GH antagonist and agonists Flashcards
which gland releases GH?
anterior pituitary
which hormones released by hypothalamus control GH?
growth hormone releasing hormone GHRH
GH inhibiting releasing hormone GHIH
what is the other regulatory effect of somatostatin?
somatostatin which is GHIH :
inhibit GH
ALSO INHIBIT TSH
what would do the effect of inhibiting TSH result in terms pharmacodynamics?
it will lead to hypothyrodism due to TSH suppression
how is GH administered ?
Always as injection cannot be given orally
What is recombinant somatotropin ? rhGH?
biosynthetic form of human growth hormone
given to patients with GH deficiency
in cause of dwarfism, how often is somatotropin administered ?
subcutaneously ONCE DAILY
what are examples of somatostatin administered ?
Somapacitan
Lonapegsomatropin
Somatrogon
all given once weekly and long acting
describe somapacitan?
Long acting rhGH analog
given to children 2.5 years old and OLDER
CANT BE GIVEN FOR KIDS YOUNGER THAN 2.5 YEARS OLD
GIVEN ONCE WEEKLY
describe lonapegsomatropin ?
sustained release preparation of rhGH
given to children 1 year of age and older
cant be given to children less than 1 years old
prodrug of somatropin
once weekly
describe somatrogon ?
long acting rhGH analong
once weekly
what is mecasermin ?
recombinant form of human IGF1
only drug in the market has similar to IGF1
when is mecaserin used?
severe primary igf-1 deficiency
hormone receptor mutation
patients with neutralizing antibodies
what is the side effect of mecaserin?
IGF 1 has insulin like effects
it can induce HYPOGLYCEMIA so must be initiated at lower doses
what is sermorelin ?
synthetic growth hormone releasing hormone ( GHRH )
what are the uses of sermorelin?
idiopathic GH deficiency in children
GH deficiency secondary to Hypothalamus damage rather than pituitary abnormalities
( IN THIS CASE PITUITARY SOMATOTROPES CAPABLE OF SECRETING GH AND ARE FUNCTIONING )
how and when sermorelin is administered?
subcutaneous injection
DAILY
what is the effect of glucocorticoid on GH?
inhibit the effects of recombinant GH
so when patient is taking both long term glucocorticoids and rhGH ——> the glucocorticoid will inhibit the growth effect of GH —->GROWTH FAILURE
what would compromise the final height of a patient ?
androgens , estrogens and thyroid hormones + anabolic steroids
these would accelerate epiphyseal closure of bones –> stopping the lengthening of the bones
what is the example of GHIH?
somatostatin like drugs –> END WITH EOTIDE
octreotide –> synthetic somatostatin
Lanreotide aceate –> prolonged secretion
pasireotide –> higher affinity
what are the uses of octreotide ?
acromegaly –> excessive GH
neoplastic diseases:
carcinoid syndrome
pituitary adenomas that secrete thyrotropin
tumors that produce vasoactive intestinal polypeptide
how and when octreotide is administered ?
subcutaneously every 8 hours
long acting intramuscular formula given once monthly
oral formulation
how is octreotide administered orally even though it is peptidal?
it is formulated with transient permeability enhancer which allows it to be absorbed easily
what is lanreotide acetate?
prolonged release formulation of octreotide
given subcutaneous injection once every 4 weeks
what is pasireotide?
somatostatin analog that has broader affinity for somatostatin receptors than octreotide and lanreotide
this high affinity results in greater GH inhibition
when is pasireotide used?
ocrtoetide / lanreotide resistant adenomas
what are the pharmacokinetics/dynamics of Somatostatin analogs?
Transient GI disturbances are common but usually subside within the first 3 months of therapy
Inhibit gallbladder contractility and decrease bile secretion —> lead to development of biliary sludge and asymptomatic gallstones —> Cholelithiasis
Cholelithiasis —> occur in patients treated for 12 month or longer ( it is only time related not age or gender related )
alter balance of hormones –> hypoglycemia / hyperglycemia
GHIH May suppress pituitary release of TSH because GHIH inhibit both GH and TSH leading to decreased thyroid hormone secretion –> hypothyroidism –> Commonly with octreotide
Sinus bradycardia, conduction abnormalities and arrhythmias —>commonly with octreotide and lanreotide
what is administered with somatostatins to reduce the adverse effects?
insulin
oral hypoglycemia agents
beta blocker
calcium channel blockers
require careful dosage adjustment
what is cabergoline?
dopamine agonists
another example is bromocriptine
what can dopamine agonists do GH?
reduce circulating levels of GH , IGF1, Prolactin
when are dopamine agonists can be used?
treatment of person with elevated growth hormone and prolactin secretion
what you should monitor when administering dopamine agonists?
visual disturbances, menstrual cycles ( cuz prolactin inhibit it ), sexual function ( men )
prolactin serum concentration every 3 to 4 weeks
what is pegvisomant?
GH receptor antagonist
what is the MOA of pegvisomant?
blocks the receptor and stops IGF1 and from binding to the receptor
when is pegvisomant used?
acromegaly patients with Resistance to octreotide like pasireotide
what are the non pharmacolgical treatments of acromegaly?
- transsphenoidal surgical resection of adenoma
- radiation therapy
