Therapeutics

Pharmacology & Toxicology Department

“Practical Section”

By : kawthar emad
Thyroid gland

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 Thyroid hormones includes:

1- Thyroxin (T4)
Bothe are released
from
follicular cells
• Ratio of T3 <<< T4
• Potency of T3 >> T4
2- Triiodothyronin (T3)
T3 is the most important because more than 90% of the thyroid
hormones physiological effects are due to the binding of T3 to
thyroid receptors in peripheral tissues.
3- Calcitonin Secreted from clear (c)
cells or parafollicular cells

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 T3 and T4 regulation

TRH: thyrotropin-releasing hormone, TSH: thyroid-stimulating hormone or thyrotropin, 4

T4: thyroxine, T3: triiodothyronine
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 Pharmacological actions of thyroid hormone

1. Metabolic function:
CHO metabolism:
•  glycogenolysis
• Increase gluconeogensis
•  glucose absorption from GIT
• Enhance uptake of glucose by the cell.
On fat metabolism:
• mobilization of fat,
• oxidation of FA   FFA
• Lower blood cholesterol due to increase formation of LDL
receptor in liver which favor hepatic removal of cholesterol
from blood

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 On GIT:
–  appetite & food intake.
–  rate of secretion of digestive juice.
–  motility of GIT  diarrhea often result in hyperthyroidism

On CVS:
• Enhance tissue sensitivity to catecholamine
• cardiac function

On nervous system:
• Excitable effect
• Has role on development of brain in fetal & 1st few weeks of
postnatal life

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Thyroid
disorders 9
Hypothyroidism

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 Hypothyroidism
(abnormally decreased activity)
1. Causes
 Primary: abnormality at the thyroid gland (>95% of cases).
• Environmental iodine deficiency.
• Hashimoto thyroiditis (chronic autoimmune thyroiditis).
• Intervention such as surgery, radioiodine, or radiation.
• Drug use: propylthiouracil, methimazole, amiodarone,….etc.
 Secondary (level of the pituitary) or tertiary (level of the
hypothalamus) (central).

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 Hypothyroidism
(abnormally decreased activity)
2. Risk factors
 woman
 older than 60
 Have a family history of thyroid disease
 Have an autoimmune disease, such as type 1 diabetes
 Treated with radioactive iodine, anti-thyroid medications, received
radiation to your neck or upper chest, thyroid surgery.

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 Hypothyroidism
(abnormally decreased activity)
•Fatigue, Increased sensitivity to cold, Depression
•Constipation
•Dry skin
•Weight gain, puffy face
•Elevated blood cholesterol level
•Cold intolerance
•Heavier than normal or irregular menstrual periods
•Thinning hair
•Bradycardia
•Impaired memory
•Enlarged thyroid gland (goiter)

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 Hypothyroidism
(abnormally decreased activity)
Lab Findings:
 Primary: abnormality at the thyroid gland (>95% of cases).
↓T3,T4
↑TSH

 Secondary (level of the pituitary) or tertiary (level of the

hypothalamus) (centrel)

↓T3,T4
↓TSH
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 Pharmacological treatment
L- thyroxin or levothyroxine (T4) T3

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 .

First-Line: Levothyroxine
• Should be taken on an empty stomach, ideally an hour before breakfast.

• Medications that interfere with its absorption should be taken 4 hours after the T4 dose:
ferrous sulfate, proton pump inhibitors, calcium carbonate, bile acid resins.

• The long (approximately 7 day) half-life allows once-a-day dosing, steady-state levels
of T4 and TSH are generally achieved in 6 weeks (approximately five to six half-lives).

• Once stabilized, periodic TSH level should be done after 6 months and then at 12-month
intervals or more frequently if the clinical situation dictates otherwise.

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 Myxedema coma
Myxedema coma is a rare but life-threatening state of extreme hypothyroidism. It
may occur in those who are known to have hypothyroidism when they develop another
illness, but it can be the first presentation of hypothyroidism.
 Hyperthyroidism
.

