1. Drugs Acting on Pituitary Hormones
&
Thyroids Drugs
Jan - 2023
Dr. BANDAR D. ALREHAILI
2. B- Anterior Pituitary Hormones
2- Gonadotrophic Hormones
A- Follicle stimulating hormone (FSH)
B- Luteinizing hormone (LH) or interstitial cell
stimulating hormone (ICSH).
Regulated by a complex interaction between the
hypothalamic releasing hormone and both positive
and negative feedback effects of circulating sex
hormones.
This control system is also influenced by prolactin
hormone.
These two hormones stimulate the normal function
of the gonads and the secretion of sex hormones in
both male and female.
3. Preparations
1- Human menopausal gonadotrophin (Menotropins or HMG):
It is a mixture of human FSH & LH
Obtained from postmenopausal women's urine.
2- Human Chorionic Gonadotropin (HCG)
Derived from the urine of pregnant women.
A placental hormone with an LH agonist, to which it is
structurally related with FSH and TSH activities.
Choriogonadotropin alfa is a recombinant form
3- Urofollitropin is FSH obtained from menopausal women and
is devoid of LH.
4- Follitropin alfa and beta are human FSH manufactured by
recombinant DNA technology
5- Lutropin alfa the first and only recombinant form of human LH.
4. Therapeutic Uses of Gonadotropins
1. Prepubertal Cryptorchidism (undescended tests) ) in boys > 2
years old.
2. Infertility in:
A- Women with potentially functional ovaries who have not responded to
other treatments.
B- Women with polycystic ovarian disease.
C- Men to induce spermatogenesis in hypogonadotropic hypogonadal
men.
3- To prepare follicles for in vitro fertilization.
4- Delayed puberty.
Toxicity &CI
1. Ovarian hyperstimulation syndrome (ovarian enlargement, ascites,
sometimes shock).
2. Multiple pregnancies (preeclampsia, preterm labor, gestational
diabetes).
3. Headache, depression.
5. Drugs Affecting GnRH
I- GnRH Analogue or Agonist [GnRHa]:
Leuprolide (Lupron ®) and goserelin
(Zoladex ®)
1. Stable potent derivatives of GnRH.
2. Long-acting agonist that suppress gonadotropin
production after an initial stimulation.
3. Can be injected monthly or even less frequently.
II- GnRH Receptor Antagonist:
Ganirelix (Antagon ®)
A newer GnRH receptor antagonist, with the
advantage of being lacking the initial stimulation.
6. GnRHa & GnRH Receptor Antagonists
(Contd.)
Uses:
1. Palliative treatment of prostatic cancer in men
2. Suppression of puberty in young children with central
precocious puberty
3. Regression of uterine leiomyomas and endometriosis in
women
4. Sometimes given along with FSH in fertility treatments
(to prevent premature ovulation caused by the release of
pituitary LH).
Side Effects:
1. The main side effects are a result of estradiol deprivation
and include hot flashes dry skin and vagina.
2. Long-term use may decrease bone density.
7. Drugs Affecting GnRH (Contd.)
III- Danazol:
Gonadotrophic inhibitor
It is a synthetic androgen that inhibits the release of
FSH and LH from the anterior pituitary and thus
inhibits the synthesis of sex hormone .
In addition ,it increases the activity of clotting
factors VII and IX.
8. Danazol (Contd.)
Clinical Indications:
Treatment of endometriosis.
Treatment of fibrocystic disease of the breast
In some hematological disorders such as
hemophilia.
Side Effects:
Weight gain ,edema, headache, deepening of voice
hot flushes, change in libido and muscle cramps.
10. 3-Prolactin (Contd.)
Pharmacological Actions:
Prolactin is responsible for Mammotropic and
lactogenic effect.
- Mammotropic Effect: Development and maturation of mammary glands.
- Lactogenic effect: Stimulation of milk production.
During pregnancy prolactin level is high but high level of
estrogen caused decrease in the effect of prolactin on
milk.
After delivery estrogen level is decreased leading to
lactation by prolactin action.
11. 3-Prolactin (Contd.)
Abnormality:
Hyperprolactinemia: Elevated prolactin levels (>100 ng/mL) in the
absence of stimulatory factors
Causes of hyperprolactinemia:
1- Prolactinoma (pituitary prolactin secreting tumors),
2- Drugs such as phenothiazines, Cimetidine, Prozac, Reserpine
3- Hypothalamic dysfunction, tumors, tuberculosis, sarcoidosis,
4- Renal failure, liver diseases and , primary hypothyroidism
Common manifestations of hyperprolactinemia
In women: amenorrhea, infertility and galactorrhea.
In men: hypogonadism, decreased sex drive, decreased sperm
production, impotence, breast enlargement (gynecomastia).
