Module 18

Question 1

What is the difference between vasopressin and antidiuretic hormone, and what are the differences between vasopressin and desmopressin? How are they administered and why? What is the most common indication for desmopressin?

Answer 1

• Vasopressin and antidiuretic hormone are the same thing. This hormone binds to two different receptors V1 and V2.
  
  • Binding to V1 mediates the vasopressin effects of the hormone, i.e. increase in blood pressure, glycogenolysis, and platelet aggregation.
    ○ Binding to V2 mediates the antidiuretic effects of the hormone, i.e. water retention in the kidney.
  • Desmopressin was designed to increase the relative antidiuretic effects and prolong the half-life of the molecule to make it a better treatment for diabetes insipidus caused by a lack of antidiuretic hormone
  • Antidiuretic hormone and desmopressin are peptides so their oral bioavailability is very low. Therefore, they are given parenterally, or more commonly intranasally or sublingually.

Question 2

What is the basis for the use of desmopressin in von Willebrand’s disease or mild hemophilia (decrease in clotting factor VIII), and what limits its chronic use in von Willebrand’s disease?

Answer 2

• Desmopressin also causes the release of clotting factor VIII; therefore, it can be used acutely to decrease bleeding. Von Willebrand’s disease is associated with a decrease in von Willebrands factor, which binds to factor VIII and prevents its rapid breakdown. However, it does not increase the synthesis of factor VIII, so it is not effective for chronic treatment of von Willebrand’s disease. This is a bit obscure so I probably would not ask it on an exam, but I think it is useful to have seen this relationship

Question 3

You should drink 8 glasses of water day.

Answer 3

• False
  There is no magic number, and it depends on many factors. The kidney is very efficient, and drinking lots of water will not “flush out toxins” relative to normal water intake. In general, thirst is a good indicator of when you should drink. Drinking too much water – psychogenic polydipsia –eliminates the osmotic gradient in the kidney, which is what makes it possible for the kidney to concentrate urine. Then patients have to drink a lot to keep up with water loss. This can lead to serious hyponatremia, seizures, central pontine myelinolysis, and even death. Psychogenic polydipsia can be difficult to differentiate from a lack of antidiuretic hormone (diabetes insipidus).

Question 4

What is the major CNS danger of inappropriate secretion of antidiuretic hormone or desmopressin, and what are the factors that potentiate this danger?

Answer 4

• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) leads to hypervolemia and dilutional hyponatremia.
  
  • Because water diffuses much more rapidly than electrolytes, this results in brain swelling. When severe, because of the rigid structure of the skull, the only way that the brain can expand is through the foramen magnum at the base of the brain. This causes severe damage to the base of the brain and is usually fatal.
  • It can be caused by several drugs, e.g. chlorpropamide, ifosfamide, cyclophosphamide, carbamazepine, MDMA (Ecstasy), opiates, and several other drugs.
  • One clinical scenario is a young woman undergoing minor surgery, often with postsurgical opiates for pain, who then develops a severe headache, which is one of the first symptoms of SIADH. This then progresses to seizures and loss of consciousness.
  • In general, surgery or other trauma leads to an increase in the release of antidiuretic hormone, possibly the body’s response to possible blood loss, but why this is more common in women of child-bearing age is unknown.

Question 5

What is pennyroyal used for and what is its toxicity? It contains pulegone. What is the metabolic pathway of pulegone that is responsible for its toxicity?

Answer 5

• Pennyroyal is said to promote uterine contractions and has been used to induce abortions. It is also promoted for many other conditions such as upset stomach, flatulence, colds, smallpox, tuberculosis, and as an insect repellent. It causes liver failure and has led to the death of several people, most commonly when used to induce abortion.
  
  • About 1 tablespoon of the oil is fatal. It contains pulegone, which is a highly toxic compound that is metabolized to at least two different reactive metabolites