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SP- Week 10 Thyroid > Drugs Affecting Thyroid Gland > Flashcards

Drugs Affecting Thyroid Gland Flashcards

1
Q

TH SYNTHESIS AND SECRETION

A
  1. Iodide uptake from blood to the follicle cell
    • Na+/I− symporter (NIS)
  2. Iodide moved into the lumen
    • Pendrin1 (PDS), an I−/Cl− porter
  3. Organification of iodide
    -.Oxidation of iodide and incorporation into thyroglobulin on tyrosine residues,
    • Catalysed by thyroperoxidase
  4. ’ Coupling
     Monoiodotyrosine (MIT)
     Di-iodotyrosine (DIT)
     MIT combines with DIT to form T3
     Two DIT molecules combine to form T4
     Thyroperoxidase involved
  5. Thyroglobulin molecule taken up into follicle cell by endocytosis
  6. Endocytotic vesicles fuse with lysosomes
  7. Proteolytic enzymes act on thyroglobulin
  8. T 4 and T3 released and secreted into the plasma
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2
Q

TH PHYSIOLOGICAL ACTION

A
  1. Metabolic effects
  2. Growth + development
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3
Q

Metabolic Effects

A

• Increase and regulation of metabolism: proteins,
fats, carbohydrates
• Oxygen consumption increase and heat
production: increase basal metabolic rate
• Increased cardiac rate and output

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4
Q

Growth & Development

A

• Directly • Indirectly via GH
production & potentiation • Skeletal development • Development of CNS

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5
Q

TH REGULATION
[TRH+ TSH]

A

Thyrotrophin-releasing hormone (TRH)
 Released from hypothalamus
 Releases thyroid-stimulating hormone (TSH) from
anterior pituitary

TSH
 Trophic action on thyroid cells
 Controls TH synthesis & secretion
 Negative feedback control via TH on anterior
pituitary
 Somatostatin reduces TSH release

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6
Q

TH REGULATION

Plasma iodide concentration

A
  1. Reduced iodine intake
     Decrease TH production
     Increase TSH secretion
     Increase in gland vascularity and hypertrophy
  2. Increased plasma iodide
     Size and vascularity of thyroid reduced
    ‘
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7
Q

THYROID FUNCTION ABNORMALITIES

For Hyperthyroidism (thyrotoxicosis)

A

Hyperthyroidism (thyrotoxicosis)

  1. Grave’s disease
    - Auto-antibodies against TSH receptor
    - Leads to activation
  2. Toxic nodular goiter
    - Benign neoplasm or adenoma
  3. Simple, non-toxic goiter
    • Iodine dietary deficiency
      • Rise in plasma TRH and eventually an increase in
      the size of the gland
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8
Q

DRUGS USED TO TREAT HYPERTHYROIDISM

A

 Radio-iodine  Thioureylenes  Iodine  Adjunct

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9
Q

RADIO-IODINE MoA

A

 Generally considered first-line treatment for
hyperthyroidism
 Isotope used is 131I
 Emits both β and γ radiation (so it’s cytotoxic to to cells)

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10
Q

-RADIO-IODINE RoA

A

 Given orally
 Taken up and processed by thyroid
 Incorporated into thyroglobulin

[Β particles exert powerful cytotoxic action
- Restricted to cells of the thyroid follicles
- Significant destruction of tissue ]

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11
Q

Radio-iodine max. effects+ AE

A

Effects seen after 1-2 months and maximal effects 2 months later

Hypothyroidism develops eventually
 Managed by replacement therapy with T 4

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12
Q

RADIO-IODINE CI

A

Best avoided in children and pregnancy

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13
Q

RADIO-IODINE Clinical use

A

Used diagnostically for thyroid function

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14
Q

THIOUREYLENES exs.

