UNIT 6

Drugs used in
Treatment of
Endocrine
System
Disorders
 INTRODUCTION
Endocrine portion of pancreas has Islets of Langerhans:
❖Alpha cells make glucagon: “counterregulatory”,
acts opposite of insulin.
❖Beta cells make insulin: Allows body cells to store
and use carbohydrate, fats, and protein.
 Diabetes Mellitus
Diabetes mellitus is a group of syndromes characterized by
hyperglycemia, altered metabolism of carbohydrate, lipid and
protein and an increased risk of complication from vascular
diseases.
 Hyperglycemia
When blood glucose becomes high then Insulin allows glucose to enter
cells as follows
Effects of insulin
Antidiabetic Medications
Medicines that control diabetes are called antidiabetes drugs. They are classified
into two categories:
❑Insulin
❑Oral hypoglycemic agents Sulfonylureas
❖Thiazolidinediones
❖Biguanides
❖Alpha-glucosidase inhibitors
❖Meglitinides
▪ Incretin based therapy
▪ GLP-1 Analogue
▪ DPP-4 Inhibitors
▪ Amylin Analogue
Time graph of various types of insulin
Methods of Adminisration
❖Insulin Syringes
❖Pre-filled insulin pens
❖External insulin pumps
Contraindications
❖There are no absolute contraindications to insulin therapy, the dose of
insulin needs to be adjusted and monitored.
❖Insulin dosing requires adjustment in patients with renal impairment
and liver failure.
• Drug Interaction
Insulin should not be given with other drugs, which also cause
hypokalemia, like diuretics.
• Toxicity
Large doses of insulin will trigger hypoglycemic symptoms in
the patient. Headache, dizziness, palpitations, sweating, stomach
pain, and impaired vision are some of the symptoms. Increasing
glucose levels is the immediate treatment for such people.
Sites of giving insulin injection
(Subcutaneous)
Anti-diabetes drugs/Oral Hypoglycemic Drugs
These drugs are given orally and are effective to manage hyperglycemia.
They are classified as:
❖Sulfonylureas
❖Biguanides
❖Meglitinides
❖Thiazolidinedione Derivatives
❖α-Glucosidase Inhibitors
❖Incretin Based Therapy
❖Amylin Based Therapy
Sulfonylureas
Sulfonylureas represent a class of medications utilized in the treatment of type 2
diabetes mellitus. It lower blood sugar as a result of increasing release of insulin
from the pancreas.
Biguanides

Biguanides are used to treat type 2 diabetes. They work by reducing the
amount of glucose produced by the liver and increasing the body's
sensitivity to insulin, which helps to lower blood sugar levels.

Commonly used biguanides is metformin.

Metformin (0.5-2.5 g per day) (orally)

Meglitinides

It is a class of glucose-lowering drugs that act by closing ATP-dependent potassium

channels in pancreatic beta cells, thus causing calcium channel opening and
subsequent insulin release.

Classification/Dose/Route

❑Repaglinide (1-8 mg per day) (orally)

❑Nateglinide (180-480 mg per day) (orally).

Thiazolidinedione Derivatives
Thiazolidinediones are medications used to manage and treat type 2
diabetes mellitus. These medications may be acting as a nuclear
transcription regulator and an insulin sensitizer.
Classification/Dose/Route
❖Pioglitazone: Initial 15 to 30 mg PO with a meal once a day; may
increase the dose by 15 mg with careful monitoring to 45 mg once a
day. The maximum dose is 45 mg.
❖Rosiglitazone: Initial 4 mg PO once a day. If inadequate response
after 8 to 12 weeks, may increase the dose to 8 mg PO once a day or 4
mg twice a day.
 Alpha glucosidase inhibitors are
effective in improving glycemic
control in type 2 diabetes. Alpha
glucosidase is an intestinal brush
α- border enzyme responsible for the
Glucosidase hydrolysis of disaccharides which is
Inhibitors necessary for the absorption of starch,
dextrins and disaccharides. Inhibition
of this enzyme causes malabsorption
and slowing of absorption of
carbohydrates and decreases the
postprandial rise in blood glucose.
Classification/Dose/Route

❖Miglitol: Miglitol is typically started at a low dose of 25 milligrams

(mg) orally three times per day and gradually increased to 50 or 100
mg three times daily.

