DRUGS TO TREAT ENDOCRINE PROBLEMS Endocrine System: Regulates the following: Reproduction Growth Immunity Energy Fluid, electrolyte

rolyte and acid base balance Maintains Homeostasis helps all other organs to function properly Organs of the Endocrine System: Small ductless glands Dispersed throughout the body Produce HORMONES Hormones: Chemical messengers Secreted into the bloodstream Carried by the blood Bind to specific receptors of target cells to alter cellular activities Homeostatic Feedback Mechanism: Negative Feedback Mechanism decreases deviation from normal Positive Feedback Mechanism increases deviation from normal

Hypothalamus: GRACE ANN L. LAGURA, RN MAN Page 1

Regulates endocrine function Between brainstem and cerebrum Releases hormones: Growth Hormone Releasing Hormone Thyrotropin Releasing Hormone Corticotropin Releasing Hormone Gonadotropin Releasing Hormone Prolactin Releasing Hormone

Major Organs of the Endrocrine System: Pituitary Gland Thyroid Gland Parathyroid Gland Pancreas Adrenal Glands Gonads Pineal Gland Thymus Pituitary Gland: Known as the Master Gland Pituitary hormones direct the activity of all other endocrine organs Located below the hypothalamus Infindibulum connects the pituitary gland to the hypothalamus 2 Regions: Posterior Lobe made up of nerve fibers storage area of 2 hormones produced by the hypothalamus: Oxytocin initiates uterine contraction Antidiuretic Hormone (ADH) also known as Vasopressin; stimulate reabsorption of water from the collecting tubules Anterior Lobe Glandular tissue produce Tropic Hormones Somatotrophs Thyrotrophs Carticotrophs Lactotrophs Gonadotrophs Melanocyte Stimulating Hormone Anterior Pituitary Hormones: Somatotrophs Thyrotrophs

Growth Hormones (GH)

Thyroid Stimulating Hormone (TSH)

GRACE ANN L. LAGURA, RN MAN

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Corticotrophs (

Gonadotrophs

Adrenocorticotrophic Hormone (ACTH) Lactotrophs

Follicle Stimulating Hormone (FSH) And Luteinizing Hormone (LH)

Prolactin Growth Hormones: Stimulates growth in bone and muscles Decreased GH = Dwarfism Increased GH = Gigantism Increased GH in adults = Acromegaly (abnormally large hands, feet and facial features) Thyroid Gland: Butterfly-shaped organ located in the neck Anterior or infront of the trachea Secrete: thyroid hormones (T3 and T4) - Increased oxygen consumption of most of the body cells Thyrocalcitonin regulates calcium Parathyroid Gland: 4 Tiny glands embedded at the back of the thyroid Secrete Parathyroid Hormone (PTH) important in calcium and phosphate regulation Adrenal Glands: Triangular glands at the top of each kidney 2 endocrine glands: Outer adrenal cortex Glucocorticoids Mineralocorticoids Androgens Inner adrenal medulla Catecholamines epinephrine and norepinephrine Pancreas: Located near the duodenum of the intestines Aids in digestion Produce hormones: regulates glucose in the body Insulin beta cells Glucagon alpha cells Somatostatin delta cells

GRACE ANN L. LAGURA, RN MAN

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Gonads: Produce sex hormones regulate reproductive functions Females gonads are called ovaries estrogen and progesterone Males gonads are called testes androgens; testosterone (most important male androgen) by Leydig cells Thymus Gland: Located posterior or behind the sternum Regresses with age 2 major hormones: help T-lymphocytes mature (immune system) Thymosin Thymopoietin Pineal Gland: Secrete and synthesize Melatonin almost entirely at night Melatonin affects the functions of the thyroid, adrenal and gonads

DRUGS FOR DIABETES MELLITUS

DIABETES MELLITUS Chronic metabolic disorder resulting from insufficient secetion of insulin Disorder of carbohydrate metabolism Signs and symptoms of Diabetes Mellitus result from: insulin insulin Principle Sign: Sustained Hyperglycemia Polyuria Polydipsia Polyphagia Ketonuria Weight loss May lead to: Hypertension Cardiac diseases Renal failure Neuropathy Amputations Impotence stroke TYPE 2 (NIDDM) Adult onset diabetes Almost always with obesity No ketoacidosis Insulin may be normal and sometimes increased Insulin not proportionate to plasma glucose level Release of insulin is delayed Page 4

TYPE 1 (IDDM) Juvenile onset diabetes Develops during childhood and adolescents Signs and symptoms are abrupt Destruction of pancreatic beta cells which is responsible for insulin synthesis Autoimmune disorder Cause: COXSACKIE INFECTION

GRACE ANN L. LAGURA, RN MAN

Peak output of insulin is abnormal Cause: Familial association

Delayed Insulin Release/Subnormal Peak Output Resistance of liver, muscles, adipose tissues to insulin Causes: receptor binding number of receptors receptor responsiveness Leads to: Destruction of pancreatic beta cells insulin production Short term complications of Diabetes Mellitus: Hyperglycemia when insulin dosage is - when allowed to persist will lead to KETOACIDOSIS Hypoglycemia when insulin dosage is Long term complications of Diabetes Mellitus: Macrovascular Disease Hypertension due to atherosclerosis; from a combination of hyperglycemia Cardiac diseases and altered lipid metabolism Stroke Microvascular Disease Microangiopathy basement membrane of capillaries thicken causing a bloodflow Destruction of small blood vessels cause kidney damage and blindness (proportionate to the degree and duration of hyperglycemia) Retinopathy caused by damage to retinal capillaries Microaneurysms Scarring and Proliferation Overgrowth of new capillaries vision Causes local ischemia kill retinal cells Accelerated by: Hypertension Hyperglycemia smoking Nephropathy Proteinuria glomerular filtration rate arterial blood pressure Page 5

GRACE ANN L. LAGURA, RN MAN

 Common cause of end stage renal disease requires dialysis or kidney transplant Increase incidence in Type 1 than in Type 2 Treatment: ACEI delay the onset of overt nephropathy and retard ARBS progression of nephropathy Neuropathy begins early but usually symptoms are absent for years; related to sustained hyperglycemia Tingling sensation in the fingers and toes Pain Suppression of reflexes Loss of sensation Amputations because of severe nerve damage Impotence caused by combination of blood vessel injury and neuropathy Gastroparesis injury to the autonomic nerves that control GI motility Nausea Vomiting Delayed gastric emptying Abdominal distention secondary to atony DOC: Metoclopramide (Reglan)

Diabetes and Pregnancy: Disappears after delivery Contributing Factors: Placenta produce HPL (anti-insulin enzyme) on the 18th -20th week AOG Production of cortisol that promotes hyperglycemia (3X during pregnancy) blood glucose level (hyperglycemia) from the maternal blood that pass through the placenta to the fetal circulation Hyperglycemia of the mother will stimulate the production of fetal insulin which causes adverse effects to the fetus Management: Blood glucose level must be monitored 6-7X daily C-section as soon as fetus is matured to be delivered (fetal death usually occurs near term) Insulin administration Diet Diagnosing Diabetes: Must be tested in 2 separate days and both must reveal (+) results. Any of the 2 tests may be employed: Fasting Plasma Glucose (FPG) 8 hrs after the last meal Normal Value: 60-110 mg/dl Casual Plasma Glucose Test Blood is drawn anytime Fasting not required 200 mg/dl and is (+) of DM but must exhibit signs and symptoms Oral Glucose Tolerance Test (OGTT) DM is suspected but FPG and Casual Plasma Glucose is not definite Give oral glucose load of 75 grams Anhydrous Glucose and measure plasma glucose 2 hrs later 200 mg/dl and = (+) DM GRACE ANN L. LAGURA, RN MAN Page 6

Not used for routine screening

Treatment: Diet Proper diet balance because Type 1 individuals are thin Carbohydrates 60 to 70% of daily energy intake Proteins 15 to 20% space evenly Polysaturated fats 10% throughout Saturated fats - <10% the day Cholesterol 300 mg/day Exercise Increase cellular responsiveness to insulin Increase glucose tolerance Insulin Must balance with glucose intake Oral hypoglycemics are ineffective with Type 1

TYPE 2 DM: Goal: to maintain blood glucose level Core Treatment: Adjunct Treatment: - diet - insulin - exercise - oral hypoglycemics Promote weight loss Normalize insulin level insulin resistance Exercise promote glucose uptake by muscles, even if insulin is Drugs supplement to caloric restriction and exercise Oral hypoglycemics Insulin Monitoring: Blood glucose levels Urine glucose reserve for patients who will not monitor Glycated Hemoglobin Self Monitoring of Blood Glucose (SMBG): Basis for fine tuning insulin dosage Type 1 3X and more per day 80 120 mg/dl AC 100 140 mg/dl HS Superior than urine glucose test Can detect hyperglycemia long before glucose spills into urine Can detect hypoglycemia urinary measurements cannot Urine Glucose Monitoring: Poor correlation between urine glucose and blood glucose concentration Indicates the level of glucose spilled into urine Example: (-) glucose test indicates blood glucose is <180 mg/dl But does not indicate how much below the threshold the glucose level is Hence, (-) glucose level could be hypoglycemia, normal glycemia or slightly Hyperglycemia Glycated Hemoglobin: Hemoglobin HbA1c Provides an index of average glucose levels over 2-3 months Glucose interacts with Hgb in RBC to form glycated derivatives Prolong hyperglycemia HBA1c gradually GRACE ANN L. LAGURA, RN MAN Page 7

RBC lifespan is 120 days reflect average glucose levels over 2-3 months Provide a picture of long term glycemic control Adjunct to daily glucose monitoring <7% - target value Measured 2X a year

Fructosamine: Provides an index of average glucose level over 1-3 weeks Glucose albumins and other proteins Frusctosamine 310 umol/L good glucose control

INSULIN: Synthesized in the pancreas by the beta cells of the islets of langerhans Proinsulin precursor of insulin Glucose stimulus of insulin production Amino acids Fatty acids may trigger release of insulin Ketones Beta agonists promote insulin Alpha agonists suppress production of insulin Action: Conservative or constructive primarily anabolic Promotes conservation of energy and build up of energy Promotes cell growth and division Insulin

Cellular transport of glucose, amino acids and k Promote synthesis of organic molecules Insulin Deficiency

Glucose is converted into amino acids, proteins and fatty acids into triglycerides

Fats

Glycogen is converted to glucose Protein into amino acids Glycerol Fatty acids

Signs and symptoms of Diabetes GRACE ANN L. LAGURA, RN MAN Page 8

Insulin Deficiency Promotes Hyperglycemia By: glycogenolysis glycogen to glucose gluconeogenesis CHONS and fats into amino acids glucose utilization

Insulin is Indicated to Patients With: Type 1 DM Diabetic Ketoacidosis to allow cells to take up K and lower K level in the blood Treat hyperkalemia

Types of Insulin:
1. Regular (Natural) Insulin Unmodified crystalline insulin Rapid onset Short duration Clear solution Only form that can be administered IV Forms aggregates if given SC Given 30-60 minutes AC 2. Lispro Insulin (Humalog) Acts faster than Natural Insulin Shorter duration: 3-6 hours Rapid acting: 15-30 minutes Can be given AC and even PC Dispense by prescription Because of its short duration, must be given with Intermediate or Long Acting Insulin To provide basal glycemic control between meals and during the night 3. Insulin Aspart (Novolog) Analog of human insulin Short duration: 3-5 hours Rapid Onset: 10-20 minutes Available in 10 ml vials Given SC eat within 5-10 minutes immediately after administration In combination with Immediate or Long Acting Insulin to provide basal glycemic control between meals and at night Can be mixed with NPH mixing is done just before administration Dispense by prescription 4. Neutral Protamine Hagedorn (NPH) Insulin Protamine the solubility of NPH; retards absorption Delayed Onset Extended duration Intermediate acting Protamine is a foreign body watch for allergic reactions 5. Lente Insulin and Ultralente Insulin less allergenic than NPH Semilente Insulin Most rapid GRACE ANN L. LAGURA, RN MAN Page 9

 Amorphous; noncrystalline Small particles of small size Ultralente Insulin Large crystals Dissoleve slowly Long duration of action Lente Insulin 70% ultralente 30% semilente Intermediate duration of action 6. Insulin Glargine (Lantus) Modified human insulin Prolonged duration of action: 24 hours SC OD for children with Type 1 and adults with Type 2 Low solubility at physiologic ph SC produces microprecipitates that slowly dissolve and release insulin in small amounts over a prolonged time Blood levels of Glargine is steady in 24 hours Less risk of hyperglycemia or hypoglycemia Clear solution but not mixed with any other insulins and not given IV Administration and Storage: Available in 100 u/ml 500 u/ml per request for emergencies and patients with severe insulin resistance 400 u/ml available in other countries All insulins are given SC Only regular insulins can be given IM, IV IM if IV is ompossible IV insulin can be absorbed in the administration set which the dose received Preparation: Insulin preparations consist of particles, they must be evenly mixed Roll the vial between the palms gently vigorous rolling can cause frothing

CLEAR Regular Insulin Lispro Glargine

Sites: Upper arms Thighs Abdomen

CLOUDY Aspart Lente NPH Ultralente

- injections must be made in only one general locale to prevent lipohypertrophy - 1 inch between sites; site is only used once a month

Compatibility of SA Insulins with LA Insulins: SA INSULINS Regular Lispro Aspart NPH Yes Yes Yes LONG ACTING INSULINS LENTE ULTRALENTE Yes Yes Yes Yes --------GLARGINE ------------Page 10

GRACE ANN L. LAGURA, RN MAN

Storage: Unopened Vials Refrigerated until needed Can be used up to the expiration date Vials in Current Use Kept at room temperature for 1 month Causes less pain than injecting cold insulin Partially-Filled Vials Discarded after several weeks if they are unused Mixtures of Insulin Prepared in Vials Stable for 1 month at room temperature 3 months under refrigeration Mixtures of Insulins at Pre-Filled Syringe Refrigerated with the needle facing up to avoid clogging

Methods of Insulin Delivery: Jet Injectors Shoot insulin through the skin No use of needle Pen Injectors With disposable needle and disposable insulin-filled cartridge Insulin Pumps Computerized device deliver basal infusion of insulin (Regular, Lipro, Aspart) Plus bolus doses before each meal Matches the patients metabolism Implantable Insulin Pumps Surgically implanted in the abdomen Delivers insulin intraperitoneally or IV Intranasal Insulin Rapid onset Brief duration Suitable for delivery of mealtime insulin supplement Cant meet basal insulin needs 10% is absorbed INSULIN THERAPY OF DM: Given to all Type 1 to maintain acceptable level of blood glucose Given to some patients with Type 2 Given to Gestational Diabetes Referred to as TIGHT GLUCOSE MONITORING Tight Glucose Monitoring: Benefits: microvascular complications in total diabetes end points Drawbacks: Hypoglycemia because glucose levels are kept relatively low Weight gain GRACE ANN L. LAGURA, RN MAN Page 11

Dosage: Must match with insulin needs caloric meals - insulin dosage Special needs to increase insulin: Infection Stress Obesity Adolescent growth Needs to Insulin: Exercise Pregnancy (during the 1st trimester)

Complications of Insulin Therapy: Blood glucose of <50 mg/dl Insulin than needed Caused by: food intake Vomiting Diarrhea alcohol exercise Parturition Insulin level RAPIDLY Activates Sympathetic Nervous System Tachycardia Palpitations Sweating Nervousness Severe Hypoglycemia: Convulsions Coma Death (irreversible brain damage) Treatment: Fast-acting oral glucose orange juice, sugar cubes Parenteral Glucagon Withhold insulin Ketoacidosis: Can produce coma Increase glucose levels Give insulin Drug Interactions of Insulin with other Drugs: Hypoglycemic Agents can intensify hypoglycemia caused by insulin Example: GRACE ANN L. LAGURA, RN MAN Page 12 Insulin level GRADUALLY Activates Central Nervous System headache confusion drowsiness fatigue

Sulfonylureas Beta blockers Alcohol Meglitinides Hyperglycemic Agents drugs that increase blood sugar level Examples: Thiazides Glucocorticoids Sympathomimetics

Beta Blockers delay awareness of insulin-induced hypoglycemia by masking signs associated with SNS stimulation impairs glycogenolysis a way for our body to counteract glucose level

ORAL HYPOGLYCEMICS FOR TYPE 2 DM: indicated only for Type 2 DM used only when diet and exercise failed to produce glycemic control 1. Sulfonylureas promote insulin release derivatives of sulfonamides but no antimicrobial effects 1st Generation Less potent Drugs: Tolbutamide Acetohexamide Tolazamide Chlorpropamide 2nd Generation More potent Will need a lower dosage Drugs: Glipizide Glyburide Glimepiride

Example: TOLBUTAMIDE (Orinase) First generation Stimulate the release of insulin from the pancreas If pancreas is unable to synthesize insulin Tolbutamide if ineffective Not effective in Type 1 DM; with prolonged use may cellular sensitivity to insulin Tolbutamide binds and blocks with K channels Glucose-dependent

Increase influx of calcium Release of Insulin Adverse Effects of Tolbutamide: Hypoglycemia may be severe and require dextrose infusion Teratogenic in pregnancy Cardiovascular toxicity 2. Meglitinides GRACE ANN L. LAGURA, RN MAN Page 13

 Same as sulfonylureas Stimulates release of pancreatic enzymes Example: REPAGLINIDE blocks K channels, increase calcium influx, increase insulin Adverse Effects of Repaglinide: Hypoglycemia patients should not eat later than 30 minutes

3. Biguanides Example: METFORMIN (Glucophage) production of glucose by the liver Suppressionof gluconeogenesis Enhances glucose uptake and utilization by the muscles Do not promote insulin release by the pancreas Do not cause hypoglycemia Given PO absorbed slowly by the small intestines Excreted in the kidneys unchanged - kidney function result to toxicity Side Effects: appetite Nausea and vomiting absorption of vitamin B12 and folic acid Weight loss Toxicity: Lactic acidosis medical emergency Myalgia Hyperventilation hemodialysis is done to remove Metformin Malaise Somnolence 4. Thiazolinediones (Glitazones) glucose level by decreasing insulin resistance the ability of the target cells to respond to insulin Used as a monotherapy Drugs: Rosiglitazone 4 mg/day to plasma glucose by 76 mg/dl Pioglitazone Troglitazone Adverse Effects: Fluid retention Edema Weight gain Mixed Effects on Plasma Lipid Panels: LDL bad HDL good triglycerides good Monitoring: Liver function tests drug is hepatotoxic Check ALT before starting treatment GRACE ANN L. LAGURA, RN MAN Page 14

5. Alpha Glucosidase Inhibitors: Delay absorption of dietary CHO blood glucose after meals postprandial rise in blood glucose For hyperglycemia not controlled by diet or exercise Used alone or in combination with insulin, metformin or sulfonylureas Drugs: Acarbose (Precose) Miglitol

Adverse Effects: caused by bacterial fermentation of unabsorbed CHO Flatulence Cramps Abdominal distention Borborygmus (rumbling bowel sounds) diarrhea Acarbose Insulin if combined, can cause hypoglycemia Sulfonylureas DIABETIC KETOACIDOSIS: Most severe manifestation of insulin Insulin Deficiency Altered Fat Metabolism Altered Glucose Metabolism

Lipolysis

Glycerol
(substrate for glucose synthesis)

Glucose production

Glucose Metabolism

FFA

Hyperglycemia

FFA Oxidation in the liver

Glycosuria (more than the reuptake of the glomeruli)

Ketoacids

Vomiting

Osmotic Diuresis

Ketosis (detected by the odor of decayed apples in the urine) GRACE ANN L. LAGURA, RN MAN

Water, Na, K loss

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Ketoacidosis Aeg hyperventilates SHOCK

Dehydration

Hemoconcentration

Diabetic Ketoacidosis: brought by altered glucose and fat metabolism altered glucose metabolism cause hyperglycemia, water loss and hemoconcentration altered fat metabolism cause production of ketoacids Treatment of Ketoacidosis: Restoration of Insulin Levels IV bolus of insulin 0.1 u/kg BW Correction of Acidosis Given with HCO3 44.6 mEq dissolve in 500 ml of 0.45% Saline Infused over 1 hour Give K also because HCO3 promoted hypokalemia Replacement of water and sodium IV saline 0.9% or 0.45% Adults require 8-10 L for the first 12 hours K Replacement If plasma K is normal, K should not be administered until plasma level in response to insulin If plasma K is low, K must be given ASAP Glucose Normalization Treat ketoacidosis with insulin will cause hypoglycemia In case of hypoglycemia give glucagon or glucose itself Glucagon for Insulin Overdose: Glucagon A hormone produce by alpha cells of the pancreatic islets plasma level of glucose Relaxes smooth muscles of the digestive tract blood glucose levels after insulin overdose Promotes breakdown of glycogen

GRACE ANN L. LAGURA, RN MAN

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DRUGS FOR THYROID DISORDERS

Thyroid Gland: Produce 2 active hormones: Triiodothyronine (T3) 3 atoms of iodine Thyroxine (T4) 4 atoms of iodine Thyroid Hormone Actions: 3 Principal Actions: Stimulation of energy use Elevates basal metabolic rate Increased oxygen consumption Increased heat production Stimulation of the heart Increases rate and force of contraction Increased cardiac output Increased oxygen demand Promotion of growth and development Essential for the normal development of the brain and other components of the nervous system Maturation of skeletal muscles Synthesis and Fate of Thyroid Hormones: Step 1 Formation of thyroid hormones through the uptake of iodide into the thyroid Uptake process produce 20-50X greater than plasma iodide concentrations Step 2 Oxidation Iodide By the enzyme Peroxidase Iodine (active form of iodide) Step 3 Iodine becomes incorporated into tyrosine residues that are bound to thyroglobulin One tyrosine molecule may receive 2 or more iodine atoms Resulting in the production of Monoiodityrosine And Diiodotyrosine Step 4 Iodinated tyrosine molecules are coupled Diiodotyrosine + Monoiodityrosine = T3 Diiodotyrosine + Diiodotyrosine = T4 Fate: GRACE ANN L. LAGURA, RN MAN Page 17

Thyroid hormones are released from the thyroid by proteolytic process Release of T4 is greater than the release of T3 T4 undergoes conversion to T3 by enzymes in the periphery The conversion of T4 to T3 accounts for 80% of the T3 found in the plasma 99.5% of the T3 and T4 are bound to plasma Only a small percentage of the circulating thyroid hormones are free to cause biologic effects thyroid hormones are excreted by hepatic metabolism metabolism takes place slowly because they are bound to proteins T of T3 = 1.5 days T of T4 = 1 week

Regulation of Thyroid Function by the Hypothalamus and Anterior Pituitary Gland: Hypothalamus Thyrotropin Releasing Hormone (TRH) Anterior Pituitary Gland Thyroid Stimulating Hormone (TSH) Thyroid Inhibition T3 & T4 Biologic Effects Influence of Iodine Levels on Thyroid Function: Low Iodine Causes in thyroid hormones Promotes release of TSH Thyroid size increases (goiter) Thyroid increases its concentration of iodine High Iodine Uptake of iodide is suppressed Synthesis and release of thyroid hormones

GRACE ANN L. LAGURA, RN MAN

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HYPOTHYROIDISM: Can occur at any age Deficiency of thyroid hormones Mild deficiency hypothyroidism Severe deficiency myxedema Hypothyroidism in infants called cretinism Hypothyroidism in Adults: Signs & Symptoms: Pale, puffy and expressionless face Skin is cold and dry Brittle hair; hair loss HR temperature Lethargy, fatigue Cold intolerance Mental impairment Goiter (due to overstimulation of TSH) Causes: Impaired thyroid gland Hashimotos disease autoimmune thyroiditis Insufficient iodine in the diet Surgical removal of the thyroid Destruction of the thyroid by radioactive iodine Insufficient secretion of TSH and TRH Treatment: Levothyroxine (T4) alone usually lifetime Levothyroxin + Liothyronine may be superior Hypothyroidism During Pregnancy: Maternal hypothyroidism- can cause congenital hypothyroidism Congenital hypothyroidism can cause mental retardation and developmental problems Maternal hypothyroidism has impact largely on the 1st trimester when the fetus is unable to produce thyroid hormones Maternal hypothyroidism must be diagnosed early or as soon as pregnancy is confirmed to start treatment immediately Thyroid level should be monitored and dosage increase as needed Hypothyroidism in Infants: Signs & Symptoms: Mental retardation Derangement of growth Large and protruding tongue Potbelly Dwarfism Impaired development of nervous system, bones, teeth and muscles Causes: Autoimmune disease GRACE ANN L. LAGURA, RN MAN Page 19

 Severe iodine deficiency TSH deficiency Exposure to radioactive iodine in utero Treatment: Replacement therapy within a few days after birth and continue for life

Thyroid Hormone Preparations for Hypothyroidism: Available as pure, synthetic compounds Extracts of animal thyroid glands Levothyroxine (T4) Levothyroxine (Levothroid, Levoxyl, Synthroid, Unithroid) DOC for most patients The drug is converted to T3 Produce nearly normal levels of T3 and T4 No need to give T3 along with Levothyroxine T of 7 days Because of long half life, onset is delayed Because of long half life, it causes hormone levels to remain steady between doses Permits OD dosing Given life time Indications: All forms of hypothyroidism (secondary to TSH and TRH) Cretinism Myxedema coma Ordinary hypothyroidism in adults and children Simple goiter Maintain proper levels of thyroid hormones following thyroid surgery, irradiation and treatment with antithyroid drugs Should not be taken to treat obesity (will accelerate metabolism and promote weight reduction if the drugs are taken high enough to establish hyperthyroid state) Adverse Effects: Thyrotoxicosis Drug Interaction: Drugs that Levothyroxine Absorption: Cholestyramine (Questran) Colestipol (Colestid) Ca supplements Sucralfate Aluminum-containing antacids Iron supplements Drugs that Levothyroxine Metabolism: Phenytoin (Dilantin) Carbamazepine (Tegretol) Rifampicin (Rifadin) Phenobarbital

Space administration by 3-4 Dosage hours and Administration: Routes of administration GRACE ANN L. LAGURA, RN MAN Page 20

Oral is taken on an empty stomach Taken in the morning before breakfast IV is used for myxedema coma IV doses are of the size of oral doses

HYPERTHYROIDISM: 2 Forms:

GRAVES DISEASE
S/S: most common cause of thyroid hormone excretion Incidence: females 20-40 years old Rapid and strong HR Dysrhythmias Angina Rapid thought flow Rapid speech Nervousness Insomnia Weak skeletal muscles; may atrophy metabolic rate heat production; temp heat intolerant Warm and moist skin appetite Weight loss (if caloric intake fails to match metabolic rate) Exophthalmos

PLUMMERS DISEASE (Toxic Nodular Goiter)

Result of thyroid adenoma Persistent condition Rarely with remission S/S: Similar with Graves disease but without exophthalmos Treatment: Antithyroid drugs symptoms return rapidly when drug is d/c Surgery radiation

THYROTOXIC CRISIS
Extremely high thyroid levels Characterized By: - hyperthermia - tachycardia - weakness - heart failure - coma

Collective signs indicate Thyrotoxicosis Cause: Thyroid stimulation is caused by thyroid-stimulating immunoglobulins (TSIs) antibodies produced by autoimmune process TSIs stimulate TSH Treatment: Surgical removal of the thyroid Radioactive iodine to destroy thyroid tissue Antithyroid drugs - Propylthiouracil - Methimazole Propanolol to treat tachycardia Thyroid Function Tests: Exophthalmos isTest not a result of Serum T4 hyperthyroidism per se, it is treated with glucocorticoids GRACE ANN L. LAGURA, RN MAN

Cause: excessive production of thyroid hormones overdose of thyroid hormone replacement Treatment: KI Iodine solution PTU Propanolol to reduce tachycardia

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Measures total thyroxine Reflects overall thyroid activity For initial screening of thyroid function Hypothyroidism: T4 level Hyperthyroidism: T4 level Used to monitor thyroid hormone replacement therapy All thyroid preparations except Liothyronine should increase T4 level

Serum T3 Test Measures total triiodothyronine Effective in diagnosing hyperthyroidism (because in hyperthyroidism, T3 often rise sooner and in greater extent than in T4 All thyroid preparations increase T3 Serum TSH Most sensitive method of diagnosing hypothyroidism Because very small reductions in T3 and T4 cause dramatic rise of TSH Used to distinguish primary hypothyroidism from secondary hypothyroidism Primary thyroidal; TSH levels are very high Secondary hypothyroidism from anterior pituitary dysfunction; TSH levels are very low Drugs for Hyperthyroidism: Propylthiouracil (PTU) Methimazole (Tapazole) Blocks thyroid hormone synthesis Prevents oxidation of iodide, inhibiting incorporation of iodine into tyrosine Prevents iodinated tyrosines from coupling Inhibits Peroxidase (the enzyme that catalyzes both reactions) Acts in the periphery to prevent the conversion of T4 to T3 Does not destroy existing stores of thyroid hormones Takes about 3-4 weeks to produce euthyroid state Given oral Rapid onset within 30 minutes T is 75 minutes drug can be given several times a day Crosses placental barrier and breastmilk Indications: 4 Applications in Hyperthyroidism: PTU can be used alone for Graves disease As an adjunct to radiation therapy - to control hyperthyroidism until the effects of radiation appear Suppress thyroid hormone synthesis in preparation for thyroid surgery For thyrotoxicosis Adverse Effects: Agranulocytosis develops during the 1st 2 months sorethroat and fever earliest signs PTU must be discontinued Treated with Granulocyte-stimulating factor (Neupogen) Hypothyroidism Neonatal hypothyroidism and goiter dosage must be kept low Radioactive Iodine (131I) Iodine 131 (Iodotope) T of 8 days GRACE ANN L. LAGURA, RN MAN Page 22

Used in Graves disease destroy thyroid tissue in hyperthyroidism Beta particles emitted by the gamma rays of the 131I do not travel outside the thyroid Initial effects appear in days or weeks Full effects in 2-3 months ADVANTAGES: DISADVANTAGES: Effect of treatment is delayed Treatment is associated with delayed hypothyroidism

Low cost Spared the risk, discomfort and expense of thyroid surgery Death is less likely to occur No other tissue is injured Who Should Be Treated With Radioactive Iodine? Patients over the age of 30 Non responsive to other antithyroid drugs Non responsive to subtotal thyroidectomy Who Should Not Be Treated with Radioactive Iodine? Children because of delayed hypothyroidism Pregnant mothers Nursing mothers Dosage: Determined by the thyroid size 4-10 millicuries (mCi) Use in Thyroid Cancer: Destroy malignant thyroid cells But all forms of thyroid cancer do not accumulate iodine Must give large doses Severe adverse effects: - leucopenia - thrombocytopenia - anemia Preparations: available in capsules and solutions odorless and tasteless

Nonradioactive Iodine Strong Iodine Solution (Lugols solution) Sodium Iodide (IV) Potassium Iodide Action: High concentrations produce paradoxical suppressant effect on the thyroid Decrease iodine uptake by the thyroid Inhibit thyroid hormone synthesis Decrease circulating T3 and T4 Propanolol (Inderal) Suppress tachycardia and other symptoms of Graves disease Occur rapidly unlike Methimazole and PTU All patients must receive Propanolol unless contraindicated

GRACE ANN L. LAGURA, RN MAN

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DRUGS RELATED TO HYPOTHALAMIC & PITUITARY FUNCTION

Pituitary Gland situated just below the brain Hypothalamus located above the pituitary gland 2 Divisions of the Pituitary Gland: Anterior Pituitary or adenohypophysis Posterior Pituitary Gland or neurohypophysis Hormones of the APG: Production & release is controlled by the hypothalamus. Growth Hormone (GH) stimulates growth of all tissues and organs Corticotropin (ACTH) acts on the adrenal cortex Thyrotropin (TSH) acts on the thyroid gland Follicle Stimulating Hormone (FSH) acts on the ovaries to promote follicular growth & development and in the testes to promote spermatogenesis Luteininzing Hormone (LH) promote ovulation and development of corpus luteum in women In men, LH is known as Interstitial cell-stimulating hormone (ICSH) acts on the testes to promote androgen production Prolactin stimulates milk production after parturition Hormones of the PPG: Hormones are synthesize in the hypothalamus & stored at the PPG Oxytocin facilitate uterine contraction at birth ADH promote renal conservation of water Hypothalamus Release-Regulating Factors: Gonadotropin Releasing Hormone (GnRH) Growth Hormone Releasing Hormone (GHRH) Prolactin Releasing Hormone (PRH) Corticotropin releasing Hormone (CRH) Thyrotropin Releasing Hormone (TRH) Somatostatin Dopamine Feedback Regulation of the Hypothalamus and the APG: Regulated by negative feedback mechanism Hypothalamu s Releasing Factor Anterior Pituitary Hormone A GRACE ANN L. LAGURA, RN MAN Page 24

Target organ Hormone B

Biologic Effects Biologic Effects: Promotion of Growth Stimulate growth of all organs and tissues Must be administered prior to epiphyseal closure GH increase bone length producing increase in height Result in enlargement of muscle mass Organs grow proportionate to body growth Brain and eyes do not respond to GH Promotion of Protein Synthesis Cells must increase production of protein GH increase amino acid uptake and utilization Increased protein synthesis result to increase net nitrogen retention (because amino acids have nitrogen content) May result in reduce urinary nitrogen excretion Result to decreased BUN Effects of Carbohydrate Metabolism Reduce glucose utilization; plasma glucose level increase When GH is given to nondiabetics, elevation of blood glucose stimulates the release of insulin When GH is given to diabetic patients, insulin is not released, hyperglycemic action of GH is unopposed Growth Hormone Deficiency GH in children result in Dwarfism Growth is retarded to an equal extent in all parts of the body Cause is primarily pituitary adenoma Dwarfism is not associated with mental impairment Growth of normal individuals cease at puberty Dwarves continue to grow throughout life Treatment: replacement therapy with human GH Growth Hormone Excess GH in children result in Gigantism (Giantism); children grow very tall In adults, it is Acromegaly; result in coarse facial features, splayed teeth, large hands and feet; height is not increased due to closure of epiphyses Signs: Cardiomegaly Hypertension Arthralgias Hyperglycemia Headache Treatment: Surgical removal of the pituitary then radiation as an adjunct treatment GRACE ANN L. LAGURA, RN MAN Page 25

 Radiation as a primary treatment may take 10-20 years to produce full response Octreotide (Sandostatin) Analog of somatostatin Suppress GH release Mimic suppressant action of somatostatin in the pituitary Primary therapy for acromegaly or adjunct to radiation and surgery Usually dose: 100 ug SC TID Side effects: GI upset but may subside of 1-2 weeks, develop cholesterol Gallstones

Therapeutic Uses: For children whose growth has been retarded by growth hormone deficiency Treatment must begin before epiphyseal closure Efficacy of treatment declines as patient grows older and lost at age 20-24 Short children with normal GH level are inappropriate for GH therapy Not very effective for children with normal GH level (average increase in height is 2 in) Adverse Effects: Hyperglycemia Hypothyroidism Antibodies to GH

GRACE ANN L. LAGURA, RN MAN

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