Term
| "___ function as regulators of the endocrine system. " |
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Definition
| Hypothalamus and Pituitary gland. |
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Term
| Name five axis of hypothalamus and pituitary gland function |
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Definition
- Mineralocorticoids (aldosterone),
- Glucocorticoids (cortisol),
- Adrenal androgens, estrogens, pogestins
(Dehydroepiandrosteone, estrone, estradiol, estriol)
- Antidiuretic hormine (ADH)
- Oxytocin" |
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Term
"Corticotrophic Releasing Hormone (CRH)
" |
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Definition
"- Hypothlamus
- secretion stimulated by parasympathetic pathways, circadian rhythms, stess, infection, hypoglycemia" |
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Term
| Adrenocoticotropic Hormone (ACTH) |
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Definition
"- Anterior pituitary
- stimulates the adrenal cortex
- synthesis of cotisol and other glucocorticoids" |
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Term
"Cortisol (hydrocortisone)
physiologic vs pharmacologic effects" |
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Definition
"- Physiologic functions: occur at low concentrations, regulation of immune status, minimal storage, synthesized as needed
- Pharmacologic effects: occur at high concentrations, exogenous (drugs): use for allergic reactions, inflammatory diseases, autoimmune diseases |
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Term
Corticol "Designated biological effects,
Acts on the hypothalamus and pituitary, suppressing further release of CRH and ACTH - feedback inhibition. "
In the ___, both ACTH and corticol stimulate conversion of ____ to ___. |
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Definition
"Adrenal Medualla, NE to Epinephrine
- Cortisol further inhibits tissue uptake of epinephrine, increasing plasma levels of available epinephrine
(This is why we give a pt IV steroids when they suffer cardiogenic or septicemic shock) "
Corticol effects on carbohydrate |
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Term
Glucocorticoids effects of Protein Metabolism |
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Definition
| - stimulate protein catabolism (breakdown): increase gluconeogenesis; chronic, high concentrations of glucocorticoids cause thinning of the skin, muscle wasting and negative nitrogen balance. |
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Term
| Glucocorticoids effects on Fat Metabolism |
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Definition
"- Stimulate Lipolysis (fat breakdown) while inhibiting the glucose uptake by adipose tissue
- chronic, high concentrations cause fat redistribution --> Cushing's syndrome:
- potbelly, ""moon face"" and buffalo hump"" on the back" |
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Term
| Glucocorticoids effects on Cardiovascular System |
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Definition
"- Functional integrity of the vascular system
- At low concentrations: capillary permeability increased, decreased ability of vessels to constrict, BP decreased
- Blood cells: increased RBC counts, increased levels of hemoglobin, PMN
- Eosinophils, basophils and monocytes are decreased (thus, increased infection)" |
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Term
| Glucocorticoids effects on Skeletal Muscle |
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Definition
"- When glucocorticoid level is insufficient, muscle perfusion is decreased
- Muscle atrophy" |
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Term
| Glucocorticoids effects on CNS |
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Definition
- Glucocorticoid insufficiency is associated with depression, lethargy and irritability. Rare cases of Psychosis.
- Excess --> generalized excitation and euphoria" |
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Term
| Glucocorticoids effects on Stress |
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Definition
"Physiological stress: anxiety, exercise, trauma, infections, surgery
- Glucocorticoid secretion increased (adrenal cortex)
- Epinephrine secretion increased (adrenal medulla)
- Both glucocortiocoid & epinephrine together maintain BP and blood glucose content. "
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Term
| ___ and ___ together maintain BP and blood glucose content |
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Definition
| Glucocorticoids and Epinephrine |
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Term
| What happens if glucocorticoids levels are insufficient? |
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Definition
"-Response to stress: negative feedback, inability to release more cortisol.
- mild stress: hypotension and hypoglycemia
- extreme stress (trauma, surgery, severe infection): circulatory collapse and death. " |
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Term
| What do you give a patient if you patient in having severe stress stress occurs or is expected? |
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Definition
| As prevention, give pt glucocorticoid |
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Term
"glucocorticoids
Mechanisms of Action" |
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Definition
"-Corticosteroid is bound to corticosteroid-binding protein (CBP) as steroid-CBP complex
-Reaches the target cells, uncouples from steroid-CBP complex --> free steroid enters cells
-In the nucleus, the dug then binds to DNA resulting in either:
(1) Repression (prevent transcription) or (2) Induction (initiate transcription) of particular genes
- This initiates signaling pathways resulting in synthesis of lipocortin-1"
Lipocortin-1 -inhibits phospholipase A2, which inhibits cyclooxygenase and 5-lipoxygenase pathways |
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Term
"Glucocorticoids
Anti-inflammatory Effects" |
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Definition
"-Inhibit the production of Arachidonic acid metabolites (Prostaglandins PGG, PGE, PGI, PGF2)
-Multiple actions on leukocytes:
(1) suppress the activation of T lymphocytes,
(2) suppress the production of cytokines by activated T cells,
(3) prevent the release of lysosomal enzymes (catabolic enzymes),
(4) cause vasoconstriction and decrease capillary permeability" |
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Term
| How does cytokines play a major role in inflammation? |
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Definition
| By recruiting and activating eosinophils and by stimulating antibody production by B cells. |
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Term
| Glucocorticoids ___(increase/decrease)___ bone _____ and antagonize the effect of vitamin ___. What diseases can it contribute to? |
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Definition
"Increase bone catabolism and antagonize the effect of Vitamin D on calicum absorption.
