Endocrinology Flashcards
Adrenal Gland
Comprised of adrenal cortex and adrenal
medulla
◦ Inner –
◦ Outer –
Adrenal cortex produces about –
different chemicals
Those with pharmacologic properties:
(3)
medulla
secretes catecholamines
cortex
secretes adrenal steroids
50
Mineralocorticoids
Glucocorticoids, cortisol
Androgens
3 layers within cortex
◦ zona glomerulosa: produces —
◦ zona fasciculata produces —
◦ zona reticularis: produces — hormones, mostly
— and small amount of —
mineralocorticoids
glucocorticoids
sex, androgens, glucocorticoids
Mineralocorticoids (produced in zona glomerulosa)
Regulate water and electrolyte balance
(2)
◦ Sodium (Na +), Potassium (K+) and fluid balance
◦ Provide important homeostatic functions
Mineralocorticoids
Aldosterone – main endogenous hormone
(2)
◦ essential for blood pressure regulation and electrolyte and fluid
homeostasis - helps to maintain normal blood pressure and
electrolyte balance
◦ acts on the Mineralocorticoid Receptor (MR)
◦ acts on the Mineralocorticoid Receptor (MR)
(3)
MR present in kidneys impacts fluid and electrolyte balance
Extra-renal MR plays a relevant role in the control of cardiovascular and
metabolic functions
Overactivation of the MR is implicated in the pathophysiology of aging related
to cardiovascular, metabolic and kidney dysfunction and progress of disease
Aldosterone Basics
(3)
Increases Na+ reabsorption by distal tubules in kidney
with concomitant increased excretion of K + and H +
Increases BP and blood volume – balance/control the
amount of sodium and fluids in the body
Work on specific intercellular receptors in kidney
Pharmacotherapeutic use of medications involving
mineralocorticoid effects
(2)
Replacement therapy Addison’s Disease/Adrenal
Insufficiency
◦ Fludrocortisone (Florinef) - mineralocorticoid
Replacement therapy Addison’s Disease/Adrenal
Insufficiency
◦ Addison’s Disease (autoimmune disease)/Adrenal Insufficiency –
adrenal do not produce enough of the steroid hormones, cortisol
and aldosterone.
◦ Fludrocortisone (Florinef) - mineralocorticoid
(4)
Functionally similar to aldosterone
Most mineralocorticoid effect of available steroids
Other steroids have much smaller amounts of mineralocorticoid effects
(example: hydrocortisone, prednisone) or no mineralocorticoid effects
(example: dexamethasone, methylprednisolone)
Other indications: orthostatic hypotension, septic shock
Drugs that Inhibit Aldosterone
Imbalances in
aldosterone and overactivity of the mineralocorticoid
receptor contribute to hypertension, kidney insufficiency, heart failure
and potentially other cardiovascular disease
◦ Due to idiopathic adrenal hyperactivity (most common) or benign tumor (Conn’s
syndrome)
Spironolactone (Aldactone) and Eplerenone (Inspra)
(4)
Common Indications:
(3)
competitive aldosterone antagonist at receptor sites in distal renal tubules (block higher
concentration of kidney-specific MR), increasing sodium chloride and water excretion while
conserving potassium and hydrogen ions – prevents mineralocorticoid effects of adrenal steroids on
the renal tubule
Steroidal structure
Also known as a potassium sparing diuretic
Hyperaldosteronism (secondary cause of hypertension and causes low potassium)
Heart failure
Hypertension
Drugs that Inhibit Aldosterone (Non-steroidal)
Finerenone (Kerendia)
(4)
◦ Blocks Mineralocorticoid receptor (MR) in kidney and heart
◦ Selectively blocks (antagonist) mineralocorticoid receptor-mediated
sodium reabsorption and overactivation of kidney, blood vessel, and heart
tissues, reducing fibrosis and inflammation
◦ MR overactivation is an important factor associated with CV events and
Chronic Kidney Disease (CKD) progression
Drugs that Inhibit Aldosterone (Non-steroidal)
Finerenone (Kerendia)
◦ Indications:
