Thyroid Drugs

What are the three thyroid hormones?

calcitonin

T3 — triiodothyronine

T4 — thyroxine

Thyromimetic Drugs

Levothyroxine

Liothyronine

Antithyroid Drugs

Propylthiouracil

Methmazole

Radioactive Iodide

Potassium Iodide

Propanolol/Atenolol

Dilitiazem

Teprotumumab

Thyroid Hormone Synthesis: Step 1

Iodide uptake

The thyroid actively pulls iodide from your bloodstream into the follicular cells using specialized transporter proteins.

Thyroid Hormone Synthesis: Step 2

oxidation of iodide and ordination of thyroglobulin

The enzyme thyroid peroxidase converts the trapped iodide into active iodine and attaches it to the tyrosines that are located on a protein precursor called thyroglobulin

Thyroid Hormone Synthesis: Step 3

coupling of iodotyrosine to form iodothyronines

This same enzyme links those iodine-attached molecules together while they are still on the protein to build the actual thyroid hormones

Thyroid Hormone Synthesis: Step 4

transport of thyroglobulin into lumen of cell

store thyroid hormone within the follicle's colloid

Thyroid Hormone Synthesis: Step 5

proteolysis of thyroglobulin and release of thyroid hormones into bloodstream

When your body needs them, the cells swallow the thyroglobulin and use enzymes to digest it (the colloid, too), releasing free thyroid hormones into your blood

What is more potent: T3 or T4?

T3

Which lasts longer (half-life): T3 or T4?

T4

___ and ___ are the main components that regulate thyroid hormone synthesis and secretion... but not the only ones:

TRH and TSH

cold, acute psychosis, circadian rhythm, severe stress

The ___ releases TRH to influence the ___

hypothalamus

pituitary gland

The influenced pituitary gland, the ___ portion, releases ___

anterior

TSH

TSH acts directly upon the ___, encouraging ___

thyroid gland

production of thyroid hormones

So, TSH causes for an increase in synthesis/secretion of T3 and T4... what else is increased via TSH?

cAMP

What are the effects of thyroid hormones?

normal growth and development

increase in basal metabolic rate

increase in plasma glucose

reduction in plasma cholesterol

increase in cardiovascular activity

thermogenic effect

CNS maturation

How does thyroid hormone increase plasma glucose?

increases in gluconeogenesis, glycolysis, cholesterol breakdown, thermogenesis

Let's talk about hypothyroidism... not having enough.. what are some common symptoms?

tiredness

sensitivity to cold

constipation

dry skin

weight gain

puffy face, hoarse voice, coarse hair

How do you treat hypothyroidism?

thromimetic drugs!

Recall them, putting the most widely used one first:

Levothyroxine

Liothyronine

Levothyroxine is given ___

orally

Levothyroxine AE:

symptoms of hyperthyroidism , such as insomnia, anxiety, weight loss, intolerance to heat, elevated glucose

Levothyroxine binds to ___ in blood

TBG

Thyroid Cancers present with which symptoms?

painless lump in neck

trouble swallowing

hoarseness

difficulty breathing

swollen lymph nodes

How do we treat thyroid cancers (hint: think about recent topic)?

surgical removal OR radioactive iodine

followed by —> Levothyroxine

Why do you proceed to give Levothyroxine?

replacement therapy, since thyroid cancer/tx may have wiped out a lot of the thyroid gland

Now let's move on to hyperthyroidism, which is dominated by ___ and ___ symptoms

CNS

cardiac

Give a few (hint: named before) ...

anxiety, irritability

insomnia

sensitivity to heat

tachycardia, palpitations

twitching

How do you go about treating hyperthyroidism?

antithyroid drugs!

Click this card for the three categories that we will have to know:

potassium iodide

radioactive iodide

thioamides

Scratch that... one of them is no longer used... which one? And why?

potassium iodide

not useful for long term therapy and not pleasant side effects

Radioactive iodide should be given for ___ weeks for clinical effect

6-12

Iodides attack which step/process of thyroid production?

organification of I

proteolysis of thyroglobulin

What is the key feature of thioamide structure?

C double bonded to S

that same C attached to an -NH

There are two primary thioamides:

propylthiouracil

methimazole

Thioamides attack which step of thyroid hormone production?

organification

Thioamides have ___ of 3-4 weeks

delayed onset

Thioamides AE:

maculopapular pruritic rash

GI upset

hypothyroidism

liver damage

may cross placenta and get into breast milk

Which thioamide drug is better to be used to AVOID liver damage?

Methimazole

What are two adjunct therapies that can be used to reduce CNS symptoms of hyperthyroidism?

beta blockers

>

Calcium channel blockers

Give some examples of serviceable beta blockers for this purpose:

Propranolol

Atenolol

Which drug can be used to treat thyroid eye disease?

Teprotumumab

very specific drug!

Thyroid Eye Disease??

think about bulging eyes in Graves'

this is inflammation...

How is Teprotumumab provided?

IV once every 3 weeks x8

How does Teprotumumab make an influence?

lowers IGF-1

Teprotumumab AE:

muscle spasm, nausea/diarrhea, hair loss, fatigue, hyperglycemia