- Contribute to the development of osteoporosis" |
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Term
Glucocorticoids ____ the gastroprotective effect of prostaglandins.
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Definition
"Inhibit
- it may stimulate the gastric acid and pepsin production --> exacerbate peptic ulcers" |
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Term
Glucocorticoids:
(1) Suppression of the response to infection or injury" |
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Definition
"-An infection may be serious and treated with antimicrobial agents along with an increase in the dose of steroid, which may suppress the response
- Impaired wound healing
"-An infection may be serious and treated with antimicrobial agents along with an increase in the dose of steroid, which may suppress the response |
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Term
| Impaired wound healing " Glucocorticoids use in concurrent with high doses of ____ may be a cause for peptic ulcerations |
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Definition
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Term
"Glucocorticoids
(2) Suppression of a patient's ability to synthesize corticosteroids"
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Definition
"-sudden withdrawal after prolonged therapy may result in acute adrenal insufficiency
-phased withdrawal/ tapeing of the thearpy should be done
-Recovery of full adrenal function usually takes about 2 months, though it can take 18 months or more
-Chronic uses may lead to adrenal atrophy"
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Term
"Glucocorticoids
(3) Metabolic effects" |
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Definition
"-Supra-physiological doses:
-water and electrolyte retention
-hypokalemia
-rounded, puffy (moon faces), fat accumulation in the supraclavicular and dorsocervical areas - Buffalo hump
-increased hair growth (hirsutism); weight gain; muscle wasting and weakness" |
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Term
| How does glucocorticoids influence bone metabolism? |
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Definition
"-regulation of calcium & phosphate metabolism
- collagen synthesis by osteoblasts and collagen degradation by collagenase" |
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Term
"Glucocoticoids:
Dental adverse effects" |
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Definition
"-Oral candidiasis -systemic and inhalation
-Hypercoagulability of blood
-osteonecrotic jaw (ONJ)" |
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Term
"Hydocortisone,
Cortisone" |
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Definition
"-Corticosteriods, short-acting
-8 to 12 hours; have equal glucocorticoid and mineralocorticoid effects
-preferred for replacement therapy -Adrenal insufficiency
-anti-inflammatory, but more potent agents are preferred agents for severe inflammatory and autoimmune diseases" |
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Term
| Pednisone, Prednisolone, Methylprednisone, Triamcinolone |
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Definition
"Intermediate acting corticosteroids
- 12-36 hours; commonly used for systemic treatment
-management of inflammation, allergy and autoimmune disorders" |
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Term
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Definition
"Long-acting corticosteriods
- Frequently used as topical treatment for skin disorders" |
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Term
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Definition
"long-acting corticosteriods
- treatment of shock as well as neoplastic, infectious and inflammatory conditions that require the use of potent and long acting agents" |
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Term
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Definition
"long-acting corticosteroids, inhalator
- nasal or lung for allergic rhinitis and asthma" |
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Term
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Definition
| the physiologic inability of the adrenal glands to produce maximal cortisol levels (equivalent to 60 mg Prednisone/day) during maximal stress |
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Term
| Which type of patient will be at risk for adrenal suppression? |
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Definition
"(1) Patients who have received 20 mg prednisone/day or equivalent for 7-10 days in the past year.
(2) patients receiving typical maintenance dose of steroids daily (10-20 mg prednisone/day o the equivalent)"
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Term
| Absolute contraindications for Corticosteroids |
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Definition
-Cataract, glaucoma, tuberculosis, ocular herpes simplex, infections (fungal, viral parasitic), peptic ulcer, osteoporosis, psychosis
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Term
| Relative contraindications for corticosteoids |
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Definition
CHF (increase fluid load); diabetes mellitus (anti-insulin effect); Digitalis therapy (hypokalemia, percipitate digitalis cardiotoxicity), hypertension
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Term
| Clinical Uses of glucocorticoids |
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Definition
| (1) Replacement therapy (Addison's disease, secondary adrenal corticol insufficiency, congenital adrenal hyperplasia). (2) Anti-allgeric and anti0inflammatoy therapies. (3) Cancer treatment (immunosuppression). (4) hypotension. (5) diagnostic use |
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Term
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Definition
"-Chronic adrenal insufficiency
-Rare, chronic endocrine disorder
-Diagnosed through diagnostic imaging
-Symptoms: Fatigue, muscle weakness, PUO, headache, orthostatic hypotension
-Hyperpigmentation (Buccal mucosa)
-Type 1 Diabetes, Hashimoto's thyroiditis"
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Term
| Topical glucocorticoids "Formulations: |
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Definition
(1) Adhesive-based vehicles: localized for prolonged periods, but may peel mucosal lining. (2) Ointments or propylene glycol creams: better penetration - hydrates the stratum corneum (3) Cream/ lotions: better patient compliance - cosmetic reasons. (4) gel: less satisfactory because of instability. (5) spray: expensive with no increased efficacy."
