Growth Hormones / Adrenocorticohormones Flashcards
(35 cards)
1
Q
IGF-1?
- induced by what hormone?
- binds to what receptor?
- has what primary effect
A
- GH
- binds to tyrosine kinase receptor (like insulin)
- primary effect: linear growth (bone muscle cartilage)
2
Q
what is acromegaly?
cause, presentation?
A
- GH oversecretion secondary to IGF-insensitivity (no long loop control of of GHRH, GH)
- presentation: overgrowth - local, esp in skull & mandible
3
Q
what is somatropin?
- MOA?
- clinical uses?
- AEs?
A
somatropin = GH
- MOA: is GH
- clinical uses: for GH deficient children with short stature (dwarfism):
- Prader-Willi / Turner
- AEs:
- glucose tolerance (hyperglycemia)*
- intracanial pressure
- fluid retention
4
Q
mecasermin
- what kind of drug?
- MOA?
- PK?
- clinical uses?
- AEs?
A
- rhIGF-1 - a recominant human IGF
- MOA: binds IFR-1 receptor (tyrosine kinase receptor)
- stimulates linear growth –> skeletal/muscle/bone/cartilage
- PK: must ingest carbohydates 20 min before tx
- clinical use: short stature in IGF-deficient children that is not responsive to exogenous GH
- AEs:
- hypoglycemia*
- intracranial hypertension
- adenotonsillar hypertrophy
5
Q
synthetic somatstatin analogs
- include what drugs?
- arewhat kind of drugs?
- MOA?
- clinical uses?
- AEs?
A
= “eotide” - octreotide, lanreotide
- type of GH antagonist
- MOA: bind somatostatin receptors (SSTRs), inducing its effects
- clinical uses:
- via GH antagonism:
- acromegaly (local bone overgrowth at mandible/skull d/t IGF long loop insensitivity)
- hormone secreting tumors (uncontrolled growth)
- diarrhea
- esophageal varices
- via GH antagonism:
- AEs:
- sinus bradycardia
-
hypothyroidism (SST agonist - inhibiton of TSH,”pulse generator”)
- sinus bradycardia
- hyperglycemia (SST agonist - inhibition of insulin/glucagon)
- chest pain)
6
Q
what two drugs can be used to treat short stature in children?
how are they different?
A
- somatotropin and mecasemin:
- both:
- increase linear growth
- AE - intracranial HTN
- somatropin - 1st choice
- GH
- AE - hyperglycemia
- mecasemin - 2nd choice
- rhIGF-1 (recombinant IGF-1)
- AE - hypoglycemia
- both:
7
Q
pegvisomant
- what kind of drug?
- MOA?
- clinical uses?
- AEs?
A
- is a GH antagonist
- MOA: is a polyethylene glycol (PEG) derivative of GH that binds & dimizes GH receptor –> inhibiting it
- clinical uses: acromegaly (local overgrowth at skull/mandible d/t insensitivtiy to IGF long loop)
- AEs: none
8
Q
what drugs are used to treat acromegaly?
A
- “-reotride”: octeotride, lanreatide (SST analogs)
- pegvisomant
9
Q
what are primary and secondary adrenal insufficiency?
A
- both: characterized by insufficient cortisol (glucocorticoid) production
- primary: @ adrenal glands: damaged adrenal glands are unresponsiveness to ACTH
- secondary @pituitary: insufficient ACTH production by pituitary
10
Q
what is Cushing’s Syndrome/Disease?
A
both characterized by prolonge excess cortisol
- Cushing Syndrome: prolonged, elevated cortisol
- Cushing’s Disease: excess cortiol due to an ACTH-secreting tumor on pituitary
11
Q
what are the glucocorticoid hormones?
A
Systemic Use (Oral / IV/ IM / SQ)
Hydrocortisone
Prednisolone / Prednisone
Triamcinolone
Dexamethasone
Betamethasone
Topical Use
Fluticasone
Budesonide
12
Q
what is fludrocortisone?
A
a mineralcorticoid with a little bit of glucocorticoid activity
13
Q
which glucocorticoid has the higest anti-inflammatory potency?
A
dexamethasone
14
Q
A
15
Q
glucocorticoids -MOA
A
16
Q
glucocorticoids - PK
A
slow onset of action: at least several hours
17
Q
what is the biggest limitation for long term use of corticosteroids?
A
- decreased muscle mass (weakness)
- thinning of skin
- osteoporosis
18
Q
how is adrenal insufficiency treated?
