Corticosteroids Flashcards
What are the major hormones produced by the adrenal gland?
Mineralocorticoid (aldosterone), glucocorticoids (cortisol), and sex hormones (testosterone)
What are the two major parts of the adrenal gland?
Medula (inner portion) and Cortex (outer portion)
Where in the adrenal glands are its three major homones produced?
They are produced in the adrenal cortex. The cortex can be divided into 3 zonas.
Zona glomerulosa (mineralocorticoid)
Zona fascisculata (glucocorticoids)
Zona reticularis (sex hormones)
What are the functions of cortisol in the body?
- Mediate stress response (prepare body for stress via increased blood sugar, downregulate parasympathetic)
- Help regulate metabolism
- Help regulate inflammatory response and immune system
What is the HPA axis?
This system regulates production and secretion of cortisol.
Negative feedback loop
Hypothalamus–>Pituitary gland–>Adrenal gland
What are the most notable actions of glucocorticoids?
Supress inflammatory and immunological responses
What is the anti-inflammatory mechanism of action for corticosteroids?
- Altering cytokine release
- Blocking increased capillary permeability
- Lower vasoactive substances
- Inhibiting leukocyte and macrophage migration/adhesion
- Interfering with phagocytosis
What is the immunosuppressive mechanism of action for corticosteroids?
- Altering cell function of specific genes
- Affecting WBC function
- Inhibiting T-cell activation
- Inhibiting IL’s, cytokines, gamma-interferon, and TNF-alpha
What are some minor corticosteroid actions?
- Anti-mitotic activity
- Anti-tumour effects
- Anti-emetic effects
What is the most common way to sort corticosteroids into two categories?
Local vs. systemic agents
Why do patients prefer local agents over systemic corticosteroids?
Fewer side effects
What are the uses of Ophthalmic/Otic corticosteroids?
Used for: redness, itching, swelling, and pain
Commonly in combo with antibiotics
Available as drops, ointments, emulsions, intravitreal implants
What are some issues with Ophthalmic/Otic drops?
Incorrect delivery technique
45% of patients failed to get drops into the eyes
What are the uses of nasal inhaled corticosteroids?
Used for: Rhinitis, polyps, sinusitis
Issues with instillation technique
What are the uses of metered-dose corticosteroid inhalers?
Used for: mainstay for asthma
Very portable, but some patients may have incorrect inhalation technique
What is an advantage of inhaled dry powder corticosteoids vs. metered dose inhalers?
They list the number of remaining doses
Patient has to guess if they still have doses on a metered dose inhaler
What is the benefit of nebulizers as a delivery device?
Young children benefit from the mask fitting that can allow the administrator to release the drug into that closed space, allowing the child to breathe in the steroid easily
What are the goalpost corticosteroid products (based on potency)?
- Hydrocortisone (potency 7)
- Betamethasone valerate (potency 3)
- Betamethasone dipropionate (potency 2)
- Clobetasol propionate (potency 1)
What factors impact the efficacy of topical corticosteroids?
- Skin moisture
- Potency
- Formulation
- Application technique
- SIte (ex. hands vs. face)
- Skin condition
What are some corticosteroid rectal dosage forms
- Enemas
- Rectal Ointments
- Suppositories
- Rectal Foams
Used for: colitis, Crohn’s disease, hemmorhoids
What the types of injectable corticosteroids?
- Intravenous
- Intramuscular
- Intralesional
- Intra-articular
What are the advantages of intravenous corticosteroids?
Faster onset of effect
Useful when high doses are required
What are the usual sites of intra-articular corticosteroids?
hip, knee, ankle, shoulder, elbow, wrist
Do not inject more than 3-4 times per year
What are some qualities of oral corticosteroids?
They exhibit rapid and complete absorption from the gut
Oral doses are equivalent to IV due to quick absorption
What is the physiologic dose for corticosteroids?
This dose is supposed to replace deficiencies
5mg/day prednisone is approximately equivalent to the amount of cortisol secreted by the adrenal gland
What are the pharmacologic doses for corticosteroids?
These doses are meant to treat disease states and provide supportive therapy
5-15mg/day (low dose)
0.5mg/kg/day (moderate dose)
1-3mg/kg/day (high dose)
15-30mg/kg/day (massive dose)
Rank corticosteroid potency from least potent to most potent
Cortisone (lowest potency)
Hydrocortisone
Prednisone
Prednisolone
Methylprednisone
Triamcinolone
Dexamethasone
Betamethasone (highest potency)
What is the common starting oral corticosteroid?
prednisone
What are the side effects of ophthalmic corticosteroids?
