DRUGS ACTING ON THE ENDOCRINE SYSTEM
Part 5-A: THYROID AGENTS
 The thyroid gland is a butterfly-shaped organ
located in the lower neck, anterior to the
trachea.
 Consists of two lateral lobes (L and R lobes)
connected by an isthmus. The gland is about 5
cm long and 3 cm wide and weighs about 30 g.
 The blood flow to the thyroid is very high (about
5 mL/min per gram of thyroid tissue),
approximately five times the blood flow to the
liver. This reflects the high metabolic activity of
the thyroid gland.
Hormones produced by the thyroid gland:
 Thyroxine (T4)
 Triiodothyronine (T3)
 Calcitonin.
THYROID HORMONES
 Thyroid Hormones (T4 and T3) - referred to
collectively as thyroid hormones
 The primary function of thyroid hormone -
control of cellular metabolic activity.
 Iodine - essential to the thyroid gland for
synthesis of its hormones.
• The major use of iodine in the body is by the
thyroid, and the major derangement in iodine
deficiency is alteration of thyroid function.
SIDE NOTE: Have enough intake of iodine in our diet to
prevent thyroid dysfunction.
CALCITONIN
SIDE NOTE: Calcitonin regulates serum calcium levels. In
response to increased serum calcium levels the
thyrocalcitonin is released from the thyroid gland into
the bloodstream causing the position of calcium into
the bones. It promotes the position of calcium to the
bones it inhibits osteoclasts and stimulates osteoblasts
and also inhibits calcium the absorption in the kidney
and also inhibits calcium absorption by the intestines
causing decreased serum calcium levels.
SIDE NOTE: Release of thyroid hormones is influenced
by the hypothalamic pituitary thyroid axis. The
hypothalamus will first secrete the hormone thyrotropin-
releasing hormone and this will stimulate the anterior
pituitary gland to secrete thyroid stimulating hormone
which will then stimulate the thyroid gland to release the
thyroid hormones.
CONTROL
• The secretion of TSH is regulated by thyrotropin
releasing hormone (TRH).
• Thyroid hormone production and release are regulated
by anterior pituitary hormone called thyroid-stimulating
hormone (TSH).
• The thyroid gland produces increased thyroid
hormones in response to increased levels of TSH.

Thyroid Dysfunction
1. Hypothyroidism – A disease condition where
there is lack of sufficient levels of thyroid
hormones to maintain a normal metabolism. This
condition occurs in a number of
pathophysiological states:
• Absence of thyroid gland
• Lack of sufficient iodine in the diet to produce
the needed level of thyroid hormone
Note: Iodine is essential ingredient in the
synthesis of thyroid hormones so if there is lack
of sufficient iodine so there would be depressed
levels of thyroid hormones.
• Lack of sufficient functioning thyroid tissue due
to tumor or autoimmune disorders
• Lack of TSH due to pituitary disease
• Lack of TRH related to a tumor or disorder of
the hypothalamus
SIDE NOTE: if there is inadequate secretion of thyroid
hormone during fetal and neonatal development it can
lead to the disease condition known as CRETINISM.
Cretinism - Inadequate secretion of thyroid hormone
during fetal and neonatal development
Clinical manifestations:
• stunted physical and mental growth because of general
depression of metabolic activity.
Hypothyroidism in adults
Clinical manifestations:
 lethargy
 slow mentation
 generalized slowing of body functions
2. Hyperthyroidism – occurs when excessive
amounts of thyroid hormones are produced and
released into the circulation.
• Grave’s disease is the most common cause of
hyperthyroidism. Goiter (enlargement of the thyroid
gland) is an effect of hyperthyroidism which occurs
when the thyroid is overstimulated by TSH.
Note: ma hypertrophy ang gland when it is over
stimulated
• Hyperthyroidism may be treated by surgical
removal of the gland or portions of the gland (TOTAL
or SUBTOTAL THYROIDECTOMY), treatment with
radiation to destroy all parts or all of the gland, or
drug treatment to block the production of
thyroxine in the thyroid gland or to destroy parts or
all of the gland.
PATHOPHYSIOLOGY
Hyperthyroidism
 Over secretion of thyroid hormones
(hyperthyroidism) manifested by a greatly
increased metabolic rate.
 Many of the other characteristics of
hyperthyroidism result from the increased
response to circulating catecholamines
(epinephrine and norepinephrine).
 Over secretion of thyroid hormones is usually
associated with an enlarged thyroid gland known
as a goiter.
 Goiter also commonly occurs with iodine
deficiency.
 SIGNS AND SYMPTOMS OF THYROID DYSFUNCTION
- The signs and symptoms of HYPOTHYROIDISM
are all related to hypometabolic rate while the Hypothyroidism: Decreased function: menorrhagia,
HYPERTHYROIDISM the clinical manifestations habitual abortion, sterility, decreased sexual function
are attributable to hyper metabolic rate. Hyperthyroidism: Altered tendency toward
oligomenorrhea, amenorrhea

