Endocrine Agents

Pituitary gland (Hypophysis)

− The Pituitary gland is an endocrine gland the size of a pea
located at the base of the skull. Divided into 2 lobes:
Anterior pituitary (adenohypophysis)-------Oxytocin, ADH
Posterior pituitary (neurohypophysis)----Growth hormone,
prolactin, FSH, Thyroid, endorphins
Pituitary Agents
Anterior pituitary agents
− cosyntropin
− somatotropin
− octreotide
Posterior pituitary agents
− vasopressin
− desmopressin

Uses
− Replacement therapy to make up for hormone deficiency
− Drug therapy to produce a specific hormone response when a hormone deficiency is present
− Diagnostic aids to determine hypofunction or hyperfunction of a specific hormonal function

Mechanism of Action
− Differ depending on the agent
− Either augment or antagonize the natural effects of the pituitary hormones

Indications
Corticotropin
− Stimulation of release of cortisol from adrenal cortex
− Used to diagnose, but not treat, adrenocortical insufficiency
− Multiple sclerosis
− corticotropin insufficiency caused by long-term corticosteroid use
− (↓inflammation ↓histamine↑edema)

Somatropin (mimics GH)

− Recombinantly made growth hormone (GH)
− Stimulate skeletal growth in clients with deficient GH, such as hypopituitary dwarfism

Octreotide (inhibits GH release)

− Alleviates or eliminates certain symptoms of carcinoid tumors, acromegaly
 − vasopressin and decompress
− (Mimic ADH)
o Used in the treatment of diabetes insipidus (not diabetes mellitus)
o Used in the treatment of various types of bleeding, especially GI bleeding
o desmopressin is useful for increasing factor VIII (anti-hemophilic factor):
▪ Hemophilia A
▪ Type I von Willebrand’s disease
Thyroid Gland
− One of the largest endocrine glands
− Secretes three hormones essential for proper regulation of metabolism
o Thyroxine (T4)
o Triiodothyronine (T3)
o Calcitonin
− Located near the parathyroid gland
− Involved in many bodily processes, growth, body temperature regulation, cardiovascular, endocrine &
neuromuscular functions.
− Iodide from diet is responsible for the synthesis thyroglobuline
− Hypothalamus secretes TSH that stimulates the thyroid to break down thyroglobulin into T3 & T4 and
is released into the circulation
Hypothyroidism: Deficiency in Thyroid Hormones

− Primary: abnormality in the thyroid gland itself. Most common cause is hashimoto’s thyroiditis.
− Secondary: results when the pituitary gland is dysfunctional and does not secrete TSH

Thyroid abnormalities
Cretinism: Hyposecretion of thyroid hormone during youth. Low metabolic rate, retarded growth and sexual
development, possibly mental retardation
Myxedema: Hyposecretion of thyroid hormone as an adult. Decreased metabolic rate, loss of mental and
physical stamina, weight gain, loss of hair, firm edema, yellow dullness of the skin

Goiter: Enlargement of the thyroid gland. Results from overstimulation by elevated levels of TSH. TSH is
elevated because there is little or no thyroid hormone in circulation

Hypothyroidism: pathologies − Common symptoms of hypothyroidism

o Thickened skin
− Hashimoto’s thyroiditis o Hair loss
− Postoperative hypothyroidism o Constipation
− Postpartum thyroiditis o Lethargy

Thyroid Preparations ◼ Anorexia

− Levothyroxine * most common

o Synthetic thyroid hormone t4
− Liothyronine
o Synthetic thyroid hormone t3
Mechanism of action
− Thyroid preparations are given to replace what the thyroid gland cannot produce to achieve normal
thyroid levels.
− Thyroid drugs work the same way as thyroid hormones
Indications

− To treat all three forms of hypothyroidism

− levothyroxine is the preferred agent because its hormonal content is standardized; therefore, its effect is
predictable
− Also used for thyroid replacement in clients whose thyroid glands have been surgically removed or
destroyed by radioactive iodine in the treatment of thyroid cancer or hyperthyroidism
Side effects
− Cardiac dysrhythmia is the most significant adverse effect
− May also cause:
o Tachycardia, palpitations, angina, hypertension, insomnia, tremors, headache, anxiety, nausea,
diarrhea, menstrual irregularities, weight loss, sweating, heat intolerance, others
Hyperthyroidism: Excessive Thyroid Hormones: free T3 & T4
− Caused by several diseases
o Graves’ disease
o Toxic nodular disease
o Multinodular disease
o Thyroid storm
o Thyroid cancer
o Pituitary hormones
− Affects multiple body systems, resulting in an overall increase in metabolism
o Wt loss
o Diarrhea – Fatigue
o Flushing – Palpitations
o Increased appetite – Nervousness
o Muscle weakness – Heat intolerance
o Sleep disorders – Irritability
o Altered menstrual flow