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 HYPERTHYROIDISM
(thyrotoxicosis)

Overactive thyroid leads to overproduction of the thyroid hormones

T3 and T4.
Causes:
1- Grave’s disease :
An autoimmune disease in which antibodies are produced which
stimulate the thyroid to secrete excessive quantities of thyroid
hormones (TSH, free T4).
2- Toxic nodular goiter :
Solitary or multi nodule secrete excess thyroid hormone
3- Secondary hyper thyrodisim:
It may be pituitary tumor increase secretion of TSH both TSH &
thyroid hormones are high 20
Toxic nodular goiter

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 Strategies of treatment

1. Reducing thyroid hormone synthesis:

• Antithyroid drugs (carbimazole, Methimazole, Propylthyouracil)
• Radioiodine (I131)

2. Reducing thyroid hormone effects:

• Propranolol
• Benzodiazepines or barbiturates

3. Reducing peripheral conversion of T4 to T3

• Propylthyouracil

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 Antithyroid drugs
(Thiouracil, Thionamides)
Thyrostatics (antithyroid drugs) are drugs that
inhibit the production of thyroid hormones.
Prevent hormone synthesis by inhibiting the
thyroid peroxidase-catalyzed reactions and
blocking iodine oxidation.
• Example:
(Carbimazole, methimazole, and
Propylthiouracil)

Propylthiouracil inhibit the peripheral

deiodination of T4 and T3 .
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 Radioactive iodine I 131

In iodine-131 radioactive isotope is trapped in thyroid

gland.

Beta radiation is then emitted destroying the thyroid

gland without affecting surrounding tissue.

Not preferred in:

Pregnancy, younger age

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 Adjuncts to Antithyroid Therapy

• Hyperthyroidism resembles sympathetic overactivity

• Propranolol, will control tachycardia, hypertension, atrial

fibrillation, tremors, and insomnia.

• Diltiazem, can control tachycardia in patients in whom beta-

blockers are contraindicated

• Barbiturates accelerate T4 breakdown and are also sedative

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 Iodides

 Iodide in high conc inhibit it’s own transporter into thyroid cell
so inhibit iodination of thyroglobulin and synthesis of T3 & T4
 Decrease the size & vascularity of the hyperplastic gland.
Uses of iodide :
• Thyrotoxic crisis
• Preparation for thyroidectomy (decrease the size &
vascularity of the hyperplastic gland)
N.B:
The anti thyroid action of long term treatment with iodide wear off
and manifestation of hyper thyrodism reappear in 2-3 weeks
(escape phenomenon) due to compensatory increase in TSH which
stimulate T3 and T4 release with loss of iodide effect
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 Nonpharmacological treatment

Surgery
(Thyroidectomy to remove the whole thyroid or a part of it) is not
extensively used because there risks as:

1- removing the parathyroid glands

2- cutting the recurrent laryngeal nerve, making swallowing

difficult, and even simply generalized staphylococcal infection as
with any major surgery.

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Practical case study

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Patient and Setting: KZ, a 34-year-old female; primary care clinic
Chief Complaint: Complaints of fatigue, weight gain, menstrual irregularities, and cold
intolerance
History of Present Illness
Patient was referred for evaluation of thyroid function tests. Her physical examination
had been remarkable for a dry skin, and puffy face Medical History: Hypertension
(HTN) × 3 years; ventricular tachycardia (controlled with amiodarone for 1 year)
Family/Social History: Father died of a stroke at 52; glass of red wine 2 to 3 nights a
week
Medications:
• Amiodarone, 200 mg PO QD(ORALLY&every day)
• Lisinopril, 10 mg PO QD
• TUMS, 1 tablet PO PRN
Results of Pertinent Laboratory Tests, Serum Drug Concentrations, and Diagnostic Tests
 TSH= 20 MU\ml (0.5-6)
 Ft4=0.3 ng/dl(0.7-1.8)
 Detection of thyroid antibodies.

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 Questions

1. KZ is experiencing symptoms consistent with which of the

following?
a. Myxedema coma
b. Menopause
c. Hashimoto's
d. Graves' disease

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 Questions

2. A potential cause for KZ's hypothyroidism is:

a. Her cardiac history
b. Amiodarone use
c. Her age
d. Family history

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 Questions

6. KZ's primary care provider should follow up on her

thyroid levels in:

a. 1 week

b. 2 weeks

c. 4 weeks

d. 6 weeks

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