❖Acarbose: The usual starting dose of acarbose is 25 mg three times

daily (orally). The dose may be gradually increased to a maximum of
100 mg three times daily.
Nursing Responsibilities for Oral
Hypoglycemic Drugs and Insulin
❖Observe the patients for signs and
symptoms of hypoglycemic reactions
such as nervousness, weakness,
sweating, cold and clammy skin, rapid
and shallow breathing and paleness of
skin.
❖Observe the patients for signs and
symptoms of hyperglycemic reactions
such as abnormal breathing, tachycardia
and fruity acetone odor to their breath.
 THYROID AND ANTI-THYROID DRUGS
Introduction
Thyroid gland secretes 3 hormones–Thyronine (T3), Thyroxin (T4) and
calcitonin.
Synthesis
❖These hormones are synthesized and stored as a part of thyroglobulin.
❖Iodide uptake via active uptake transporter.
❖Oxidation and iodination happen via peroxidase to iodinium and
combine with tyrosine to mono iodo tyrosine (MIT), di-iodo tyrosine
(DIT).
❖Coupling MIT and DIT couple to form T3/T4.
❖Storage and release via endocytosis.
❖Peripheral conversion of T4 to T3.
Actions of Thyroid Hormones

❖Growth and development–metamorphosis of tadpole, deficiency

causes cretinism–delayed milestones.

❖Intermediary metabolism–enhance lipolysis, glycogenolysis,

gluconeogensis, hyperglycemia, negative nitrogen balance.

❖Calorigenesis–increases BMR.

❖CVS–hyper dynamic state of circulation.

Indications
Replacement therapy:
❖Cretinism–thyroxin is used.
❖Adult hypo
❖thyroidism
❖Myxoedema coma–emergency–liothyronine intravenous +
corticosteroids
Thyroid Hormones

❖T4 produced in greater quantities than T3.

❖Approximately 50% of T4 converted to T3 by deiodination at peripheral tissue

cells.

❖Approximately 70-90% of circulating T3 is derived by deiodination of T4.

Thyroid Hormone Supplements

Synthetic T4 (Levothyroxine), Synthroid [brand]):

❑Mainstay of therapy for many years.

❑Partially converted to T3 in periphery.

❑Starting dose 50-100 mcg/day.

✓Starting dose 25-50 mcg/day. Patients with CAD.

✓Patients > 60 years old.

Antithyroid Drugs (Thyroid Inhibitors)

Antithyroid medications are used to treat hyperthyroidism, a disease in

which the thyroid gland produces an excessive amount of thyroid
hormone. These medications work by either inhibiting thyroid hormone
synthesis or interfering with iodine uptake by the thyroid gland.
Mechanism of Action

Methimazole (MMI) is an anti-thyroid drug that belongs to drug class

thionamides. The primary mechanism of action of methimazole is to
block thyroid hormone production from the thyroid gland. It interferes
with the step that causes the iodination of tyrosine residues in
thyroglobulin, mediated by the enzyme thyroid peroxidase, thus
preventing the synthesis of thyroxine (T4) and triiodothyronine (T3).
Drug Toxicity
❖Agranulocytosis or aplastic anemia
❖Hepatitis
❖Nephrotic syndrome
❖Nerve damage
❖Dermatitis
❖Stimulation or depression of the nervous system
Indications
❖Hyperthyroidism
❖Used before thyroidectomy or radioactive iodine therapy to treat hyperthyroidism.
❖In thyroid storm and thyrotoxicosis crisis (off-label treatment), to treat the
hyperthyroidism.
❖It is a preferred antithyroid drug in the first trimester of pregnancy.

Contraindications
❖Previous history of hypersensitivity to PTU.
❖Hepatic impairment or myelosuppression.
❖Pediatric patients.
Drug Interaction
❖Oral anticoagulants.
❖Beta-blockers
❖Digitalis
❖Theophylline

Drug Toxicity
❖Vomiting
❖Epigastric distress
❖Headache
❖Fever
❖Arthralgia
 STEROIDS
Steroids are complex lipophilic molecules that have many actions in the
body to regulate cellular, tissue and organ functions across the life-span.
Steroid hormones such as cortisol, aldosterone, estradiol and
testosterone are synthesised from cholesterol in specialised endocrine
cells in the adrenal gland, ovary and testis, and released into the
circulation when required.
Two main types of steroids are as follow:
❖Corticosteroids
❖Anabolic steroids
Corticosteroids

