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

Exam 2: Lecture X, Thyroid Hormones Flashcards

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
90% of Thyroid hormone released in form of....
T4
26
How many times more potent is T3 vs T4?
4-10 times
27
T4 converted into T3 by...
stripping of iodine in liver and kidneys
28
Drugs that increase T4 binding to Thyroxine-binding globulin?
``` Estrogens Methadone 5-Fluorouracil Heroin Tamoxifen ```
29
Drugs that decrease T4 binding to Thyroxine-binding globulin?
``` Glucocorticoids Androgens L-Asparaginase Salicylates Phenytoin,Carbamazepine,Furosemide ```
30
Systemic factors affecting binding of T4 to Thyroxine-binding globulin?
Liver disease Inheritance Porphyria Illness HIV infection
31
Hypothyroidism disorders....
Cretinism in children | Myxedema in adults
32
Hyperthyroidism disorders....
Thyrotoxicosis, Thyroid storm, Grave's disease Plummer's disease
33
Thyroid Storm/Crisis
DRAMATIC INCREASE IN METABOLISM BODY TEMPERATURE RISES (HYPERPYREXIA) LOSS OF BODY FLUIDS/ELECTROLYTES CNS EFFECTS (CONVULSIONS) ARRHYTHMIA SHOCK
34
Drugs for Hypothyroidism?
thyroid Agents
35
Drugs for Hyperthyroidism?
Antithyroid agents Iodides B-Blockers Radioactive iodine
36
Physiological actions of T3/T4?
Every tissues is affected.....increases effect in all
37
Hypothyroidism Clinical effects?
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
Hyperthyroidism clinical effects?
``` 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
thyroid Hormones replacement
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
Equivalent Daily Doses
Levo sodium - 100 microgram Liothyronine sodium - 25 microgram Thyroid tab/Thyroglobulin = 60 mg
41
Levothyroxine sodium
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
Liothyronine Sodium (Cytomel)
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
Thioamide prototype?
Propylthiouracil (Generic)
44
Propylthiouracil (Generic)
2 hr half life
45
Methimazole (Tapazole)
rapidly absorbed 3-5 hr half life Cross placenta/breast milk conc in thyroid renal excretion
46
Propylthiouracil (Generic) and Methimazole (Tapazole) MOA
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
Propylthiouracil (Generic) and Methimazole (Tapazole) Therapeutic Uses
Hyperthyroidism in children, young adults, and pregnant women Before surgical treatment May be used alone May be used with radioiodine
48
Antithyroid Drugs Adverse effects
Idiosyncratic agranulocytosis (less with Methimazole) Transient leukopenia Hepatitis Rash, fever, joint pain
49
Iodide Salts
Lugol's solution (5% of iodine reduced to iodide + 10% potassium iodide) Potassium iodide (solution/solid)
50
Iodide Salts MOA
Inhibit iodination of tyrosine + decrease vascularity of the thyroid gland
51
Iodide Salts Therapeutic Uses
Preoperatively in Grave's disease Preparation for thyroidectomy (10 days before the operation )
52
Acute Adverse effects Iodide Salts
Hypersensitivity angioedema cutaneous hemorrhages
53
Chronic Adverse effects Iodide Salts
Iodism brassy taste, salivation,teeth and gum soreness, eyelid swelling symptoms of respiratory infection inflammation of pharynx and larynx skin lesions
54
Radioactive Iodine Pharmacokinetics
iodine 131 ( 131I ) t1/2 life 8 days source of beta-particles, gamma-rays
55
Radioactive Iodine MOA
Radioactive sodium iodine 131 (131I) concentrates in the thyroid gland Severely damages the gland without damaging other tissues.
56
Radioactive Iodine Therapeutic Uses
Highly effective in treatment of hyperthyroidism Treatment of choice for recurrent hyperthyroidism Useful diagnostic tool **Can produce permanent cure
57
radioactive Iodine Preparations
Sodium iodide labeled with 131I or 125 I Solutions/Capsules Orally/Intravenously
58
Radioactive Iodine Adverse effects
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
Iodinated Radiocontrast Media
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
B-Blocker
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
B-blocker Therapeutic uses
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
Thyroid drug warning
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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