- Stinging, redness
- Tearing, burning
- Secondary infection (due to immunosuppression)
- Glaucoma and cataracts
What some adverse events for patients that use corticosteroid oral inhalers?
- Thrush (rinse mouth to prevent)
- Hoarseness
- Dry mouth
- Dysphoria
- Difficulty swallowing
What are some side effects seen in patients that use corticosteroid nasal spray?
- Rhinnorhea
- Burning
- Sneezing
- Bloody nose (spray awy from septum to prevent)
What are some adverse effects seen in patients that use topical corticosteroids?
- Burning
- Irritation
- Skin atrophy
- Taxgyphylaxis (developing dose tolerance)
- Telangiectasia (spider veins)
What are some systemic complications associated with oral corticosteroid use?
- CNS (starts with euphoria, insomnia, restlessness. Can progress into depression, mania, and psychosis)
- Face/Back - Cushingoid features (Far redistribution from periphery to trunk)
- Ophthalmic (cataracts and glaucoma) More common in topical, but still a concern with oral dosage forms
- GI (take with food and do not take oral corticosteroid with NSAIDs due to ulcer risk)
What factors contribute to the severity of adverse effects while on corticosteroids?
High potency
High dose
High frequency
Long duration of therapy
What is the effect of corticosteroid use on blood glucose?
Increase in blood glucose due to corticosteroid induced gluconeogenesis and reduced glucose utilization by tissues
Elevated blood glugose can persist for months following discontinue
What is the effect of corticosteroids on blood pressure?
Corticosteroids with the greatest mineralocorticoid activity can cause increased fluid retention and subsequently elevate BP
What are the effects of corticosteroids on appetite?
Increases appetite
Especially beneficial for cancer patients who have lost their appetite
What are the effects of corticosteroids on growth?
Dose-dependent and most pronounced with oral therapy
Multiple mechanisms (decreasing osteoblasts, decreased growth hormone secretion)
What is the HPA-Axis?
A connection between the brain and adrenal glands
It is the body’s main stress system
When are endogenous levels of cortisol the highest?
They are highest in the morning and are at their lowest at midnight
Cortisol levels can jump 10x in period of acute stress
In a patient with HPA-Axis suppression, what will happen if corticosteroid therapy is abrupty stopped?
They will experience adrenal insufficiency. They symptoms are the opposite of too much cortisol
- Hypotension
- Hypoglycemia
- Flu-like symptoms
- Weight loss
- Confusion
What factors affect the severity of HPA-Axis suppression?
Dose
Administration
Potency
Interval (10mg QID is not the same as 40mg OD)
Route of administration
Time of administration (usually taken in the morning)
Can we easily predict which patients will experience HPA-axis suppression?
Not really
But patients on dosed of over 15mg/day will most likely experience HPA-axis suppression
How long can it take for HPA-axis suppression to reverse and cortisol production to return to normal?
It depends on the unique situation of each patient. But on average it can be between 1 to 3 years after cessation of exogenous steroids
What are the side effects of corticosteroids on the immune system?
Impair antibodies and phagocytosis
Susceptibility to viral infections (varicella zoster), bacterial infections (cellulitis), fungal infections (candida)
What are the side effects of corticosteroids on the skin and connective tissue?
Inhibit epidermal cell division and DNA synthesis
Thin skin
Striae
Acne (can occur following short course of corticosteroids)
What are the effects of corticosteroids on the bones?
Bone loss with corticosteroids occurs most rapidly in the first 3 months
30-50% will develop osteoporois with chronic treatment
Risk of fracture increases with doses as low as 2.5-7.5mg/day
What is the effect of corticosteroids on muscle tissue?
Muscle weakness due to decreased protein synthesis in the muscle
What are the most common side effects seen in children who are on corticosteroids chronically?
- Weight gain
- Growth retardation
- Cushingoid features
Infection is the most serious adverse effects
What are the most common side effects seen in short course corticosteroid therapy in children?
- Vomiting
- Behavourial changes
- Sleep disturbances
What is the use of corticosteroids in COVID-19 therapy?
