•
Chapter 14 Drugs of the Endocrine System and Metabolic Agents Introduction Patient instruction may be provided by the dental hygienist for application of some topical agents If endocrine-related drugs are reported on health history consider – – Drug effects Assessment of disease control
• •
•
•
Dental hygiene functions – – – Providing information related to effects of dental hygiene treatment Specific drugs and implications for potential adverse drug effects The Endocrine System
• • •
Secretes humoral substances internally into systemic circulation Primary function = to regulate cellular metabolism and maintain homeostasis Endocrine glands do not act in isolation – – Series of complex interactions Abnormality in a gland produces compensatory reactions in others
• • • • • •
Mechanism of action – bind to receptors and cause cellular activity Pituitary Gland Master gland Endocrine drugs – mimic effects of hormones produced by pituitary Location: sphenoid bone – sella turcica Two parts – Anterior portion • – Superior hypophysial arteries derived from internal carotid
Posterior portion
• • •
Branches of inferior hypophysial arteries
Anterior Pituitary Anterior pituitary drugs – – Control function of thyroid, adrenal glands, and ovaries and testes When used therapuetically - administered by injection
•
Humoral substances that stimulate or inhibit ant pituitary – – Originate in hypothalamus Transported to gland via portal vessels of pituitary stalk through bloodstream
• • •
Posterior Pituitary Stores and releases vasopressin and oxytocin Vasopressin – – – Regulates reabsorption of water by kidneys Antidiuretic hormone (ADH) – major action Diabetes insipidus – absence of ADH; failure to concentrate urine • • Clinical manifestations – polyuria, plydipsia Desmopressin acetate (Octostem, DDAVP) • Treats diabetes insipidus and certain clotting disorders
• •
Posterior Pituitary cont’d Oxytocin – – – Induces contractions in uterus and promotes lactation Supplied by injection or intranasally Adrenal Hormones
•
Located on kidney – cortex and medulla – – Secretes glucocorticoids and mineralocorticoids Synthesis and secretion of glucocorticoids is under control of adrenocorticotropic hormone (ACTH)
–
Glucocorticoids – variety of actions • Cortisol
–
Mineralocorticoids – controlled by renin-angiotensin pathway • Aldosterone • Regulates salt and water balance
• • • • •
Cortisol Regulates cell metabolism Induces anti-inflammatory and immunomodulatory effects Allows other hormones to modulate cardiac contractility, vascular tone, and blood pressure Provides negative feedback to hypothalamus and anterior pituitary – Regulating CRH (corticotropin-releasing hormone) and ACTH
• • • •
Glucocorticosteroids Actions – c highlight Topical formulations used for treatment of oral inflammatory lesions Box 14-2 Should never be used for treatment of mucocutaneous viral infections because of actions – Exception – coadministration for management of severe herpes (varicella) zoster
•
Mechanism of action – – – Decrease inflammation Suppress immune system Adverse effects – delayed wound healing, infection
• •
Indications Addison’s disease – very low to undetectable levels of aldosterone and cortisol in blood – – – Cortisol levels do not increase in response to stress and ACTH Clinical manifestations – c highlight Treatment
• • –
Oral glucocorticoid and mineralocorticoid daily Stressful events may require additional doses
Adrenal crisis rare event in dentistry • Most treatment can be performed without additional supplementation
• •
Indications cont’d Inflammatory conditions – Steroids prescribed for • Anti-inflammatory effect • • • • – Prednisone – most common for oral administration
Immunosuppressive therapy Spinal cord injury Lymphocytic leukemia chemotherapy
Supraphysiologic • Cushing’s syndrome
• • • •
Inflammatory Conditions cont’d Administered in medicine at target doses equal to or greater than normal daily output of cortisol Physiologic cortisol secretion 15–20 mg/day Agents – – – Hydrocortisone – 20 mg/day Prednisone and prednisolone – 55 mg/day Dexamethasone – 0.75 mg/day
•
Administration of drug may include stepped-down approach – Dental Uses of Glucocorticoids
• •
Dental Uses Topical agents or short-term therapy most often used
– •
No risk of cortisol and aldosterone suppression
Triamcinolone (Kenalog), clobetasol (Temovate), fluocinonide (Lidex) – – – Topical Applied 3x–4x/day after meals and at bedtime with cotton-tipped applicator Formulated with non–water-soluble products with adsorptive qualities
• • •
Doseforms – oral doseforms have greater potential to produce ADEs Adverse Drug Effects Affect dental hygiene management – Masked symptoms of infection, candidiasis, nervousness, hyperglycemia, vision disturbances, edema, hypertension, peptic ulceration, osteoporosis, and Cushing’s syndrome
• •
Signs and symptoms of Cushing’s syndrome – “moon face, buffalo hump” Steroid spray – – – Monitor oral tissues for yeast infection Report findings to dentist Rinse mouth after spray to reduce candidiasis
