Corticosteroid Pharmacology

Carbohydrate metabolism: The glucocorticosteroids are protecting the body during stress (surgery, trauma, etc). Specifically they are trying to protect the two most important organs: the heart and the brain and nothing else. It makes sure that there’s enough calories and nutrients for them. It increases the breakdown of proteins and glycogen in our body and turns them into sugars (gluconeogenesis).

The corticosteroids also reduce the peripheral utilization of sugar. In other words, outside of the heart and brain, other cells of the body won’t be able to accept the sugar into the cells as well, making the person look like a diabetic. Insulin is required to push sugar into the cells. Due to the gluconeogenesis and lack of sensitivity to insulin, their blood sugar is going to look really high and they are going to look like a diabetic. This is what it looks like when a person is heavily stressed or going into shock.

Lipid Metabolism: The corticosteroids cause lipogenesis (creation of fat) and lipolysis (breakdown of fat). Basically the fat is getting redistributed in the body. A hump on the back could be created or a moon face.

Electrolyte Balance: Sodium and water retention occurs, causing hypertension. There’s also a loss of potassium causing hypokalemia.

In Addison’s disease (hypoglucocorticosteroidism), it’s the opposite effect. We have a loss of water/sodium and retention of potassium. This is a very easy disease to diagnose on a basic blood test because this hyponatremic (not enough sodium) and hyperkalemic (too much potassium) combination doesn’t show up for other diseases.

Pharmacology of Corticosteroids in the CNS

Long term use of corticosteroids can and does lead to depression.

Conversely, in Addison’s Disease, where we have a lack of corticosteroids, the person will be apathetic and psychotic.

Pharmacology of Corticosteroids on the Immunological System

Hematologic system: Corticosteroids decrease WBC counts. Specifically it affects lymphocytes. Lymphocytes protect us typically from viral infection. (Neutrophils/granulocytes protect from bacteria.) Review the Immune System.

Decreased immune response: Corticosteroids decrease immune response and that may be a wanted effect such as in the case of Rheumatoid Arthritis or Lupus since they are auto-immune diseases. Also, if the patient had a transplant. You may also not want the body to reject an organ.

Anti-inflammatory response: It also reduces inflammation, again useful for RA.

Retard growth in children: Systemic corticosteroids retard the growth in children. Overall we feel it’s safe to give them orally inhaled corticosteroids to treat asthma because it’s going right to the site of action. Systemically (oral or IV), means it gets in the blood stream and we want to avoid that in children.

Corticosteroid Withdrawal

Acute adrenal insufficiency

Typically we don’t want an individual on a systemic treatment (oral, IV) for more than 7 days because they will go through withdrawals (almost like an addiction). Ideally we want to get them off of the drug in 7 days. (Note: Injecting into joints or inhaling are not considered systemic.) If you don’t get them off in 7 days is the development of acute adrenal insufficiency. When we give corticosteroids exogenously, it turns off the ACTH production from the pituitary gland so both the pituitary and adrenal glands will be shut off. What tends to be problematic is that after a week, the adrenal gland doesn’t turn on very quickly. After the person is on a week or more of therapy, the adrenal gland doesn’t turn on and the patient develops symptoms of acute adrenal insufficiency.

Symptoms of acute adrenal insufficiency: Fever, myalgia (muscle pain), arthralgia (joint pain), malaise. So they will feel worse than before. We must gradually withdraw them off of it as a result. If you treat a person for RA, you wouldn’t want to stop the therapy abruptly.

Consequences of Prolonged Therapy

We don’t want to put a person on corticosteroids for more than 7 days, but sometimes we have no choice. Sometimes we may find RA patients, asthmatic patients or ones who need prolonged immune suppression and this may last for more than 7 days. The consequences include:

• Fluid and electrolyte imbalance. (They’re gonna be large cause they’re retaining fluid)
• They will experience adrenal suppression.
• Increased risk of peptic ulcers
• Increased risk of depression
• Increased risk of cataracts.
• Increased risk of osteoporosis.

Clinical Use of Corticosteroids

Adrenal insufficiency such as Addison’s disease: Both mineralcorticoid and glucocorticoids will be used and only in this case are both used. Everything else we talk about after this deals only with glucocorticoids.

Rheumatoid Arthritis: To utilize its anti-inflammatory effects and decrease the immune system response.

Allergic Disorder (not anaphylactic): We want to utilize its anti-inflammatory effects and decrease the immune system response. This is not for anaphylactic shock because we need instantaneous results in that case and we use epinephrine for that.

Asthma: We utilize the anti-inflammatory effect in the bronchioles and decreased immune response.

Ocular disease: Something may be going on in the persons eye, such as an infection. This causes swelling of the eye. So we use the anti-inflammatory property of this drug. But is to be avoided if it’s a viral infection, such as Pink Eye, since this drug reduces the lymphocytes and lymphocytes are needed to fight that viral infection.

Skin disorder: This may be used topically, for something such as psoriasis, again for its anti-inflammatory and reduced immune response.

Lymphocytic anemia: When a person has lymphocytic anemia cancer, their lymphocyte counts may be sky high. This drug may be used to lower that lymphocyte count.

Corticosteroid Agents

• Beclomethasone (QVar, Beconase) is an oral inhaler used to treat asthma and also a nasal inhaler to treat allergic rhinitis. Our long term therapy are these nasal steroids and since it’s not systemic, there’s no problem.
• Dexamethasone (Decadrone) is used in cancer chemotherapy and also for asthma.
• Fluticasone (Flonase) – Probably the most common nasal inhaler for allergies because a generic is available for it.
• Flunisolide (Aerobid) (inhaler) used for asthma
• Hydrocortisone (Cortef) – Utilized for asthma. Topically on the skin used for psoriasis. It’s very mild and can be bought topically OTC and people typically buy it for a rash of some sort (allergic reaction or bug bites).
• Methylprednisolone (Medrol) – Used for asthma in the ambulatory setting. The Medrol pack has instructions for each day of the week. On day 1 they take 6 tablets throughout the day. On day two they take 5 tablets. 4..3..2..1… By day 7 they are totally off it. For these individuals, we’re treating respiratory inflammation. Sometimes we’re dealing with inflammation of other parts of their body. The nice thing about the medrol dose pack is they are off the drug in 7 days.
• Prednisone – This is commonly utilized and can be used for arthritis or asthma.
• Triamcinolone (Aristocort, Azmacort) – A nasal inhaler used to treat allergies. Topically on the skin this is a potent skin steroid for something like psoriasis. Typically it’s a long acting injection into the joints and hopefully it reduces the RA pain for 3 months.

Inhibition of Adrenocorticoid Synthesis

Aminoglutethimide (Cytadren): This inhibits adrenocorticoid synthesis. It blocks the production of adrenocorticoids. We do this sometimes because the adrenal corticosteroids may be a precursor to male/female sex hormones because of their cholesterol backbone. When we are dealing with a woman, sometimes there’s a cancer involved that’s an overproduction of estrogen by the ovaries or adrenal glands. To stop the production of it from the adrenal glands, this drug can be utilized. For men there may be a testosterone overproduction and it will stop the adrenal glands from producing testosterone.

Adrenocorticolytic

Mitotane (Lysodren): These drugs destroy the adrenal glands. And we may do this because the person may have a cancer of the adrenal gland.