Corticosteroids Flashcards
What is the function of the adrenal glands in regards to steroid production?
Secrete mineralcorticoids, glucocorticoids, and sex hormones
Where are the adrenal glands located?
Sit on top of the kidneys
What are the two main areas of the adrenal glands?
Cortex and Medulla
What composes the cortex of the adrenal glands?
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
(GFR on top of kidneys)
Describe the pathway of hormone synthesis in the zona Glomerulosa?
Cholesterol –> Desoxycorticosterone –> Corticosterone –> 18-Hydroxyxosterone –> Aldosterone
What is the main steroid product of the zona glomerulosa?
Aldosterone
Describe the pathway of hormone synthesis zona fasci?
Cholosterol –> Prenolene –> Progesterone –> 17-Hydroxyprogesterone –> 11-Deoxycortisol –> Cortisol
What is the main steroid product of the Zona Fasci?
Cortisol
Describe the pathway of hormone synthesis in the zona reticularis?
Cholesterol –> 17-Hydroxypregnenolone –> Dehydroepiandrosterone –> Androstenedione –> Testosterone
What cholesterol is used for steroid synthesis?
LDL Cholesterol
Where is testosterone mainly produced? In Who?
Testosterone can be produced in the Zonba reticularis; however, in males, most testosterone is synthesized in the testes
- Little testosterone production in the female ovaries
What does cortisol regulate in the body?
- Mediate the stress response
- Help regulate metabolism
- Help regulate the inflammatory process
- Help regulate the immune system
When is cortisol released? What does it help restore?
Cortisol is released in response to stress and also helps to restore hormone levels when stress resolves
Describe the physiologic pathway of short term stress?
Hypothalmus –> Nerve Impulse –> Spinal Cord –> Preganglionic Symapthetic Fibres –> adrenal Medulla (Secretes amino-acid based hormones) –> Catecholamines (epinephrine and norepinephrine)
What is the physiologic response of short term stress?
- Increased heart rate
- Increased blood pressure
- Liver converts glycogen to glucose and releases glucose to blood
- Changes in blood floe patterns leading to decreased digestive system activity and urine output
- Increased metabolic rate
- bronchodilation
Describe the physiologic pathway of prolonged stress?
Stress –> Hypothalamus –> CRH (corticotropin-releasing hormone) –> Corticotroph cells of anterior pituitary –> ACTH –> Adrenal Cortex ( secretes steroid hormones) –> Releases Mineralcorticoids and Glucocorticoids
In the long term stress response, mineralcorticoids function to:
Retention of sodium and water by kidneys
Increased blood volume and blood pressure
In long term stress, glucocorticoids function to:
- Proteins and fats converted to glucose or broken down for energy (muscle wasting)
- Increased blood glucose
- Suppression of the immune system
What controls the production and secretion of cortisol?
HPA Axis
What is the main function of the HPA axis?
Control the production and secretion of cortisol by the hypothalamus-pituatary-adrenal (HPA) axis
Describe the HPA axis pathway?
Circadian Regulation and/or stressors (hypoglycemia, hypotension, surgery, fever, injury)
V
Hypothalmus
V
Pituatary (acted on by vasopressin and pro-inflammatory cytokines)
V
ACTH
V
Adrenals
V
Cortisol (exhibits negative inhibition on the hypothalamus and pitautary to inhibit cortisol release)
In the HPA axis pathway, cortisol exhibits ________ on the pitauatary and hypothalmus to…..
Negative Inhibition
- Inhibits its own release, when cortisol levels are high, the cortisol inhibits further production
What are the main actions of glucocorticoids?
They suppress inflammatory and immunological responses
Describe the basics of inflammation? What are its purposes?
- Inflammation is a process whereby WBC’s and other mediators protect against foreign substances
- The inflammatory process serves several purposes initially (e.g. removal of damaged cells) but may eventually become counterproductive (e.g. edema impedes blood flow)
Describe the inflammatory response
Stimulus –> Antigen-Antibody Response
V V
Release of Inflammatory Mediators
and
Cell Mobilization –> Increased Capillary Permeability
V V
Edema, Erythema, and Pruritis
How do corticosteroids exert an anti-inflammatory effect? (Specific)
- Alter cytokine release
- Blocking increased capillary permeability
- Causing less vasoactive substance release
- Inhibits leukocyte and macrophage migration/adhesion
- Interfering with phagocytosis
When corticosteroids are used pharmacologically, they exert an anti-inflmmatory response by….. (Basic)
- Impede the inflammatory process
How do corticosteroids exhibit immunosuppressive effects? (specific)
- Alter the cell function of specific genes
- Affect the function of WBC’s
- Inhibit T-cell activation
- Inhibit IL’s, cytokines, gamma-interferon, and TNF-alpha synthesis
What are the actions of corticosteroids?
Anti-inflammatory
Immunosuppressive
Anti-mitotic
Anti-tumour
Anti-emetic
How do corticosteroids exhibit anti-mitotic activity? When is this useful?
Inhibit DNA synthesis and epidermal cell turnover
- Useful in psoriasis
How do corticosteroids exhibit anti-tumour effects? When is this useful?
May be related to inhibition of glucose transort or induction of cell death in immature lymphocytes
- useful in cancer (used in certain chemo regimens)
How do corticosteroids exhibit anti-emetic effects? When would this be beneficial?
May be due to a blockade of cerebral innervation of the emetic center
- Block the emetic effects of chemo therapeutic agents
In asthma, what is the standard of care?