• • •
Adverse Drug Effects cont’d Topical gels unlikely to result in yeast infection Periodontal health should be assessed using probing depth information – Monitor attachment loss caused by masked infection
• • •
Potential Drug–Drug Interactions in the Dental Setting Possible methylprednisolone toxicity when macrolides are taken. Avoid concurrent use Decreased metronidazole effect when corticosteroids are taken concurrently. Avoid concurrent use Increased risk of peptic ulcers with COX-1 inhibitors. Monitor clinical status Potential Medical Emergencies Addisonian crisis (acute adrenal insufficiency)
• • •
– •
Most likely after stressful surgical procedures when Addison’s disease reported
Hypertensive syndrome – Question individual about • • – Ability to respond to stressful situations History of blood pressure fluctuations
Monitor blood pressure during appointment
• • •
Stressful dental treatment (oral surgery), individual with dental phobia Clinical Considerations for Systemic Corticosteroid Administration Review
The steroid doseform with the most potential to produce ADEs is? A) Topical B) Sprays C) Elixirs D) Tablets E) Gels • Answer
D) Tablets Oral doseforms have greater potential to produce adverse drug effects (ADEs). • • • • • • • Hormones of Reproduction Hypothalamic lutenizing hormone releasing factor stimulates LH and FSH Lutenizing hormone actions - ovulation Follicle-stimulating hormone actions development of ovarian follicles, spermatogenisis in males LH and FSH regulated by feedback inhibition Estrogens and protesterones taken for supplementation Oral contraceptives contain a variety of hormones
– • • • • • •
Reported on health history
Estrogens Synthesized mainly in ovaries, the placenta, and the adrenal glands Menopause – fat main source of estrogen in women Influence growth and development of female reproductive organs Supplemental hormones may be prescribed during menopause Products in top 200 most prescribed drugs – Used alone or in combination
• •
Estrogens cont’d Mechanism of action – Inhibit release of gonadotropin-releasing hormone and reduce the release of FSH and LH • Action permits use of estrogen in anticontraception • • Reduces thinning of mucosal tissues of vaginal area Prevents vasomotor symptoms
• • • • •
Therapeutic Indications for Estrogen Oral Contraceptives Use both estrogen and progesterone Actions Preparations and cycles – – – Monophasic – fixed dose Biphasic Triphasic - resemble normal physiology
• • •
Recent study – users had poorer perio health than nonusers Indications for use Estrogens cont’d
•
Pharmacokinetics – – Well absorbed, extensively metabolized by liver Active metabolites eliminated by kidney
•
Adverse drug effects – Affecting dental hygiene management • Candidiasis, peripheral edema, hypertension, thromboembolism, stroke, and myocardial infarction Smoking tobacco increases risk for thromboembolism, stroke, and myocardial infarction Estrogens cont’d
•
• •
Potential medical emergencies – Hypertensive syndrome and conditions involving intravascular blood clot formation • • Question patient concerning previous history of conditions Analyze blood pressure values
•
Potential drug–drug interactions – – – No documented interactions between estrogen and drugs used in dental office Oral contraceptives and potential drug interactions should be communicated to patient Clinical Considerations
• •
Hypertension and oral contraceptive use Monitor blood pressure when estrogen taken – ADA recommendations
• •
Smoking cessation program for females using estrogen Antibacterial agents and oral contraceptives – – – No pharmacokinetic data to support interaction AMA and ADA Council of Scientific Affairs recommendations Use and treatment for cancer
– • Review
Consider dental implications for specific indication
Adverse drug effects associated with estrogen therapy that can affect dental hygiene management include all of the following except one. Which one is the exception? A) Candidiasis B) Peripheral edema C) Hypertension D) Thromboembolism E) Nervousness
•
Answer
E) Nervousness Candidiasis, peripheral edema, hypertension, thromboembolism are all potential ADEs associated with estrogen therapy. Nervousness is not. • • • • • • • • • Thyroid Hormones Location and secretion Euthyroid (normal), hypothyroid (inadequate), and hyperthyroid (excessive circulating) levels Thyroid disorders Regulation of thyroid gland - by TSH Action of gland – growth and metabolism, BMR Drugs Used to Treat Hypothyroidism Thyroid Drugs cont’d Mechanism of action – Promote oxygen consumption by tissues, increasing basal metabolic rate and metabolism of carbohydrates, lipids, and proteins Glycogenolysis
– •
Indications
– – • •
Prescribed for effects of hypothyroidism and to return individual to euthyroid state Used in treatment or prevention of goiters and management of thyroid cancer
Thyroid Drugs cont’d Adverse drug effects – Affect dental hygiene treatment plan • Nervousness, palpitations, dysrhythmias, hypertension, angina, and shortness of breath Monitor vital signs and qualities Patient interview
