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Pharmacy Year 3 > Thyroid > Flashcards

Thyroid Flashcards

1
Q

What do thyroid follicular cells secrete?

A

T3 and T4

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2
Q

What are parafollicular C cells responsible for?

A

Section of calcitonin

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3
Q

What does thyroglobulin contain?

A

Iodide to supply thyroid hormones for 90 days

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4
Q

What effect does TSH have on thyroid follicular cells?

A

Stimulates thyroid follicular cells to produce thyronine hormones (T3 and T4)

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5
Q

What role of cAMP have on thyroid cells?

A

Activates functional aspects of thyroid cells e.g.
Thyroglobulin synthesis
Iodide pumping
Iodination by thyroid peroxidase
Endocytosis, proteolysis and hormone release

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6
Q

Describe the process of iodide transport in follicular cells

A

Iodide ions are transported from the bloodstream into cells via NIS which transports 2Na+ or each I- anion into the cell

Iodide ions are transported from the cells into the lumen via Pendrin transporter

Once inside the lumen, I- is oxidised into atomic iodine

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7
Q

Describe the action of thyroid peroxidase enzyme

A

TPO spends the apical membrane and is responsible for the iodination of thyroglobulin

TPO adds iodide onto thyroglobulin backbone - consists of tyrosine residues. Can be added in 2 different places to give mono/di-iodotyrosine

Iodinated thyroglobulin is taken into cells by endocytosis,. Proteolysis occurs by lysosomes which release T2 and T4 from the backbone of thyroglobulin

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8
Q

Give examples of 2 thyroid hormones

Discuss their abundance/characteristics

A

Thyronine - T3: more active/potent
Thyroxine - T4: major form in the blood and has a longer half life than T3

T4 can be converted to T3 as required to protect the body from excess

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9
Q

Which drugs are used to treat hypothyroidism?

A

Levothyroxine sodium T4: tablets or oral solution

Liothyronine T3: tablets or slow iv infusion

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10
Q

Which drugs are used to treat hyperthyroidism?

A

Carbimazole

Propylthiouracil

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11
Q

Describe the characteristics of thyroxine

A

Insoluble in serum - transported in serum in conjunction with specific binding proteins which are synthesised in the liver

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12
Q

What effect does lover disease have on T4?

A

Loss of effective T4 transport to peripheral tissues

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13
Q

How doe thyroid hormones enter cells?

A

Via specific transporters

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14
Q

Describe the location and actions of iodothyronine deiodinases

A

DIO1 - predominant in the liver, kidney and muscle. Also found in thyroid. Produces most of the circulating T3

DIO2 - predominant in areas of CNS and pituitary thryrotropes. Controls intercellular T3 concentration. Important for feedback regulation. Found in skeletal muscle in some species

DIO3 - produces inactive rT3 and prevents thyroid hormone access to specific tissues

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15
Q

Where are thyroid hormone receptors located?

A

TR⍺ and TRβ are found in the nucleus

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16
Q

Describe thyroid hormone action

A 
Functions as a transcription factor
Bind to thyroid responsive element
Higher affinity for T3 and T4
Increases gene transcription 
Can inhibit gene transcription
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17
Q

Describe the action of thyroid hormones in the anterior pituitary

A

Thyroid gland predominantly secretes T4
Human serum has a high conc of T4 binding proteins this causes high circulating levels of protein bound T4
Only free T3 and T4 are biologically active
T3 and T4 bind to nuclear hormone receptors to alter gene transcription in target cells

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18
Q

List the biological actions of thyroid hormones

A
  1. Control of metabolic rate
  2. Growth
  3. Foetal development
  4. Cardiovascular effects
  5. Musculoskeletal effects
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19
Q

How are thyroid hormones involved in growth?

What do deficiencies lead to?

A

Affect most bodily functions
Often synergise with other hormones

Deficiencies lead to abnormal growth, development, reproduction, behaviour and metabolism

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20
Q

How are thyroid hormones involved in foetal development?

What happens when there is a low supply of T4?

A

Develop neural and skeletal systems

Loss of T4 supply to the foetus leads to irreversible mental impairment and dwarfism - congenital iodine deficiency syndrome.

