181b - Pituitary/Adrenal/Thyroid Pharm Flashcards
Describe the signaling pathway activated by the growth hormone receptor
JAK tyrosine kinase phosphorylates STAT5
- > Homodimerization
- > Effects gene transcription
Which hormone can be used to induce labor?
Oxytocin
All of the following are symptoms or results of excessive thyroid hormone, except
- elevated heart rate
- decreased TSH
- increased glycogenolysis
- increased basal metabolic rate
- increased cholesterol
e. increased cholesterol
* Thyroid hormone lowers cholesterol*
What is the predominant thyroid hormone receptor in the hypothalamus?
What is are the effects?
TR-Beta2
Important for negative feedback
What is the effect of thyroid hormone on glycogenoloysis?
Thyroid hormone increases glycogenlolysis
Why is it important to taper patinets off of exogenous glucocorticoids after weeks of use?
Prevent secondary hypo-cortisolism
- Exogenous glucocorticoids suppress ACTH
- Need to taper to allow time for upregulation of ACTH production
What is the 1st line treatment for central diabetes insipidus?
What abour peripheral?
- Central: Desmopressin
-
Peripheral: Thiazides, NSAIDs, amiloride
- If pt is taking lithium, give amiloride
- Thiazides and NSAIDs will increase serum Li levels (amiloride will decrease - need to dose adjust, but less risk of toxicity)
Which drugs inhibit 5’-deiodinase?
Propylthiouracil (PTU)
Propanolol (weak inhibitor)
Inhibiting 5’-deiodinase = inhibiting peripheral conversion of T4 to T3
What signaling pathway is activated by the oxytocin receptor?
What is the effect?
Gq -> PLC -> Ca2+
-> Smooth muscle contraction, protaglandin and leukotriene release
List 2 IGF-1 agonists
Mecasermin
Mecasermin rinfabate (longer 1/2 life)
Mecasermin rinfabate contase serum binding protein IGFBP-3, which gives it a longer half life
c. Dexamethasone test is used to determine the etiology of adrenal hyperfunction
- Addison’s disease is treated with glucocorticoids and mineralcorticoids - primary adrenal insufficiency
- 11-hydroxylase deficiency is treated wtih glucocorticoids only
- Steroid withdrawal syndrome results from chronic reduction of ACTH secretion
Prednisone has the advantage over hydrocortisone that prednisone
- is less likely to increase blood glucose
- doesn’t suppress the immune response
- has a longer duration of action
- is orally effective
- has greater glucocorticoid/mineralocorticoid activity
e. has greater glucocorticoid/mineralocorticoid activity
=> prednisone has more anti-inflammatory effects, causes less hypertension
What are the stimuli for endogenous vasopressin (ADH) release? (2)
Low blood pressure
Hypertonicity
Even if hypotonic, ADH will be released to preserve blood volume at the expense of osmolarity
How should dosing of methimazole be changed in pregnant patients?
Dose should be lowered
- Also, contraindicated in the 1st trimester (use PTU instead)
Which agents can be used to inhibit glucocortidoid synthesis? (4)
-
Metyrapone
- –| 11-hydroxylase
-
Ketokonazole
- –| 17-alpha hydroxylase, desmolase
- (Also –| 17,20 lyase to block testosterone synth)
-
Aminoglutethimide
- –| cholesterol side chain cleavage
-
Mitotane
- Toxic
Mifepristone can also be used as tx for hyper-cortisolism MOA = glucocortidoid receptor antagonist
21-hydroxylase deficiency
- Cortisol:
- Mineralcorticoids:
- Androgens:
- Cortisol: None
- Mineralcorticoids: None
- Androgens: High
17-hydroxylase deficiency
- Cortisol:
- Mineralcorticoids:
- Androgens:
- Cortisol: None
- Mineralcorticoids: High
- Androgens: Low
What is the MOA of pegvisomant?
Growth hormone receptor antogonist
Allows receptor dimerization, but blocks downstream signaling
Use to treat acromegaly
Binding of which hormone to its receptor results in the release of hsp90?
Cortisol
(binds to receptor in cytoplasm -> hsp90 release, which exposes the DNA binding domain of the receptor)
D - both are polypeptides with 9 AA residues
- Vasopressin works to increase fluid volume
- Thiazides treat nephrogenic DI
- Desmopressin activates V2 >>> V1
List 2 dopaminergic agonists that can be used to inhibit GH secretion
Cabergoline
Bromocriptine
Cabergloine = more potent, longer half life
Which drugs inhibit TPO to treat hyperthyroidism? (2)
Propylthiouracil (PTU)
Methimazole - more potent
PTU also inhibits 5’-deiodinase
What is the predominant thyroid hormone receptor in the liver?
What is are the effects?
TR-Beta1
- Increased glucose/energy output
- Lipogenesis
- Gluconeogenesis
- Decreased energy storage
- Decreased glycogen synthesis
List 4 side effects of octreotide
- Nausea
- Bloating
- Gallstones
- Bradycardia
What kind of bone growth does growth hormone stimulate?