• • •
Potential drug–drug interactions in the dental setting – Administer local anesthetics with vasoconstrictor with caution using aspirating technique and low concentration of vasoconstrictor – 2 cartridges 1:100,000 or 4 cartridges 1:200,000 Antithyroid Hormones
– •
Hyperthyroidism – – – Characteristics of disease - goiter Therapeutic strategies – c highlight Antithyroid drugs • • • Primary treatment or preparative therapy before surgery or radioiodine therapy Stopped or tapered off after 12–18 months Propylthiouracil (PTU), methimazole (Tapazole), carbimazole, iodine or iodide
• •
Hyperthyroidism cont’d Potential medical emergencies – Hypertensive crisis, angina pectoris, and cardiac arrhythmia (thyroid storm) leading to acute coronary syndrome Thyroid storm • Signs and symptoms – c highlight
–
•
Drug interactions – Caution with use of local anesthetic with vasoconstrictor if pt. taking nonselective betaadrenergic antagonist to reduce heartrate and cardiac workload • – Should be balanced against importance of profound anesthesia
Combination analgesics with ASA contraindicated
• •
Hyperthyroidism cont’d Clinical considerations – Develop and implement preventive and therapeutic strategies compatible with patient’s physical and emotional stability Uncontrolled hyperthyroidism – greatest risk for dental hygiene procedures Hyperthyroidism – Clinical Considerations
– – •
Functional capacity – METs – individual’s ability to perform spectrum of common daily tasks • – – Increased cardiac risk if unable to meet 4 MET
Monitor vital signs Use vasoconstrictor with caution owing to possibility of dose-related initiation of hyperthyroidism
• •
Parathyroid Hormones Used to treat – – Postmenopausal women with osteoporosis at high risk for fracture Men with osteoporosis to increase bone mass
• •
Action of gland – reg. Ca and phosphate metabolism Teriparatide (Forteo) – – – – Administration - subcu Uses - stimulates bone formation Warnings – increase in osteosarcoma ADEs and drug interactions - dizziness, leg cramps
• •
Parathyroid Hormones cont’d Clinical implications – Potential for periodontal attachment loss • • • Evaluate periodontal condition Refrain from excessive pressure on jaw No dental hygiene treatment prohibitions
•
Bisphosphonate derivatives – Lead to osteoclast apoptosis (cell death)
• • •
Drugs in Top 200 Used to prevent or treat osteoporosis, Paget’s disease of the bone, and cancer chemotherapy Alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva) – Nitrogen-containing bisphosphonate oral formulations
•
Pamidronate (Aredia) and zoledronate (Zometa, Reclast) – Nitrogen-containing bisphosphonate formulations administered by IV
•
Tiludronate (SKelid) and etidronate (Didronel) – – Non-nitrogen-containing bisphosphonate formulations Used in treatment of Paget’s disease of the bone
• •
Bisphosphonates cont’d Mechanism of action – Inhibit bone resorption by suppressive action on osteoclasts or osteoclast precursors
•
Indications – Oral doseforms of BIS most often used • – Higher dose level for treatment of Paget’s disease
IV formulations
•
Adverse Drug Effects
•
Osteonecrosis of the jaw (ONJ) – most important – – ADEs most often with IV formulations but some reports with oral doseforms (rare) Mechanism for ONJ • • – Reports of ONJ and BIS after oral surgery, and dental or periodontal infections Reports of spontaneous ONJ also
Lesion characteristics – c highlight
• • •
Gastroesophageal reflux disease and dysphagia may affect the dental hygiene treatment plan Clinical Considerations ADA recommendations based on management recommendations by the American Academy of Oral Medicine Dental hygiene management and the effects of osteoporosis – – Patients may be susceptible to pathologic fractures Relationship to pressure placed during instrumentation unclear
•
• •
Prevention of ONJ From Bisphosphonate Therapy Dental hygienists play role in AAOM recommendations for individuals having taken a BIS – Prevention and management considerations • – See Table 14-5
Provide patient information to prevent ONJ
• • • • • •
Prevention of Bisphosphonate-Associated Osteonecrosis of the Jaw Bisphosphonate Potential medical emergencies – none Potential drug–drug interactions in the dental setting – none have been documented Pancreatic Hormones Location and secretion – Glucagon and insulin
•
Medical management
–
Goals of therapy • • Reduce fasting blood glucose to levels <120 mg/dL and HbA1c levels to <6% Evidence for recommendations
– •
Insulin and Oral Hypoglycemic Agents
Type 1 DM – absolute deficiency of insulin – Short-, intermediate-, or long-acting injectable insulin preparations, and inhaled insulin
•
Type 2 DM – decreased release of insulin or decreased number of insulin receptors – – Treated initially with an orally administered hypoglycemic agent May progress to insulin-dependency
• •