Clinical Effects: Goiter

Hypothyroidism: Rare; simple nontoxic type may occur
Clinical Effects: CNS Hyperthyroidism: Diffuse,
Hyperthyroidism: Localized highly
with vascular,
accumulation
very of
Hypothyroidism: Depressed: Hypoactive reflexes, mucopolysaccharides in eyeballs, (protruding eyeballs) ocular
lethargy, sleepiness, slow speech, emotional muscles; periorbital edema, lid lag, exophtlamos, periorbital
dullness. NOTE: Ang patient na hypothyroidism daw edema
lutang, walang ganagana, permi ginatuyo.
Hyperthyroidism: Stimulated: Hyperactive reflexes, Clinical Effects: Ovaries
anxiety, nervousness, insomnia, tremors, Hypothyroidism – Decreased function menorrhagia habitual
restlessness, increased basal temperature abortion sterility decreased sexual function.
Hyperthyroidism – Altered tendency toward oligomenorrhea,
Clinical Effects: CV System amenorrhea
Hypothyroidism: Depressed: Bradycardia,
hypotension, anemia, oliguria, decreased sensitivity Clinical Effects: goiter (both hypo and hyperparathyroidism can
to catecholamines. have goiter)
Hyperthyroidism: Stimulated: Tachycardia, Hypothyroidism – Rare; simple non-toxic type may occur
palpitations, increased pulse pressure, systolic Hyperthyroidism – diffuse, highly vascular, very frequent
hypertension, increased sensitivity to
catecholamines Thyroid Agents

Clinical Effects: Skin, hair, nails 1. Thyroid Hormones - Used as replacement

Hypothyroidism: Skin is pale, coarse, dry, thickened;
puffy eyes and eyelids;
Hyperthyroidism: Skin is flushed, warm, thin, moist,
sweating, hair is fine and soft, nails are soft and thin
Clinical Effects: Metabolic rate
Side Note: because nubo imo thyroid hormones so
depressed mn imo metabolic rate
Hypothyroidism: Decreased: Lower body
temperature, intolerance to cold, decreased
appetite, higher levels of fat and cholesterol, weight
gain, hypercholesterolemia
Hyperthyroidism: Increased: Overactive cellular
metabolism, low-grade fever, intolerance to heat,
increased appetite with weight loss, muscle wasting
and weakness, thyroid myopathy
Clinical Effects: Generalized Myxedema
Hypothyroidism: Accumulation of mucopolysaccharides
in the heart, tongue, and vocal chords, periorbital edema,
cardiomyopathy, hoarseness and thickened speech
therapy in hypothyroidism
2. Antithyroid Agents - Treatment of
Hyperthyroidism
a. Thioamides
b. Iodine Solutions
Pharmacologic Therapy for Hypothyroidism
Therapeutic Actions and Indications
Side Note: thyroid hormones, in hypothyroidism we lack
the thyroid hormones which are we really need to
maintain equilibrium in our body and the thyroid
hormones available are synthetic form so meaning they
work just the same as the endogenous thyroid
hormones
 Thyroid replacement hormones increase the
metabolic rate of body tissues, increasing oxygen
consumption, respiration, heart rate, growth and
maturation, and the metabolism of fats,
carbohydrates, and protein.
THYROID HORMONES available are
Levothyroxine, Liothyronine, Liotrix, and Thyroid
desiccated. All of these are used as replacement
therapy in a hypothyroidism but usually what
comes up in local and foreign exams is this
Levothyroxine Synthroid.
 NOTE! : Always remember that THYROXINE must be
given on empty stomach at least 30 minutes before
taking breakfast so this medication should not be
CHEWED or CRUSHED and the medicine must be taken
with a FULL GLASS of WATER
All of the available hormones have indications of
TREATMENT of MYXEDEMA COMA and
THYROTOXICOSIS
NOTE! Remember that this medication should not be
used during acute thyrotoxicosis unless they are used in
conjunction with anti-thyroid drugs.
Thyrotoxicosis – this is the name given to the clinical
effects experienced with the patient due to an excessive
levels of thyroid hormones in the bloodstream.
Contraindications and cautions
 should not be used with any known allergy to
the drugs to prevent hypersensitivity reactions.
 Should not be used during acute thyrotoxicosis
unless used in conjunction with antithyroid
drugs.
 During acute myocardial infarction (unless
complicated by hypothyroidism).
 Caution should be used during lactation, with
hypoadrenal conditions.
 Liothyronine and liotrix - have a greater
incidence of cardiac side effects and not
recommended for use in patients with potential
cardiac problems or patients prone to anxiety
reactions.