Longitudinal bone growth (at the growth plate, until it closes)
11-hydroxylase deficiency
- Cortisol:
- Mineralcorticoids:
- Androgens:
- Cortisol: None
- Mineralcorticoids: High
- Androgens: High
Note: Aldosterone itself is low, but 11-deoxycorticosterone acts similarly to increase Na+ and H2O absorption -> HTN
How does chronic levothyroixine treatment affect blood glucose?
Can lead to insulin resistance -> elevated blood glucose
How does the treatment of Addison’s disease differ from the treatment of ACTH deficiency?
-
Addison’s = primary adrenal insufficiency
- Replace glucocorticoids AND mineralcorticoids
-
ACTH deficiency = secondary adrenal insufficiency
- Replace glucocorticoids only
- ACTH is not needed to stimulate mineralcorticoid synthesis - mediated by RAAS
(although, ACTH does increase mineralcortidoid synthesis by stimulating desmolase; it’s just not physiologically necessary)
What element is used to radioactively ablate the thyroid gland?
131I
(127I is for diagnostic tests)
What are the indications for the following tests?
- Exogenous ACTH:
- Metyrapone test:
- Dexamethasone:
- Exogenous ACTH: hypocortisolism, to stimulate adrenal
- Will stimulate cortisol synthesis in secondary
- No effect in primary
- Metyrapone test: hypocortisolism, to stimulate pituitary
- Inhibits 11-hydroxylase -> very low cortisol
- Will stimulate ACTH production in primary
- No effect in secondary
- Dexamethasone: hypercortisolism, to suppress pituitary
- Will suppress ACTH if there is a pituitary adenoma
- Has glucocorticoid receptor
- Will NOT suppress ectopic ACTH (ex: small cell lung)
- No glucocorticoid receptor
- Will suppress ACTH if there is a pituitary adenoma
Octreotide…
- inhibits secretion of growth hormone
- is an antagonist peptide analog of growth hormone
- is a dopamine receptor analog that inhibits secretion of hypothalamic hormones
- acts through tyrosine kinase-linked receptors
- side effects include stimulation of secretion of glucagon and gastrin
a. inhibits secretion of growth hormone
MOA: Mifepristone
Glucocorticoid receptor antagonist
Used in the tx of hyperfunctional adrenal glands
What is the predominant thyroid hormone receptor in the heart?
What is are the effects?
TR-Alpha1
Potentiates beta-adrenergic signaling
(TR-alpha1 activation potentiates Beta1 adrenegic activation?)
What is the difference between 5-deiodination of T4 vs. 5’-deiodination of T4?
5-deiodination -> reverse T3 (inactive form)
5’-deiodination -> T3 (active form)
Which pharmacologic treatment for acromegaly has the side effect of orthostasis?
Dopaminergic agonist (cabergoline, bromocriptine)
C - Somatostatin is a physiological inhibitor of GH secretion
- GH stimulates the production of IGF-1 in the liver
- Mecasermin is an IGF-1 agonist
- Cabergoline inhibits GH production via D2 receptor agonism
How will hypothyroidism affect bone age?
Hypothyroid -> Bone age < real age
b. 131I kills follicular cells by beta emission
- PTU inhibits peripheral conversion of T4 to T3 (by inhibiting 5’-deiodinase), in addition to inhibiting TPO
- Dose of methimazole should be decreased for pregnant women
- KI inhibits proteolysis and secretion of thyroid hormone
List two growth hormone analogs
Somatotropin
Somatrem
Somatotropin is identical to human GH, somatrem has an additional methionine -> longer half life
To stop bleeding from esophageal varices, would you give vasopressin or desmopressin?
Vasopressin
Need to cause vasoconstriction; desmopressin preferentially activates V2 receptors, and thus does not have a great action on vascular smooth muscle (V1 mediated)
Describe the signaling pathway and effect of activation of each receptor:
- V1 receptor:
- V2 receptor:
- V1 receptor:
- Gq -> PLC -> increaesd Ca2+
- Vasoconstriction (vascular smooth muscle)
- V2 receptor:
- Gs -> cAMP/PKA
- Water reabsorption (collecting duct)
- Increased Factor VIII, vWF release (vascular endothelium)
How does the effect of endogenous desmopressin differ from the effect of endogenous vasopressin?
Desmopressin preferentially activates V2 > V1 receptor
-> Desmopressin results in more water reabsorption, vascular endothelial activation (Factor VIII and vWF)
Less vasoconstriction/HTN (V1 mediated)
What is the first-line treatment for SIADH?
-vaptans
Conivaptan, tolvaptan
How does potassium-iodine (KI) affect hyroid hormone production and action?
KI inhibits proteolysis and secretion of thyroid hormone
- Must be given at a high dose
- Adverse effects
- Crosses placenta -> Fetal hypothyroidism
- Not useful long-term
Name 2 somatostatin analogs
Octreotide
Lanreotide (long acting)