Produced by adrenal cortex–corticoids collectively referred to

glucocorticoids, mineralocorticoids and their synthetic analogue.
Glucocorticoids are steroid hormones produced from the cortex of
adrenal glands (gluco-corti-coids: glucose-cortex-steroids).
Glucocorticoids have a pivotal role in the glucose, protein, and fat
metabolism of the body. They originate from steroid precursors and are
synthesized primarily in the zona fasciculata of the adrenal cortex. Their
medical significance arises from their anti-inflammatory, anti-allergic,
and immune-suppressive role in the body, and this particular role used
for medical treatment purposes.
Action of Corticosteroids
Mineralocorticoids
The mechanism of action of mineralocorticoids mimics that of
aldosterone. By acting on the mineralocorticoid receptors,
fludrocortisone (Mineralocorticoids are a drug class within the
corticosteroid family and fludrocortisone is the primary medication
within this class) induces the expression of proteins responsible for Na+
reabsorption and K+ excretion by renal tubule cells, which results in
Na+ and water retention. Mineralocorticoids are used in the
management of diseases characterized by insufficient (or absent)
aldosterone activity, such as adrenal insufficiency and congenital
adrenal hyperplasia.
Glucocorticoids
Promotes glycogen deposition, gluconeogensis, inhibits glucose
utilization, diabetes like state, protein breakdown, uric acid excretion,
promotes lipolysis, redistribution of body fat, inhibit intestinal
absorption and promote excretion of Ca2+, maintains normal GFR,
hypertension, lower seizure threshold, Euphoria, aggravate peptic ulcer,
enhance destruction of lymphoid cells, suppress inflammatory response,
impair immunological competence.
Classification of corticosteroid drugs
Side effects of glucocorticosteroids
 Role of Nurse

❑Before starting corticosteroid treatment, a history and physical exam

are necessary to evaluate any risk factors or preexisting conditions that
could be worsened by corticosteroid treatment.
❑Children and adolescents merit special consideration because of the
risk of growth suppression.
❑Should be aware of the possibility of adrenal suppression in all
patients on corticosteroids.
❑Fluid and electrolyte levels should be monitored in patients on
corticosteroids with higher mineralocorticoid activity.
 ANDROGENS (ANABOLIC STEROIDS)

An androgen, or male sex hormone, is defined as a substance capable of

developing and maintaining masculine characteristics in reproductive
tissues (notably the genital tract, secondary sexual characteristics, and
fertility) and contributing to the anabolic status of somatic tissues.
Testosterone together with its potent metabolite, dihydrotestosterone
(DHT), are the principal androgens in the circulation of mature male
mammals.
Classification/Dose/Route

Anabolic steroids administration can be via oral pills, injections, creams or topical gels, and skin
patches.

❖Testosterone cypionate: 50 to 400 mg intramuscularly once to 4 times a month for primary

hypogonadism and hypogonadotropic hypogonadism.

❖Testosterone undecanoate: Initial dose of 750 mg, then 750 mg given four weeks after the first
dose, and 750 mg subsequently, given at ten weeks intervals between each dose.

❖Testosterone gel is given as 11 mg 3 times daily, with a total dose of 33 mg daily.

❖Transdermal testosterone is applied as 50 mg once daily in the morning to the upper limb, shoulder,
or abdomen with a maximum dose of 100 mg per day.
 Mechanism of Action

The mechanism of action of anabolic steroids involves binding to

androgen receptors in the body, which are found in various tissues,
including muscle, bone, liver, and the central nervous system. Once the
anabolic steroid molecules bind to these receptors, they stimulate the
production of messenger RNA, which in turn leads to an increase in
protein synthesis in the body. This increased protein synthesis results in
an increase in muscle mass, strength, and endurance.
Indications

Testicular failure, hypopituitarism, AIDS related, hereditary

angioneurotic edema. Bone marrow stimulation in leukemia, aplastic
anemia, growth failure,
Contraindications

Severe renal, cardiac and hepatic disease, men with breast cancer and
prostate cancer, venous thromboembolism
Drug Interactions
❖Anticoagulants
❖Corticosteroids
❖Erythropoietin
❖Cyclosporine
Drug Toxicity
High blood pressure, hepatotoxicity, hormonal imbalances, infertility,
and decreased sex drive, mood changes, including irritability,
aggression, and depression, muscle and tendon injuries, including
tendon rupture.
 Role of Nurse
❑Should obtain the patient's lipid profile, hepatic function tests,
hemoglobin, and hematocrit.
❑Monitor the patient for any adverse reactions or side effects, such as
changes in vital signs or allergic reactions.
❑Provide emotional support to the patient, who may be undergoing
physical changes and psychological effects associated with the
medication, such as mood swings or aggression.
 PARATHYROID HORMONE (PTH)

❑PTH functions to preserve normal blood calcium (and phosphate).

