Drugs Used in Endocrine Alteration

1. Hormones
and
Related Drugs
S. Parasuraman, M.Pharm., Ph.D.,
Associate Professor
Faculty of Pharmacy
AIMST University, Malaysia
Drug altering sections of
• Pituitary hormones
• Thyroid Hormones
• Pancreatic Hormones
• Corticosteroids
• Androgens
• Estrogens & Progestins
• Oxytocin

2. Pituitary hormones
Drug altering the anterior pituitary hormone secretion

3. Pituitary hormones
Ref: https://labpedia.net/hypothalamus-and-pituitary-gland-hormones/

4. Anterior pituitary hormones
Ref: https://labpedia.net/hypothalamus-and-pituitary-gland-hormones/
• Adrenocorticotropic hormone (ACTH): This hormone stimulates the
secretion of cortisol by the adrenal gland.
• Growth Hormone (GH): This hormone promotes growth in soft tissue,
cartilage, and bone.
• Thyroid stimulation hormone (TSH): This hormone stimulates the
secretion of the thyroid hormone T3 and T4 by the thyroid gland.
• Prolactin Hormone (PRL): This hormone’s main role is in the initiation
and maintenance of lactation. Prolactin induces ductal growth, the
lobular alveolar system, and the synthesis of milk production.
• Follicle-stimulating hormone (FSH): This hormone controls the functional
activity of gonads. In the male, this stimulates spermatogenesis. In
females stimulate the growth of ovarian follicles in the presence of LH.
• Luteinizing hormone (LH): This hormone controls the functional activity
of the gonads. Males produce testosterone through the Leydig cells of
the testes. In females, it leads to the release of the ovum from the
ovarian follicle, in which FSH ripens.

5. Posterior Pituitary Gland hormones
Ref: https://labpedia.net/hypothalamus-and-pituitary-gland-hormones/
• Adrenocorticotropic hormone (ACTH): This hormone stimulates the
secretion of Antidiuretic Hormone (ADH). This maintains water
homeostasis. This also leads to vasoconstriction to increase blood
pressure.
• Oxytocin: This will stimulate uterine contraction during labor. This may
be used to induce labor. It helps in milk release from the mammary ducts.

6. Drug altering the anterior pituitary hormone
secretion

7. Thyroid Hormones
Drug altering the thyroid hormones secretion

8. Thyroid Hormones and Thyroid Inhibitors
• The thyroid gland secretes 3 hormones - thyroxine (T4),
triiodothyronine (T3) and calcitonin.
• The thyroid hormones are synthesized and stored in
the thyroid follicles as part of thyroglobulin molecule -
which is a glycoprotein synthesized by thyroid cells.
• Iodine is an element that plays an essential role in the
functioning of a healthy thyroid. It is used for the
production of thyroid hormones.
• The total body content of I2, obtained from food and
water, is 30 - 50 mg.
Ref: https://www.btf-thyroid.org/iodine-and-thyroid

9. Thyroid Hormones - Actions
• The actions of T4 and T3 are qualitatively similar and are nicely
depicted in the features of hypo- and hyperthyroidism.
• Increases the basal metabolic rate.
• Depending on the metabolic status, it can induce lipolysis or
lipid synthesis.
• Stimulate the metabolism of carbohydrates.
• Anabolism of proteins. Thyroid hormones can also induce
catabolism of proteins in high doses.
• Permissive effect on catecholamines.
• In children, thyroid hormones act synergistically with growth
hormone to stimulate bone growth. The impact of thyroid
hormone in CNS is important. During the prenatal period, it is
needed for the maturation of the brain.
• In adults, it can affect mood. Hyperthyroidism can lead to
hyperexcitability and irritability. Hypothyroidism can cause
impaired memory, slowed speech, and sleepiness.
• Thyroid hormone affects fertility, ovulation, and menstruation.
Ref: https://www.ncbi.nlm.nih.gov/books/NBK500006/

