2© paradigm publishing, inc. chapter 17 the endocrine system and drug therapy

© Paradigm Publishing, Inc. 2

Chapter 17

The Endocrine System and Drug Therapy


Chapter 17

Topics

• Anatomy and Physiology of the Endocrine System• Diabetes• Thyroid Disorders• Adrenal Gland Disorders• Herbal and Alternative Therapies


Anatomy and Physiology of the Endocrine System

The Endocrine System• A collection of glands in various parts of the body that

produce hormones that regulate bodily functions Hormones are secreted substances that regulate

metabolism, growth, and fluid balance in various ways• A negative feedback system regulates hormone release;

often is a series of hormones, with one activating the next As more hormones are released into the bloodstream,

receptors detect the rise in concentration of the hormone and signal the gland to slow production



Pituitary Gland• It controls other endocrine glands and bodily functions• Part of the hypothalamic-pituitary axis• Pituitary gland plays a key role in growth, onset of puberty,

and reproduction cycles Core feedback mechanism that controls endocrine

function



Pituitary Gland • This gland

stimulates other glands in the endocrine system to release hormones into the bloodstream• These hormones

trigger responses in target tissues



Thyroid Gland • It releases T3 and T4 in response to TSH released from the

pituitary gland• T3 controls most of the physiological action

• Both T3 and T4 regulate basal metabolic rate and affect metabolism of carbohydrates, fats, and proteins

• Thyroid hormones increase conversion of food to energy which raises body temperature Iodine is required for formation of thyroid hormones



Adrenal Glands • Glands are located on top of the kidneys• Adrenal cortex (outer layer) releases corticosteroids

Mineralocorticoids regulate fluid and electrolyte balance

Glucocorticoids affect day/night cycles and metabolism• Adrenal medulla (inner layer) produces adrenaline

(epinephrine) Adrenaline increases blood pressure, diverts blood

from organs to muscles, releases stored glucose and fat



Adrenal Glands (continued)• Adrenaline readies

the body for “fight or flight” • It can give someone

tremendous strength or speed when encountering a fearful situation



Hypothalamus • Hypothalamus produces corticotropin-releasing factor that

stimulates the pituitary gland to make ACTH• ACTH stimulates adrenal glands to release cortisol (the

primary glucocorticoid) in a circadian rhythm• Cortisol affects glucose metabolism, fat deposition, water

retention, and anti-inflammatory action of the immune system



Pancreas• It produces and releases digestive enzymes into intestine• Alpha islet cells of pancreas produce glucagon, which

activates liver cells to break down stored glycogen into glucose and release it into the blood

raises blood glucose levels facilitates breakdown of fats and proteins into

alternative sources of energy, producing ketones• Beta islet cells of pancreas produce insulin, which

is released in response to a rise in blood glucose allows glucose to enter cells and provide energy



Normal GlucoseMetabolism• The pancreas

releases insulin after eating to lower blood glucose and releases glucagon when fasting to maintain adequate blood glucose



Blood Glucose Levels• Various

hormones produced in the endocrine system maintain blood glucose levels after eating and between meals


Diabetes

About Diabetes Mellitus• Diabetes is elevated blood glucose that results in damage

to small blood vessels and nerve tissue It has significant and life-threatening effects

• Three types: Type 1, Type 2, and gestational diabetes

Type 1 Diabetes• Least common type; affects about 10% of patients with

diabetes (sometimes called juvenile diabetes) • Autoimmune process impairs body’s ability to make insulin• Without insulin, glucose climbs to dangerous blood levels;

body uses alternative energy sources, producing ketones


Diabetes

Type 1 Diabetes• In the absence of

insulin, ketones accumulate to toxic levels in the blood, producing a life-threatening emergency called ketoacidosis• Therefore, insulin is

given to patients with Type 1 diabetes


Diabetes

Type 2 Diabetes• A multifactorial disorder causing high blood glucose;

accounts for around 90% of patients with diabetes• It begins with central obesity (accumulation of abdominal

fat) that causes insulin insensitivity Pancreas still makes insulin, but the insulin does not

work as well• Insulin insensitivity triggers overproduction of glucagon,

which increases blood glucose• Beta cells try to produce more insulin but can’t keep up• First treated with oral agents; eventually insulin is needed


