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Pharmacology & Medical Chemistry II > Exam 2: Lecture X, Thyroid Hormones > Flashcards

Exam 2: Lecture X, Thyroid Hormones Flashcards

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1
Q

Thyroid Gland contains….

A

Thyroid follicular cells and colloid

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2
Q

Follicular cells produce

A

Thyroxin (T4) and Triiodothyronine (T3)

Both derivatives of Tyrosine, affect all cells in body

exerts a calorigenic and stimulatory effect

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3
Q

Colloid is

A

extracellular storage site for thyroid hormones

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4
Q

Thyroid Hormone Synthesis

A

Enough Tyrosine is made, iodine need for Thyroid hormone must come from diet

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5
Q

Hypothalamic TRH Stimulates (+) AP to release….

A

TSH

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6
Q

Somatostatin has an….

A

inhibitory effect (-) upon TSH release

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7
Q

TSH Stimulates

A

(+) T3/T4 synthesis

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8
Q

T4/T3 through negative feedback….

A

Inhibit (-) both TRH and TSH

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9
Q

Small amounts of iodide stimulate…

A

(+) T4/T3 production

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10
Q

Large amounts of iodide inhibit….

A

(-) T4/T3 production

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11
Q

Hypothyroidism and cretinism occur in…

A

situation of sever iodine deficiency

Thyroid gland is efficient in extracting iodide from the blood

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12
Q

General outline T3/T4 synthesis….

A

Iodine is transported and undergoes per oxidation and organification with formation of MIT-DIT -> T3/T4

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13
Q

T3 (Triiodothyronine) made from…

A

1 MIT + 1 DIT

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14
Q

T4 (Thyroxine) made from….

A

1 DIT + 1 DIT

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15
Q

MIT made from….

A

1 Iodine + Tyrosine

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16
Q

DIT made from…

A

2 iodine + Tyrosine

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17
Q

T4 half-life

A

6-7 days

3-4 days in Hyperthyroidism
9-10 days in Hypothyroidism

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18
Q

T3 half-life

A

1 day

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19
Q

T4 degrade into….

A

T3

Liver major site of degradation

T3 further degraded to 3 different DIT

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20
Q

T3/t4 onset of action….

A

oral 3-5 days

IV 6-8 hrs

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21
Q

What binds T4 with….

A

Thyroxine-binding globulin

Thyroxin-binding prealbumin

Albumin

Lipoproteins (HDL2/3)

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22
Q

Percent of free T4/T3….

A

T4 = 0.03%

T3 = 0.3%

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23
Q

Plasma proteins effects on T4/T3

A

protects hormones from metabolism/excretion

results in longer half-life

Change in protein conc/bidning affinity = major effect upon T3/T4 conc in blood.

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24
Q

When conc of T3/T4 drops in blood then….

A

TSH is released from AP gland

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25
Q

90% of Thyroid hormone released in form of….

A

T4

26
Q

How many times more potent is T3 vs T4?

A

4-10 times

27
Q

T4 converted into T3 by…

A

stripping of iodine in liver and kidneys

28
Q

Drugs that increase T4 binding to Thyroxine-binding globulin?

A 
Estrogens
Methadone
5-Fluorouracil
Heroin
Tamoxifen
29
Q

Drugs that decrease T4 binding to Thyroxine-binding globulin?

A 
Glucocorticoids
Androgens
L-Asparaginase
Salicylates
Phenytoin,Carbamazepine,Furosemide
30
Q

Systemic factors affecting binding of T4 to Thyroxine-binding globulin?

A

Liver disease

Inheritance

Porphyria

Illness

HIV infection

31
Q

Hypothyroidism disorders….

A

Cretinism in children

Myxedema in adults

32
Q

Hyperthyroidism disorders….

A

Thyrotoxicosis,
Thyroid storm,
Grave’s disease
Plummer’s disease

33
Q

Thyroid Storm/Crisis

A

DRAMATIC INCREASE IN METABOLISM

BODY TEMPERATURE RISES (HYPERPYREXIA)

LOSS OF BODY
FLUIDS/ELECTROLYTES

CNS EFFECTS (CONVULSIONS)

ARRHYTHMIA

SHOCK

34
Q

Drugs for Hypothyroidism?

A

thyroid Agents

35
Q

Drugs for Hyperthyroidism?

A

Antithyroid agents
Iodides
B-Blockers
Radioactive iodine

36
Q

Physiological actions of T3/T4?

A

Every tissues is affected…..increases effect in all

37
Q

Hypothyroidism Clinical effects?

A

tired

Decreased metabolism
Decreased appetite
Decreased cardiac output
Muscle fatigue
Hypoventilation
Bradycardia, Hypotension

Impaired water excretion

Decreased erythropoiesis

Hormone deprivation in early life results in irreversible mental retardation

Dropping of eyelids

Essentially tired and decrease a bunch of stuff

38
Q

Hyperthyroidism clinical effects?

