glucocorticoids

what are glucocorticoids?

a class of steroid hormones (corticosteroids) that help regulate functions and processes such as metabolism, immune functions and the body’s response to stress. they are produced naturally by the adrenal glands, which sit on top of the kidneys

what is an example of a endogenous glucocorticoid?

cortisol, which is the main glucocorticoid in humans

what is an example of exogenous glucocorticoids?

1. prednisone

2. prednisolone

3. dexamethasone

4. hydrocortisone

what is the adrenal gland divided into?

1. adrenal cortex, which makes up 80% of adrenal gland weight, outer layer

2. adrenal medulla, which makes up 20% of adrenal gland weight, inner layer

what does the adrenal cortex consist of?

3 zones, which are:

1. zona glomerulosa (outermost) subcapsular

2. zona fasciculata (middle)

3. zona reticularis (inner zone)

what does zona glomerulosa produce?

mineralocorticoids, with the main one being aldosterone

what does zona fasiculata produce?

produces glucocorticoids with the main one being cortisol

what does zona reticularis produce?

androgen and small amounts of estrogen (sex hormones)

what does adrenal medulla produce?

epinephrine (adrenaline) and norepinephrine (noradrenaline), known as catecholamines

what happens to the zona fasiculata if glucocorticoids are used for a prolonged time?

it will stop working effectively, becoming suppressed (atrophied and less functional), causing adrenal suppression. requires more than two weeks of chronic use

what is mechanism of action of corticoidsteroids?

they bind first to cell surface receptors, then to cytoplasmic receptors, or carries, then they are transported to the nucleus where it interacts with many DNA receptors, affecting their function. it is a negative feedback loop

what happens if a patient takes prednisone for a prolonged time?

body receives glucocorticoids from outside (exogenous) → blood glucocorticoids increase → the body then responds to this through negative feedback. repeat use will make natural production weaker

what are dental clinics considered to be?

procedures such as extractions are considered to be stressful situations. make sure to take good drug history and medical history prior to any procedure to verify if the patient takes any glucocorticoids

if a patient takes glucocorticoids and comes for an appointment, what must be done in dental clinics?

a medical consultation must be done. if it is found they are a chronic user of glucocorticoids, double their standard dose prior to a procedure such as extraction. for example, a 60 mg (1 pill) dose would be doubled to 120 mg (2 pills)

what is the anti inflammatory potency of hydrocortisone?

1

what is the anti inflammatory potency of cortisone?

0.8

what is the anti inflammatory potency of prednisolone?

4

what is the anti inflammatory potency of triamclonolone?

5

what is the anti inflammatory potency of dexamethasone?

30

what is the anti inflammatory potency of betamethasone?

30

what is the Na⁺-retaining potency of hydrocortisone?

1

what is the Na⁺-retaining potency of cortisone?

0.8

what is the Na⁺-retaining potency of predinsolone?

0.3

which glucocorticoids do not cause any sodium retention?

triamcinolone, dexamethasone and betamethasone all have a Na retaining potency of 0

which glucocorticoids have a short duration?

• hydrocortisone

• cortisone

• prednisolone

which glucocorticoids have an intermediate duration?

triamcinolone

which glucocorticoids have a long duration?

• dexamethasone

• betamethasone

which glucocorticoid is kept in dental clinics for emergencies?

hydrocortisone, as it helps with adrenal crisis and severe allergic reactions such as anaphylaxis. it is used due to the fact it raises blood pressure and sugar

what is the absorption of glucocorticoids like?

all glucocorticoids are completely and rapidly absorbed by all routes

what is the distribution of hydrocortisone like?

• 85% binds to a plasma protein called corticosteroid-binding globulin (CBG or transcortin).

• About 10% binds to albumin.

• Only about 5% remains free, and this free fraction is the active form that can enter cells and produce effects.

what is the half life of hydrocortisone like?

the plasma half life is about 60–90 minutes, meaning half of the drug is removed from the bloodstream within this time, however, its duration is prolonged due to its effect on gene functions

what are some pharmacological effects of glucocorticoids?

it effects the metabolism, immune system, cardiovascular system, it has hematological and CNS effects. it also affects the eyes, bones and growth and development

how do glucocorticoids affect metabolism?

they increase blood sugar (hyperglycemia) by decreasing peripheral glucose utilization

how do glucocorticoids affect protein metabolism?

they increase proteolysis (destruction of protein), so it decreases muscle mass and causes thin limbs

how do glucocorticoids affect fat metabolism?

they increase lipolysis and then redistributes the fat to the center of the body

how do glucocorticoids affect the water and electrolyte balance?

it causes sodium-water retention, and causes hypokalemia (low potassium), which causes edema and hypertension

what are some examples of glucocorticoids?