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21
Q

What are the effects of low T4 on a foetus, neonate and child & adolescent?

A

Foetus: miscarriage, still births, congenital abnormalities, perinatal morbidity, mortality and congenital iodine deficiency syndrome

Neonate: goitre hypothyroidism and impaired mental function

Child and adolescent: goiter hypothyroidism, impaired mental function, impaired physical development

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22
Q

How are thyroid hormones involved in cardiovascular events?

A

T3 increases cardiac contraction and output heart rate, oxygen supply to tissues and CO2 removal from tissues

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23
Q

What are the direct effects of thyroid hormones on the heart?

A

Increased myocardial Ca2+ uptake

Increase expression of ⍺-myosin heavy chain and decrease β heavy chain

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24
Q

What are the indirect effects of thyroid hormones on the heart?

A

Increased metabolism - thermogenesis and vasodilation

Increased sensitivity to catecholamamines

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25
How are thyroid hormones involved in musculoskeletal system?
T3 has potent stimulatory effects on bone turnover, increasing formation and resorption T3 increases linear bone growth after birth T3 increase rate of muscle relaxation Normal skeletal muscle function requires T3
26
How is calcium involved in bodily functions?
``` Growth Maintenance of skeletal system Neurotransmitter release Muscle contraction Hormone secretion Blood clotting Intracellular Ca2+ signaling Apoptosis ```
27
Give examples of calcium rich foods
Dairy, kale, spinach, organic tofu, broccoli, almonds and flax/sesame seeds
28
How is calcium homeostasis governed?
Careful balancing of absorption, excretion and storage of ions
29
Give 2 examples of main hormones involved in the regulation of calcium homeostasis
Calcitonin | Parathyroid hormone
30
Name the cells involved in bone turnover
Osteoblasts: synthesise bone tissue Osteoclasts: resorb bone tissue - they are critical in the maintenance and repair of long bones in the mammalian skeleton
31
Describe primary hyperparathyroidism and treatment
Inappropriate excess production and secretion of PTH Caused by a single benign growth or nodule in one parathyroid gland Signs and symptoms: increases calcium in blood and urine and calcium deposits in the kidney Mild disease doesn't usually need treatment but should be monitors, can offer vitamin D supplements
32
Describe secondary hyperparathyroidism and treatment
Long term high PTH levels to attempt to raise blood calcium due to chronic hypocalcaemia Commonly de to vitamin D deficiency and CKD Symptoms: muscle aches and weakness Treat with vitamin D and calcium supplements
33
Give examples of disease states caused by ineffective Ca2+ homeostasis
``` Primary hyperparathyroidsim Secondary hyperparathyroidism Osteoporosis Rickets Calcium stones Receptor mutation ```
34
What is the function of calcitonin?
Reduce blood concentration Ca2+ It opposes the effect of PTH: reduces osteoclast activity to reduce bone resorption, allows rapid bone deposition by osteoblasts and to reduce blood Ca2+
35
Describe the parathyroid gland
Most people have 4 parathyroid glands located on the posterior surface of the thyroid Has 2 cell types: chief cells and oxyphil cells Chief cells are responsible for the production of PTH
36
Describe parathyroid hormone
Small helical protein T half life <20 mins Function is to increase blood concentration of Ca2+ when it gets too low Opposes effect of calcitonin
37
Describe the action of parathyroid hormone
Low calcium is detected by GPC Ca2+ sensing receptors Indirectly stimulate oesteoclasts to release more Ca2+ from bone resorption Increases renal Ca2+ reabsorption, reducing excretion through infiltration Increases production of vitamin D - increases absorption of Ca2+ from the intestine
38
How is parathyroid hormone regulated?
Regulation occurs through negative feedback - increase in blood decreases PTH secretion - increases bone formation
39
What are the different levels of thyroid disease?
Primary thyroid disease: affects production of T3 and T4 Secondary thyroid disease: affects pituitary glands, there are problems with T3 and T4 but also with TSH Tertiary thyroid disease: knocks out THR