A
= primary adrenal insufficiency
tx with glucocorticoid
-
hydrocortisone - start with since its s_hort-acting_ and can mimic circadian rhythm
- dosing: multiple 20-30 mg doses throughout the day
-
prednisoned/dexamethasone are alternatives:
- longer acting ones that be used for patients with difficult compliance
- fludrocortisone (mineralcorticoid > glucorticoid) - most pts eventually require mineralcorticoids prevent sodium loss, volume depletion, hyperkalemia
19
Q
glucorticoids effects
A
- fuid / electrolyte abnormality effects
- hypertension
- glaucoma/cataracts
- hypertension
- catabolic effects:
- hyperglycemia [inc blood glucose]
- osteoporosis [inc bone resorption]
- immunosuppression
- inc reased of infection
- inc risk of peptic ulcers
- behavioral changes - psychoses
20
Q
common AEs of glucocorticoid use typically present after what duration of time?
A
after long term use (>2 weeks) of glucocorticoid use
21
Q
why might one reduce/stop dosage of corticosteroids?
how should this be done?
A
- if AEs start to present (typically after 2 weeks + use)
- corticosteroid discontinuation should be tapered:
- endogenous cortisol levels may not not return for another 6-9 months
22
Q
C/Is of glucocorticosteroid use?
A
line up with AEs:
- HTN w/ HF
- diabetes
- osteoporosis
- peptic ulcer
- glaucoma
- aggresive infections: varicella/tuberculosis
23
Q
fludrocortisone
- what type of drug
- MOA
A
- mineralcorticoid > glucocorticoid
- MOA = binds mineralcorticoid receptor - a nuclear receptor (Subclass II) on the zona glomerulosa, increasing transcription of
- N/K-ATPases & ENac channels (kidney)
- this inc Na+ reabpsrotion at several tissues
- N/K-ATPases & ENac channels (kidney)
24
Q
fludrocortisone
clinical uses
A
aldosterone insufficiency secondary to Addison’s diseases (primary adrenal insufficiency)
25
fludricortisone - AEs
* increased palsma volume --\> HTN
* hypokalemia
* metabolic alkalosis
* general steroid effects: myopathy / immunosupression / psychiatric distrurbanc
26
adrenaocortical antagonists
include what classes / drugs?
* glucocorticoid (cortisol) synthesis inhibitors
* **ketoconazole**
* **metryapone**
* **spironolactone**
* **mitotane**
27
ketoconazole
* is what kind of drug?
* has what MOA?
* what clinical uses?
* AEs?
* a glucocorticoid antagonist (adrenal antagonist)
* MOA: enters adrenal cortex cells and inhibits both _glucocorticoid_ (**cortisol**) AND _androgen_ (**testosterone**)
* lower circulating levels of cortisol , testosteorne
* clinical uses:
* **Cushing's Syndrome** - lowers circulating cortisol
* **Prostate Cancer** - lowers cirulating testosterone
* **Fungal infections** - is also an anti0fungal
* PK - strong **CYP-3A4 & P-gp inhibitor**
* AE - **hepatotoxicity**
28
metyrapone
* what kind of drug?
* MOA?
* clinical uses?
* AEs?
* is a glucocorticoid synthesis inhibitor (adenocortical antagonist)
* MOA: selective inhibitor of ***11-hydoxylation*** of steroids, **inhibiting cortisol synthesis**
* clinical uses:
* **Cushing's Syndrome** - lowers levels of circulating cortisol
* can be used in _pregnant_ women\*
* AEs:
* water retention
* hurisitsm
29
mitotane
* what kind of drug?
* MOA?
* clinical uses?
* AEs?
* adrenal antagonist
* MOA: unknown
* clinical uses: **Cushing's syndrome** - lowers levels of circulating cortisol
* AEs:
* depression
* somnolence
30
spironolacatone
* what kind of drug?
* MOA
* clinical uses
* AEs
* a mineralcorticoid inhibitor (adrenal antagonist)
* MOA: binds to & inhibits _aldosterone receptors_ in zona glomerulosa
* clinical uses:
* **fluid retention -** **edema, HTN** ( induces diuresis )
* **primary hyperaldosteroism** - excess aldosterone secretion at the level of the _adrenal gland_ (idiopathic /adrenocortical neoplasm / ect)
31
which drug lowers both cortisol and testosterone levels? what does it treat?
ketoconazole
can treat:
* cushing's disease
* prostate cancer
32
which adrenocortical antagonists increases fuid retention ? which lowers fluid retention?
* metyrapone - inc fluid retention
* spironolactone - dec fluid retention: tx for edema / HTN
33
which drug can be used to treat cushing's in pregnant women?
metyrapone
34
which drugs can be used to treat Cushing's Disease?
what are their individual AEs?
* ketoconazole - hepatotoxicity
* metyrapone - fluid retention/hirsutism
* mitotane - depression / somnolence
35
which adrenal antagonist can be used to treat primary hyperaldosteronism?
spironolactone