Pharmacokinetics Adverse Effects:

✓ Thyroid hormones are well absorbed from the GI tract
and bound to serum proteins. ✓Skin reactions and loss of hair (during first few months
✓ Thyroid hormones do not cross the placenta and seems of treatment in children) note: and because they are
to have no effect on the fetus. replacement hormones they can work just the same as
Side Note: that is why if the women is hypothyroid and the endogenous hormones.
then she becomes pregnant thyroid replacement ✓Arrhythmias, hypertension (cardiac stimulation)
therapy should not be discontinued and actually ga taas ✓Anxiety, sleeplessness, headache (CNS)
ang metabolism during a pregnancy so the need for ✓Difficulty of swallowing with esophageal atresia
thyroid hormones often becomes apparent or it (patient must be instructed to take the drug with a full
increases during pregnancy so the if the woman gets glass of water to alleviate this effect)
pregnant she should go back to the Doctor so that the Side Note: Patient must be instructed to take the drug
hormone levels can be checked as well as necessary with a full glass of water to elevate this effect
adjustments can be done based on the patients signs
and symptoms or the results of the laboratory. Clinically important Drug-Drug Interactions
✓ decreased drug absorption of thyroid hormones if
✓ Enters breast milk in small amounts. Caution should be
used during lactation. they are taken concurrently with cholestyramine (should
be taken 2 hours apart)
✓ effectiveness of oral anticoagulants like
RIVAROXABAN is increased if they are combined with
thyroid hormone (bleeding time should be checked
periodically)
✔️ Decreased effectiveness of digitalis glycosides
can occur when these drugs are combined. (Digitalis
levels should be monitored, and increased dose may
be required).
✔️ Theophylline clearance is decreased in
hyperthyroid states. As the patient approaches
normal thyroid function the theophylline dose may
need to be adjusted frequently.
 Pharmacologic Therapy for Hyperthyroidism
Antithyroid Agents- Drugs used to block the
production of thyroid hormone and to treat
hyperthyroidism.
Two forms of pharmacotherapy for treating
hyperthyroidism and controlling excessive thyroid
activity:
A. Thioamides
B. Iodine solutions
Antithyroid Agents
Therapeutic Actions and Indications
1. Thioamides
 Indicated for the treatment of hyperthyroidism
 Lower thyroid hormone levels by preventing
the formation of thyroid hormone in the thyroid
cells, which lowers the serum levels of thyroid
hormone.
 They also partially inhibit the conversion of T4
and T3 at the cellular level.
 Thioamides include propylthiouracil (PTU) and
methimazole (Tapazole)
 Both of these drugs can be fatal to a developing
fetus. But if it is needed;
A. Propylthiouracil (PTU) – preferred drug during
pregnancy.
Once the thyroid toxicity is under control, the dose
is decreased to prevent fetal hypothyroidism.
Antithyroid medications are contraindicated in late
pregnancy, because they may produce goiter and
cretinism in the fetus (Cooper, 2005).
Take Note: the mother has hyperthyroid case not the
baby, if this drug will cross the placenta makadto sya sa
baby, fetus might develop a fetal hypothyroidism. If it’s
really needed, because the patient is symptomatic ->
the doctor should explain the risks and benefits of giving 
these medications.
 Onset and duration of PTU (Propylthiouracil)
B. Methimazole (Tapazole) –
2. Iodine Solutions
- Iodine is needed in synthesis of thyroidhormones
 Low doses of iodine are needed in the body for the
formation of thyroid hormone. High doses block thyroid
function
 Iodine solutions will cause the thyroid cells to become
oversaturated with iodine and stop producing thyroid
hormone. In some cases, the thyroid cells are destroyed.
 Radioactive iodine (sodium iodide 131) is taken up into the
thyroid cells which are then destroyed by beta-radiation
given off by radioactive iodine
(How do these Iodine Solutions perform?)
Iodine Solutions
 The use of iodine iodide is reserved for those patients who
are not candidates for surgery, women who cannot become
pregnant, and elderly patients with such severe,
complicating conditions that immediate thyroid destruction
is needed.
Iodine solutions available include:
1. Strong iodine solution (a.k.a. Lugol’siodine/
aqueous iodine, potassium triiodide)
2. Potassium iodide (Brand names: SSKI,
Iosat, Thyrosafe, Thyroshield)
3. Sodium Iodide I131 (comes incapsule)
Pharmacokinetics
Thioamides
Well absorbed from the GI tract and are then
concentrated in the thyroid gland
varies with eachpatient
 Methimazole onset of action:
30-40minutes, peak: 60 minutes
o Crosses the placenta and is
found in high ratio in the breast
milk
o If an antithyroid medication is
really needed during
pregnancy, the drug of choice is
PTU, but it doesn’t mean that
PTU will not have any effects
to the pregnancy or fetus
that’s why the mother should
informed by the physician
about the risks and benefits of
giving the medication.
Iodine solutions

