1. HORMONES AND RELATED DRUGS

2. Hormones 1. Pituitary Anterior Growth hormone (GH), Prolactin (Prl),
Adrenocorticotropic hormone (ACTH, Corticotropin),
Thyroid stimulating hormone (TSH, Thyrotropin),
Follicle stimulating hormone (FSH)
Luteinizing hormone (LH)
Posterior
Oxytocin,
Antidiuretic hormone (ADH, Vasopressin).
2. Thyroid
Thyroxine (T4),
Triiodothyronine (T3),
Calcitonin.
3. Parathyroid
Parathormone (PTH).
4. Pancreas (Islets of Langerhans)
Insulin,
Glucagon.
5. Adrenals
Cortex
Glucocorticoids (hydrocortisone)
Mineralocorticoids (aldosterone)
Medulla
Adrenaline,
Noradrenaline
6. Gonads
Androgens (testosterone)
Estrogens (estradiol)
Progestins (progesterone)

3. Hormones
In addition, hypothalamus, which is a part of the CNS and not a gland, produces many releasing and inhibitory hormones which control the secretion of anterior pituitary hormones.

4. GROWTH HORMONE (GH)
Excess production of GH is responsible for gigantism in childhood and acromegaly in adults.
Hyposecretion of GH in children results in pituitary dwarfism. Adult GH deficiency is rare, but when it occurs, it results in low muscle and bone mass, lethargy, decreased work capacity, hyperlipidaemia and increased cardiovascular risk.

5. GROWTH HORMONE (GH)
Somatropin –human GH produced by recombinant DNA technique for clinical use.
Indications :
pituitary dwarfism
catabolic states (severe burns, bedridden patients, chronic renal failure, osteoporosis)
Adverse effects:
Pain at injection site,
hypothyroidism
hand stiffness,
Myalgia,
Cancer.

6. GH Inhibitors Somatostatin
It inhibits the secretion of GH, prolactin, and TSH by pituitary; insulin and glucagon by pancreas, almost all GIT secretions including gastrin and HCl.
It constricts splanchnic, hepatic and renal blood vessels
Indications :
Acromegaly
For controlling upper g.i.bleeding (esophageal varices and peptic ulcer)
Antisecretory action is beneficial in pancreatic, biliary or intestinal fistulae
ADR:
steatorrhoea, diarrhoea, hypochlorhydria, dyspepsia and nausea as side effect.
Short action (t½ 2–3 min)

7. Octreotide (SANDOSTATIN)
GH Inhibitors
Octreotide (SANDOSTATIN)
40 times more potent in suppressing GH secretion and longer acting (t½ ~90 min),
Help to stop esophageal variceal bleeding
It is preferred over somatostatin for:
Acromegaly
Pancreatic surgery
Acute pancreatitis
ADR: abdominal pain, nausea, steatorrhoea, diarrhoea, and gall stones (due to biliary stasis)

8. Prolactin inhibitors Bromocriptine Actions
This is a dopamine agonist (D2)→ D2 activation :
Decreases prolactin release from pituitary → is a strong antigalactopoietic
Decreases GH release
Antiparkinsonian effects
Produces nausea and vomiting
Uses:
Hyperprolactinemia (galactorrhoea, infertility, gynaecomastia, impotence and sterility in men)
Acromegaly
Parkinsonism

9. Bromocriptine Side effects: Early: Nausea Vomiting
Postural hypotension /syncope.
Late:
Behavioral alterations, mental confusion
Hallucinations, psychosis
Abnormal movements

10. Cabergoline
It is a newer D2 agonist; more potent; more D2 selective and longer acting (t½ > 60 hours) than bromocriptine.
It is preferred for treatment of hyperprolactinemia and acromegaly.

11. GONADOTROPINS (Gns)
Menotropins (FSH + LH): drugs obtained from urine of menopausal women (PREGNORM, PERGONAL)
Urofollitropin or Follitropin (pure FSH): PUREGON
Human chorionic gonadotropin (HCG): is derived from urine of pregnant women.
Uses
Induction of ovulation → to treat infertility
Hypogonadism in males
Cryptorchidism (undescended testes)
Adverse effects
Ovarian hyperstimulation—polycystic ovary, ovarian bleeding
Precocious puberty in children.
Hormone dependent malignancies (prostate, breast)
Mood changes.

