Corticosteroids and Dentistry

Hard work beats talent

              when talent doesn’t work.

Steroids beat hard work

                        no matter how hard talent works!!

 

A diverse group of hormones responsible for the metabolic control or body’s response to stress is produced by the adrenal gland. The medullary portion of the adrenal gland secretes epinephrine and norepinephrine while the cortex produces a number of substances, collectively termed as CORTICOSTEROIDS.

The Historical aspect……..

It was only by the middle of the 19th century when the adrenal glands were demonstrated as essential for life. The importance of cortex as compared to that of the medulla was deciphered lately in the literature. Kendall and his co-workers isolated a number of steroidal active principles and elucidated the structural aspect in the 1930s. However, the gate to their great therapeutic potential was opened by Hench (1949) who obtained striking improvement in rheumatoid arthritis by using cortisone. The Nobel Prize was awarded the very next year to Kendall and Hench. Currently, corticosteroids are drugs with one of the broadest spectrum of clinical utility.

Classifying the steroids…  

  1. General classification
    1. Adrenal Cortical Steroids
      1. Mineralocorticoids: Fudrocortisone, Desoxycorticosterone
      2. Glucocorticoids: These are classified based on origin and duration of action
        1. Based on origin
          1. Natural: Cortisol
          2. Synthetic: Prednisolone, Triamcinolone
        2. Based on duration of action
          1. Short acting: Cortisone, Hydrocortisone
          2. Intermediate acting: Prednison, Prednisolone, Methylprednisolone, Triamcinolone
          3. Long acting: Betamethasone, Dexamethasone, Paramethasone
      3. Adrenal Androgens
    2. Sex hormones
      1. Androgens: Danazol, Fluoxymesterone, Nandrolone, Stanozolol,         Testosterone cypionate
      2. Progestins: Hydroxyprogesterone, Medroxyprogesterone, Norethindrone, Norgestrel
      3. Antiprogestins: Mifeprostone
      4.   Estrogens: Chlortrianisene, Diethylstilbesterol, Estradiol, Estriol, Estrone, Ethinyl estradiol, Mestranol, Quinestrol
      5. Selective estrogen modulators: Raloxifene
      6. Anti-estrogens: Clomiphene, Tamoxifen
  2. According to relative potency of corticosteroids
    1. On sodium retention
    2. Anti-inflammatory effects 

Secretion of the hormones…….

Catecholamines including adrenaline and nor-adrenaline are secreted by the inner medulla. The outer cortex secretes diverse range of steroid hormones which includes glucocorticoids and mineralocorticoids.

 

Steroid Class Prototype Physiological effect
Mineralocorticoid Aldosterone (z.glomerulosa) Na, K and water homeostasis
Glucocorticoid Hydrocortisone or Cortisol (z.fasiculata) Glucose and many other homeostasis

 

Zone of Adrenal Cortex

Hormones
Zona glomerulosa Aldosterone, Desoxycorticosterone
Zona Fasiculata Cortisone, Cortisol
Zona Reticularis Dehydroepiandrosterone, Androstenidione, Traces of estrogens

 

Glucocorticoids is secreted in the range of 10-20 mg daily and Mineralocorticoids 0.125 mg daily. Hypothalamus (CRH) and Pituitary (ACTH) regulates the corticosteroid secretion through negative feedback mechanism. Pulsatile secretion of ACTH is based on the Circadian rhythm while the neural effects of HPA axis is due to emotional/physical stress as in hypoglycaemia or any physical stress.

The corticosteroids are degraded mainly in the liver. They conjugate to form glucuronides on a larger scale and to a lesser extent form the sulphates. 25% of all the corticosteroids are excreted in bile faeces and 75% in urine.

Uses of corticosteroids…..

The corticosteroids have a wide range of uses both in the medicine and dentistry.

In medicine: Broadly, steroids found two main uses in medicine, i.e., replacement therapy and the pharmacotherapy.

Replacement therapy-

  1. Acute adrenal insufficiency: The intravenous injections of Hydrocortisone or Dexamethasone are first given as a bolus injection and then as infusion along with isotonic saline and glucose solutions.
  2. Chronic adrenal insufficiency: Oral preparation of Hydrocortisone along with adequate salt and water allowance is given.
  3. Congenital adrenal hypoplasia: Here, the corticosteroids are given as 0.6 mg/kg daily in divided doses round the clock.

Rule of twos

            The “rule of twos” states that adrenal suppression may occur if a patient receiving invasive dental treatment is taking more than or equal to 20 mg of cortisone daily for 2 weeks and for 2 subsequent years. Such patients must require preprocedural supplemental/replacement corticosteroids.

Iatrogenic adrenal insufficiency is caused by suppression of the HPA axis due to exogenous glucocorticoid therapy in pharmacological doses at more than 5.7 mg/m2/day (~10 mg/day) of cortisol.

Pharmacotherapy-

A single dose of steroids (even in excess) is used to tide over the mortal crisis even when the beneficial effects are uncertain. Short courses (even high doses) are not likely to be harmful in the absence of contraindications. In severe disease progression, the starting doses of the steroids can be high and without any harmful effects. Long term use can be potentially hazardous. Hence, the dose should be kept to minimum which is found by trial and error method. There should never be any abrupt withdrawal after a corticoid has been given for more than 2 to 3 weeks else it may precipitate adrenal insufficiency. Corticosteroids have a widespread use in the diseases like arthritis, collagen diseases, severe allergic reactions, autoimmune disorders, bronchial asthma, infective diseases, eye diseases, skin diseases, intestinal diseases, cerebral edema and in malignancies. 

In dentistry: Primarily, the corticosteroids are used to decrease the post-operative edema and manage oral inflammatory diseases. The drugs are found useful in almost all the areas of dentistry including odontogenic and mucosal diseases. So let us discuss all these in detail…..

  1. Steroids in Oral Medicine: Corticosteroids have found their effective use in diseases like ulcerative, vesiculoerosive lesions, benign lesions including CGCG, salivary gland disorders, TMJ disorders, neuralgias and in oral submucous fibrosis.

Ulcerative and vesiculobullous diseases- Immunologically mediated diseases affecting the oral mucosa attack the epithelial connective tissue targets through cellular and/or humoral immunity. Such diseases are present with inflammation and the loss of epithelial integrity. The main clinical findings include ulceration and reddening of the mucosa along with severe and debilitating pain. Corticosteroids play a central role in the treatment of ulcerative and vesiculobullous lesions. But, an increased frequency and severity of the adverse effects associated with systemic corticosteroid therapy led to an increased use of topical corticosteroids (TCs).

Criteria for usage-: Short course of TCs can be effectively used without any adverse effects in recurrent apthous stomatitis (RAS), some cases of erythema multiforme (EM), and drug-induced ulcerations. For longer and less predictable periods, TCs are effective in severe cases of RAS, erosive form of oral lichen planus (OLP), some specific forms of EM, and mucous membrane pemphigoid (MMP). In very severe cases of ulceration, a short course of systemic corticosteroids followed by maintenance regimen of topical therapy is quiet effective. Also, simultaneous use of both systemic and topical therapy proves beneficial in some cases of ulceration.

Protocol for use-: The basic rule for using topical corticosteroid for a prolonged course is that a topical corticosteroid of potency appropriate to the severity of the clinical symptoms at the lowest possible concentration and frequency should be used while maintaining the effectiveness of the treatment. It should always be taken into account that these drugs do not cure the disease but rather control or relieve the symptoms.

Factors that influence the effectiveness of topical corticosteroids include:

  1. The contact time between the drug and lesion and the vehicle used to apply it.
    The various of the vehicles that can be used effectively include-

    1. Orabase (Stoy, 1966)
    2. Cyanoacrylate (Jasmin et al, 1993)
    3. Bioadhesive patches made of cellulose derivatives (Mahdi et al., 1996)
    4. Gels (Regezi and Sciubba, 1999)
    5. Denture adhesive pastes (Lo Muzio et al., 2001)
  2. Concentration of the drug, which can increase its clinical effectiveness, although no additional advantage is obtained beyond certain limits.

Patients who are being prescribed with topical corticosteroids in an adherent vehicle, should be instructed to apply a small amount to the target area after meals, and not to eat or drink anything at least till 30 minutes. The high potent topical steroids should be advised to apply 2-3 times per day while the TCs with lowered potency can be applied up to 5-10 times daily. It is best not to rub the TC in, as it would lead to irritation.

Systemic therapy for ulcerative, vesiculobullous lesions:

Prednisone therapy should be started at 1.0 mg/kg/day in patients with severe RAS and should be tapered after 1 to 2 weeks. For minor erythema multiforme, 20 – 40 mg/day for 4 – 6 days and for severe or rapidly progressing lesions, 60 mg/day slowly tapered by 10 mg/day over 6 weeks. For pemphigus vulgaris, initial dose of treatment is 0.5 mg/kg/day to 3 mg/kg/d. Dose that achieves clinical control is maintained for 2-3 weeks and then gradually tapered. For Cicatricial Pemphigoid, Prednisolone 30-60 mg/day for 2-3 weeks to stop the new bullae formation is given. The dose is tapered by 20% every 2-3 weeks until the dose of 10 mg is reached. Dose is maintained on alternate days and reduced by 5 mg every 2 weeks, then stopped. Clobetasol propionate 20 -40 mg/day is more effective for the treatment is effective in the treatment of bullous pemphigoid. Prednisolone 1mg/kg/d for <7 days and a tapered to 10-20mg per day for 2 weeks is used in the treatment of lichen planus. Lupus erythematosus is treated by Predisolone 20 – 30 mg/day for 2- 6 weeks, which is tapered gradually.

Pulse therapy: It is also known by short term therapy. In high dose therapy, an intensive course of steroid administration is required for at least 48-72 hours. A dose of 0.5-2 gm of prednisolone or equivalent is given in single intravenous injection of supra-physiological dose. The pulse therapy helps in avoiding the complications and side effects of the long term steroid therapy and helps in achieving the immunosuppressive effects.

Steroids in the treatment of benign lesions- For treating the Central Giant Cell Granuloma cases, intralesional injection of triamcinolone can be given in a dose of 1 to 2 mg/kg/d (maximum of 60 mg) with treatment interval of 4-6 weeks.

In hemangioma, corticosteroids are used to decrease Cytokines platelet-derived growth factor-alpha (PDGF-alpha), Platelet-derived growth factor beta (PDGF beta), IL-6, TGF-beta1 and TGF-beta3. Prednisone at a dose of 20-30 mg/d can be given for 2 weeks to 4 months or intralesional triamcinolone acetonide (4 mg/mL) can be effectively used in the treatment of Hemangioma.

Steroids in Salivary gland disorders- 0.05% clobetasol propionate 3 times a day for 4 weeks in a mucosal adhesive base is used to treat mucocele. Prednisone 40 mg/day is used effectively in the treatment of Sjogren’s syndrome.

Steroids in Neuralgia- Prednisolone 20 to 30 mg/day for 7 – 10 days tapered to 10 mg/day for 1 week is used to reduce incidence of post herpetic neuralgia. For the treatment of post herpetic neuralgia, Dexamethasone 0.75-9 mg/d PO in divided doses q6-12h or Prednisone 5-60 mg/d PO or bid/qid; taper over 2 weeks as symptoms resolve or Methylprednisolone with a loading dose of 125-250 mg IV and maintenance dose of 0.5-1 mg/kg/dose IV q6h for up to 5 d can be used.

Steroids in TMJ disorders- For Rheumatoid Arthritis, Intraarticular injection 10 to 40 mg/ml is used and for osteoarthritis, Intraarticular injection 20 mg/ml (2 injections 14 days apart) can be used effectively.

Miscellaneous uses- Significant improvement can be achieved when Prednisolone is started within 72 hours of onset of the symptoms in cases of Bell’s palsy. 1 mg/kg body weight (maximum 70 mg) in divided doses with meals for six days is used, and the dose can be reduced gradually over the next four days. Corticosteroids are used in reducing the fibrotic bands in oral submucous fibrosis cases. For treating Desquamative gingivitis, topical triamcinolone in the dosage of 0.1%-3% to 4 times/day or flucocinamide and Systemic prednisolone 30 to 40 mg/day can be used.

  1. Steroids in Oral Surgery: Steroids are used in the prevention of postoperative pain, edema, trismus after 3rd molar surgery, prevention of postoperative edema after orthognathic surgery and in the prevention of alveolar osteitis.
  2. Steroids in endodontics: In endodontics, corticosteroids are used in the form of intracanal medicaments. Ledermix is an effective corticosteroid- antibiotic intracanal paste used to lessen the severity of post-operative pain associated with acute apical periodontitis.

Protocol for Supplementation of Patients on Glucocorticoid Therapy Who Are Undergoing Dental Care

Dental procedure Previous systemic steroid use Current systemic steroid use Daily alternating systemic steroid use Current topical systemic steroid use
Routine procedures If prior usage lasted for >2 weeks and ceased <14-30 days ago, give previous maintenance dose.

 

If prior usage ceased >14-30 days ago, no supplementation needed

 

No supplementation required Treat on steroid dosage daily, no further supplementation needed No supplementation needed
Extractions, surgeries, or extensive procedures If prior usage lasted for >2 weeks and ceased <14-30 days ago, give previous maintenance dose.

 

If prior usage ceased >14-30 days ago, no supplementation needed

 

Double daily dose on the day of procedure.

 

 

 

 

 

 

Double daily dose on the day of first post-operative day when pain is anticipated.

Treat on steroid dosage day, and give double daily dose on the day of procedure.

 

 

 

 

Give normal daily dose on first post-operative day when pain is anticipated.

 

 

 

 

 

No supplementation needed.

 

Adverse effects

Due to extention of pharmacological action occurring with prolonged therapy, adverse effects of mineralocorticoid include sodium and water retention, edema, hypokalemic alkalosis, progressive rise in B.P, weight gain and fluid and electrolyte disturbance. On GIT, the effects of glucocorticoid include acute erosive gastritis with hemorrhage, peptic ulcer, interstitial perforation and pancreatitis. The metabolic effects of glucocorticoid include hyperglycemia, ketoacidosis, hyperosmolar coma and hypophosphatemia. Cushingoidism occurs due to prolonged therapy of glucocorticoid. Glucocorticoid may even cause hypertension, salt and water retention and hypokalemic alkalosis.

Drug interactions

Glucocorticoid dosage is decreased when given in combination with antibiotics (erythromycin), cyclosporine, isoniazid, ketokonazole and estrogen as these drugs decrease the metabolic clearance of the steroid used. The dose of glucocorticoid is increased when given in combination with cholestyramine, antiepileptic drugs including barbiturates, phenytoin, carbamazepine and rifampicin. Some adjustments are required in glucocoticoid dosage when the patient is taking drugs like antianxiety and antipsychotic drugs, antihypertensives, hypoglycemics or sympathomimetics.

Precautions during therapy: The patient should be enquired about and thoroughly checked for hypertension, diabetes mellitus, peptic ulcer or any other infection.

Precautions taken during the therapy: The patient should always be advised to take the steroid with meals. The diet should be low in calories and sodium while rich in potassium supplements. Hypertension, hypoglycaemia and weight gain by the patient should be periodically checked.

Precautions while stopping the drug: The dose should be increased in cases of stress. The steroid should never be should abruptly instead a tapering dose should be administered.

Conclusion

Corticosteroids play an important role in control of pain & inflammation associated with numerous disease states of oral cavity. Currently corticosteroids are drugs with one of the broadest spectrum of clinical utility. But it should never be used as a substitute to other treatments. Let’s keep it mind that these drugs do not cure the disease but rather control or relieve the symptoms. It should be used cautiously as it is a two edged sword.

 

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