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Pharmacology > Thyroid & Antithyroid Drugs > Flashcards

Thyroid & Antithyroid Drugs Flashcards

1
Q

What are the general functions of thyroid hormones?

A

Growth and development

increased body temperature

Increased energy metabolism

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2
Q

What protein facilitates iodide uptake into thyroid gland?

A

Sodium/iodide symporter (NIS)

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3
Q

Describe path and modification of iodide from blood stream to T3 or T4

A

Iodide taken up by NIS into follicular cell

Converted within cell to Iodine by peroxidase

Diffuse into colloid?

Attached to tyrosine residues to form MITs and DITs

MITs and DITs combined to form T3 and T4

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4
Q

Which form of thyroid hormone is the active form?

A

T3

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5
Q

Which molecule is predominately secreted?

A

T4 (5:1 ratio)

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6
Q

In what form are T3, T4 present in the blood?

A

Majority bound to thyroxine-binding-globulin (TBG)

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7
Q

Describe thyroid hormone secretion.

A

Thyroglobulin is phago-/pinocytosed, degraded and released from follicular cell

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8
Q

Where is the T3 receptor and what is its function in ABSENCE of thyroid hormone?

A

Homo-dimer bound to TRE (thyroid response element)

Inhibits gene expression with co-repressors

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9
Q

Where is the T3 receptor and what is its function in PRESENCE of thyroid hormone?

A

T3 binds to receptor in the nucleus (T4 is converted to T3, then enters.)

Co-repressors, and 1 thyroid receptor dissociate, and are replaced with RXR; now increased gene transcription

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10
Q

What effect does TRH have on thyroid hormone synthesis? Regulation?

A

TRH promotes TSH release by pitiutary

Both hypothalamus and pituitary have negative feedback from T3, T4.

“High” serum iodide inhibits thyroid hormone synthesis in the short term
“low” iodide promotes thyroid synthesis (also short term?)

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11
Q

Effects of thyroid hormone on SNS?

A

Increase beta receptors

Decrease alpha receptors

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12
Q

Effects of thyroid hormone on growth and development

A

Brain development

Activation of osteoclasts, osteoblasts

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13
Q

Effect of thyroid hormone on Respiratory system

A

increase tissue O2 consumption, increases Co2 formation

RR increases

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14
Q

Effect on GI

A

increase secretions and motility

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15
Q

Effect on CNS

A

think faster, affect muscle tone

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16
Q

Effect on Skin and Hair

A

promote skin, hair, nail growth

Prevent glycosaminoglycan accumulation (myxedema)

17
Q

Effect on CV

A

Increase HR
increase inotropy/contractility
Increase cardiac output

Decrease vascular resistance

18
Q

Metabolic effects

A

Decrease circulating faat
Increase carb absorption, glycolysis, insulin secretion
Increase protein synthesis and breakdown (?)
Increased need for vitamins and cofactors
Increased basal metabolic rate

19
Q

Signs of hypothyroidism

A

Bradycardia

Slow bone growth/MR

Fatigue, hypokinetic muscles

Myxedema

Dry scaly skin, depressed hair and nail growth

Increased body weight, atherosclerosis, cold intolerance

20
Q

Signs of hyperthyroidism

A

Tachycardia, sweating, tremors

High respiratory rate, possible failure

Anxiety, nervous, worry, paranoia, restlessness

Diarrhea

Exophthalmos, sweating

Decreased body weight, increased appetite

21
Q

Causes of hypothyroidism?

Primary and secondary

A

Primary:

  • Congenital underdeveloped thyroid
  • Autoimmine thyroiditis (Hashimoto’s)
  • Iodide deficiency
  • Surgery/radiation

Secondary:
- impaired TSH production secondary to ICP, neoplasm, irradiation, surgery

22
Q

Treatment of hypothyroidism

A

Hormone replacement with synthetic hormone

23
Q

Levothyroxine

MoA, pharmacokinetics

A

T4 analogue, activates T3 receptors

adverse effects: hyperthyroid sx

longer half-life, higher oral absorption than T3 analogue

24
Q

Liothyronine

MoA, pharmacokinetics

A

T3 analogue, acts on T3 receptors

Adverse effects similar to other synthetic thyroid hormones

Shorter half-life, higher oral absorption, very potent!

25
Q

Causes of hyperthyroidism

Primary and secondary

A

Primary:

  • Grave’s disease; antibodies stimulate TSH receptors
  • adenoma/carcinoma
  • Hashimoto’s disease; causes hyperthyroid state during follicular cell destruction
  • thyroid storm!; physiologic stress induced response
  • excess iodide; common with underlying disease, regulatory breakdown?

Secondary: hypersecretion of TRH, TSH

26
Q

Agents used to treat hyperthyroidism

A

Thioamides, iodides, radioactive iodine, anion inhibitors

Plus adjuncts

27
Q

Methimazole, propylthiouracil

MoA, Adverse effects, pharmacokinetics

A

Inhibit peroxidase reaction, organification, and coupling of MIT and DITs

Adverse effects:
Methimazole- altered taste and smell
Propylthiouracil: severe hepatitis

Pharmacokinetics:

  • methimazole has much higher potency
  • propylthiouracil has rapid absorption (use for thyroid storm, use for pregnant bc binds to plasma proteins)
28
Q

Potassium iodide, Lugol’s solution (iodine + potassium iodide)

MoA, Adverse effects, pharmacokinetics

A

Inhibit hormone release, can’t proteolyze Tgb

Adverse effects: metallic state, cold feeling, skin lesions, decreased vascularity, size and fragility of gland, fetal goiter

Pharmacokinetics: will only inhibit for 2-8 weeks, withdrawal leads to thyrotoxicosis, rapid onset within 2-7 days

29
Q

Radioactive iodine

MoA, Adverse effects, pharmacokinetics

A

emission of beta, gamma rays

  • beta destroy parenchyma of thyroid
  • gamma used to detect remaining RAI

Adverse effects: hypothyroidism, cancer (but little evidence), contraindicated if pregnant

30
Q

Perchlorate (ClO4-)
Pertechnetate (TcO4-)
Thiocyanate (SCN-)

MoA, Adverse effects, Uses

A

Inhibit uptake of iodide into thyroid cell by NIS

Adverse: perchlorate can cause aplastic anemia

Use: iodide-induced hyperthyroidism (??)

31
Q

Propranolol

MoA, Adverse effects, Uses

A

antagonize B1, B2 adregnergic, inhibit conversion to T4 to T3

Adverse: asthma, AV blockage, hypotention, bradycardia

Uses: thyroid storm!

32
Q

Diltiazem

Adjunct effect for treating hyperthyroidism?

A

control tachycardia in asthmatics

33
Q

Barbiturates

Adjunct effect for treating hyperthyroidism?

A

increase T4 metabolism

34
Q

Bile acid sequestrants

Adjunct effect for treating hyperthyroidism?

A

increase biliary T4 excretion

Pharmacology (6 decks)

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