Chapter 55 - Drugs for Thyroid Disorders

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C

HAPTER

55D

RUGS

FOR

T

HYROID

D

ISORDERS

Thyroid hormones have profound effects on metabolism, cardiac function, growth anddevelopment.- stimulate the metabolic rate of most cells, increase the force and rate of cardiac contraction- promote maturation- severe deficiency can produce dwarfism and permanent mental impairment Thyroid drugs are the most misused drugs in the diet industry.

I. T

HYROID

P

HYSIOLOGY

A. C

HEMISTRY

& N

OMENCLATURE

- thyroid gland produces two active hormones:triiodothyronine (T

3

)thyroxine (T

4

, tetraiodothyronine)- T

3

is more potent than T

4

- the body secretes more T

4

than T

3

and converts it to T

3

as needed

B. T

HYROID

H

ORMONE

A

CTIONS

- thyroid hormones are protein bound- synthetic drugs are better than natural drugs to mimic the natural thyroidhormone actions

1. Stimulation of Energy Use

– elevates the basal metabolic rate, resultingin increased oxygenconsumption and increased heat production

2. Stimulation of the Heart

– increases both the rate and force of contraction, resulting in increasedcardiac output and increased oxygen demand

3. Promotion of Growth and Development

– essential for normaldevelopment of the brain and othercomponents of the nervous system, and have a significant impact onmaturation of skeletalmuscle

II. T

HYROID

P

ATHOPHYSIOLOGY

A. H

YPOTHYROIDISM

– mild deficiency of thyroid hormone; malfunction of the thyroidgland-

myxedema

- severe deficiency in adults-

cretinism

– hypothyroidism in infancy

1. Hypothyroidism in Adults

a.

Clinical Presentation

- produces pale, puffy and expressionless facialcharacteristics, cold anddry skin, hair is brittle and loss occurs, heart rate andtemperature are lowered, patient

may have complaints of lethargy, fatigue, and intolerance tocold- mentality is impaired- thyroid enlargement (goiter) may occur if reduced levels of T

3

and T

4

promoteexcessive release of TSH (thyroid stimulating hormone)

b.

Causes

- usually due to malfunction of the thyroid itself - in iodine sufficient countries, the principal cause is

chronicautoimmune thyroiditis

(Hasimoto’s disease)- other causes are insufficient iodine in the diet, surgicalremoval of the thyroid anddestruction of the thyroid by radioactive iodine- may also result from insufficient secretion of TSH and TRH(thyrotropin releasinghormone)

c.

Therapeutic Strategy

- requires replacement therapy with thyroidhormones and treatment mustcontinue for life- standard replacement regimen consists of

levothyroxine

(T

4

)alone- when adequate, doses eliminate all signs and symptoms of deficiency

2. Hypothyroidism During Pregnancy

- maternal hypothyroidism can result in permanent neuropsychologicdeficits in the child-

congenital

hypothyroidism can cause mental retardation and otherdevelopmental problems- in the absence of fetal hypothyroidism, maternal hypothyroidismcan decrease IQ and otheraspects of neuropsychologic function- limited largely to the first trimester, a time during which the fetusis unable to produce thyroidhormones on its own- maternal hypothyroidism must be diagnosed and treated very early- symptoms of hypothyroidism are often nonspecific (irritability,tiredness, poor concentration,etc.) – or there may be no symptoms at all- recommended routine screening as soon as pregnancy is confirmed- thyroid hormone levels should be monitored and dosage increasedas needed

3. Hypothyroidism in Infantsa.

Clinical Presentations

- causes mental retardation and derangementof growth- the child develops a large and protruding tongue, potbelly,and dwarfish stature

- development of the nervous system, bones, teeth, andmuscles is impaired- cretinism usually results from a failure in thyroiddevelopment- other causes include autoimmune disease, severeiodine deficiency, TSHdeficiency, and exposure to radioactive iodine

inutero

- requires replacement therapy with thyroid hormones- if treatment is initiated within a few days of birth,physical and mentaldevelopment will be normal- if treatment is delayed for several months, somepermanent retardation will beevident- treatment must continue for life

B. H

YPERTHYROIDISM

- elevated levels of thyroid hormones-

thyrotoxic crisis

– extremely high levels of thyroid hormone

1. Graves’ Disease

(Barbara Bush has this disease)- most common cause of excessive thyroid hormone secretion- occurs most frequently in women 20 to 40 yrs. old (incidence infemales is 6 times greaterthan males)- results from elevated levels of thyroid hormone- heartbeat is rapid and strong, and dysrhythmias and anginamay develop- central nervous system is stimulated, resulting in rapidthought flow and rapid speech,nervousness and insomnia- skeletal muscles may weaken and atrophy- metabolic rate is raised, resulting in increased heatproduction, increased bodytemperature, intolerance to heat and skin that is warmand moist- appetite is increased; however, despite increased foodconsumption, weight lossoccurs is caloric intake fails to match the increasedmetabolic rate- patients often present with

exophthalmos

(protrusion of theeyeballs)Cause:- thyroid stimulating immuglobulins (TSIs) which areantibodies produced by anautoimmune process- increase thyroid activity by stimulating receptors for TSH on the thyroid gland(mimic the effects of TSH on thyroid function)

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