Hypothalamic and Pituitary Pharmacology Flashcards
what increases GH release from the anterior piruitary
GHRH, exercise, hypoglycemia, dopamine, l-DOPA, arginine
what is the treatment for patients who are growth hormone insensitive (receptor mutation) as in Laron dwarf
recombinant IGF-1 (Mecasermin)
______ is a GHRH analog available for use in HIV patients with lipodystrophy secondary to use of highly active retroviral therapy (HAART) - reduces excess abdominal fat
Tesamorelin (Egrifta)
what is the MOA of somatostatin
Inhibits GH release via GPCR coupled to Gi decreasing cAMP levels and activating K+ channels
What is the MOA of GHRH
Rapidly stimulates GH synthesis and secretion via binding to GPCR coupled to Gs -> increasing cAMP and Ca++ levels in somatotrophs - no receptor down-regulation with continuous stimulation
what are the Uses of Somatostatin Analogs
1) treat excess of growth hormon: Acromegaly, gigantism
2) To Control of bleeding from esophageal varices and GI hemorrhage
What is Pegvisomant
GH receptor antagonist
what are the side effects of somatostatins
1) transient hyperglycemia
2) Abdominal cramps and loose stools
3) cardiac (bradycardia, conduction disturbances)
Prolactin release is under inhibitory control by _____
hypothalamic dopamine at D2 receptors
The Main stimulus for prolactin release is ______
suckling - causes 10-100-fold increase within 30 min
what are Cabergoline and Bromocriptine
Dopamine agonists used on the Tx of hyperprolactinemia
which dopamine agonist is more effective in reducing prolactin secretion and Better tolerated
Cabergoline
what is Desmopressin?
ADH analog
what are the Renal actions of ADH
Mediated by V2 receptors (GPCRs coupled to Gs)
Increases the rate of insertion of water channels (aquaporins) into luminal membrane -> increased water permeability -> leading to an antidiuretic effect
what is the treatment of choice for Central Diabetes Insipidus
Desmopressin
What is Chlorpropamide
1st generation sulfonylurea, that can be used in the treatment of ADH defieciency.
• Potentiates action of small or residual amounts of ADH - mechanism not clear
• Option for patients intolerant (side effects-allergy) to desmopressin
what are the causes of drug induced Nephrogenic diabetes insipidis
- Lithium: reduces V2-receptor mediated stimulation of adenylyl cyclase. As many as 1/3 of patients treated with Li+ may develop nephrogenic diabetes insipidus
- Demeclocyline (tetracycline antibiotic): mechanism not completely understood but possibly acts via block of ADH binding to receptor
what is the treatment for Nephrogenic Diabetes Insipidus
- Thiazide diuretics: Paradoxically reduce the polyuria of patients with DI. Mechanism not completely understood but antidiuretic effect parallels ability to cause natriuresis - used in doses that mobilize edema fluid.
- NSAIDs: Since prostaglandins attenuate ADH-induced antidiuresis, inhibition of PG synthesis by indomethacin may relate to the antidiuretic response seen. Indomethacin has greatest efficacy among NSAIDs.
what is the Treatment of hyponatremia seen in SIADH
1) Restriction of free water intake is initial conservative approach
2) Demeclocyline inhibits ADH effect on distal tubule and has been preferred drug in patients with inadequate response to conservative measures
3) V2 receptor antagonist - potential therapeutic advance for hyponatremia (also tried in HF).
Tolvaptan (Samsca®) - oral route, expensive
Conivaptan (Vaprisol®) - IV infusion (useful in hospitalized SIADH patients) - if severe symptomatic hyponatremia present, conivaptan can be given with hypertonic saline (3%), permitting a more rapid initial correction
too rapid correction of hyponatremia can cause _____
cerebellar pontine myelinolysis
Von Willebrand’s disease and moderate hemophilia A can be treated by _____
IV desmopressin, (elevates von Willebrand factor,
elevates factor VIII)
nocturnal enuresis can be treated with ____
oral desmopressin
