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MD1 Endocrine > Drug Effects on the Hypothalamic Pituitary Axis > Flashcards

Drug Effects on the Hypothalamic Pituitary Axis Flashcards

(64 cards)

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1
Q

What stimulates the release of growth hormone?

A

Ghrelin

Growth hormone releasing hormone (GHRH)

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2
Q

What inhibits the release of growth hormone?

A

Somatostatin

Insulin-like growth factors (IGFs)

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3
Q

What carries out the functions of growth hormone?

A

IGFs

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4
Q

What happens in growth hormone insensitivity?

A

High growth hormone levels
Liver doesn’t secrete IGF in response to growth hormone
No negative feedback of IGF to growth hormone release

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5
Q

What is a secondary growth hormone deficiency?

A

Growth hormone not secreted

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6
Q

What is a tertiary growth hormone deficiency?

A

No signal for growth hormone release from hypothalamus

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7
Q

What is another name for growth hormone?

A

Somatotropin

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8
Q

What is the bioavailability of growth hormone aver oral administration?

A

Zero

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9
Q

How must growth hormone be administered?

A

Daily/multi-daily parenteral administration

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10
Q

Why must the dose of growth hormone be titrated to effect?

A

Because replacing physiologically regulated hormone

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11
Q

What hormone can growth hormone affect?

A

Can cause reduced T4 levels

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12
Q

What does activation of the GHRH receptor lead to biochemically?

A

Elevates cAMP

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13
Q

What does the activation of the ghrelin receptor lead to biochemically?

A

Elevates Ca

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14
Q

What are the effects of both GHRH and ghrelin?

A

Synergistic effect on release of growth hormone

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15
Q

When is IGF-I administered?

A

Growth hormone insensitivity; eg: Laron dwarfism

Patients with anti-growth hormone Abs

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16
Q

What are the side effects of IGF-I therapy?

A

Muscle hypertrophy

Sometimes hypoglycaemia

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17
Q

What do anti-growth hormone antibodies do?

A

Bind and inactivate growth hormone

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18
Q

What does too much growth hormone cause?

A

Acromegaly

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19
Q

What is often a cause of acromegaly?

A

Growth hormone releasing tumours

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20
Q

What are the effects of too much growth hormone in adults?

A

Continued growth of

  • Hands
  • Feet
  • Cartilage
    • Nose
    • Ears
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21
Q

What are the effects of too much growth hormone in children?

A

Long bones don’t stop growing

Organ damage

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22
Q

What are the treatment options for too much growth hormone?

A 
Remove tumour
- If relevant
- Not always large
- Can be anywhere
Reduce growth hormone release
- Somatostatin analogues
- Dopamine agonist
Inhibit growth hormone action
- Growth hormone antagonist
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23
Q

Why is somatostatin itself not often administered?

A

Has short half life

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24
Q

Do somatostatin analogues work on growth hormone secreting tumours?

A

Work on many because have somatostatin receptors

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25
What is pegvisomant?
Growth hormone antagonist
26
What is one way of finding a growth hormone secreting tumour?
Use radioactively labelled somatostatin analogue Somatostatin receptors internalised > take peptide ligand with them Can be imaged by in vivo receptor scintigraphy
27
Why is radioactively labelled somatostatin not used to ablate tumours?
Other cells also express somatostatin receptors
28
What other hormone does somatostatin affect?
Reduces TSH
29
How is somatostatin removed?
Enzymatic cleavage | Renal elimination
30
What is octreotide?
Somatostatin analogue
31
What is lanreotide?
Somatostatin analogue
32
How do somatostatin analogues resist enzymatic cleavage and thus, have a longer half life?
D-amino acids > don't fit into cleavage enzymes
33
How are octreotide and lanreotide administered?
Via injection
34
What may increase the effectiveness of somatostatin analogues?
Addition of dopamine agonists
35
What does ligand binding to the growth hormone receptor cause?
Dimerisation of the receptor
36
What is G120K-GH?
Growth hormone antagonist with high affinity
37
What is the half life of G120K-GH?
Short > not useful therapeutically
38
What is PEGylation?
Attach polyethylene glycol groups to bioactive molecule
39
How does PEGylation change the molecule?
Size increase > reduced renal filtration PEG hydrophilic > improved solubility Decreased accessibility for proteolytic enzymes
40
At which amino acid does PEGylation occur?
Lysine
41
How does PEGylation dramatically decrease the affinity of a growth hormone antagonist?
2 lysines involved in binding to site 1 on growth hormone receptor
42
What is the in vivo efficacy of pegvisomant?
Decreased affinity balanced with increased exposure
43
What does iodide do to the thyroid gland at high doses?
Acutely suppresses thyroid hormone synthesis and release
44
What isotope of iodide ablates the thyroid gland?
Radioactive iodide-131
45
What isotopes of iodide protect against radioactive isotopes?
Stable isotopes
46
What is carbimazole?
Inhibits thyroid peroxidase
47
What is the dosing of carbimazole?
Once daily
48
What is propylthiouracil?
Inhibits thyroid peroxidase and conversion of T4 to T3
49
What is the dosing of propylthiouracil?
2-4 doses daily
50
What are the adverse effects of carbimazole and propylthiouracil?
May lead to - Goitre - Agranulocytosis
51
What is the effect of propylthiouracil on hepatic function?
Can cause hepatotoxicity > measure baseline liver function
52
Why is it difficult to get the dose of carbimazole and propylthiouracil right?
Because physiological mechanisms slow to adapt
53
What does the amount of drug that is bound to a carrier protein depend on?
Affinity and relative concentrations of drug and protein
54
What is thyroxine binding globulin?
Specific carrier protein for thyroid hormones
55
When is T3 useful in hypothyroidism?
In severe cases, because more active and acts faster
56
What is the half life of T3?
1 day
57
Which has more stable levels during the day: T3 or T4?
T4
58
What is hypothyroidism often treated with?
T4
59
When does T4 act?
Mostly after conversion to T3
60
What is the half life of T4?
7 days
61
What can lead to initial poor compliance to thyroxine?
Slow accumulation and onset of action
62
When are dose adjustments for thyroxine done?
Long intervals
63
Why is the dose of thyroxine adjusted?
Normalise TSH levels
64
What is the interplay between T3 and cortisol?
Cortisol inhibits conversion of T4 to T3 | T3 inhibits cortisol production

MD1 Endocrine (18 decks)

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