❑PTH stimulates bone resorption and, thus, increases blood calcium.

❑PTH stimulates renal tubular reabsorption of calcium, and thus,

increases blood calcium.
CALCITONIN

Calcitonin is a thyroid hormone that aids in the regulation of calcium

amounts in the body. It works by inhibiting the activity of osteoclasts,
which are cells that break down bone tissue and release calcium into the
bloodstream, to reduce blood calcium levels. Calcitonin also increases
calcium absorption by the bones and kidneys, and it can have an effect on
the gastrointestinal system by decreasing calcium absorption.
Dose/Route

Calcitonin, Human

Paget’s disease: Starting dose of 0.5 mg/day subcutaneously;

some patients may respond to 0.5 mg two to three times per
week or 0.25 mg/day. Severe cases may require up to 1 mg/day
for 6 mo. Discontinue therapy when symptoms are relieved.
Calcitonin, Salmon

❖Skin testing: 0.1 mL of a 10 IU/mL solution injected subcutaneously.

❖Paget’s disease: Initial dose 100 IU/day IM or subcutaneously. For

maintenance dose, 50 IU/day or every other day.

❖Postmenopausal osteoporosis: 100 IU/day IM or subcutaneously,

with supplemental calcium (calcium carbonate, 1.5 g/day) and vitamin
D (400 units/day) or 200 IU intranasally daily.
Indications
❖Postmenopausal osteoporosis
❖Paget’s disease
❖Hypercalcemia

Contraindications
❖Hypersensitivity
❖Pregnancy and breastfeeding
Side Effects/Adverse Effects
❖Runny Nose
❖Sinus pain
❖Crusts, dryness, redness, or swelling of nose
❖Back pain
❖Joint pain
❖Stomach upset
Drug Toxicity
❖Allergic reactions
❖Low blood pressure
❖Seizures

Role of Nurse
❖Before administering calcitonin, nurses should assess the patient's
medical history, current medication regimen, and vital signs.
❖Monitor the patient for any adverse reactions or side effects related to
calcitonin.
Classification/Dose/Route
❖Teriparatide: 20 mcg once daily via subcutaneous injection.
❖Abaloparatide: 80 mcg once daily via subcutaneous injection.

Teriparatide
❖Recombinant human parathyroid hormone.
❖Intranasal dose: 20 mcg/d, subcutaneous once a day.
❖Should be supplemented with calcium and vitamin D.
Mechanism of Action
Its main mechanism of action is to raise calcium levels in the blood by
stimulating calcium release from bone, decreasing calcium excretion in
the urine, and increasing calcium absorption from the intestines. PTH is
released into the bloodstream by the parathyroid glands when blood
calcium levels are insufficient. PTH then binds to receptors on the
surface of bone cells known as osteoblasts, stimulating them to produce
and release another protein known as RANKL. (Receptor Activator of
Nuclear Factor Kappa-B Ligand). Then, RANKL binds to another group
of receptors on the surface of osteoclasts (bone-breaking cells) and
stimulates them to resorb bone tissue, releasing calcium into the
bloodstream.
Indications
• Calcium regulation, phosphate regulation, Vitamin D metabolism,
bone metabolism.
Side Effects
• Headache, numbness, par aesthesia, pain and cramping in joints, legs,
arms, neck and stomach, diarrhea, twitching of facial muscles,
seizures, dizziness.
Contraindications
• Paget’s disease, open epiphysis, hypercalcemia, H/O osteosarcoma or
chondrosarcoma paget's disease.
Drug Toxicity

Hypercalcemia can include nausea, vomiting, abdominal pain,

constipation, muscle weakness, confusion, and lethargy. In severe cases,
hypercalcemia can lead to kidney stones, bone pain, and even coma.
 Nurses responsibilities

