Platinum containing medications

Definitions & Key takeaways

Platinum-containing medications are a class of drugs that contain platinum and are commonly used to treat. These drugs are cell cycle-nonspecific agents because they target all cell cycle phases. Examples include cisplatin and carboplatin which treat solid malignant tumors like testicular, ovarian, cervical, and lung carcinomas. There is also oxaliplatin, used in advanced colon cancer, hepatobiliary, pancreatic, as well as lymphomas. Side effects of these drugs include nephrotoxicity, neurotoxicity, gastrointestinal disturbances, myelosuppression, and allergic reactions.

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Introduction0:00–0:19

Platinum containing agents, informally called platins, are a class of medications that are used to treat cancer. They disrupt the structure of DNA by acting on consecutive guanine bases within a strand of DNA and can affect all phases of the cell cycle.

Physiology0:19–1:29

Okay, now the cell cycle refers to the events that somatic cells, which includes all of the cells in our bodies except the reproductive cells, go through from the moment they’re formed until the moment they divide into two identical daughter cells.
This cycle varies in length depending on the type of cell. For rapidly dividing cells, like skin cells, it takes less than a day, whereas for other cells, like liver cells, the cell cycle can last years.
Now, the cell cycle can be divided in two phases: interphase and mitosis. Interphase comprises of the G1 phase, during which the cell grows and performs its cell functions, the S phase, during which DNA is replicated, and the G2 phase, during which the cell grows again before entering mitosis.
Mitosis can be broken down into prophase, metaphase, anaphase, and telophase, during which the replicated DNA divides equally for the two daughter cells, and ends with cytokinesis, which is when the cell membrane actually divides to form the two new cells.
There’s also a G0 phase which is an extended G1 phase, where the cell is resting and not actively preparing to divide. Alright, now imagine a cancer cell.

Pathology1:29–1:45

This cell is going through the phases of the cell cycle without regulation, and its DNA also replicates more frequently, with less error-correcting than healthy cells.
Therefore, it’s more sensitive to DNA damage. Here’s a DNA base, guanine.

Platins1:45–2:56

Platinum containing agents attach at the number 7 nitrogen atom of two adjacent guanines on the same strand of DNA leading to the formation of cross-bridges, or intra-strand cross-linking of the DNA.
The resultant cross-linking inhibits DNA repair and prevents DNA from being separated for replication, eventually leading to cell death.
Platins are cell cycle-nonspecific agents, meaning they act on tumor cells during all phases of the cell cycle, including the resting G0 phase.
Platins are sometimes described as ‘alkylating-like’ agents as they act like DNA alkylating medications, although they do not have an alkyl group.
Okay, platinum containing agents include cisplatin, carboplatin, and oxaliplatin, which are all administered intravenously and eliminated through the kidneys.
As their names imply, they are coordination complexes of platinum, meaning they consist of a central atom of platinum and a surrounding array of bound molecules, or ions, that are called ligands.

Indications2:56–3:34

Cisplatin has revolutionized the treatment of solid tumors. Today, cisplatin and carboplatin are used to treat a variety of solid tumors including testicular, bladder, ovarian, cervical, and lung carcinomas.
They are also used in the treatment of osteosarcoma, which is a common malignant bone tumor in children and teens, which arises from osteoblasts.
Oxaliplatin however, is only used in advanced colon cancer. Note that platins are eliminated unchanged through the kidneys.
Alright, moving on to the side effects. Platins can cause gastrointestinal disturbances, including very severe nausea and vomiting, which can be prevented by the use of ondansetron.

Side effects3:34–5:01

It’s also seriously nephrotoxic, which is the main dose-limiting side effect. We can prevent nephrotoxicity with adequate hydration; diuresis using mannitol, an osmotic diuretic; or saline, to prevent the medications from building up in the kidneys.
Nephrotoxicity seems to be related to reactive oxygen species, which are chemically reactive compounds containing oxygen-like peroxides, superoxides, and hydroxyl radicals.
We can also use amifostine, a free radical scavenger, to prevent renal damage. Next, these medications are neurotoxic and can cause peripheral neuropathy and ototoxicity due to acoustic nerve damage.
The ototoxic effect usually presents as tinnitus or ringing in the ear and hearing loss. Finally, they can cause allergic reactions and mild bone marrow suppression, which can lead to decreased platelets, red blood cells, and white blood cells.
Now, cisplatin causes the most severe nephrotoxic and neurotoxic side effects, while carboplatin is more likely to cause bone marrow suppression.
Oxaliplatin, causes even less ototoxicity. nephrotoxicity, and bone marrow suppression than cisplatin or carboplatin.
Now, let’s make a simple and fun mnemonic that’ll help you efficiently memorize these pharmacology facts about platinum-containing agents.

Memory Palace5:01–7:03

So first, let’s go to a music store where DJ Crabby-D’s album just went platinum. This will help you remember that the platinum containing medications are used to treat cancer.
To celebrate, his sister coated herself in platinum, for cisplatin and she’s holding a platinum coated cardboard box for carboplatin.
Now she’s an MD, so behind her is a poster of the female reproductive system with the ovaries and cervix circled, since cisplatin and carboplatin are used to treat cervical and ovarian cancer.
Another poster shows a man with his testicles, bladder, and lungs circled, to help you remember these medications also treat testicular, bladder, and lung cancer.
Finally, under the posters is a scarecrow made of bones for osteosarcoma. Okay, so next let’s have her pet an ox, who’s also covered in platinum to represent oxaliplatin.
This ox has a large colon wrapped around him to help you remember it’s mainly used to treat colon cancer. Okay, so the first fan to show up at the music store will represent the side effects, and she’s wearing headphones for ototoxicity.
The headphones are also kidney shaped for nephrotoxicity. Next, her arms are all bandaged up, which represents peripheral neuropathy, and her black T-shirt has a broken bone on it for bone marrow suppression.
She partied too hard and vomited on the floor to represent the severe GI disturbances these medications can cause. All right, as a quick recap…Platinum containing agents are a class of medications used in the treatment of cancer.
They are cell cycle-nonspecific agents, meaning they target all phases of the cell cycle. Cisplatin and carboplatin can treat solid tumor malignancies like testicular, bladder, ovarian, cervical, and lung carcinomas, while oxaliplatin is used only in advanced colon cancer.

Review7:03–7:52

Side effects of all platinum containing agents, which vary in frequency and intensity for each drug, include nephrotoxicity, neurotoxicity, gastrointestinal disturbances, myelosuppression, and allergic reactions.
But wait, there’s more: Here’s a mind map with all of the mnemonics. Go ahead and pause the video so you can test yourself to see what you remember.
Stay tuned for the answers after the credits.

Mind Map7:52–7:30