Improve clinical outcomes and decrease mortality in hospitalized patients requiring oxygen
Are corticosteroid doses standardized?
No there are no set guidelines
Dosing is up to prescriber preference and comfort level
Need to balance disease activity and toxicity
Are corticosteroid doses tapered when ending therapy?
Corticosteroids need to be tapered upon discontinuation if HPA-axis suppression is suspected
Tapering is usually done if patient has been on corticosteroid therapy for longer than 3 weeks (reduce 5mg every 3-7 days)
Refer to page 77-78 for Alternate Day Dosing for corticosteroids
Do patients that undergo high stress situations need to adjust corticosteroid dose?
Yes, but only in situations like moderate illness and surgery.
HC is given for a few days and is tapered rapidly
What is the utility of steroid pulse therapy?
short term and high dose steroids can be given in situations where rapid remission of serious conditions is desired
ex. juvenile rheumatoid arthritis, nephrotic syndrome
What are the advantages of steroid pulse therapy?
- More rapid control of condition
- Helps prevent adverse effects from prolonged steroid therapy
What are some disadvantages of steroid pulse therapy?
- Hypertension
- Infection
- Siezure
- Psychosis
Do corticosteroid adverse effects disappear once discontinued?
They do not go away immediately, but it can take months for patient to fully recover
What is the effect of aldosterone?
Na+ and water retention (helps increase BP)
K+ excretion
What is the main androgen secreted by the adrenal gland?
DHEA
It is the primary source of androgens in women
What causes Cushing’s syndrome?
A disorder caused by persistant exposure to excesive glucocorticoids (exogenous or endogenous)
Is endogenous overproduction of cortisol the leading cause of Cushing’s syndrome?
No, endogenous overproduction of cortisol is a very rare disorder (1-10 in a million)
1% of the population uses exogenous glucocorticoids, but 10% of these patients have Cushing’s syndrome
Are women more affected by Cushing’s syndrome than men?
Yes, women are almost 5 times more likely to have Cushing’s syndrome
What is the etiology of endogenous overproduction of cortisol?
- ACTH dependent (80%):
A benign pituitary tumour over produces ACTH which stimulates production of cortisol in the adrenal glands - ACTH independent (20%):
Adrenal gland tumours
Is Cushing’s syndrome easy to diagnose?
No, it is often difficult and delayed because it mimic other conditions
How is Cushing’s syndrome diagnosed?
- Establish if hypercortisolism is present (Urine free of cortisol, midnight serum cortisol, and low-dose dexamethasone suppression test)
- Establish the cause (HIgh dose dexamethasone suppression test, Plasma ACTH via radioimmunoassa, etc.)
What are some common clinical features associated with Cushing’s syndrome?
Obesity
Rounded face
Growth retardation in children
Depression/emotional lability
Decreased libido
What are some signs that can help distinguish obesity symptoms of Cushing’s syndrome from regular obesity?
- Protein wasting (Thin skin, unusual bruising, muscle weakness)
- Suddenly apearing striae
What are the therapeutic goals in Cushing’s syndrome?
- Remove the source of hypercortisolism
- Restore secretion to normal
- Reverse clinical features
- Prevent dependency on medications
What are the consequences of leaving Cushing’s syndrome untreated?
5 yr survival rate of 50%
With appropriate treatment most signs will resolve within 2-12 months
What are some treatment options for Cushing’s syndrome?
Surgery is the main treatment option in Cushing’s syndrome
Pituitary adenoma and adrenal tumours can be removed
Ectopic ACTH syndrome (multiple tumour sites): most need drugs following surgery
For drug induced Cushing’s syndrome, taper off corticosteroids
What is the utility of pharmacological therapy for Cushing’s syndrome?
- To decrease cortisol levels before surgery
- As adjunct treatment after unsuccessful surgery or radiation
- For tumours that cannot be removed easily
- To help treat severe symptoms
What are some examples of pharmacological agents used in the treatment of Cushing’s syndrome?
Steroidogenesis Inhibitors:
1. Ketoconazole
2. Metyrapone
3. Mitotane
ACTH secretion inhibitors:
Pasireotide
How does ketoconazole work to treat Cushing’s syndrome?
Blocks the synthesis of cortisol in the adrenal gland
Ketoconazole is the drug of choice (effective and side effect profile is not as bad as the other agents)
200-400mg TID
Does ketoconazole have many drug interactions?
