Exam 2: Lecture X, Growth Hormone Flashcards
Bromocriptine (Parlodel) Toxicity
GI symptoms
Orthostatic hypotension
Psychiatric symptoms
Pulmonary infiltrates
Vasospasm
Bromocriptine (Parlodel) Clinical applications
Treatment of acromegaly
Treatment of hyperprolactinemia
Treatment of Parkinson’s disease
Bromocriptine (Parlodel)
Activates D2 receptors
Suppresses pituitary secretion of GH
Suppresses pituitary secretion of prolactin (more effectively)
Octreotide (Sandostatin) Toxicity
GI disturbances
Gallstones formation – after 6 months in 20-30% of patients
Bradycardia
Cardiac conductive system problems
Vitamin B12 deficiency may develop with long-term use
Octreotide (Sandostatin) Clinical Applications
Acromegaly treatment
Given subcutaneously every 8 hours
Reduces many symptoms of hormone-secreting tumors
Acute control of bleeding from esophageal varices
Octreotide (Sandostatin)
Clinical analog of somatostatin (GHIH)
Long-acting formulation t1/2 is about 80 minutes
Agonist at somatostatin receptors
Somatostatin receptors are found in the CNS, pancreas, and the GI tract
Inhibits the release of GH
To a lesser extent inhibits the release of TSH, glucagon, and gastrin
Somatostatin….
Half life = 1-3 min
clinically cannot be used
Secretion of GH is regulated by a hypothalamic (GHRH) and somatostatin
Somatostatin (GHIH) has an inhibitory effect upon GH release
Somatostatin is a 14 aminoacid peptide
Somatostatin also inhibits the release of TSH, insulin, and gastrin
Somatostatin receptors are found in the CNS, pancreas, and GI tract
Somatostatin analogs can be used clinically
Pegvisomant (Somavert)
GH antagonist
Blocks conformational shift of GH receptors
Interrupts signal transduction
Blocks activation of JAK2 signaling system
Ameliorates the effects off excessive GH production
Approved for acromegaly treatment
GH Excessive secretion treatment strategies
Growth hormone antagonists = Pegvisomant (Somavert)
Somatostatin analogs= Octreotide (Sandostatin)
Dopamine agonists = Bromocriptine (Parlodel)
Somatropin Adverse effects
Joint pain / Muscle pain Progression of scoliosis Edema Hyperglycemia Upper airway obstruction/Sleep apnea P450 system induction Hypothyroidism Intracranial hypertension Acceleration of neoplasia growth Formation of antibodies to GH
Somatropin contraindications
Closed epiphyses
Neoplasia
Active intracranial lesion
Somatropin precautions
Children tolerate GH relatively well Restores normal growth in some children Restores metabolic effects of GH Precautions: Diabetic patients –risk of hyperglycemia due to insulin resistance
Somatropin info
Somatotropin is used in treatment of growth hormone deficiency in children
Somatropin is the recombinant 191 AA form of human GH
Genetically engineered human synthetic GH is identical to natural human GH
Growth hormone from animal sources is not effective in humans
Self-administered subcutaneously at bedtime – to mimic normal secretion
Half-life is much greater than of the secreted hormone and administered once/day
Somatropin other uses
Treatment of wasting in AIDS patients
Treatment for patients with short bowel syndrome
Acceleration of wound healing in children with large burns (unapproved use)
“Anti-Aging” - ↑glucose level, ↑number of cells, ↑size of cells – Alt. medicine treatments
Athletic training - GH is banned by the Olympic Committee
GH actions related to growth
GH plays no role in fetal development
Only after birth GH affects normal growth
Acts in conjunction with other hormones
Stimulates protein synthesis
Stimulates secretion of several polypeptide somatomedins from the liver
Somatomedin IGF-1 is the main mediator of GH action.
IGF-1 mediates anabolic effects acting on skeletal muscle, cartilage, and epiphyses
