Transcript HORMONES AND RELATED DRUGS ( part 1)

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)
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.
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.
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.
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)
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)
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
Bromocriptine
Side effects:
Early:
 Nausea
 Vomiting
 Postural hypotension /syncope.
Late:
 Behavioral alterations, mental confusion
 Hallucinations, psychosis
 Abnormal movements
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.
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.
GONADOTROPIN RELEASING HORMONE (GnRH):
GONADORELIN
 Synthetic analogues of GnRH, e.g. Goserelin (ZOLADEX),
Nafarelin, Triptorelin:
1. Pulsatile exposure induces release of LH and FSH →
treatment of hypogonadism.
2. 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
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
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)
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
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
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.
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.
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)
THYROID INHIBITORS
 Thyrotoxicosis is a
hypersecretion of thyroid
hormones.
Causes:
 Graves’ disease
(autoimmune disorderantibodies bind to and
stimulate thyroid cells and
produce TSH-like effects)
 Toxic nodular goiter
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.
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
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.
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
RADIOACTIVE IODINE

I is concentrated by thyroid → emits radiation →
destructive effect on thyroid cells
131
Insulin, Oral Hypoglycaemic Drugs
Diabetes mellitus (DM)
It is a metabolic disorder
characterized by:
 Hyperglycaemia
 Glycosuria
 Hyperlipidaemia
 Negative nitrogen balance
 Ketonaemia
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
Types of insulin preparations and
insulin analogues
Onset (hr)
Peak (hr)
Duration (hr)
Insulin lispro
10 min
1
3
Insulin aspart
10 min
1
3
30 min
2
6
30
2
6
Insulin zinc suspension or Lente
1
8
20
Isophane (Neutral protamine
hagedorn or NPH) insulin
1
8
20
Insulin glargine
2
-
24
Ultralente
2
-
24
Type
Rapid acting
Short acting
Regular (soluble) insulin
Semilente
Intermediate acting
Long acting
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 intermediateacting.
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)
USES OF INSULIN
 Diabetes mellitus
 Diabetic ketoacidosis (Diabetic coma)
 Hyperosmolar (nonketotic hyperglycaemic) coma
Insulin delivery devices
 Insulin syringes
 Pen devices
 Insulin pumps
 Implantable pumps
 Inhaled insulin (withdrawn due to risk of pulmonary
fibrosis)
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.
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
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
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
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
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