10. Thyroid Hormones - Disorders
• Hyperthyroidism
• Hypothyroidism
• Graves Disease
• Hashimoto Thyroiditis
Ref: https://www.ncbi.nlm.nih.gov/books/NBK500006/

11. Relation between T4 and T3
• Thyroid secretes more T4 than T3.
• T4 is the major circulating hormone because it is 15
times more tightly bound to plasma proteins.
• T3 is 5 times more potent than T4 and acts faster. Peak
effect of T3 comes in 1–2 days while that of T4 takes 6–
8 days.
• T3 is the active hormone, while T4 is mainly a transport
form which functions as a prohormone of T3.
Preparations
• l-thyroxine sod. (synthetic levothyroxine sod.)
• 25 - 150 μg tabs

12. Thyroid hormones preparation - uses
• The most important use of thyroid hormone is for
replacement therapy in deficiency states.
• Cretinism: Due to failure of thyroid development or a defect
in hormone synthesis or due to extreme iodine deficiency.
• Adult hypothyroidism (Myxoedema): This is one of the
commonest endocrine disorders which develops as a
consequence of autoimmune thyroiditis or thyroidectomy.
• Myxoedema coma: It is an emergency; characterized by
progressive mental deterioration due to acute
hypothyroidism carries significant mortality.
• Nontoxic goiter: Enlargement of thyroid with euthyroid
status.
• Thyroid nodule: It is solid or fluid-filled lumps that form
within thyroid.
• Papillary carcinoma of thyroid

13. Thyroid inhibitors
• These are drugs used to lower the functional capacity
of the hyperactive thyroid gland.
• Thyrotoxicosis is due to excessive secretion of thyroid
hormones due to Graves’ disease and toxic nodular
goiter.

14. Antithyroid drugs - Thioamides
• Thioamides (propylthiouracil, methimazole and
carbimazole) act principally by blocking the synthesis
of T4 by preventing iodination of tyrosine residues.
• Propylthiouracil also inhibits peripheral conversion of
T4 to T3.
• Carbimazole is rapidly converted to thiaimazole, the
active metabolite.
• Thioamides cross the placenta, propylthiouracil less
than carbimazole.
• Adverse effects: Hypothyroidism and goiter
Ref: doi: 10.1016/B978-0-443-10281-3.00016-6

15. Inhibit iodide trapping
• Inhibit iodide trapping by Sodium iodide symporter
(NIS) into the thyroid.
• Consequently, T4/T3 cannot be synthesized.
Ref:

16. Inhibit hormone release
IODINE, RADIOACTIVE IODINE
• Iodine is a constituent of thyroid hormones; it is the
fastest acting thyroid inhibitor.
• Use:
• Preoperative preparation: Thyroidectomy in Graves’ disease
- Iodine is generally given for 10 days just preceding surgery.
• Thyroid storm
• Prophylaxis of endemic goiter
• Antiseptic
Ref:

17. Treatment
• Treatment of hypothyroidism:
• Levothyroxine
• Treatment of hyperthyroidism (thyrotoxicosis):
• Removal of the thyroid
• Inhibition of thyroid hormone synthesis
• Blockade of hormone release
• Thyroid storm
Ref:

18. Pancreatic Hormones
Drug altering the pancreatic hormones secretion

19. Pancreatic Hormones

20. Functions of pancreas
Ref: https://biology.reachingfordreams.com/biology/endocrine-system/14-function-of-pancreas-in-human-body
Pancreatic polypeptide
cells (PP cells)

21. Functions of pancreas
• The pancreas made up of two types of tissues that
independently function as exocrine and endocrine glands.
• Exocrine part of the pancreas secretes digestive enzymes
into the duodenum.
• Endocrine portion of the pancreas secretes glucagon and
insulin, two non-steroid protein hormones. These
hormones regulate the body’s metabolism of glucose and
other carbohydrate molecules. They are produced by the
islets of Langerhans.
Ref: https://biology.reachingfordreams.com/biology/endocrine-system/14-function-of-pancreas-in-human-body