Insulins and Antidiabetic Drugs in the Top 200 Goal of therapy – provide adequate glucose control through each 24-hour period while minimizing the number of injections required Regimens combine short-acting insulin with an intermediate- or long-acting agent Risk for ADEs – Hypoglycemia – most likely to occur when insulin at peak effect • Treat patients in morning, after taking agent, and after eating a normal breakfast • Places patient in oral healthcare setting before peak activity of agent is reached
• •
• •
Insulins and Antidiabetic Drugs Risk for ADEs cont’d – Monitoring for disease control • HbA1C determines long-term control and is completed at quarterly medical appointments
• • •
First-generation sulfonylureas – older drugs Meglitinide classification – used uncommonly Combination products
– – – • •
Second-generation sulfonylureas and metformin “Glitazones” and metformin Glitazones and sulfonylureas
Mechanism of Action Actions various based on type of drug – – – Stimulate insulin release from pancreatic β-cells (sulfonylureas) Reduce glucose output from the liver (biguanides) Increase sensitivity of peripheral target cells in insulins (thiazolidinediones)
• • •
Insulin or oral sulfonylurea agents most likely to cause hypoglycemia Pancreatic Hormones cont’d Indications – – – Insulin hormone – Type 1 DM Insulin hormone, oral antidiabetic agents, or combination of both – Type 2 DM Form of DM often can be determined based on drug used
•
Adverse drug effects – – Investigate each agent in drug reference Question patient for ADEs or side effect with relationship to oral healthcare appointment
• •
Pain Management for DM patients Treatment strategies should include postoperative pain management – – – – Opioid-based analgesics Salicylates Opioid/ASA vs opioid/ibuprofen combinations Opioid/APAP combination – secondary therapeutic agent
• •
Pancreatic Hormones cont’d Potential medical emergencies
– –
Hypoglycemia – most common Hyperglycemic crisis (diabetic coma) rarely occurs in dental office • Uncontrolled individuals – infection and stress can promote development of diabetic coma
•
Potential drug–drug interactions in the dental setting – – Glipizide and fluconazole – hypoglycemic coma Epinephrine at levels in the dental setting should not raise blood glucose levels appreciably ACE inhibitors and beta1-adrenergic receptor antagonists
– • • •
Clinical Considerations Clinician should consider the type of DM and side effects of drug therapy used Judge glycemic control – – Patient’s self-monitored blood glucose level on appointment day Patient’s most current HbA1C result (at least 6)
•
Risk for hypoglycemia – – – Clinical signs and symptoms of hypoglycemia Question patient about hypoglycemic drug therapy and if meal was consumed Clinical Considerations cont’d
• • • •
Treat patient soon after breakfast Consider drug interactions that predispose to hypoglycemia Monitor vital signs – DM patients often develop hypertension Prophylactic antibacterial agents – No studies support recommendation of administration of antimicrobial prophylaxis before dental therapy Any infection must be managed promptly and aggressively
– • •
Clinical Considerations cont’d Prophylactic antibacterial agents cont’d
– –
No evidence that antibiotic therapy decreases infection or increases healing DM with significant oral infection – consult primary physician • • Instruct patient to practice meticulous oral hygiene Recall at regular intervals to monitor resolution of infections and compliance with recommended preventive measures
•
Review
The most common medical emergency in diabetes is A) Hyperglycemia B) Diabetic coma C) Nausea and vomiting D) Hypoglycemia E) Blood dyscrasias • Answer
D) Hypoglycemia Hypoglycemia is the most common medical emergency in diabetes. • • • • • • Dental Hygiene Applications Endocrine disease chronic conditions not cured with drugs, but managed with drugs Drugs taken for lifetime Consider the effects of disease, potential ADEs when planning treatment Vital sign values may reveal information regarding how appointment should proceed Attention paid to potential emergency situations – • • • Prevent or manage emergency quickly
Management of Patient Taking or Has Taken Corticosteroids Dentist-Prescribed Topical Steroids Instructions provided by dental hygienist on proper use of steroid gel – Place small amount on cotton-tipped applicator for application to ulcer, lesion
– – • • •
Notify dentist if area worsens and stop applying agent Patient Taking Thyroid Hormone or Antithyroid Drugs
Question patient concerning reason for drug Consider pathophysiology of disease and relationship to dental hygiene procedure Monitor vital signs – If elevated refer for medical evaluation
• • • • • • • • •
Investigate any ADEs Assess functional capacity – equal to 4 METs Determine potential for a medical emergency – thyroid storm Dental Hygiene Management of Patient Taking or Has Taken Bisphosphonate Drug Management of Patient Taking Antidiabetic Agents Clinical Application Activities Exercise 1 – patient information for Fosamax Exercise 2 – follow-up questions for diabetic taking insulin; clinical considerations? Exercise 3 – Web activity