Chronic kidney disease (CKD) associated with type 2 diabetes
to reduce the risk of kidney function decline, kidney failure,
cardiovascular death, non-fatal heart attacks, and hospitalization for
heart failure in adults with type 2 diabetes and chronic kidney disease
Glucocorticoids (endogenously produced in zona fasciculata)
Mechanism of action –
complex: work through specific
glucocorticoid intracellular receptors to regulate several vital cell
activities
◦ Metabolic
◦ Immune function
Glucocorticoids (endogenously produced in zona fasciculata)
Widespread actions on intermediate metabolism, affecting
(3) metabolism
Potent regulatory effects on host defense mechanisms including
(2) function
◦ Glucocorticoid receptors up regulate expression of anti-
inflammatory proteins and down regulate expression of pro-
inflammatory proteins
carbohydrate (glucose), protein and fat
inflammation and immune
Glucocorticoids = Corticosteroids
Main endogenous hormone in humans
– hydrocortisone
(also called cortisol)
◦ Produce 24-30 mg endogenous hydrocortisone/cortisol
◦ Use up to 300 mg/day in times of significant stress
Secreted in circadian rhythm in healthy humans
◦ highest concentrations in early morning
HPA Axis Pathway:
◦ Hypothalamus releases Corticotrophin-Releasing Hormone [CRH]
◦ Adrenocorticotropic hormone [ACTH] released from the anterior
Pituitary
◦ Adrenals release glucocorticoids
◦ Negative feedback mechanism to inhibit CRH and
ACTH when glucocorticoid concentrations increase in the
blood
Therapeutic Use of Corticosteroids
Many have partial mineralocorticoid
and glucocorticoid properties
Most are used for anti-inflammatory
and immunosuppressive properties
Common indications:
(5)
◦ Addison’s disease/Adrenal
Insufficiency (deficiency in
corticosteroid production)
◦ Cancer therapy (usually in
combination with cytotoxic drugs or
to reduce edema in brain tumors)
◦ Anaphylaxis (use in combination with
epinephrine, antihistamines – note:
steroids have slow onset)
◦ Hypersensitivity states (severe
allergic reactions)
◦ Shock
Therapeutic Use of Corticosteroids
Common indications, continued:
(7)
◦ Autoimmune disease
Systemic Lupus Erythematosus
Rheumatoid arthritis
Inflammatory bowel disease
Connective Tissue Diseases
◦ Asthma (inhaled)
◦ Chronic obstructive pulmonary disease
(inhaled)
◦ Respiratory distress syndrome in infants
◦ Suppressing rejection of skin grafts or graft-
versus-host disease following organ transplant
◦ Acute renal insufficiency
◦ Inflammatory conditions of eyes, ears, nose or
skin /rashes of the skin (topical application)
Use of Steroids in Dentistry
(7)
Use for anti-inflammatory, pain management and auto-immune
properties
Oral lesions
Restorative dentistry/pain management
Bell’s palsy
Post herpetic neuralgia
Temporomandibular joint disorder
Temporal arteritis
Oral lesions
(7)
◦ Aphthous ulcers/stomatitis
◦ Oral lichen planus
◦ Erythema multiforme
◦ Behcet’s disease
◦ Pemphigus
◦ Bullous pemphigoid
◦ Systemic lupus erythematosus
Formulations of Corticosteroids
Dental (topical oral) applications
◦ Pastes, ointments/orabase, gels, lozenges, intralesional therapy, rinses – commercially
available or compounded
◦ Importance of contact time with lesion
◦ Example of commercially available product:
Kenalog® in Orabase® / Triamcinolone Dental Paste
◦ Patient education:
* Using a cotton swab, press (do not rub) a small amount of paste onto the area to be treated
until the paste sticks and a smooth, slippery film forms. Do not try to spread the medicine
because it will become crumbly and gritty.
* (Usually applied 2-3 times per day – see dosing information of the product). Apply the paste at
bedtime so the medicine can work overnight. The other applications of the paste should be
made following meals.