Yes
Ketoconazole has drug interactions with a diverse set of drugs
How does Metyrapone treat Cushing’s syndrome?
Inhibits conversion of precursor molecule into cortisol
Commonly used if experiencing dose limiting SE effect with ketoconazole OR adjuct therapy with ketoconazole
Androgenic side efffcts (hirsutism and acne)
How does Mitotane treat Cushing’s syndrome?
Greatly decreases cortisol synthesis
Used for inoperable adrenal carcinoma and usually started in hospital
Are steroidogenic inhibitors effective in long-term therapy of Cushing’s syndrome?
Not effective as monotherapy, but often used in combo with interventions like surgery and radiation
How does pasireotide treat Cushing’s syndrome?
Inhibits ACTH secretion in ACTH-producing adenomas
This drug is used when surgery has been ruled out
It is not commonly used because it has too many side effects and not effective enough
What is Addison’s Disease (Primary adrenal insufficiency)?
A rare disorder in which the adrenal glands cannot synthesize enough glucocorticoids and mineralocorticoids
(all 3 zones of the adrenal cortex have been destroyed)
What causes Addison’s Disease (Primary Adrenal Insufficiency)?
- Autoimmune mediated destruction of the adrenal cortex (common in the Western world)
- Infectious diseases like TB, HIV, CMV (more common in developing world)
- Hemorrhage (bleeding into the adrenal glands)
- Injury to adrenal glands
What is secondary adrenal insufficiency?
It is caused by a decrease in the amount of cortisol/corticosteroids in the body
- Abruptly stopping corticosteroids
- Pituitary and hypothalmic tumours
- Surgical removal of pituitary
- Other medications
What are some signs and symptoms of adrenal insufficiency?
- Fatigue (95%)
- Weight Loss (76%)
- Hypotension
- Skin hyperpigmentation (usually the first symptom)
What causes hyperpigmentation in adrenal insufficiency?
In adrenal insufficiency, a not a lot of ACTH is converted into cortisol. This results in a buildup of ACTH.
ACTH will bind to melanocytes and overstimulate them into developing more than usual melanin
(most prominent on sun-exposed areas, knuckles, elbowsm knees, mucous membranes)
Is adrenal insufficiency easy to diagnose?
Patients experience non-specific symptoms, so diagnosis can be difficult to ascertain
These symptoms will build up gradually
How is adrenal insufficiency diagnosed?
- Clinical presentation
- Lab tests
- Cortisol levels
- Medical Imaging
What are the treatment options for adrenal insufficiency?
Required daily glucocorticoid and mineralocorticoid replacement
ex. Hydrocortisone(gluco.) and Fludricortisone(mineralo.)
Why is hydrocortisone the glucocorticoid drug of choice in adrenal insufficiency?
It is preferred because of its good glucocorticoid and mineralocorticoid activity
10-15mg/day (2/3 at 8am, 1/3 at noon)
How do practitioners know their treatment plan for adrenal insufficiency is working?
Reduction in hyperpigmentation is a good sign
No longer loosing weight, blood pressure is returning to normal
Do patients with adrenal insufficiency need to take supplemental stress dosing?
Yes, they need to give themselves an extra dose after experiencing stress. This is why patients with adrenal insufficiency should carry an extra dose on hand.
- Strenous activity (add 5-10mg HC)
- Minor febrile illness or trauma (double dose until recovery)
- Emergency self-treatment necessary (HC 75-300mg/day IM)
What is a consequence of adrenal insufficency that women uniquely experience?
The adrenal glands produces majority of the androgens produced in a woman’s body
Loss of androgen supply can be supplemented with DHEA 25-50mg/day
What is acute adrenal crisis?
This is a medical emergency following a rapid decrease in cortisol/corticosteroid levels
Due to abrupt steroid withdrawal or lack of appropriate stress-dosing
How are acute adrenal crises treated
Parenteral glucocorticoids for rapid gluco. delivery
Hydrocortisone IV is the drug of choice in acute adrenal crises
What are some important patient education points in adrenal insufficiency?
- Seriousness of disease
- Importance of adherance
- Medication effects/ side effects
- Have extra meds or glucocorticoid injection on hand
- Recognizing worsening of condition
- Importance of wearing Medic Alert bracelet