Diabetes

Type 2 Diabetes(continued)• Progressive disease

that causes insulin insensitivity, impaired insulin production, and altered glucagon release


Diabetes

Type 2 Diabetes: Metabolic Syndrome• Many patients with Type 2 diabetes have metabolic

syndrome• Condition refers to a triad of problems: high BP, high

cholesterol and triglycerides, and high blood glucose• Patients may not have high blood glucose all of the time

May have impaired fasting glucose or impaired glucose tolerance

• Condition puts patients at high risk for cardiovascular disease


Diabetes

Gestational Diabetes• Insulin resistance caused by excess hormones produced

during pregnancy; preserves glucose for developing fetus• It mimics Type 2 diabetes and often precedes it

Symptoms of All Types of Diabetes• Common: increased urination (polyuria), excessive

urination at night (nocturia), glucose in the urine (glycosuria), thirst (polydipsia), hunger (polyphagia), blurred vision, fatigue

• Other: frequent infections, slow wound healing, weight gain or loss, numbness and tingling in fingers and toes


Diabetes

Risk Factors for Developing Type 2 Diabetes

• Age over 45 years• Family history of diabetes

(parents/siblings)• Overweight (BMI over 25

kg/m2)• Habitual physical inactivity• Race/ethnicity• Impaired fasting glucose or

glucose intolerance

• Hypertension (BP over 140/90 mmHg)

• Low HDLs and high triglycerides

• History of gestational diabetes or birth of baby over 9 pounds

• Polycystic ovary syndrome


Diabetes

Untreated Diabetes: Microvascular Complications• Nephropathy: damage to kidneys, affecting their ability to

filter the blood If untreated, can lead to kidney failure and transplant

• Neuropathy: damage to tiny nerves in the extremities; in the feet, loss of sensation can lead to ulcers If untreated, can lead to infection and amputation

• Retinopathy: damage to retinal tissue in the eyes If untreated, can progress to blindness


Diabetes

Untreated Diabetes: Macrovascular Complications• Macrovascular complications for Type 2 diabetes

Heart disease Heart attack

Patient with diabetes half as likely to survive as someone without diabetes

Strokes


Diabetes

Hypoglycemia • Low blood glucose or low blood sugar reaction• Commonly results from injecting too much insulin or

skipping meals when taking medication for diabetes• Symptoms: shakiness, dizziness, sweating, headache,

irritability, confusion, vision changes, hunger• If have symptoms, test blood glucose and consume

simple sugar right away 15–30 g of carbohydrate such as nondiet soda, juice,

hard candy, glucose tabletsDo not ingest large amounts of food


Diabetes

Measuring Blood Glucose• Diabetes is detected by measuring blood glucose (sugar)

concentrations via lab blood tests or fingerstick at home• Blood glucose levels

Normal: 70–120 mg/dL Indicative of diabetes: 200 mg/dL or greater or a fasting

result (8+ hours since eating) of 126 mg/dL or greater• Glucose meters

Available for home use; technicians can help patients with selection and demonstration

Goal is to maintain blood glucose within normal range


Diabetes

Measuring Blood Glucose: Hemoglobin A1C Test• Test used to assess overall blood glucose control• Measures the percentage of RBCs with glucose stuck to the

hemoglobin molecules contained inside Glucose binds to hemoglobin for life of RBCs (3 months) This test provides an overall average of glucose

concentration over the previous 3 months• Normal range for an A1C is 4–6%; patients with untreated

diabetes can have an A1C of 10% or greater• The test can be run via a blood draw in the laboratory or

fingerstick technology in a clinic or pharmacy setting


Diabetes

Drugs for Diabetes• Drug therapy treats but does not cure disorder• Treatment for Type 1 diabetes is insulin• Initial treatment for Type 2 diabetes is lifestyle changes

Reduction of carbohydrate, fat, and calorie intake; regular exercise; smoking cessation; weight loss

• Drug therapy for Type 2 diabetes begins with metformin, followed by combination therapy, and eventually leading to insulin Insulin is required to achieve goals for blood glucose

and A1C


Your Turn

Question 1: What is the function of glucose in the body?Answer: Glucose provides the energy for all the cells in the body to live.

Question 2: A patient who has Type 2 diabetes has made various lifestyle changes. She has lost excess weight, watches her carbohydrate and fat intake, and exercises most days. What is likely to happen next?

Answer: Because Type 2 diabetes is progressive, the patient will eventually need drug therapy, beginning with metformin.


Diabetes

Drugs for Diabetes: Metformin• Indication (initial): Type 2 diabetes, alone or in

combination with other agents• Mechanism of Action: inhibits excess hepatic glucose

production, increases insulin sensitivity in body tissues• Route: all are oral; take with food or milk• Side Effects (common): stomach upset, abdominal cramps,

nausea, diarrhea, flatulence, metallic taste• Side Effects (severe, rare): lactic acidosis (potentially fatal)• Cautions: Contraindicated in patients with kidney

dysfunction, liver problems, heart failure


Diabetes

Drugs for Diabetes: Insulin Secretagogues• Two classes: sulfonylureas and glinides• Indication (sulfonylureas and glinides): Type 2 diabetes,

alone or in combination with other agents• Mechanism of Action: stimulate insulin production from

the pancreas to directly lower blood sugar• Route: all are oral; different onsets and durations of action

Sulfonylureas: 30 minutes or more to start working, last 8 hours or longer

Glinides): 10 minutes to start working, last for about 2 hours


Diabetes

Drugs for Diabetes: Insulin Secretagogues (continued)• Side Effects (common): hypoglycemia• Side Effects (other): nausea, diarrhea, constipation• Cautions: patients should know the symptoms of low

blood sugar and how to treat it; monitor regularly• Cautions: patients with liver or kidney disease may not be

able to take sulfonylureas


Diabetes

Drugs for Diabetes: Thiazolidinediones • Also called glitazones or TZDs• Indication: Type 2 diabetes, used in combination with

metformin or sulfonylureas• Mechanism of Action: cause increased production of

insulin receptors to increase insulin sensitivity in body • Route: all are oral; onset varies (weeks or months)• Side Effects (common): fluid accumulation (edema),

weight gain• Side Effects (severe, rare): liver toxicity, macular edema• Caution: patients with heart failure should not take TZDs

© Paradigm Publishing, Inc.

Diabetes

Drugs for Diabetes: Incretin Therapies• Indication: Type 2 diabetes, in combination with

metformin or sulfonylureas• Mechanism of Action: either mimic endogenous incretin

hormones or change their metabolism to increase activity• Route: SC or oral• Side Effects (GLP-1, common): nausea, vomiting, diarrhea,

dizziness, fatigue, headache• Side Effects (DPP-4 inhibitors, common): headache,

nasopharyngitis, upper RTIs• Caution: refrigerate injectables until dispensed or used

32


Diabetes

Drugs for Diabetes: Insulin• Indication (Type 1): combination of basal and bolus insulin• Indication (Type 2): same as Type 1 or an injection of long-

acting insulin at bedtime added to oral medications• Four types of insulin: rapid-acting, short-acting,

intermediate-acting, long-acting (see Table 17.6)• Route: SC injection only; self-injections used

Abdomen is preferred injection site due to consistent rate of absorption into blood

Insulin available in vials (for syringes) and self-injector pen devices; patients must be instructed on use


Diabetes

Drugs for Diabetes: Insulin (continued) Insulin pumps also available; deliver insulin through a

tiny tube just under the skin• Side Effects (common): serious hypoglycemia• Side Effects (severe): diabetic coma if blood glucose levels

are lower than 40 mg/dL Diabetic coma (loss of consciousness and brain

damage) is a medical emergency• Caution: insulin should be refrigerated until

dispensed or used; do not use if insulin clumps or looks frosty


Diabetes

Drugs for Diabetes: Alpha-Glucosidase Inhibitors• Indication: adjunctive treatment for Type 2 diabetes, but is

limited by side effects• Mechanism of Action: inhibit digestion of carbohydrates

within the GI system, which reduces glucose absorption• Route: oral; taken with first bite of each meal to keep

carbohydrates in the food from entering the bloodstream in high amounts

• Side Effects (common): abdominal pain, gas, bloating, diarrhea


Thyroid Disorders

Hypothyroidism • Too little thyroid hormone is produced (more common

than hyperthyroidism)• Causes: pituitary or hypothalamus dysfunction, removal of

thyroid, Hashimoto’s disease; radioactive iodine therapy• Symptoms: constipation, bradycardia, dry skin, tremors,

weight gain, cold intolerance, depression, fatigue, reduced mental acuity, memory loss


