Drugs Effect on the HPA-Axis Flashcards
growth hormone is released from the […] in response to stimulation from GHRH and [….]
anterior pituitary
Ghrelin
[…..] acts to inhibit release of GH from the pituitary.
somatostatin
the action of growth hormone on long bones is mediated by [….] released from the […]
IGF-1
(insulin like growth factor 1)
liver
growth hormone (somatotropin) has [.%..] bioavailability after oral administration
zero
because it’s a protein, gastric peptidases
too much GH (somatostatin) can result hypertrophy of long bones, in a condition know as […..]
acromegaly
the GHRH receptor acts to elevate levels of [….] and the ghrelin receptor acts to elevate levels of […..], together they have a [….] relationship on elevating circulating GH levels (in plasma).
cAMP
calcium
synergistic
in patients with GH-insensitivity or anti-GH antibodies a potential therapy would be tx with mediator, [……].
Side effects?
IGF-1 (since this would bypass the insensitive liver receptor problem)
albeit side effect of hypoglycaemia.
in patients with excess of GH (ex. acromegaly) what drugs may be used to mitigate GH release?
To inhibit GH action?
Release: somatostatin analogues (suppress GH from pituitary and tumours alike)
dopamine antagonist (bromocriptine)
Action:
GH receptor antagonist, pegvisomant
–>used when surgery, radiation and dopamine antagonist fail
to surgically remove a tumour releasing GH, how does one localize the tumour tissue expressing GH?
administer a tagged SST (radioactive) that will be taken up by somatostatin receptors. image this via scintigraphy (otreoscan)
somatostatin can reduce GH release from pituitary (and also TSH), however it’s efficacy is limited by [….] due to […..] and […..]
short half-life
proteolytic enzyme degredation and renal elimination
analogs of somatostatin, [….] and […], decrease enzymatic cleavage by the addition of a [….], and are thus able to extend their half life
octreotide and lanreotide
unnatural amino acid (d tryp)
the addition of [….] antagonists may improve the efficacy of somatostatin analogues
dopamine (bromocriptine or cabergoline)
G120-K inhibits GH action by preventing [….] of GH receptors by binding to [….] with high affinity. However, it’s efficacy is limited by […..]
dimerization
Site 2 (replaces lysine with glycine–>bigger molecule, steric inhibition)
short half-life
pigvisomant drug attempts to overcome short half-life of G120-k by adding a [….] molecule that affectively reduces […..] and [….].
however it is limited by poor […] for Site 1 of the GH receptor.
PEG (polyethylene glycol)
renal filtration and accessibility for proteolytic enzymes
affinity
in hyperthyroid conditions, treatment with the element […] can reduce thyroid hormone release via [….] feedback
Iodide
biochemical
hyperthyroid disorders can be treated with carbimazole which acts by inhibiting […..].
thyroid peroxidase
requires one daily dose
Tx of hyperthyroidism with propylthiouracil will act to reduce […..] and inhibit conversion of […..]
the major side effect is […..]
thyroid peroxidase
T4 to T3 (T3 is much more active and potent)
hepatotoxicity
requires 2-4 daily doses
thyroxin (t4) is circulated bound to […..]
TBG (thyroxin binding globulin)
Triiodothryonine (T3) is […more/less active…] than Thyroxin (T4), acts more rapidly, […more/less bound…] to protein in circulation, and levels are […more/less stable…] during the day.
–>safer, more reliable to Tx patients with {..T4/T3…]
more active
less bound
less stable
T4
T4 (thyroxin) has a {low/high] volume of distribution and is half life that is […longer/shorter….] than T3
very low Vd
longer (7 days vs 1 day)
many people with hypothyroidism are also afflicted by addison’s disease, this is because TS3 inhibits [….] production. cortisol also inhibits conversion of [……]
cortisol
T4 to T3
Growth hormone insensitivity is due to […..]
Secondary growth hormone deficiency is due to […]
Tertiary GH deficiency is due to [….]
GH insensitivity: growth hormone not having an effect on the liver
secondary: low levels of GH
tertiary:dysfunction in higher centres preventing the release of GH that is
present
treatment of GH deficiency can be treated with IV injection of GH. This tx also has the effect of [….] T4.
decreasing t4 levels (thyroxine).