1. hydrocortisone

2. cortisone

3. prednisolone

4. betamethasone

5. dexamethasone

what are some immunologic effects of glucocorticoids?

they have anti immunological and inflammatory effects by:

• inhibiting B cell function, so it decreases antigen-antibody reaction

• inhibiting T cell function, so it decreases inflammatory mediators and cytokine release

• inhibiting macrophage activity and stabilizing lysosomal membranes

• inhibiting mast cells so it decreases histamine release and capillary permeability

• inhibiting phospholipase A2 enzymes, so it decreases the synthesis of prostaglandins

what makes glucocorticoids so good for allergies?

they inhibit mast cells, which decreases histamine release and capillary permeability

what makes glucocorticoids so good for organ transplant recipients?

since they inhibit B and T cell function, it decreases the chance of rejection. essentially, they work as immunosuppressants

what are some cardiovascular effects of glucocorticoids?

• hypertension due to sodium-water retention. occurs only if the glucocorticoid has mineralocorticoid effects

• anti-shock effects due to hypertension and improving the function of the CVS

what are some therapeutic uses of glucocorticoids?

1. inflammatory diseases

2. autoimmune diseases

3. allergic diseases such as urticaria and branchial asthma

4. organ transplantation to aid against rejection

5. as replacement therapy as in addison’s disease in adrenocortical insufficiency disease

6. shock and hypotension

7. malignancy

8. cerebral edema

9. stimulation of lung maturation in the fetus

for replacement therapy for conditions such as addison’s disease, which glucocorticoid is preferred?

hydrocortisone

for shock and hypotension, which glucocorticoid is preferred?

hydrocortisone

for stimulation of lung maturation in the fetus, which glucocorticoid is used?

dexamethasone

how is dexamethasone administered to pregnant women expecting a premature delivery and need to stimulate lung maturation in the fetus?

6mg via I.M or I.V every 12 hours for 3 or 4 doses

what are some adverse effects of glucocorticoids?

• iatrogenic cushing syndrome

• immune suppression

• hypertension due to sodium-water retention

• hyperglycemia

• peptic ulcer

• increases intraocular pressure (IOP) or glaucoma

• osteoporosis

• growth retardation in children

• depression

• teratogenic effects, can cause cleft palate, not recommended in early pregnancy

• skin atrophy

• sudden withdrawal causes adverse effects

what is Iatrogenic Cushing syndrome?

a hormonal disorder caused by the prolonged use of high-dose glucocorticoid medications. occurs when glucocorticoid such as hydrocortisone is taken 100mg daily for more than two weeks

what happens if a patient suddenly withdraws from glucocorticoids after prolonged use?

• hypopigmentation in prolonged topical

• acute Addisonian crisis

it must be tapered off slowly or else severe withdrawal will occur

what is acute Addisonian crisis?

a life-threatening medical emergency caused by a severe deficiency of the hormone cortisol

how can prolonged use of glucocorticoids cause osteoporosis?

they decrease bone matrix, increase calcium excretion, leaving the bones soft and fragile, which is something to be considered in dentistry

what are some relative contraindications of glucocorticoids?

1. can worsen diabetes mellitus or trigger uncontrollable hyperglycemia

2. hypertension due to water-sodium retention and can cause heart failure in high risk patients

3. peptic ulcer as they decrease the synthesis of PGE2, which protects the stomach

4. high doses during first trimester may slightly increase the risk of cleft palate in the developing fetus

what is the best way for glucocorticoids to be administered?

in the morning, as it mimics the body’s physiological releasing cortisol naturally in the morning

what is a new, suggested way of administrating glucocorticoids?

alternative-day therapy, where it is taken every other day rather than every day, to try and prevent natural cortisol production from being impacted

what are some common physical indications of chronic glucocorticoid use?

• moon face

• thinning hair

• thin limbs with central obesity

• buffalo hump

prednisone can be used to treat anti-inflammatory diseases, true or false?

true

hydrocortisone can be used to treat autoimmune diseases, true or false?

false, it is preferred for short-term emergency use or hormone replacement

glucocorticoids can also be used to treat allergy diseases, true or false?

true

uses and side effects of dexamethasone

• given via IV (slowly) or IM

• relives inflammation (swelling, heat, redness and pain)

• long-acting and considered a potent, or strong steroid

• can be used to prevent respiratory distress syndrome (RDS) in fetuses by giving it to pregnant women at risk for premature delivery

• can cause hyperglycemia

• it, along with other glucocorticoids for patients with severe or critical COVID-19 who required supplemental oxygen or mechanical ventilation.

which glucocorticoid has been found to help with postoperative pain, edema and trismus following mandibular third molar surgery?

dexamethasone via submucosal, due to it being a potent, long-acting glucocorticoid