22. Exocrine Functions
• Amylase: Secreted in
mouth and pancreas;
breaks down complex
carbohydrates.
• Lipase: Secreted in the
pancreas; breaks down fats
• Protease: Secreted in the
pancreas; breaks down
proteins.
Endocrine Functions
• Glucagon: Glucagon plays
an important role in blood
glucose regulation; low
blood glucose levels
stimulate its release.
• Insulin: Elevated blood
glucose levels stimulate the
release of insulin.
• Gastrin and amylin:
Secreted in the pancreas;
breaks down proteins

23. Islets of Langerhans
• There are three main types of cells in the pancreatic
islets:
• α (alpha) cells produces the hormone glucagon [Glucagon
increases blood glucose levels]
• β (beta) cells produces the hormone insulin [insulin
reduces blood glucose levels]
• δ (delta) cells secrete somatostatin [inhibits the secretion
of both insulin and glucagon]

24. Common pancreatic problems and digestion
• Diabetes
• Type I Insulin-dependent diabetes mellitus (IDDM)/ juvenile
onset diabetes mellitus
• Type II Noninsulin-dependent diabetes mellitus (NIDDM)/
maturity onset diabetes mellitus
• Pancreatitis
• Pancreatic cancer

25. Diabetes
• The incidence of diabetes is growing rapidly worldwide.
• Malaysia has the highest rate of diabetes in Western Pacific
region and one of the highest in the world and costing
around 600 million US dollars per year.
• The prevalence of diabetes raised from 11.2% in 2011 to
18.3% in 2019, with a 68.3% increase. According to a
national survey report, in Malaysia in 2019, 3.6 million
adults had diabetes. Diabetes is expected to affect 7 million
Malaysian adults aged 18 and older by 2025.
Ref: PMID: 35085366

26. Comparison of type 1 and type 2 diabetes

27. Insulin
• Insulin is a two-chain polypeptide having 51 amino acids
and MW about 6000. The A-chain has 21 while B-chain has
30 amino acids. Under basal condition ~1U insulin is
secreted per hour by human pancreas.
Human proinsulin

28. Insulin
• Mechanism of action: Exogenous insulin is administered to
replace absent insulin secretion in type 1 diabetes or to
supplement insufficient insulin secretion in type 2 diabetes.
• Pharmacokinetics: Insulin is a polypeptide; it is degraded in
the gastrointestinal tract if taken orally. Therefore, it is
generally administered by subcutaneous injection. Inhaled
insulin formulation is also available
• Adverse effects: Hypoglycemia, weight gain, local injection
site reactions, and lipodystrophy. Hypoglycaemia is
managed by administering glucose (or glucose yielding
carbohydrate, e.g., sugar) 15–20 g orally reverses the
symptoms.

29. Insulin preparations
• Rapid-acting and short-acting insulin preparations
• Intermediate-acting insulin
• Long-acting insulin preparations
• Insulin combinations
• Insulin delivery devices

30. Insulin preparations
• Rapid-acting and short-acting insulin preparations:
• Five preparations fall into this category: regular insulin, insulin
lispro, insulin aspart, insulin glulisine, and inhaled insulin.
• Regular insulin (peck level at 50 to 120 minutes) is a short-acting,
soluble, crystalline zinc insulin.
• Insulin lispro (peck level at 30 to 90 minutes), aspart, and glulisine
are classified as rapid- acting insulins.
• Inhaled insulin is also considered rapid-acting. This dry powder
formulation is inhaled and absorbed through pulmonary tissue,
with peak levels achieved within 45 to 60 minutes.
• Regular insulin should be injected subcutaneously 30 minutes
before a meal, whereas rapid-acting insulins are administered in
the 15 minutes proceeding a meal or within 15 to 20 minutes
after starting a meal.
• Rapid-acting insulin suspensions are commonly used in external
insulin pumps, and they are suitable for IV administration.