A

Carbimazole, methimazole (active metabolite of
carbimazole), propylthiouracil PTU

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15
Q

THIOUREYLENES MoA

A

Clinical response may take several weeks

Mechanism of action: decrease the output of
thyroid hormones from the gland

- May competitively inhibit the thyroperoxidase- Clinical response may take several weeks catalysed oxidation reactions :
       • Oxidation of iodine and thyroglobulin 
       • Organification of iodine 
       • Coupling
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16
Q

Methimazole CI

A

Methimazole is the preferred antithyroid
medication except in the first trimester of
pregnancy

17
Q

PTU advantage

A

(Give to preg in 1st trimester)
 Additional effect of reducing the deiodination of T
T 3 in peripheral tissues (5’ deiodinase inhibition)
 May act more rapidly
 Concerns over hepatotoxicity
 Safer in pregnancy
- Methimazole is a possible teratogen (aplasia cutis)

18
Q

Methimazole AE

A

Methimazole is a possible teratogen (aplasia cutis)

19
Q

ADVERSE EFFECTS of THIOUREYLENES

A

 Rashes  Headache  Nausea  Jaundice
 Neutropenia and agranulocytosis (if infxns present)
 Incidence of 0.1–1.2%
 Reversible on cessation of treatment

20
Q

IODINE/ Lugols iodine

A

Converted to iodide (I-) in vivo
 Temporarily inhibits release of thyroid
hormones
 Marked reduction of vascularity and size of
gland

21
Q

Iodine max effects reached

A

Maximum effects reached by 10-15 days, then
effects decrease

22
Q

Iodine MoA

A

MOA not well-understood
May inhibit iodination of thyroglobulin, possibly by reducing H2O2 generation
May temporarily inhibit proteolytic release of T 3
/T4 from thyroglobulin

23
Q

IODINE/IODIDE
Clinical uses

A

 Preparation of hyperthyroid subjects for surgical
resection
 As part of the treatment of severe thyrotoxic crisis
(thyroid storm)

24
Q

IODINE/IODIDE
AE

A

Adverse effects
 Allergic reactions
 Lacrimation
 Conjunctivitis
 Pain in the salivary glands
 Cold-like syndrome

25
Q

Adjunct drugs for Hyperthyroidism

A
  1. β blocker
    • for Exophthalmos
26
Q

Beta-blockers
Clinical uses

A

 Useful for decreasing signs and symptoms of
hyperthyroidism: tachycardia, dysrhythmias, tremor, agitation initially
 Preparation of thyrotoxic patients for surgery
 Acute hyperthyroid crisis

27
Q
A

Exophtalmos:

 Guanethidine eye drops
- Noradrenergic-blocking agent
- Relaxes smooth muscle that causes eyelid retraction
 Glucocorticoids: Hydrocortisone useful in thyroid storm treatment
 Surgery

28
Q

ABNORMALITIES OF THYROID FUNCTION
For HYPOthyroidism + causes

A

Hypothyroidism
- Decreased activity of the thyroid

 Causes
-Therapy with radioiodine
- Immunological
•Hashimoto’s thyroiditis

29
Q

'’HYPOTHYROIDISM TREATMENT

A
  1. Iodine deficiency
  2. Thyroid Replacement therapy
30
Q

Iodine deficiency tx

A

Iodine deficiency
 Treated with iodide

31
Q

Thyroid replacement therapy
(T4+ T3)

A

Off-label use as weight loss supplements
, Synthetic T4 (official name: levothyroxine)
- Synthetic T3 (official name: liothyronine)

32
Q

Synthetic T4 (RoA+ MoA)

A

 First-line treatment  Oral formulation  Converted in vivo to T3

33
Q

Synthetic T3 RoA + clinical uses+ axn durn

A

 Faster-onset  Shorter duration of action  Generally given for acute emergencies  IV route

34
Q

AE of Replacement therapy

A

 Hyperthyroidism  Tremors  Heat intolerance  Angina pectoris  Cardiac dysrhythmias  Cardiac failure  Increased bone resorption: Osteoporosis (watch out : elders)

35
Q

Other drugs for Hypothyroidism

A
  1. Amiodarone
  2. Iodine-containing radiocontrast agents drugs
  3. Sulfonamides
  4. Lithium
36
Q

Amiodarone

A

 Rich in iodine
 Can cause hyperthyroidism or hypothyroidism

37
Q

Iodine-containing radiocontrast agents drugs

A

 Iopanoic acid
 for Hypothyroidism

38
Q

Sulfonamides ex+ clinical use

A

 E.g. sulfonyureas
 Hypothyroidism

39
Q

Lithium

A

 for Hypothyroidism

SP- Week 10 Thyroid (2 decks)

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