12. Drug treatment of Hyperprolactinemia
Dopamine agonists
Suppress the release of prolactin as well as GH
1- Bromocriptine and pergolide The doses, usually 5
mg/day, the main side effects, nausea and postural
hypotension.
2- Cabergoline: Long-lasting dopaminergic agonist have been
found to be at least as effective and has a lower incidence of
side effects and can be taken once or twice/week
3- Quinagolide: non ergot drug bitter tolerated
Other uses of dopamine agonists:
Infertility, parkinsonism, acromegaly and to stop
lactation
13. B- Anterior Pituitary Hormones
4- Adrenocorticotrophic Hormone (ACTH, or
corticotropin)
ACTH acts on adrenal cortex
1. Stimulating the synthesis of :
A- Glucocorticoids, like cortisol ,
B- Mineralocorticoids, like aldosterone
C- Androgens (male sex hormones, like testosterone)
2. Stimulates the secretion of cortisol from the adrenal
glands.
3. In the fetus, ACTH stimulates the synthesis of
dehydroepiandrosterone sulfate (DHEA-S) which
prepare the mother for giving birth.
4. Responsible for the maintenance of adrenal weight.
14. ACTH agents and uses
1- ACTH (corticotropin) available in three preparations:
Corticotropin injection
Repository corticotropin
Corticotropin zinc hydroxide
2- Cosyntropin: synthetic form closely resembles ACTH
with longer duration can be taken monthly.
Used to
Diagnose adrenal disorders.
Treat deficiencies (rarely, since it is easier and less
expensive to treat with glucocorticoid).
Adverse reactions:
Painful swelling at the site of injection
Anaphylactic reactions.
It has adverse effects of both glucocorticoids and
mineralocorticoids, WHY?
15. B- Anterior Pituitary Hormones
5- Thyroid-Stimulating Hormone (Thyrotropin, TSH)
1. Stimulates growth of thyroid gland
2. Increases blood flow to thyroid
gland.
3. Stimulates synthesis and release
of T3& T4 from the thyroid.
4. Stimulates iodide uptake.
TSH is available for diagnostic
purposes:
To differentiate between pituitary and
thyroid gland failure.
- Increase plasma thyroid hormone
indicates abnormal function of pituitary
while no rise in thyroid hormone indicates
thyroid insufficiency.
16. Thyroid Gland
There is a large pool of T4 in the body; it has a low turnover
rate and is found mainly in the circulation.
There is a small pool of T3 in the body; it has a fast turnover
rate and is found mainly intracellularly.
Within target cells, the T4 is converted to T3, which interacts
with a nuclear receptor to regulate gene transcription.
Thyroid hormones affect the function of virtually every organ
system.
In the child, thyroid hormone is critical for normal growth and
development.
In the adult, the major role of thyroid hormone is to maintain
metabolic stability (stimulation of metabolism, causing
increased oxygen consumption and increased metabolic
rate).
17. Thyroid Disorders
1- Hypothyroidism :
Hypothyroidism is the clinical state resulting from decreased
production of thyroid hormones or very rarely from tissue
resistance.
Myxoedema is severe hypothyroidism with swelling of the
skin and subcutaneous tissues. It may rarely cause fatal
coma (precipitated by hypothermia, stress, infection, trauma
and certain drugs, notably β-blockers and respiratory
depressants.
18. Thyroid Disorders (Contd.)
2-Thyrotoxicosis :
Thyrotoxicosis refers to the hypermetabolic syndrome associated with
prolonged exposure to elevated levels of thyroid hormones.
It can be caused by thyroid hyperfunction (hyperthyroidism) or due to
other causes (Ex. thyroiditis, hormone ingestion, drug-induced).
Thyroid storm (thyrotoxic crisis), is an acute, life-threatening
thyrotoxicosis.
Note: Goitre (or goiter):
It is a swelling (diffuse or nodular) of the thyroid gland that causes a lump
to form in the front of the neck. The lump will move up and down when
you swallow.
It may be caused by hypo- or hyperthyroidism.
20. Drugs for Hypothyroidism
1. Levothyroxine Sodium (T4 salt): drug of choice
2. Liothyronine Sodium (T3 salt)
Levothyroxine (T4) Liothyronine (T3)
low cost higher cost
Long t1/2 (7days)
Given once daily
Shorter t1/2 (24h)
Multiple daily doses
Uses:
The preparation of choice
for replacement therapy in
hypothyroid patients.
Uses: only for
Short-term suppression of
TSH in patients undergoing
surgery for thyroid cancer.
Less risk of cardiotoxicity Greater risk of cardiotoxicity
21. Drugs for Hypothyroidism (Contd.)
Adverse effects:
As a result of overdose
Cardiac arrhythmias (tachycardia, palpitation, atrial fibrillation,…)
Weight loss
Tremor, headache, insomnia
Heat intolerance.
Interactions:
Rifampin, carbamazepine and phenytoin increase the metabolism
of T4, thus increasing their requirements.
