Steroidal Anti-inflammatories

Describe the basic functional structure of the adrenal gland.

-capsule

-cortex

>Zona Glomerulosa --> produces mineralocorticoid

>Zona Fasciculata --> produces glucocorticoid

>zona reticularis --> produces androgens

-Medulla --> catecholamines

chromaffin cells

neuroendocrine cells w/in the adrenal medulla that release catecholamines (epinephine/adrenaline, norepinephrine/noradrenaline)

Describe the Hypothalamic-Pituitary-Adrenal Axis

Hypothalamus releases corticotropin releasing hormone (CRH) --> stimulates anterior pituitary gland to release adrenocorticotrophic hormone (ACTH) --> stimulates the adrenal gland to release cortisol

*regulated via negative feedback ==> increased cortisol inhibits release of CRH from hypothalamus

Mineralocorticoid

corticosteroids released from the zona glomerulosa of adrenal cortex ==> regulates Na+/water & K+ retention/excretion

Glucocorticoid

corticosteroids released from the zona fasciculata of adrenal cortex

-changes carbohydrates & protein metabolism

-fat redistribution

-suppression of inflammation, immune function, & allergy response

-mood changes

-alters calcium absorption & excretion

-reduces the growth of new cells --> not recommended to prescribe to kids

Why shouldn't glucocorticoids be prescribed to children to manage inflammation?

b/c glucocorticosteroids reduces the growth of new cells (thus they stunt the growth of kids)

What is the body's immediate response to stress?

sympathomedullary pathway ==> hypothalamus activates adrenal medulla --> releases adrenaline & noradrenaline into bloodstream --> fight or flight; reinforces the pattern of sympathetic activation -->>> energy

What is the body's response to chronic stress?

Hyp-pit-adrenal axis ==> higher brain centers activate hypothalamus --> hypothalamus releases corticotrophin (CRF) --> pituitary gland releases adrenocorticotrophic (ACTH) --> adrenal cortex releases corticosteroids -->>> increased metabolic rate, increased Na+/water retention, & blood vessels more responsive to NE

Adrenal Insufficiency

disorders in which the adrenal glands do not produce enough corticosteroids ==> Adrenal Crisis due to mineralocorticoid & glucocorticoid deficiency

*glucocorticoid deficiency ==> low or absent cortisol --> decrease in liver function + decrease in stomach enzymes --> extremely low blood sugar + vomiting, diarrhea, cramps + low fluid volume --> shock --> coma &/or brain death

* mineralocorticoid deficiency ==> low/absent aldosterone --> Na+/water loss from kidneys + heart irregular + decreased cardiac output --> low fluid volume + low blood pressure --> shock --> coma &/or brain death

ex: Addision's Disease

Addision's Disease

adrenal insufficiency disease due to autoimmunity against adrenal glands ==> extremely decreased glucocorticoids & mineralocorticoids --> extremely low blood sugar, blood pressure, blood volume -->>> coma & death

What are the effects of glucocorticoid deficiency?

low or absent cortisol --> decrease in liver function + decrease in stomach enzymes --> extremely low blood sugar + vomiting, diarrhea, cramps + low fluid volume --> shock --> coma &/or brain death

What are the effects of mineralocorticoid deficiency?

low/absent aldosterone --> Na+/water loss from kidneys + heart irregular + decreased cardiac output --> low fluid volume + low blood pressure --> shock --> coma &/or brain death

Corticosteroid Excess

syndromes characterizes by overactive adrenal cortex (hyper secretion of corticosteroids)

*symptoms (CUSHINGOID)

-cataracts

-ulcers

-dermal thinning, red straie (red stretch marks)

-hypertension, hyperglycemia

-infections --> c.steroids are immunosuppressant

-avascular necrosis

-glycosuria

- osteoporosis & obesity --> characteristic dorso cervical fat pad = buffalo hump

-immunosuppression

-diabetes

Cushing Syndrome

corticosteroid disease due to pituitary gland tumor ==> hyper stimulation of adrenal cortex --> hyper secretion of c.steroids

How are corticosteroids classified?

-duration of action

>short acting --> hydrocortisone, cortisone

>intermediate-acting --> prednisone, triamcinolone, methylprednisone

>long-acting --> dexamethasone & betamethasone

-activity

>both glucocorticoid & mineralocorticoid activity --> hydrocortisone & cortisone

>only glucocorticoid activity --> prednisone & dexamethasone

-potency (as compared to hydrocortisone)

>dexamethasone 25x more

>prednisone 4x more

>methylpredisolone 5x more

>hydrocortisone 1x more

How is hydrocortisone classified?

-short-acting corticosteroid

-has both glucocort & minerolcort activity

-has the same potency has hydrocortisone

How is cortisone classified?

