Drug Reference (34e)" Mosby (2021)
  4. "Saunders Comprehensive Review for the NCLEX-RN Examination (7e)" Saunders (2016)
  5. "Lewis's Medical-Surgical Nursing (11e)" Mosby (2020)
  6. "Saunders Comprehensive Review for the NCLEX-RN Examination (8e)" Saunders (2016)