Ferrous and calcium salts, Aluminum antacids and bile
sequestrants (Ex. Cholestyramine) decrease T4 absorption.
Drugs that decrease thyroxin production (lithium, amiodarone and
iodine-containing drugs) will also increase T4 requirements.
T4 can enhance metabolism of warfarin.
Dose of insulin, oral hypoglycemics and digoxin may require
increase with T4 treatment.
22. Drugs for Hypothyroidism (Contd.)
T4 Dose:
1.7 µg/kg (oral on empty stomach except in myxedema coma use
IV).
For most cases of mild to moderate hypothyroidism, a starting T4
dosage of 50-75 µg/day will suffice.
Dosing changes should be made every 6-8 weeks until the patient's
TSH is in target range.
In patients with central (ie, pituitary or hypothalamic)
hypothyroidism, T4 levels rather than TSH levels are used to guide
treatment.
Pregnancy increases the requirements of T4.
Some cardiovascular disorders (Ex. Angina and hypertension) may
require decreasing T4 dose (T4 can increase heart rate and
contractility).
23. Management of Thyrotoxicosis
1. Pharmacotherapy using:
A- Thyroid inhibiting drugs (Thioamides e.g.,
propylthiouracil, methimazole and carbimazole).
B. Iodides
C- Beta-blockers for CV symptoms
2. Radioactive iodine
3. Surgical treatment
25. Management of Thyrotoxicosis
1- Thyroid Inhibiting Drugs - Thioamides
Propylthiouracil, methimazole, carbimazole
Mode of action: They reduce the formation of thyroid hormone
(but not affect formed ones) by:
1. Inhibiting oxidation and organinfication
2. Inhibit the coupling of iodotyrosines to form T4 and T3.
3. Propylthiouracil (PTU): above effects + inhibits peripheral
conversion of T4 to T3, but only at the high doses used in
treatment of thyroid storm
Synthesis rather than the release of hormones is affected thus the
onset requires 3-4 weeks before stores of T4 are depleted.
26. Management of Thyrotoxicosis
1- Thyroid Inhibiting Drugs - Thioamides
Uses:
1. Methimazole is preferable to propylthiouracil (except in pregnancy)
because it can be administered once daily (long-acting), greater
bioavailability and 10 times more potent than PTU.
2. Carbimazole is the prodrug of methimazole
3. Propylthiouracil is safe in pregnancy
4. They are first-line treatment in children, adolescents and pregnancy, but
their cure rate is low (40-50%).
5. Used also to make patients euthyroid before surgery.
Adverse effects:
Nausea, gastrointestinal distress and maculopapular pruritic rash.
The most dangerous complication is agranulocytosis.
27. Management of Thyrotoxicosis
2- Thyroid Inhibiting Drugs - Iodides
Potassium iodide (KI) or Lugol’s iodine (5% iodine and 10% KI)
Mode of action: A pharmacologic dose of iodide inhibits:
The iodination of tyrosines (lasts only a few days).
The release of thyroid hormones from thyroglobulin.
Uses (oral):
1- Treat potentially fatal thyrotoxic crisis (thyroid storm)
2- Decrease the vascularity of the thyroid gland prior to surgery
Iodide is not useful for long-term therapy, because the thyroid ceases to
respond to the drug after a few weeks.
Adverse effects:
Sore mouth and throat, Swelling of the tongue or larynx, Rashes,
Ulcerations of mucous membranes, and A metallic taste in the mouth.
28. Management of Thyrotoxicosis
3- Thyroid Inhibiting Drugs - Radioactive Iodine
I131 is used Orally (usually a single dose).
Mode of action:
It is rapidly absorbed and then concentrated by the thyroid gland.
It emits mainly β-particles (90%) and γ-rays.
β-particles penetrate only O.5 mm off tissues producing destructive
effect on parenchymal cells of the gland (decreases growth and
hormone production) with little or no damage on surrounding
tissues.
The half-life of I131 is 8 days.
Use:
A cure for hyperthyroidism (best treatment of toxic nodules and toxic
multinodular goiter).
Treatment of thyroid carcinoma.
Adverse effects:
High incidence of delayed hypothyroidism.
Worsening of ophthalmopathy.
It is contraindicated in pregnant or lactating women and children.
29. Management of Thyroid Storm
1- Beta blockers :
Propranolol controls cardiovascular symptoms (ex. BP,HR, tremors) and
prevent conversion of T4 to T3. It does not affect thyroid function.
2- Iodides:
KI or Lugol’s iodine to inhibit release of thyroid hormones.
3- Propylthiouracil:
High dose to inhibit peripheral conversion of T4 to T3.
4- Corticosteroids:
Hydrocortisone or dexamethasone (IV) are used (also in some cases of
thyroiditis).
5- Bile sequestering agents:
Cholestyramine to decrease reabsorption of thyroid hormones in gut.