-short-acting corticosteroid

-has both glucocort & minerolcort activity

-has the standard potency that all other c.steroids are compared to

How is prednisone classified?

-intermediate-acting corticosteroid

-only has glucocorticoid activity

-4x as potent as hydrocortisone

How is methylprednisone classified?

-intermediate-acting corticosteroid

-5x potent as hydrocortisone

How is dexamethasone classified?

-long-acting corticosteroid

-only has glucocorticoid activity

-25x has potent as hydrocortisone

How is betamethasone classified?

long-acting corticosteroid

Therapeutic Uses of Corticosteroids

-corticosteriod replacement (Tx adrenal insufficiencies)

-arthritis

-asthma

-inflammatory bowel disease

- non- infectious various skin conditions --> can't use on skin infection b/c c.steroids are immunosuppressant & will make the infection worse

-immunosuppression

-allergy

-antiemetic --> stop vomiting

What is the mechanism of action of analgesic & antipyretic effects of corticosteroids?

inhibits the synthesis of prostaglandins & leukotrienes ==> inhibits phospholipase A2 from converting phospholipid into arachidonic acid (a. acid is metabolized to prostaglandins & leukotrienes

How are corticosteriods anti-inflammatory & immunosuppressive?

-stabilize lysozyme membranes

-decrease the release of inflammatory mediators

-decrease capillary permeability

-interfere w/ complement pathway activation

-interfere w/ formation of inflammatory mediators

Dental Uses of Corticosteroids

-systemic steroids --> oral lesions due to noninfectious inflammatory disease, 3rd molar EXT, for minor/major surgeries to reduce edema, pain, trismus (can't open the mouth), & TMJ disorder

-topical steroids--> noninfectious ulcerative diseases in oral cavity, inhibit inflammatory rxn, decrease redness & edema

Synalar and Lidex

topical steroid paste used in dentistry to treat noninfectious ulcerative diseases in oral cavity, inhibit inflammatory rxn, decrease redness & edema

What are some major side effects of corticosteroids that are directly applicable to dental care?

-bigger dose of c.steroids needs to be prescribed to Tx oral/dental related inflammation in patients who have been taking steroids within the past year ==> b/c pt's have already been taking steroids, they have stopped producing endogenous steroids via negative feedback (hyp-pit-ad axis regulation) --> won't produce own cortisol due to stress of dental procedure --> will need higher dosing of steroid prescription to manage inflammation (give high dose prior to procedure or right after & then taper down to normal maintenance dose)

-immunosuppression==> pts on c.steroids have decreased immunity = higher risk of infection. Pts who take steroids will need antibiotic therapy before/following oral surgical procedures

-suppression of beneficial inflammatory process ==> slow wound healing post dental/oral surgical procedures & suppressed inflammatory response may mask early symptoms of disease = interfere w/ proper diagnosis

True or False: Patients who have been routinely taking steroids will require less corticosteroid therapy to manage inflammation prior to major dental procedures.

False ==> bigger dose of c.steroids needs to be prescribed to Tx oral/dental related inflammation in patients who have been taking steroids within the past year b/c pt's have already been taking steroids, they have stopped producing endogenous steroids via negative feedback (hyp-pit-ad axis regulation) --> won't produce own cortisol due to stress of dental procedure --> will need higher dosing of steroid prescription to manage inflammation (give high dose prior to procedure or right after & then taper down to normal maintenance dose)

True or False: A Patient who has stopped routinely taking corticosteroids 6 months ago still does not have fully normal functioning adrenal glands

True ==> if taking steroids within the past year, patients have stopped producing endogenous steroids via negative feedback (hyp-pit-ad axis regulation)

*adrenal fxn won't return to normal until up to a year after cessation of steroid therapy

What are some precautions dentists should consider when prescribing corticosteroids regarding their immunosuppressive action?

-pts taking steroids may have increased susceptibility to infection ==> may be necessary to provide antibiotic therapy for pts on long term steroids when an oral surgical procedure is planned

-pre-existing minor or superficial infections may become systemic

-quiescent infections may become active (ex: contraindicated in patients w/ latent TB)

-a normally nonpathogenic organism may cause systemic disease

-use of corticosteroid inhalers associated w/ increased occurrence of oral candida

What are some precautions dentists should consider when prescribing corticosteroids regarding their anti-inflammatory action?

-suppression of beneficial inflammatory process ==> slow wound healing post dental/oral surgical procedures & suppressed inflammatory response may mask early symptoms of disease = interfere w/ proper diagnosis

What are some general considerations regarding corticosteroid use?

-multiple adverse side effects due to wide ranging effects & potencies of these drugs ==> limit use to emergency use & short-term therapy at the smallest effective dose (should opt to use NSAIDs when possible)

-do not prescribe as analgesic (due to side effects)