40
What are the causes of primary hypothyroidism?
Autoimmune - most common Result of previous treatment for hyperthyroidism Iodine imblanace Congenital hyperthyroidism
41
What are the symptoms of hypothyroidism?
``` Lethargy Weakness Dry scaly skin Dislike of cold weather Depression Hair loss Memory loss Weight gain Constipation Gruff voice ```
42
What would TFTs should in hypothyroidism?
Increase in TSH and decrease in free T4
43
What is the initial treatment for hypothyroidism?
In adults ≤50 years - 50-100µg Levothyroxine OD - adjusted by 25-50µg every 3-4 weeks Adults >50 years and in heart disease - 25µg OD - adjusted by 25µg every 4 weeks Congenital hypothyroidism - 10-15µg/kg for neonates - adjusted by 5µg/kg every 2 weeks Elderly adults and neonates have similar initial doses
44
What is the maintenance treatment for hypothyroidism?
Adults: 100-200µg Children: 50-200µg Monitor TSH yearly - should be in the lower half of reference range
45
Can be used as a combination treatment for hypothyroidism?
Liothyronine and levothyroxine
46
Give the counselling points for a patient with hypothyroidism
Life long treatment Single daily dose Don't take at the same time as calcium/iron preparations 3 strengths of tablet Need monitoring Entitled to medical exemption certificate
47
What are the symptoms of hyperthyroidism?
``` Anxious Palpitations Tremour Weight loss Tachycardia Goitre Sleeping Diarrhoea ```
48
What would TFTs should in hyperthyroidism?
Reduced TSH and increased T4
49
Which patient groups are thioanamides preferred as treatment for hyperthyroidism?
``` Children, Pregnancy, Breast feeding, Uncomplicated disease in young adults Acute phase prior to surgery ```
50
How do thionamadies work?
Interfere with thyroid hormone synthesis by inhibiting thyroperoxidase activity in the follicular lumen
51
Which drug is is first line in hyperthyroidism? | How should it used?
Carbimazole 15-40mg OD initially depending on severity Maintain until TFTs are normal (4-8 weeks) Maintenance for 12-18 months
52
What is the blocking replacement regimen in hyperthyroidism?
Carbimazole 40-60mg for 4 weeks then | Carbimazole 40-60mg + thyroxine 50-100mg
53
Give the counselling points for a patient with hyperthyroidism
Carbimazole OD Tell them duration of treatment and tapering Short term use of beta blockers Report signs of agranulocytosis and hepatic dysfunction Regular medicines review Management of relapse
54
What is the treatment regime for propylthiouracil?
200-400mg daily initial and in divided doses | Reduce to 50-150mg daily maintenance
55
What are the disadvantages of propylthiouracil and carbimazole?
They cause drug induced agranulocytosis - bone marrow suppression White cell count is suppressed which increases risk of infection
56
When would radioactive iodine be used in hyperthyroidism?
When patient has failed to respond to drug treatment, relapse after drugs and toxic nodular goitre
57
When would surgery be used in hyperthyroidism?
Oesophageal obstruction Intolerance to drug treatment Young age
58
What is adjuvant therapy in hyperthyroidism?
Beta blockade | Provides rapid relief of symptoms within 4 days
59
Which drugs can induce thyroid disease?
Iodine Aminodarone Lithium
60
How does iodine induce thyroid disease?
Acute overdose: inhibits release of T3/T4 Prolonged overdose: suppressed T3/T4 Iodine deficiency can cause hypothyroidism due to inability to produce T3/T4
61
How does amiodarone induce thyroid disease?
Contains organic organic iodine Hypothyroidism: can occur at any time in treatment, causes inhibition of synthesis and release of T3 and T4. Continue amiodarone and start replacement T4 therapy is necessary Mild hyperthyroidism: blocks conversion of T4 to T3, this increases TSH and T4. Transient when treatment is started but normalised in 3-4 months Severe hyperthyroidism: increased production of T4 because of iodine content. Direct thyroiditis - excessive release of T4 into circulation. Withdraw treatment or use carbimazole
62
How does lithium induce thyroid disease?
Causes hypothyroidism Inhibits iodine uptake and prevents T3 and T4 release Can be transient and subclinical Hyperthyroidism: rare paradoxical effect

Pharmacy Year 3 (11 decks)

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