Aromatase Inhibitors

Breast cancer can be oestrogen-sensitive, so a treatment target for such types is to inhibit oestrogen.

In premenopausal women, selective oestrogen receptor modulators, more conveniently called SERMs, include tamoxifen. This particular medication acts as an oestrogen receptor antagonist at the breast but an oestrogen receptor agonist at the uterus, which is why it minority increases the risk of endometrial cancer.

In postmenopausal women, aromatase inhibitors are an option. These interrupt the production of oestrogen by suppressing the action of the enzyme aromatase. Anastrazole and letrozole are the names to know here; they’re non-steroidal, reversible binders of aromatase from the third generation of aromatase inhibitors.

Why are aromatase inhibitors less effective in premenopausal women? Premenopausal women have a large quantity of aromatase in the ovary. Note that ovarian aromatase is sensitive to changes in the gonadotropin LH, which is produced by the pituitary gland. If aromatase is suppressed with an aromatase inhibitor, gonadotropins increase in response, according to the usual feedback pattern, which stimulates more ovarian aromatase. This makes aromatase inhibitors less proficient at inhibiting oestrogen production in the ovary in such a group.

References

  1. Fabian, C. J. (2007). The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. International Journal of Clinical Practice, 61(12), 2051–2063. http://doi.org/10.1111/j.1742-1241.2007.01587.x
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Contraindications To Lumbar Puncture

A lumbar puncture is a procedure that involving drawing out cerebrospinal fluid, fondly known as CSF. For example, it can be used to check CSF for immune cells and glucose levels in suspected meningitis.

Lumbar puncture is considered an invasive procedure. But even with that aside, it’s not appropriate for everyone. That is, it does not suit all patients.

Contraindications to lumbar puncture are:

  • Skin infection at the lumbar puncture site
  • Uncorrected coagulopathy
  • Increased intracranial pressure
  • Trauma to the spinal cord

References

  1. Queen’s University School of Medicine. (n.d.). Contraindications. [online] Available at: https://meds.queensu.ca/central/assets/modules/lumbar_puncture/contraindications.html [Accessed 2 Feb. 2018].

Why Don’t NSAIDs Cause Malignancy?

Do topical NSAIDs increase the risk of skin cancer? After all, NSAIDs dampen inflammation and immune suppression is a factor that can promote malignancy. The answer is no!

For, on the contrary, research focuses more on the potential of using NSAIDs in the fight against cancer. How can this be?

Think of the mechanism of NSAIDs. They’re non-steroidal anti-inflammatory drugs, meaning they’re medications that reduce inflammation without being from the corticosteroid class.

NSAIDs indirectly inhibit prostaglandin synthesis by directly inhibiting COX enzymes. This provides anti-inflammatory effects and analgesia.

Prostaglandins play a starring role in situations such as fever.

In contrast, other things that are associated with increased malignancy risk have different ways of working.

For example, HIV impacts CD-4 T cells.

Meanwhile, chemotherapy agents have different mechanisms. For example, vincristine disruptively acts on microtubules.

Let’s not forget UV rays, which wreak havoc on the DNA process by inducing mutations.

These are just some of the villains of medicine. Thankfully, there are emerging medications that meet them in combat. But that’s a story for another day!

Mechanisms Of Hypercalcaemia In Malignancy

Milk is famous because it comes from animal breasts and is widely touted as a source of calcium.

https://static.simpsonswiki.com/images/thumb/3/3c/Malk.jpg/250px-Malk.jpg

In the body, calcium is primarily stored in bones and teeth, because it’s good to have a regulated amount circulating in the blood. You know, to avoid things going wrong.

Hypercalcaemia means too much calcium in the blood.

What controls calcium?

Parathyroid hormone (PTH) is a substance released from the parathyroid glands, which are 4 tiny structures located behind the thyroid gland.

https://68.media.tumblr.com/cf1138a8c09f8b9d32a63d399f7bebf9/tumblr_ntgujo9CT51uykqfqo2_1280.png

Let’s analyse this, like language-obsessed…language obsessors. Real poetic, yes.

Para: beside.

Thyroid: thyroid.

Gland: a bunch of cells that collectively secretes things.

https://s-media-cache-ak0.pinimg.com/736x/8a/d2/f5/8ad2f5e2dbc23c417c84a72c6b458691.jpg

Yet another medical acronym!

Why is PTH important?

Because PTH liberates calcium from bones into blood.

In political terms, PTH is the Joan Of Arc freeing the oppressed French calcium from the English occupation of bone.

But if there’s too much or too little PTH, the blood calcium level can be thrown off.

And yes, if your PTH is burnt at the stake, things will also not be good.

PTH 101

More PTH ==> more calcium release from bones ==> blood calcium level goes up.

Less PTH ==> less calcium release from bones ==> blood calcium level goes down.

Simplified mechanisms of hypercalcaemia in cancer

What are the ways in which blood calcium levels can be elevated? There are 2 main ones.

1. Too much PTH

Fake PTH

Most commonly, some cancers involve the release of PTH-related protein, a substance similar to PTH that isn’t PTH.

On investigation, endogenous PTH will be low, due to endocrine suppression. From blood tests, expect high PTH-related protein and low actual PTH; your body thinks there is enough PTH around, so it stops making as much. The fake PTH isn’t measurable according to normal PTH tests.

Real PTH

More uncommonly, a cancer can abnormally make its own PTH.

On investigation, endogenous PTH will be high, due to excessive production. Your parathyroids again stop making PTH because there’s too much already, but the extra PTH is measurable in blood because it’s actual PTH…even if it doesn’t come from the right place.

2. Too much calcium from other sources

Bones

If cancer spreads to bone, it can induce calcium release that way. The blood calcium level goes up.

Intestines

Cancer can make extra vitamin D, a substance that normally encourages intestinal calcium absorption.

If too much calcium is absorbed from the intestines, the blood calcium level rises.

Detailed mechanisms of hypercalcaemia in cancer

  1. PTH-related protein: most common cause of hypercalcaemia in non-metastatic solid tumours.
  2. Osteolytic lesions: caused by metastases to bone.
  3. Tumour-produced 1,25-dihydroxyvitamin D: most common cause of hypercalcaemia in Hodgkin lymphoma.
  4. Tumour-produced PTH: rare occurrence where the cancer makes its own PTH.

References

  1. UpToDate. (2016, August 22). Hypercalcemia of malignancy: Mechanisms. Retrieved 3 April 2017, from https://www.uptodate.com/contents/hypercalcemia-of-malignancy-mechanisms
  2. History.com. Joan of Arc relieves Orleans. Retrieved 3 April 2017, from http://www.history.com/this-day-in-history/joan-of-arc-relieves-orleans