12. GONADOTROPIN RELEASING HORMONE (GnRH): GONADORELIN
Synthetic analogues of GnRH, e.g. Goserelin (ZOLADEX), Nafarelin, Triptorelin:
Pulsatile exposure induces release of LH and FSH → treatment of hypogonadism.
At constant administration → inhibition of FSH and LH secretion → suppression of gonadal function to castration levels
Uses:
Precocious puberty
Prostatic carcinoma
Breast cancer
Polycystic ovarian disease

13. ADRENOCORTICOTROPIC HORMONE (ACTH, CORTICOTROPIN)
Stimulation of adrenal cortex → rapidly increases in the production of gluco- and mineralosteroids.
High doses cause hypertrophy and hyperplasia.
Lack of ACTH results in adrenal atrophy.
Uses:
For the diagnosis if the adrenals are functional
Hypocorticism

14. OXYTOCIN Secreted by the posterior pituitary ACTIONS Uterus :
↑ the force and frequency of uterine contractions
Mammary glands:
contracts the mammary alveoli → milk 'lets down' → excretes via the nipple.
USES
Induction of labour in case of slow childbirth
Postpartum bleeding
To stimulate milk release (intranasal spray)

15. Vasopressin Antidiuretic Hormone (ADH)
Actions:
Vasoconstriction
Increasing the water reabsorption in collecting ducts
Desmopressin (DDAVP) is used in conditions featuring low vasopressin secretion, as well as for control of bleeding
Terlipressin is used as vasoconstrictors for esophageal varices

17. Synthesis, storage and secretion of thyroid hormone
The thyroid gland secretes 3 hormones—thyroxine (T4), triiodothyronine (T3) and calcitonin.
Synthesis, storage and secretion of thyroid hormone
TG—Thyroglobulin;
MIT—Monoiodotyrosine;
DIT—Diiodotyrosine;
T3—Triiodothyronine;
T4—Thyroxine (Tetraiodothyronine);
HOI—Hypoiodous acid;
EOI—Enzyme linked hypoiodate;
NIS—Na+-iodide symporter; Thyroid-stimulating hormone (TSH) activates steps 1, 2, 3, 4,5;
Ionic inhibitors block step 1;
Excess iodide interferes with steps 1, 2, 3 and 5 with primary action on step 3 and 5;
Propylthiouracil inhibits steps 2 and 6;
Carbimazole inhibits step 2 only

18. T4 and 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.
About 1/3 of T4 is converted to T3
Thus, T3 is the active hormone, while T4 is mainly a transport form; functions as a prohormone of T3.

19. THYROID HORMONE DRUGS Triiodothyronine (Liothyronine)
L-thyroxine (Levothyroxine)
Clinically, l-thyroxine is preferred for all indications over liothyronine because of more sustained and uniform action as well as lower risk of cardiac arrhythmias.
Liothyronine is occasionally used i.v. in myxoedema coma.

20. Indications
Cretinism during infancy or childhood (due to thyroid deficiency)
Adult hypothyroidism (Myxoedema)
Myxoedema coma (It is an emergency; characterized by progressive mental deterioration due to acute hypothyroidism)

21. THYROID INHIBITORS
Thyrotoxicosis is a hypersecretion of thyroid hormones.
Causes:
Graves’ disease (autoimmune disorder- antibodies bind to and stimulate thyroid cells and produce TSH-like effects)
Toxic nodular goiter

22. CLASSIFICATION 1. Inhibit hormone synthesis (Antithyroid drugs)
Propylthiouracil
Thiamazole (Mercazolil)
Carbimazole (ANTITHYROX)
2. Inhibit iodide trapping (Ionic inhibitors)
Perchlorates (–ClO4)
3. Inhibit hormone release
Iodine
Iodides of Na and K
4. Destroy thyroid tissue
Radioactive iodine (I131).
Compounds in groups 1 and 2 may be collectively called goitrogens because, if given in excess, they cause enlargement of thyroid by feedback release of TSH.

23. ANTITHYROID DRUGS Mechanism of action:
Inhibit iodination of tyrosine residues in thyroglobulin
Inhibit coupling of iodotyrosine residues to form T3 and T4
Do not affect release of T3 and T4
Adverse effects
Hypothyroidism
Goiter
Agranulocytosis
g.i. intolerance, skin rashes and joint pain

24. IONIC INHIBITORS
Inhibition of iodide trapping into the thyroid → T4/T3 cannot be synthesized.
They are toxic and not clinically used now.
Can cause:
liver, kidney, bone marrow and brain toxicity.
aplastic anaemia
agranulocytosis.