A 
Increased metabolic rate
Muscle wasting
Heat intolerance
Weight loss
Insomnia
Hyperventilation
Dyspnea
Tachycardia
Increased heart rate
Hypertension
Polyuria
Increased erythropoiesis
Protrusion of eyeball
Retraction of upper lid with wild stare

essentially wired and increase a bunch of stuff

39
Q

thyroid Hormones replacement

A

Levothyroxine sodium (t4) = sodium salt of L-thyoxine

Liothyronine sodium (T3) = sodium salt of L-triiodothyronine

  • Both prob better to avoid*
    Thyroid tablets = extract of thyroid gland

Thyroglobulin = extract of pig thyroid

40
Q

Equivalent Daily Doses

A

Levo sodium - 100 microgram

Liothyronine sodium - 25 microgram

Thyroid tab/Thyroglobulin = 60 mg

41
Q

Levothyroxine sodium

A

Drug of choice

Long half-life (7 days)

Oral tablets/capsules;parenteral
Stable agent

Low cost

Lack of allergic foreign proteins

Intracellular conversion of T4 to T3

42
Q

Liothyronine Sodium (Cytomel)

A

Not recommended for routine treatment

24 hr half-life

Reserved for care condition of Myxedema coma, rapid action required

Requires multiple daily doses, High cost

Greater risk of cardiotoxicity

Levothyroxine (T4) and Liothyronine (T3)

Mechanism of Action:
Activation of nuclear receptors > Gene Expression > RNA > Protein synthesis

43
Q

Thioamide prototype?

A

Propylthiouracil (Generic)

44
Q

Propylthiouracil (Generic)

A

2 hr half life

45
Q

Methimazole (Tapazole)

A

rapidly absorbed

3-5 hr half life

Cross placenta/breast milk
conc in thyroid
renal excretion

46
Q

Propylthiouracil (Generic) and Methimazole (Tapazole) MOA

A

Inhibit formation of thyroid hormones

Inhibit incorporation of iodine into residues of thyroglobulin

Block coupling of DIT and MIT

Inhibits peripheral conversion of T4 to T3

Suggested inhibition of peroxidase enzyme

47
Q

Propylthiouracil (Generic) and Methimazole (Tapazole) Therapeutic Uses

A

Hyperthyroidism in children, young adults, and pregnant women

Before surgical treatment

May be used alone

May be used with radioiodine

48
Q

Antithyroid Drugs Adverse effects

A

Idiosyncratic agranulocytosis (less with Methimazole)

Transient leukopenia

Hepatitis

Rash, fever, joint pain

49
Q

Iodide Salts

A

Lugol’s solution (5% of iodine reduced to iodide + 10% potassium iodide)

Potassium iodide (solution/solid)

50
Q

Iodide Salts MOA

A

Inhibit iodination of tyrosine + decrease vascularity of the thyroid gland

51
Q

Iodide Salts Therapeutic Uses

A

Preoperatively in Grave’s disease

Preparation for thyroidectomy (10 days before the operation )

52
Q

Acute Adverse effects Iodide Salts

A

Hypersensitivity

angioedema
cutaneous hemorrhages

53
Q

Chronic Adverse effects Iodide Salts

A

Iodism

brassy taste, salivation,teeth and gum soreness,

eyelid swelling

symptoms of respiratory infection

inflammation of pharynx and larynx

skin lesions

54
Q

Radioactive Iodine Pharmacokinetics

A

iodine 131 ( 131I )

t1/2 life 8 days

source of beta-particles, gamma-rays

55
Q

Radioactive Iodine MOA

A

Radioactive sodium iodine 131 (131I) concentrates in the thyroid gland

Severely damages the gland without damaging other tissues.

56
Q

Radioactive Iodine Therapeutic Uses

A

Highly effective in treatment of hyperthyroidism

Treatment of choice for recurrent hyperthyroidism

Useful diagnostic tool

**Can produce permanent cure

57
Q

radioactive Iodine Preparations

A

Sodium iodide labeled with 131I or 125 I

Solutions/Capsules

Orally/Intravenously

58
Q

Radioactive Iodine Adverse effects

A

Relatively high incidence of delayed hypothyroidism

Delayed onset in control of hyperthyroidism

Some suspicions of the effects of radioactivity

Contraindicated in pregnancy/nursing mothers

59
Q

Iodinated Radiocontrast Media

A

Iodinated radiocontrast media (iodinated) – Ipodate

Effectively suppresses conversion of T4 to T3 in: liver, kidneys and other peripheral tissue

Ipodate proved to be very useful in rapidly reducing T3 level in thyrotoxicosis

60
Q

B-Blocker

A

Beta-blockers are effective in counteracting wide-spread sympathetic activation during hyperthyroidism. Agents are effective by decreasing many symptoms of hyperthyroidism. An example of “functional” (noncompetitive) antagonism

61
Q

B-blocker Therapeutic uses

A

Alleviate symptoms of Grave’s
hyperthyroidism(tremors, anxiety, palpitations)

Very useful in controlling tachycardia, arrhythmias, tremors, and agitation

Very useful in controlling severe thyrotoxicosis

May be used as a part of the treatment of thyroid storm

Moderate symptoms and may be used in preparation for surgery

Synthesis/secretion of thyroid hormone are not affected

Propranolol (only) inhibits deiodination of T4 to T3

62
Q

Thyroid drug warning

A

Many of the effects of thyroid hormone and beta-receptors agonists are similar (tachycardia, increased metabolism, nervousness, and tremors).

Thus, combination of thyroid hormone and adrenergic agents (epinephrine/norepinephrine) may be synergistic!!!

Pharmacology & Medical Chemistry II (43 decks)

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