Inhaled corticosteroids
In atopic dermatitis, what is the standard of care?
Topical corticosteroids
In transplant induction, what is standard of care?
All will use a corticosteroid
In rheumatoid arthritis, how many in % will a corticosteroid?
- 30-40% will use (up to 75% will use at some time in their life)
What are the two types of corticosteroid dosage forms? Examples?
Local Agents:
- Otic
-Opthalmic
-Inhaled
-Topical
Systemic Agents:
- Injectables
-Oral
Why would you want to use an agent locally as opposed to systemically?
Fewer side effects
Opthalmic and Otic corticosteroids are available as…..
Drops, ointments, emulsions and intravitreal implants
In regards to the eyes and ears, corticosteroids often come in combination with…..
Anti-biotics
Opthalmic/Otic corticosteroids are used for:
Redness, itching, swelling and pain
What is the main issue with opthalmic and otic eye drops?
Correct delievery technique
Nasal Inhaled steroids uses:
Rhinitis
Polyps
Sinusitis
What is an issue with inhaled nasal corticosteroids?
Installation technique
What are the pros and cons of metred-dose inhalers?
Pros - Portability
Cons - Inhalation technique
- Always guessing how many doses are left
What are some device pros and cons with dry powders for inhalation?
Pros:
Actuation
Portable
Shows remaining doses
Cons:
Powder despostion in mouth
requires good lung function
Age restrictions (large strong deep breth, children often can’t do this)
What is a combo inhaled product composed of? When are they often used?
Corticosteroid and Beta-2 Adrenergic Agonist (LABA)
- Often used in COPD
Solutions for inhalation are referred to as:
Nebulizers
What is an example of a solution for inhalation?
Budesonide
What are some pros of nebulizers?
Reasonable lung delievery when cannot generate sufficient flow rate
Easy for infants (mask)
Young Children
What are some cons of nebulizers?
Time consuming (10-15 min/dose)
Expensive
Non-portable equipment
False sense of superiority
What are the topical corticoidsteroids dosage forms? What is the rating of their strengths/potency?
Lotions < Creams < Gels < Ointments
When are lotions most useful?
Least occlusive, non-greasy
- Useful for axillia, foot, groin, large, hairy areas and acute weeping lesions
When are creams useful?
Medium occlusion
- Cosmetically most acceptable
Suitable for non-acute/wet lesions, intertriginous areas (skin folds)
When are gels useful?
Non-greasy, non-occlusive
- Quick drying, can apply to face, hairy areas
- Do not leave residue, useful on scalp or hairy areas
- Irritating
When are ointments useful?
Most occlusive
- Greasy; for very dry, scaly or hyperkeratized skin area, palms and soles
What is the rating scale of corticosteroids? What does each category indicate for usage?
Potency - Scale of 1 -7
Group 1 - Ultra-high Potency
Group 2,3 - High Potency
–> Generally limit to daily-BID dosing and limit length of therapy
–> Avoid use on large areas, thin skin areas, skin folds, and face
–> Caution in young children/infants
–> Suitable for short term intermittent usage (< 2-4 week usage)
Group 4,5 - Mid-potency
–> Suitable for intermittent long-term usage
–> Chronic use in thick skin areas is suitable
–> Avoid on thin skin areas (e.g. face)
Group 6,7 - Low potency
–> Safest in infants, children and elderly or for larger areas or higher risk areas (e.g. face, perianal, eyelids)
–> Caution still required
–> Suitable for maintenance of chronic conditions after initial control obtained
–> often applied BID-QID, less frequent (OD -BID) if ongoing
What are the main corticosteroid creams and their respective potency?
Clobetasol propionate 0.05% - 1
Betamethasone Dipropionate 0.05% - 3
Betamethasone Valerate 0.1% (Fucibet: beta 0.1% + fuscidic acid 2%) - 5
Hydrocortisone 2.5% (1% and 0.5% OTC) - 7
What are the main corticosteroid ointments and their respective potency?
Clobetasol propionate 0.05% - 1
Betamethasone dipropionate 0.05% - 2
Betamethasone Valerate 0.1% - 3
Betamethasone Valerate 0.05% - 5
Hydrocortisone (1% or 0.5 % OTC) - 7
What are the main corticosteroid lotions/solutions and their respective potency?
Clobetasol Propionate (0.05% Scalp Lotion, 0.05% topical spray) - 1
Betamethasone Dipropionate 0.05% Lotion - 3-5
Betamethasone Valerate (0.1% Scalp lotion, 0.1% lotion, 0.05% lotion) - 5-6
Non-steroidal corticosteroids:
Tacrolimus, Pimecrolimus - Calcineurin Inhibitor
Crisaborole 2% oint - PDE0- 4 Inhibitor
Roflumilast 0.3% - PDE0-4 Inhibitor
What factors influence the cutaneous penetration of corticosteroids?
- Moisture of skin (more absorbed when wet)
- Heat
- Potency of the steroid
- Dosage form
What are some forms of dosage forms used for rectal usage? What factor is important in considering what dosage form to use? What sx are they used to tx?
Enemas, Rectal ointments, supposoitories, rectal foams
- Depends on how far you need to go into the colon (ulcerative cholitis vs hemmrhoids)
- For inflammation, itching and discomfort
What are the common corticosteroids for enemas?
- Betamethasone
- Budesonide
- Hydrocortisone
What is the common corticosteroid for rectal ointments?
Hydrocortisone