CYP17 Inhibitors Drug Class

CYP17 Inhibitors are drugs that inhibit or block the action of the enzyme 17alpha-hydroxylase (CYP17). This is the enzyme that is involved in production of weak androgen steroids which are DHEA (dehydroepiandrostenedione) and androstenedione. This is possible through a reaction catalyzed by the enzyme(CYP17) whereby pregnenolone and progesterone are converted into the weak steroids, DHEA and androstenedione respectively. The weak steroids are later converted to testosterone and then into dihydrotestosterone(DHT) through a series of other reactions. Medical evidence suggests that the enzyme CYP17 is critical in the synthesis of androgens in several organs in the body including the prostate, testes and adrenal glands.

CYP17 Inhibitors Drugs

Drugs classified as CP17 inhibitors are listed below.

CYP17 Inhibitors Uses

The therapeutic value of CYP17 inhibitors is derived from the fact that androgens have been cited as a major risk factor contributing towards the development of prostate cancer. Therefore, these drugs inhibit androgen production by blocking the enzyme CYP17 that is involved in their synthesis leading to reduction in the levels of androgens in the body. This is deemed as a viable treatment for prostate cancer resistant to castration (CRPC), including metastatic CRPC because with low levels of androgens the disease progression is halted. CRPC is a cancer that has proved unresponsive to anti androgens or deprivation of androgens. These drugs have achieved satisfactory results in the treatment of these conditions provided the patient is not on chemotherapy.

Usually, these drugs are not used alone. They are combined with prednisolone or prednisone in treating the above conditions.

CYP17 Inhibitors Side Effects

The common side effects of CP17 inhibitors are due to secondary mineralocorticoid excess. This is because there is an increase in production of mineralocorticoids in the adrenal glands as an alternative route or diversion due to inhibition of CYP17. The symptoms include:

These side effects can be managed by administering eplerenone which blocks the binding of the mineralocorticoid to their receptors hence ablates their effects.

Other side effects may include:

  • Sepsis
  • Myopathy
  • Tachycardia
  • Cardiac failure
  • Rash
  • Hematuria
  • Arrhythmia
  • Elevated liver enzymes (AST and ALT)
  • Adrenal insufficiency
  • Atrial fibrillation
  • Hypertriglyceridemia

CYP17 Inhibitors Interactions

These drugs are not to be used concurrently with several other drugs which may either ablate their effects or exaggerate their effects and vice versa. These include drugs such as strong CYP3A4 inducers (such as Rifampin) or inhibitors (such as cimetidine).

CYP17 Inhibitors are not to be used in women are pregnant or can become pregnant. Also, they are inadvisable in patients who are hypersensitive to abiraterone. These drugs are not to be used by people with various underlying conditions as they elicit an adverse reaction leading to severity of the underlying defect or complications such as death. Such conditions include:

  • Patients who are allergic to the drugs
  • Patients with liver failure or insufficiency
  • Patients with Hypokalemia
  • Patients suffering from a heart disease
  • mineralocorticoid excess