Thyroid Disorders

Hyperthyroidism • Too much thyroid hormone is produced• Causes: Graves’ disease, thyroid nodules or tumors,

pituitary nodules or tumors• Symptoms: diarrhea, skin flushing, nervousness, insomnia,

hyperactivity, heat intolerance, tachycardia, weight loss• Sign: exophthalmos (fat collects behind the eyeball,

causing protrusion and inability for eyelids to fully close)


Thyroid Disorders

TSH and the Hypothalamic-Pituitary Axis • TSH is the lab test

used to monitor thyroid disorders

• TSH, released by the pituitary gland, stimulates thyroid to make T3 and T4

• High TSH results means that T3 and T4 are low (hypothyroid)


Thyroid Disorders

Drugs for Thyroid Disorders • Treatment for hypothyroidism involves oral thyroid

hormone supplementation• Treatment for hyperthyroidism involves

Surgery to remove or reduce the malfunctioning gland or ablation (destroys thyroid via radioactive iodine)

Afterward, oral thyroid supplementation is given to artificially provide adequate hormone levels

• Route: daily oral doses; doses are individualized to each patient using blood tests to measure hormone levels Each tablet strength of thyroid hormone is color-coded


Thyroid Disorders

Drugs for Thyroid Disorders (continued)• Side Effects (common): usually related to therapeutic

overdose; patient exhibits hyperthyroid symptoms such as heart palpitations, elevated BP, fever, tremors, headache

• Side Effects (long-term overdosage): loss of bone density and impaired fertility; for gross overdosing, cardiac arrest

• Caution: when filling thyroid hormone products, use the same product for the same patient for each refill Do not switch between brands and generic forms Various brands may contain slightly different amounts,

enough for changes to be felt by individual patients


Your Turn

Question 1: A patient who has diabetes is taking insulin. Because he is very busy at work, he decides to skip breakfast and lunch. Now he feels like he might pass out. His blood glucose concentration is 40 mg/dL. What will likely happen next?

Answer: The patient may be experiencing a diabetic coma, requiring emergency care.

Question 2: How is drug therapy for hypothyroidism and hyperthyroidism alike?

Answer: In hypothyroidism, thyroid hormone supplementation is accomplished with the same oral medications as used after thyroid removal or ablation in hyperthyroidism.


Adrenal Gland Disorders

About Adrenal Gland Disorders• Disorders can be categorized by either the overproduction

or the underproduction of hormones• Two types of adrenal gland disorders include Addison’s

disease and Cushing’s disease

Addison’s Disease • Deficiency (underproduction) of glucocorticoids and

mineralocorticoids; this condition can be serious• Symptoms: weakness; hyperkalemia, hyperpigmentation

of skin, low blood sodium and glucose, low BP, weight loss• Treatment: oral corticosteroids


Adrenal Gland Disorders

Cushing’s Disease • Overproduction of steroid hormones; often caused by

tumors in the adrenal glands, but overmedication with corticosteroids is also a cause

• Symptoms: moon face, abdominal weight gain, buffalo hump, osteoporosis, mood changes, hypertension, cataracts, PUD

• Normal sleep and wake cycles may also be affected• Treatment: surgery to remove tumors; sometimes

cytotoxic drug therapy


Herbal and Alternative Therapies

• Chromium An essential trace element used for diabetes

prevention and treatment Patients with diabetes have a chromium deficiency

Patients with kidney or liver disease should avoid• Cinnamon

Taken for Type 2 diabetes Research shows that it has minimal effects on

blood glucose Patients with liver diseases should avoid


Summary• The endocrine system regulates metabolism, growth, and

fluid in various ways• Insulin is used exclusively to treat Type 1 diabetes• Type 2 diabetes is treated with oral agents first; most

patients need insulin at some point• Metformin, sulfonylureas, TZDs, and incretins are oral

agents used to treat Type 2 diabetes• Oral thyroid hormones are used to treat hypothyroidism• Addison’s disease and Cushing’s disease are adrenal gland

disorders

2© paradigm publishing, inc. chapter 17 the endocrine system and drug therapy

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