25. IODINE AND IODIDES Uses Preoperative preparation for thyroidectomy
Thyroid storm/to stop release of T3/T4 from the thyroid
Prophylaxis of endemic goiter
Antiseptic
Adverse effects
Acute sensitivity to iodine (angioedema of larynx)
Chronic overdose (iodism) (Inflammation of mucous membranes, salivation, rhinorrhoea, sneezing, lacrimation, swelling of eyelids, burning sensation in mouth, headache, rashes, g.i. symptoms, etc.)
Hypothyroidism

26. RADIOACTIVE IODINE
131I is concentrated by thyroid → emits radiation → destructive effect on thyroid cells

27. Insulin, Oral Hypoglycaemic Drugs
Diabetes mellitus (DM) It is a metabolic disorder characterized by:
Hyperglycaemia
Glycosuria
Hyperlipidaemia
Negative nitrogen balance
Ketonaemia

28. Types of diabetes Type I Insulin-dependent diabetes
There is β cell destruction in pancreatic islets → insulin levels are low or very low
Type II Noninsulin-dependent diabetes
Reduced sensitivity of peripheral tissues to insulin → reduction in number of insulin receptors → insulin in circulation is normal or even high

29. Types of insulin preparations and insulin analogues
Onset (hr)
Peak (hr)
Duration (hr)
Rapid acting
Insulin lispro
10 min 1 3
Insulin aspart
Short acting
Regular (soluble) insulin
30 min 2 6
Semilente 30
Intermediate acting
Insulin zinc suspension or Lente 8 20
Isophane (Neutral protamine hagedorn or NPH) insulin
Long acting
Insulin glargine - 24
Ultralente

30. Types of insulin Regular (soluble) insulin
It is a buffered neutral pH solution of unmodified
insulin stabilized by a small amount of zinc.
Lente insulin (Insulin-zinc suspension):
Two types of insulin-zinc suspensions have been produced.
The one with large particles is crystalline and practically insoluble in water (ultralente). It is long-acting.
The other has smaller particles and is amorphous (semilente), is short-acting.
Their mixture is called ‘Lente insulin’ and is intermediate-acting.

31. ADR TO INSULIN
Hypoglycaemia (mental confusion, abnormal behaviour, seizures and coma)
Treatment - Glucose must be given orally or i.v.(for severe cases)—reverses the symptoms rapidly.
Glucagon i.v. or Adr s.c. may be given as an expedient measure in patients who are not able to take sugar orally and injectable glucose is not available
Local reactions
Swelling, erythema and stinging at the injected site
Lipodystrophy of the subcutaneous fat around the injection site
Allergy (Urticaria, angioedema and anaphylaxis)

34. USES OF INSULIN Diabetes mellitus
Diabetic ketoacidosis (Diabetic coma)
Hyperosmolar (nonketotic hyperglycaemic) coma

35. Insulin delivery devices
Insulin syringes
Pen devices
Insulin pumps
Implantable pumps
Inhaled insulin (withdrawn due to risk of pulmonary fibrosis)

36. ORAL HYPOGLYCAEMIC DRUGS
CLASSIFICATION
Sulfonylureas
Glibenclamide (Glyburide)
Glipizide
Gliclazide
Glimepiride
Meglitinide analogues
Repaglinide
Biguanide
Metformin
Thiazolidinediones
Pioglitazone
α-Glucosidase inhibitors
Acarbose
Oral hypoglycaemics are indicated only in
type 2 diabetes, in addition to diet and exercise.

37. Sulfonylureas Mechanism of action
Provoke a brisk release of insulin from pancreas
Improvement in glucose tolerance / increase in number of insulin receptors
Adverse effects
Hypoglycaemia
Hypersensitivity (Rashes, photosensitivity, transient leukopenia, agranulocytosis).
Nausea, vomiting, flatulence, diarrhoea or constipation, headache and paresthesias

38. Meglitinide analogues
Act as sulfonylurea
It induces fast onset short-lasting insulin release → It is administered before each major meal to control postprandial (“after meal”) hyperglycaemia
Indicated only in type 2 diabetics
Side effects
Hypoglycaemia
Headache
Dyspepsia
Arthralgia
Weight gain

39. Biguanides Mechanism of action
Do not stimulate pancreatic β cells → do not cause insulin release
Suppresse hepatic gluconeogenesis and glucose output from liver. (This is the major action responsible for lowering of blood glucose in diabetics)
Enhance insulin-mediated glucose uptake and disposal in skeletal muscle and fat.
Retard intestinal absorption of glucose
Adverse effects
Lactic acidosis
Abdominal pain, anorexia, bloating, nausea, metallic taste, mild diarrhoea and tiredness
cause hypoglycaemia in overdose

41. Thiazolidinedione Pioglitazone
Rosiglitazone (withdrawn in Europe due to high risk of myocardial infarction, CHF, stroke and death)
Mechanism of action
Suppresse hepatic gluconeogenesis and glucose output from liver.
Enhance insulin-mediated glucose uptake and disposal in skeletal muscle and fat
Adverse effects
edema,
weight gain,
headache,
myalgia
anaemia

42. α Glucosidase inhibitors
It slows down and decreases digestion and absorption of polysaccharides (starch, etc.) and sucrose.
Acarbose (GLUCOBAY) is a mild antihyperglycaemic and not a hypoglycaemic; may be used as an adjuvant to diet in obese
ADR:
Flatulence
Abdominal discomfort
Loose stool