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Term
| Topical Glucocorticoids - Dental Clinical Applications |
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Definition
"1. Oral lesions: aphthous stomatitis, vesiculo-bullous diseases, burning mouth/tongue, stomatitis {drug induced} and cancer (all the ""-itis"" that occurs orally)
2. Magic mouth wash cocktail: local anesthetics, antihistamines, antimicrobials
3. Ulcerations or irritations: oral lichen planus, lupus erythematosus
4. Systemic absorption does occur - prolonged and/or overuse have systemic adverse effects" |
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Term
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Definition
"Corticosteroid synthesis inhibitors
-inhibit a rate limiting step of the biosynthetic pathway.
-Treatment of breast cancer and malignant Adrenocortical tumors.Combined with Metyaprone to treat Cushing's syndrome."
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Term
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Definition
"Corticosteroid synthesis inhibitors
-Inhibit synthesis of glucocorticoids by inhibiting the 11 beta-hydroxylase enzyme.
-Treatment of Cushing's syndrome who are refractory to other treatments" |
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Term
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Definition
"Corticosteriod Synthesis Inhibitors
-Azole antifungal
-Inhibits P450 enzymes involved in the biosynthesis of glucocorticoids
-Treatment of Cushing's syndrome"
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Term
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Definition
"Thyroid Gland
(1) Follicular thryoid cells secrete Thyroxine (T4) and Triiodothyronine (T3) -Regulate energy metabolism and growth, from oxygen consumption to cardiac contractility
(2) Parafollicular C cells secretes Calcitonin - regulator of bone mineral homeostasis" |
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Term
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Definition
Thyroxine, T4 is eventually converted to T3
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Term
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Definition
"Triiodothyronine: Active component
-circulates thoughout the body. Influences: growth, development and maturation of various tissues; metabolic effects through control of DNA transcription and protein synthesis; Gluconeogenesis; increases utilization and mobilizations of glycogen stores; increases basal metabolic rate"
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Term
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Definition
| Graves disease, Toxic multinodular goitre (Plummer's disease), Toxic adenoma, Hashimoto's Dieases, subacute thyroiditis |
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Term
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Definition
Excessive circulating thyroid hormones; excessive heat, increase sympathetic activity, increase pain sensitivity, protruding eyes, anxiety, avoid epinephrine
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Term
"Hyperthyroidism:
Non pharmacological management" |
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Definition
"-Adequate nutrition, hydration and rest (especially in the elderly)
-Subtotal thyroidectomy
- Patients with Grave's disease; Toxic adenoma, Toxic Multinodular Goitre"
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Term
"Hyperthyroidism:
Pharmacological Management" |
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Definition
-Thioamides: methimazole, popylthiouracil (PTU; Iodine (potassium iodide); radioactive iodine (131 I) - except in subacute thyroiditis and during pregnancy; Beta-blockers
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Term
| Thioamides Tx of hyperthyroidism |
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Definition
Methimazole, Propylthiouracil (PTU) "Thioamides:
Indicated for hyperthyroid patients except in subacute thyroiditis.
-MOA: Decrease T4 and T3 productions/synthesis. Decrease conversion of T4 to T3
-Adverse Effects: maculopapular pruritic rash +/- fever, urticaria rash, vasculitis, arthralgia, Lupus-like reaction" |
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Term
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Definition
"Non-radioactive. Inhibits Iodine dependent hormone release. Decrease the size and vascularlity of the hyperplastic gland.
-Prior to surgery, given orally or IV to patients with Grave's disease.
-Adverse Effects: salivary gland swelling/tenderness"
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Term
| Radioactive Iodine (131 I) |
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Definition
"-Oral administration, taken up by thyroid and incorporated into storage follicles
- Destruction of thyroid parenchyma"
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Term
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Definition
"use for hyperthyroidism treatment.
-Adjuvant agent
-Reduce hyperthyroid symptoms - palpitations, tremor, sweating
-Do not alter circulating T4
-Non-selective beta blockers decrease circulating T3 levels"
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Term
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Definition
"-Syndrome characterized by low circulating levels of T4 and T3.
-rare cases where tissue becomes resistant to thyroid hormones.
-Have a reversible slowing down of all body function. Infants & children - growth and developmental retardation. (Mental retardation is irreversible)" |
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Term
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Definition
-Primary Hypothyroidism (Thyroid)
-Secondary Hypothroidism (Pituitary)
-Tertiary Hypothroidism (Hypothalamus)
-Generalised resistance to thyroid hormones (peripheral tissues)
-Usualy caused by a defect in the beta recepor for T3 and T4 |
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Term
Hypothyroidism Management |
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Definition
-Replacement with T4 or T3 or thyroid extract products
-Dosage should not take place more frequently than 4 to 6 weeks
-Sodium Levothyroxine
-Synthetic T4 hormone
-Thyroid, USP
-Liothyronine
-Synthetic T3
-Liotrix
-Synthetic T4/T3 Combination preperation
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