Action and Spectrum

Actions and spectrum: 

metyrapone is an inhibitor of steroidogenesis, specifically the enzyme 11-beta-hydroxylase. It inhibits the conversion of 11-deoxycortisol to cortisol, resulting in reduced cortisol synthesis.

This action can be used in the diagnosis of certain adrenal disorders and in the treatment of Cushing’s syndrome. The spectrum of metyrapone is mainly focused on its effects on cortisol production and its role in managing conditions related to cortisol excess. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Bone marrow depression (rare) 

Dizziness 

Headache 

Increased Pulse rate 

Vertigo 

Abdominal discomfort 

Decreased leukocyte count (rare) 

decreased arterial blood pressure 

Nausea 

Sedation 

Black Box Warning

Black Box Warning: 

There were no black box warnings associated with metyrapone 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: It should not be used in individuals with a known hypersensitivity or allergy to metyrapone or any of its components. 
• Severe Liver Impairment: metyrapone is primarily metabolized by the liver, and its use should be avoided in patients with severe liver impairment or liver failure. 
• Adrenal Cortex Tumor: metyrapone is used in the diagnostic test for Cushing’s syndrome, but it should not be administered to patients with primary adrenal cortical insufficiency due to an adrenal cortex tumor. 
• Pregnancy: metyrapone may harm the developing fetus and is contraindicated during pregnancy. 
• Lactation: metyrapone should be avoided during breastfeeding as it may pass into breast milk and potentially affect the nursing infant. 

Caution: 

• Liver Dysfunction: metyrapone is metabolized by the liver, and its clearance may be affected in individuals with mild to moderate liver impairment. Close monitoring of liver function is essential in such cases. 
• Cardiovascular Disease: metyrapone may cause hypertension (high blood pressure) as a side effect. It should be used cautiously in patients with a history of cardiovascular disease or hypertension. 
• Adrenal Crisis Risk: metyrapone blocks cortisol synthesis, which may increase the risk of adrenal crisis in patients with adrenal insufficiency. In such cases, careful monitoring and adjustment of glucocorticoid replacement therapy are necessary. 
• Drug Interactions: metyrapone may interact with other medications, including corticosteroids and drugs metabolized by the liver. Caution should be exercised when using Metyrapone in combination with other medications to avoid potential drug interactions. 
• Endocrine Disorders: metyrapone affects the hypothalamic-pituitary-adrenal (HPA) axis, and its use may alter hormone levels. It should be used cautiously in patients with endocrine disorders. 
• Ocular Effects: metyrapone may cause vision changes and blurred vision. Patients should be advised to use caution while driving or operating machinery if side effects occur.

Comorbidities: 

• Cushing’s Syndrome: metyrapone is commonly used to test and diagnose Cushing’s syndrome, a condition caused by excessive cortisol production. Comorbidities associated with Cushing’s syndrome may include hypertension, diabetes, osteoporosis, obesity, and cardiovascular diseases. 
• Congenital Adrenal Hyperplasia (CAH): metyrapone is used to manage CAH, a genetic disorder that affects the adrenal glands’ ability to produce certain hormones. Comorbidities may include growth and developmental issues, electrolyte imbalances, and fertility problems. 
• Adrenal Insufficiency: metyrapone may be used to assess adrenal function in cases of suspected adrenal insufficiency. Comorbidities may include fatigue, weakness, electrolyte imbalances, and low blood pressure. 
• Pituitary Disorders: metyrapone may be employed to evaluate pituitary function in cases of suspected pituitary disorders. Comorbidities may vary depending on the specific pituitary hormone deficiencies. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category: C 

Lactation: unknown, use caution  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

metyrapone is a synthetic steroid derivative with pharmacological properties that primarily affect the adrenal gland’s function and cortisol production. It acts as an inhibitor of the enzyme 11-beta-hydroxylase, which is involved in the synthesis of cortisol (a stress hormone) in the adrenal glands. By inhibiting this enzyme, metyrapone decreases the cortisol production and, to a lesser extent, aldosterone. 

In cases of suspected adrenal insufficiency, metyrapone is used to test the adrenal gland’s response to decreased cortisol levels. metyrapone is employed as a diagnostic tool to differentiate between pituitary and adrenal causes of Cushing’s syndrome. 

metyrapone is available in oral form and is typically used under medical supervision due to its specific indications and potential side effects. The drug’s pharmacology plays a critical role in its clinical applications and aids in the diagnosis and treatment of various endocrine disorders related to cortisol regulation.  

Pharmacodynamics: 

• Cortisol Reduction: The primary effect of metyrapone is the reduction of cortisol levels. This is particularly important in conditions where excessive cortisol production is present, such as Cushing’s syndrome. 
• Increase in Precursor Hormones: By blocking the conversion of 11-deoxycortisol to cortisol, metyrapone leads to an accumulation of 11-deoxycortisol and other cortisol precursors in the blood. 
• Feedback Mechanism: The reduced cortisol levels due to metyrapone administration trigger a feedback mechanism that stimulates the production of adrenocorticotropic hormone (ACTH) from the pituitary gland.  
• Diagnostic Tool: metyrapone is used as a diagnostic tool to assess the function of the adrenal glands in cases of suspected adrenal insufficiency or to differentiate between pituitary and adrenal causes of Cushing’s syndrome.

Pharmacokinetics: 

Absorption 

metyrapone is administered orally, and its absorption occurs in the gastrointestinal tract. However, it has a low bioavailability, which means only a small fraction of the drug reaches the systemic circulation. Food intake can affect its absorption, so it is usually taken on an empty stomach. 

Distribution 

Once absorbed, metyrapone is distributed throughout the body via the bloodstream. It crosses the blood-brain barrier and can also enter the placenta during pregnancy. 

Metabolism 

metyrapone undergoes hepatic metabolism, primarily through the action of the liver enzyme cytochrome P450 (CYP3A4). It is metabolized into several inactive metabolites. 

Elimination and excretion 

The elimination of metyrapone and its metabolites primarily occurs through the kidneys. A small portion of the drug may also be excreted in the feces. 

Adminstartion

Administration: 

metyrapone is typically administered orally in the form of tablets or capsules. The dosing schedule and duration of treatment will depend on specific medical condition being treated and the healthcare provider’s recommendations.  

metyrapone is commonly used for diagnostic testing in the evaluation of adrenal function and in the treatment of certain adrenal gland disorders, such as Cushing’s syndrome. For diagnostic purposes, a single dose is usually given at a specific time, and blood tests are taken at specific intervals to assess the adrenal response. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: metyrapone 

Pronounced: (meh-TI-ruh-pohn)  

Why do we use metyrapone? 

• Diagnostic Testing for Adrenal Function: metyrapone is used in diagnostic testing to evaluate the function of the adrenal glands. It is particularly useful in assessing the ability of the adrenal glands to produce cortisol, a hormone that plays a vital role in stress response, metabolism, and various physiological processes. metyrapone is administered as part of a test known as the metyrapone test, which helps healthcare providers diagnose conditions related to cortisol production. 
• Treatment of Cushing’s Syndrome: metyrapone is used in the treatment of Cushing’s syndrome, a condition characterized by excessive cortisol production by the adrenal glands. By inhibiting an enzyme involved in cortisol synthesis, metyrapone reduces the excessive production of cortisol, leading to a decrease in symptoms associated with Cushing’s syndrome, such as weight gain, high blood pressure, and glucose intolerance.