31. Insulin preparations
• Intermediate-acting insulin: Neutral protamine
hagedorn (NPH) insulin is an intermediate-acting insulin
formed by the addition of zinc and protamine to regular
insulin. NPH insulin is used for basal (fasting) control in
type 1 or 2 diabetes and is usually given along with
rapid- or short-acting insulin for mealtime control. NPH
insulin should be given only subcutaneously (never IV).
• Long-acting insulin preparations: It has a slower onset
than NPH insulin and a flat, prolonged hypoglycemic
effect with no peak. Eg: Insulin glargine, Insulin
degludec.

32. Insulin preparations
• Insulin combinations: Various premixed combinations
of human insulins [70% NPH insulin + 30% regular
insulin/ 50% NPH insulin + 50% regular insulin]. Use of
premixed combinations decreases the number of daily
injections but makes it more difficult to adjust
individual components of the insulin regimen.
• Insulin delivery devices:
• Syringes
• Pens
• Durable pens
• Pumps
• Jet injectors
• Others

33. Oral antidiabetic drugs
• These drugs lower blood glucose levels in diabetics and
are effective orally. The main drawback of insulin is - it
must be given by injection.

34. Oral antidiabetic drugs

35. Oral hypoglycemic agents, dose range and dose frequency
MEDICINE USUAL DAILY DOSE FREQUENCY
Glibenclamide 5 mg 2.5–20 mg • Up to 10 mg as a single dose
• >10 mg in divided doses
• Taken with or immediately before food
Glipizide 5 mg 2.6–40 mg • Up to 15 mg as a single dose
• >15 mg in a twice daily dosage taken
• immediately before meals
Gliclazide 80 mg 30–120 mg • Daily
Glimepiride 1/ 2 mg 1–4 mg • 2–3 per day
Metformin 500 mg, 1g 0.5–1.5 g • 1–3 times/day taken with or immediately
after food
Repaglinide 0.5 mg, 1/ 2 mg 0.5–16 mg • 2–3 per day
Pioglitazone 15 mg, 30 mg 4–8 mg • Daily
Rosiglitazone 2 mg, 4 mg 4–8 mg • Daily
Acarbose 50/ 100 mg 50–100 mg • TDS with food thrice a day
Voglibose 0.2/ 0.3 mg 0.2–0.3 mg • TDS with food thrice a day
Sitagliptin 50/ 100 mg 100 mg per day in BD
regimen. In combination with
metformin, or a sulfonylurea
• With or without food
Vildagliptin 50 mg • With or without food

36. Corticosteroids
Drug altering the Corticosteroids secretion

37. Corticosteroids
• Corticosteroids are a class of steroid hormones
released by the adrenal cortex, which includes
glucocorticoids and mineralocorticoids.
• Glucocorticoids are primary stress hormones that
regulate a variety of physiologic processes and are
essential for life.
• Use:
• Corticosteroids used to treat conditions like Asthma, Allergic
rhinitis and hay fever, Urticaria, Atopic eczema, Chronic
obstructive pulmonary disease (COPD), Painful and inflamed
joints, Muscles and tendons, Lupus, Inflammatory bowel
disease (IBD) including Crohn's disease and ulcerative colitis,
Giant cell arteritis and polymyalgia rheumatica and, Multiple
sclerosis (MS).
Ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662771/
https://www.nhsinform.scot/tests-and-treatments/medicines-and-medical-aids/types-of-medicine/corticosteroids

38. Corticosteroids

39. Corticosteroids

40. Uses:
• Replacement therapy
• Acute adrenal insufficiency
• Chronic adrenal insufficiency (Addison’s disease)
• Congenital adrenal hyperplasia (Adrenogenital syndrome)
Ref:

41. Uses:
• Pharmacotherapy (for nonendocrine diseases)
• Arthritides (Rheumatoid arthritis, Osteoarthritis, Rheumatic
fever, Gout)
• Collagen diseases (systemic lupus erythematosus,
polyarteritis nodosa, dermatomyositis, nephrotic syndrome,
• Glomerulonephritis and related diseases)
• Severe allergic reactions
• Autoimmune diseases (Autoimmune haemolytic anaemia,
idiopathic thrombocytopenic purpura, active chronic
hepatitis)
• Bronchial asthma and lung diseases
• Infective diseases
• Eye diseases
• Skin diseases
• Intestinal diseases
• Neurological conditions
Ref:
• Nausea and vomiting
• Malignancies
• Organ transplantation
• Septic shock
• Thyroid storm