Treatment of Hyperthyroidism
− Radioactive iodine (131I) works by destroying the thyroid gland
− Surgery to remove all or part of the thyroid gland
− Antithyroid drugs: thioamide derivatives
o methimazole
o propylthiouracil (PTU)
Antithyroid Agents
− Used to palliate hyperthyroidism and to prevent the surge in thyroid hormones that occurs after the
surgical treatment or during radioactive iodine treatment for hyperthyroidism
− May cause liver and bone marrow toxicity.
Adrenal Gland

− An endocrine gland that sits on tops of the kidneys

− It is composed of Adrenal cortex & Adrenal medulla
- chiefly responsible for regulating the stress response through the synthesis of corticosteroids and
catecholamines, including cortisol and adrenaline.
- Each portion has different functions and secretes different hormones

Adrenal medulla secretes: Epinephrine & Norepinephrine

Adrenal cortex secretes corticosteroids: Glucocorticoids, Mineralocorticoids (primarily aldosterone) & All
adrenal cortex hormones are steroid hormones

Adrenocortical Hormones
Over secretion leads to Cushing’s syndrome
↑ cortisol in the blood. Cushings disease is very similar to Cushings syndrome in that all physiologic
manifestations of the conditions are the same.
↑wt gain, moon face, ↑sweating,thinning of skin,buffalo hump, histuism
Under secretion leads to Addison’s disease
Addison's disease is an endocrine or hormonal disorder that occurs in all age groups and afflicts men and
women equally. The disease is characterized by weight loss, muscle weakness, fatigue, low blood pressure, and
sometimes darkening of the skin in both exposed and nonexposed parts of the body.
 − Can be either synthetic or natural
− Many different agents and forms
− Glucocorticoids
o Topical, systemic, inhaled, nasal
− Mineralocorticoid
o Systemic
− Adrenal steroid inhibitors
o Systemic

Glucocorticoids
− betamethasone (several formulations) − cortisone
− fluticasone propionate − methylprednisolone
− hydrocortisone (several formulations) − prednisone

Mineralocorticoid
− fludrocortisone acetate (Addison’s disease)
Adrenal steroid inhibitors
− Ketoconazole (Cushing's syndrome (high blood levels of cortisol)
− Mitotane (adrenocortical carcinoma)

Mechanism of action

− Most exert their effects by modifying enzyme activity

− Different agents differ in their potency, duration of action, and the extent to which they cause salt and
fluid retention
− Glucocorticoids inhibit or help control inflammatory and immune responses.
Indications
− Wide variety of indications
o Adrenocortical deficiency
o Cerebral edema
o Collagen diseases
o Dermatological diseases
o GI diseases
o Exacerbations of chronic respiratory illnesses, such as asthma and COPD
o Organ transplant (decrease immune response)
o Palliative management of leukemias and lymphomas
o Spinal cord injury

Glucocorticoids given:
o By inhalation for control of steroid-responsive bronchospastic states
o Nasally for rhinitis and to prevent the recurrence of polyps after surgical removal
o Topically for inflammations of the eye, ear, and skin
Antiadrenals (adrenal steroid inhibitors)
o Used in the treatment of Cushing’s syndrome
Contraindications

− Drug allergies
− Serious infections, including septicemia, systemic fungal infections, and varicella
Side Effects
− Potent effects on all body systems
o Cardiovascular
▪ Heart failure, cardiac edema, hypertension—all due to electrolyte imbalances
o CNS
▪ Convulsions, headache, vertigo, mood swings, nervousness, insomnia, others.
o Endocrine
▪ Growth suppression, Cushing’s syndrome, menstrual irregularities, carbohydrate
intolerance, hyperglycemia, others
o GI
▪ Peptic ulcers with possible perforation, pancreatitis, abdominal distention, others
o Integumentary
▪ Fragile skin, petechiae, ecchymosis, facial erythema, poor wound healing, hirsutism,
urticaria
o Musculoskeletal
▪ Muscle weakness, loss of muscle mass, osteoporosis
o Other
▪ Weight gain

Diabetes Mellitus

− Two types: Type 1 & Type 2

− Hyperglycemia: Fasting plasma glucose >7 mmol/L
− Hypoglycemia: Blood glucose level <2.8 mmol/L
− Gestational diabetes

Signs & Symptoms of DM

− Polydipsia − Polyphagia − Fatigue
− Polyuria − Wt loss − Blurred vision
Type 1 Diabetes Mellitus IDDM

− Characterized by loss of the insulin-producing beta cells of the islets of Langerhans of the pancreas
leading to a deficiency of insulin.
− Affected clients need exogenous insulin
− Complications
o Retinopathy, nephropathy, neuropathy
− Diabetic ketoacidosis (DKA)
− Oral antihyperglycemic agents not effective

Type 2 Diabetes Mellitus

− Most common type
− Caused by insulin deficiency and insulin resistance, but there is not an absolute of insulin production
− Many tissues are resistant to insulin
o Reduced number insulin receptors
o Insulin receptors less responsive
− ↑Obesity among children and adolescent is increasing the incidence

Type 2 diabetes Metabolic syndrome

− The cluster of co-occurring conditions of:
− ↑ Abdominal obesity, ↑triglycerides, ↑BP
− Are strongly associated with the development of type 2 diabetes.
− Obesity worsens insulin resistence because adipose tissue is the site of large porportions of the body’s
defective insulin receptors.
Type 2 Diabetes Mellitus
− Several comorbid conditions
o Glucose intolerance o Microalbuminemia (protein in the
o Obesity urine)
o Dyslipidemia o Enhanced conditions for embolic
o Hypertension events (blood clots)
o Insulin resistance o Heart disease
o Hyperinsulinemia

Types of Antidiabetic Agents

− Insulins
− Oral antihyperglycemic agents
− Both aim to produce normal blood glucose states
Human-Based Insulins
− Rapid acting, (aspart, lispro)
− Short acting (regular, humulinR, Toronto)
− Intermediate acting (Humulin N, NPH)
− Long acting (glargine, detemir)
− Combination Insulin products (humulog, humulin 30/70 20/80)
o Regular insulin
▪ The only insulin product that can be given by IV bolus, IV infusion, or even IM
Sliding-Scale Insulin Dosing
− SC regular insulin doses adjusted according to blood glucose test results
− Typically used in hospitalized diabetic clients
− Subcutaneous regular insulin is ordered in an amount that increases as the blood glucose increases

Oral Antidiabetic Agents

− Used for type 2 diabetes

− Treatment for type 2 diabetes includes lifestyle modifications
o Diet, exercise, smoking cessation, weight loss
− Oral antihyperglcemic agents may not be effective unless the client also makes behavioural or lifestyle
changes
− Insulin secretagogues: 2 classes of drugs able to stimulate insulin secretion:
- Sulfonylureas: chlorpropamide, tolbutamide, glimepiride, gliclazide, glyburide
- Nonsulfonureas: repaglinide, nateglinide
- Biguanides: metformin
- Alpha-glucosidase inhibitors: Acarbose
- Thiazolidinediones (Actos): pioglitazone, rosiglitazone. Also known as “glitazones”

Oral Antihyperglycemic Agents: Mechanism of Action

− Sulfonylureas (Glyburide)
o Stimulate insulin secretion from the beta cells of the pancreas, thus increasing insulin levels
o Forces the extra glucose out of the blood into the cells where it can be stored and used for
energy.
o Beta cell function must be present
o Improve sensitivity to insulin in tissues
o Result: lower blood glucose levels
− Biguanides (metformin)
o Decrease production of glucose by the liver
o Increase uptake of glucose by tissues
o Do not increase insulin secretion from the pancreas therefore does not cause hypoglycemia
 − Alpha-glucosidase (New drug category!) inhibitors: Acarbose (Precose)
− Reversibly inhibit the enzyme alpha-glucosidase in the small intestine
o Result: delayed absorption of glucose
o Must be taken with meals to prevent excessive postprandial blood glucose elevations

Thiazolidinediones (Actos) (New drug category!)

− Decrease insulin resistance
− “Insulin sensitizing agents”
− Increase glucose uptake and use in skeletal muscle
− Inhibit glucose and triglyceride production in the liver

Oral Antihyperglycemic Agents: Indications

- Used alone or in combination with other agents and/or diet and lifestyle changes to lower the blood
glucose levels in clients with type 2 diabetes

Oral Antihypoglcemic Agents: Side Effects

− Sulfonylureas (Glyburide)
o Hypoglycemia, hematological effects, nausea, epigastric fullness, heartburn, many others
− Biguanides (Metformin)
o Abdominal bloating, nausea, cramping, diarrhea, metallic taste, reduced vitamin B12 levels
− Alpha-glucosidase inhibitors (arcabose)
o Flatulence, diarrhea, abdominal pain
− Thiazolidinediones (Actos)
o Moderate weight gain, edema, mild anemia, hepatic toxicity

Symptoms of hypoglycemia include:

− hunger
− nervousness and shakiness
− perspiration
− dizziness or light-headedness
− sleepiness
− confusion
− difficulty speaking
− feeling anxious or weak

Lessening Fingertip Pain From Testing

− Don't use rubbing alcohol. Repeated use will thicken the skin. Instead, wash your hands in warm, soapy
water prior to your fingerstick. Warm water will help you produce a better drop of blood. Once your
finger is pricked, do not squeeze immediately. Instead, hang your hand down and let gravity do the
work for you. Try 'milking' your finger prior to lancing. Excessive squeezing to get the blood to flow
could cause bruising.
− Try a shallower puncture.
The deeper you lance, the more tissue you damage.
− Try different lancets.
Many lancets on the market are interchangeable with different lancing devices. Look for shorter and
finer products and talk to your diabetes educator. It's better to 'spread the damage' over as many sites as
 possible instead of abusing that favourite spot. Target the sides of your fingers instead of the soft centre
area where there are more nerve endings.
− suggest clients go in a 'horseshoe' pattern around their fingertips.
− Apply firm pressure at the site of the finger prick: using a tissue, for several seconds or until you have
no more leakage. You want to make sure that the bleeding has completely stopped at the site to prevent
bruising and further pain.
− Canadian diabetes Association