 Rapidly absorbed from the GI tract and widely

distributed throughout the body fluids. Excretion
occurs through the urine.
 Potassium iodide and sodium iodide are taken
orally and have a rapid onset of action, which
effects within 24 hour and peak effects seen in 10-
15 days.
 The effects are short-lived and may even precipitate
further thyroid enlargement and dysfunction. For
this reason, iodides are not often used and are used in
cases of radiation emergencies
Contraindications and Cautions
 Contraindicated in the presence of any known allergy
to antithyroid drugs to prevent hypersensitivity
reactions
 During pregnancy, because of adverse effects on the
fetus and the development of cretinism (teratogenic)
When mother has hyperthyroid, the mother is being
treated sang hyperthyroid and the baby is euthyroid.If
this medication crosses the placenta, the fetus will be
most likely to develop congenital hyperthyroidism or
cretinism.
 If antithyroid is essential and the mother has been
informed about the risk of cretinism in the infant, PTU
is thedrug of choice, but caution should still be used.
 PTU has been associated with severe liver toxicity
and is no longer recommended for use in children
because they are more susceptible to the toxic
effects in the liver
 Use of strong iodine products is
contraindicated with pulmonary edema and
tuberculosis
Adverse Effects
Thioamides
 Adverse effects are thyroid suppression: (patient may
manifest hypothyroidism)
- Drowsiness, lethargy, bradycardia, nausea, skin rash,
and so on.
- (Because itis an antithyroid medication, the patient
may manifest signs and symptoms of
hypothyroidism).
 PTU – associated with nausea, vomiting, GI
complaints, and severe liver toxicity
 Methimazole – (drug of choice for patients who
are unable to tolerate PTU or patients
with known liver dysfunction)
- GI complaints, bone marrow suppression, so the
patient using this drug must have frequent blood
tests to monitor this effect.
- Check for bone marrow suppression byreviewing
the CBC results with differential
Iodine solutions
 Common adverse effect is
hyperthyroidism; the patient will need to
be started on thyroid replacement
hormone to maintain homeostasis.
 Thyroid hormone should not be given
during acute thyrotoxicosis. You can only
give that if it is accompanied by
antithyroid medications because
antithyroid medications can cause
hyperthyroidism.
 Iodism (metallic taste and burning in the
mouth, sore teeth and gums, diarrhea,
cold symptoms, and stomachupset)
 Staining of teeth (Give iodine solution
through a straw to decrease staining of
teeth), skin rash, and development of
goiter.
Take Note: Sodium Iodide (I131) [radioactive
iodine] - is usually reserved for use in patients who
are older than 30 years of age because of the
adverse effects associated with radioactivity.
• A special precaution for women: For pregnant women or
women who wants to be pregnant in the next 6 months, they
shouldnot use radioactive iodine because the treatment can
destroy the fetus’s thyroid and impair its development.
Women should wait at least a year before conceiving if they
have been treated with radioactive iodine. Women who are
breastfeeding should also not take radioactive iodine. They can
use alternative ways of feeding like formulafeeding or using
donated breastmilk.
 Iodine Solutions
Nursing Considerations (Radioactive Iodine Therapy):
 Drugs that have a small margin of safety that could
 Use of an ablative dose of radioactive iodine initially
be altered by the change in thyroid function should
causes an acute release of thyroid hormone from
be monitored closely.
the thyroid gland and may cause increased
symptoms.  These drugs include: anticoagulants, theophylline,
digoxin, metoprolol and propranolol.
The patient must be observed for signs of thyroid
storm, a life-threatening conditionmanifested by: Antithyroid Agents
 Cardiac dysrhythmias
 Fever
 Neurologic impairment

✓ Thyroid Storm – (also known as thyrotoxic crisis) is an

acute state of hyperthyroidismwhere all the signs and
symptoms are exaggerated. It can be life threatening
butwith quick response can be controlled and manage.

To control these symptoms, we will give:

 Propranolol (Inderal) is useful in controlling

these symptoms
 The patient is monitored closely until the
euthyroid state is reached. In 3-4 weeks,
symptoms of hyperthyroidismsubside
 Radioactive iodine is contraindicated during
pregnancy (because it crosses the placenta) and
during breastfeeding (because it is secreted in the
breastmilk) to prevent hypothyroidismin the fetus.
 Pregnancy should be postponed for at least 6
months after the treatment. Women are still
advised to wait until or at least 1 year to make sure
that the body is clear from the radioactive iodine.

Clinically Important Drug-Drug Interactions

Thioamides

 Increased risk of bleeding when PTU is

administered with anticoagulants like
rivaroxaban
 Changes in serum levels of theophylline,
metoprolol, propranolol, and digitalis may lead
to changes in the effects of the PTU as the
patient moves from hyperthyroid to euthyroid
state.