❖Inform your physician if you are taking vitamin D and calcium

supplement, alendronate, digoxin, as dose needs to be adjusted.
❖Inform your physician if you have any kidney disease.
❖Clean the skin with alcohol swab prior to injection.
❖If skin is red and have any infection, change the site.
❖Do not stop the use of drug without consultation of the physician.
 VITAMIN D3

Vitamin D3, also known as cholecalciferol, is a type of vitamin D that is

produced in the skin when it is exposed to sunlight. It is commonly used
to support bone health and maintain normal calcium and phosphate
levels in the body. Vitamin D3 is important for absorption of calcium and
helps to regulate other important functions in the body, including the
immune system, muscle functions, cell growth and differentiation.
Mechanism of Action
Cholecalciferol (vitamin D3) is a provitamin. The active metabolite,
1,25-dihydroxyvitamin D (calcitriol), stimulates calcium and phosphate
absorption from the small intestine, promotes secretion of calcium from
bone to blood; promotes renal tubule phosphate resorption.
Classification
❖ Available in various forms such as capsules and injectables
❖ Ergocalciferol
❖ Calcitriol
❖ Doxercalciferol
❖ Calcifediol
Indications
❖ Refractory rickets (or vitamin D resistant rickets)
❖ Hypoparathyroidism
❖ Hypophosphatemia
Contraindications
❖ Hypercalcemia
❖ Renal disease
❖ Arcoidosis
❖ Lymphoma
Drug Interactions
❖Glucocorticoids
❖Thiazide diuretics
❖Anticonvulsants
❖Cholestyramine
❖Phenytoin
❖Phenobarbital

Drug Toxicity
Chronic or acute administration of excessive doses of cholecalciferol may lead to
hypervitaminosis D, manifested by hypercalcemia. Early symptoms of hypercalcemia
may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic
taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia.
CALCIUM METABOLISM

In the body, calcium plays a significant role in numerous metabolic

processes. It serves as an enzymatic signal in biochemical processes and
is crucial for healthy heart function, bone structural integrity, and
muscle contraction. The parathyroid hormone (PTH), calcitonin, and
calcitriol, which control serum calcium levels, strictly regulate calcium.
Calcium metabolism
 CALCIUM SALTS
❑Amount of elemental calcium is important, given as calcium
carbonate or calcium citrate or gluconate, with calcium citrate add
proton pump inhibitor or antacids.
❑For best absorption, most calcium supplements should be taken with
food. Calcium citrate is an exception; it can be taken with or without
food.
Example/Dose/Route

❖Calcium carbonate: 500-1000 mg taken once or twice daily.

❖Calcium citrate: 200-500 mg taken two to three times daily.

❖Calcium lactate: 200-1000 mg taken one to three times daily.

❖Calcium gluconate: Doses can vary depending on the condition being

treated and the route of administration
Drugs Affecting Calcium Balance
❖Calcium
❖Vitamin D
❖Parathyroid hormone analogue (Teriparatide)
❖Bisphosphonates (Alendronate)
❖Selective estrogen receptor modulator (SERM) (Raloxifene)
❖Calcimimetics (Cinacalcet)

Bisphosphonates (BPs)
❖Risedronate
❖Alendronate
❖Zolendronate
Indications
❖Postmenopausal osteoporosis
❖Glucocorticoids induced osteoporosis
❖Pagets disease
❖Hypercalcemia of malignancy
❖Multiple myeloma and bone metastasis of solid tumours
(Zolendronate)
Contraindications
❖Patients with renal impairment or chronic kidney disease (CKD) and
history of calcium-containing kidney stones.
Adverse Effects
❖Esophagitis: Specially with oral nitrogenous BPs.
❖Osteonecrosis of Jaw: Mostly High dose I.V prep, especially after a
dental procedure.
❖Severe bone, joint or muscular pain.
❖Fatigue
 Role of nurse

❖Review the patient's medical history to determine if they have any

conditions that may affect their ability to absorb or use calcium. For
example, patients with kidney disease may require a different dosage
or type of calcium supplement.
❖Monitor patients for potential side effects of calcium supplements,
such as constipation or gastrointestinal upset. They can also monitor
for signs of calcium toxicity, such as confusion or muscle weakness.
❖Oral BPs should be taken early morning 30 min before taking
anything else.