42. Adverse effects
• Mineralocorticoid: Sodium and water retention,
edema, hypokalaemic alkalosis and a progressive rise
in BP.
• Glucocorticoid:
• Weight gain
• Feeling very hungry
• Water retention or swelling
• Mood swings
• Blurred vision
• Feeling nervous or restless
• Trouble sleeping
• Muscle weakness
• Acne
• Stomach irritation, etc.,
Ref:

43. Androgens
Drug altering the androgens secretion

44. Androgens and Related Drugs
• Androgens (Male Sex Hormones) are substances which
cause development of secondary sex characters in the
castrated male. Testes of adult male produce 5–12 mg
of testosterone daily.
• Actions:
• Testosterone is responsible for all the changes that occur in a
boy at puberty
• Testosterone accelerates erythropoiesis by increasing
erythropoietin production and probably direct action on
haeme synthesis.
• Preparations and Dose:
• Testosterone (free): 25 mg i.m. daily to twice weekly
• testo. propionate 25 mg + testo. enanthate 100 mg in 1 ml
amp; 1 ml i.m. weekly
• Transdermal androgen Delivery of androgen

45. Androgens and Related Drugs
Ref:

46. Estrogens, Progestins and Contraceptives

47. Estrogens
• Estrogens (Female Sex Hormones) it helps develop and maintain
both the reproductive system and female characteristics.
• Actions:
• The estrogens bring about pubertal changes in the female including
growth of uterus, fallopian tubes and vagina.
• Estrogens augment rhythmic contractions of the fallopian tubes and
uterus.
• Secondary sex characters.
• Estrogen is important in maintaining bone mass primarily by retarding
bone resorption.
• Preparations and Dose:
• Estradiol benzoate/cypionate/enanthate/valarate: 2.5–10 mg i.m
• Conjugated estrogens: 0.625–1.25 mg/day oral
• Use:
• Hormone replacement therapy (HRT)

48. Estrogens
Ref:

49. Progestins
• Progestin (favouring pregnancy) plays an essential role in
pregnancy and fertility. Progestin convert the estrogen primed
proliferative endometrium to secretory and maintain pregnancy
after conception.
• Actions:
• The main function of progesterone is preparation of the
uterus for nidation and maintenance of pregnancy.
• Preparations and Dose:
• Progesterone: 10–100 mg i.m. OD
• Hydroxyprogesterone caproate: 250–500 mg i.m. at 2–14
days intervals
• Lynestrenol (Ethinylestrenol): 5–10 mg OD oral
• Use:
• Hormone replacement therapy (HRT), As contraceptive,
Dysfunctional uterine bleeding, Endometriosis, Premenstrual
syndrome/tension, Endometrial carcinoma

50. Progestins

51. Antiprogestin
• Mifepristone: Given during the follicular phase, its
antiprogestin action results in attenuation of the
midcycle Gn surge from pituitary. This causes slowing
of follicular development and delay/ failure of
ovulation.
• Uses:
• Termination of pregnancy (of up to 7 weeks: 600 mg as
single oral dose causes complete abortion in 60–85% cases).
To improve the success rate, current recommendation is to
follow it up 48 hours later by a single 400 mg oral dose of
misoprostol (synthetic prostaglandin).
• Ulipristal: Inhibits ovulation by suppressing LH surge as
well as by direct effect on follicular rupture.

52. Hormonal contraceptives

53. Oxytocin and Other Drugs Acting on Uterus

54. Oxytocin and Other Drugs Acting on Uterus
Ref:
• The two main physical functions of oxytocin are to
stimulate uterine contractions in labor and childbirth
and to stimulate contractions of breast tissue to aid in
lactation after childbirth.

55. Thank you
Ref: