pituitary hypothalamus pharmacology Flashcards
Growth hormone replacements
Somatropin (native GH aa sequence), somatrem (additional methionine)
Somatropin pharmacokinetics
Canbe given daily at bedtime via SC (more effective) or IM 3X per week. Active levels persist 36hrs.
Somatropin uses
GH deficiency replacement in children, poor growth in Turners syndrome, Prader Willi and Chronic renal insufficiency, GH deficiency in adults, Wasting or cachexia in AIDs patients, short bowel syndrome, controversial in children with idiopathic short stature
GH insensitive deficiency
GH receptor mutation- Laron dwarf
Mecasermin- MOA and uses
Recombinant IGF-1 used in GH insensitive deficiency
Mecasermin- concerns
concern with hypoglycemia, so carb intake prior to SC injection
What increases release of GH
GHRH, exercise, hypoglycemia, dopamine, arginine, Ghrelin
What decreases release of GH
somatostatin and paradoxically decreased by dopamine agonists in acromegaly
Off label uses of somatriptin
NOT APPROVED/ illegal: performance enhancing, Anti-aging (small changes in body composition and increased rates of adverse events like edema, growth of malignant cells, diabetes)
GHRH pharmacokinetics
Given IV, intranasally or subQ.
GHRH adverse effects
rare, facial flushing, Ab formation with continued use
Tesamorelin- MOA and uses
GHRH analog- usd in HIV patients with lipodystrophy scondary to use of highly active retroviral therapy. Reduces excess abdominal fat
Uses of GHRH
Potential use in GH deficient children (if secondary to inadequate GHRH release). Potentially fewer side effects but synthethic GH is choice of treatment for GH deficiency
Functions of somatostatin
Inhibits GH release (Gi/o), decreased secretion of gastric acid and enzymes, reduces insulin and glucagon release
List somatostatin agents with method of administration
Octreotide- SC or IM, lanreotide- SC. Note lanreotide is converted into octreotide which then inhibis the anterior pituitary release of GH
Pegvisomant
GH receptor antagonist- mutated GH molecule administered SQ
Treatment of excess GH
- surgery. 2. Long acting lanreotide. 3. dopamine agonists (cabergoline, bromocriptine). 4. GH receptor antagonist: Pegvisomant
Non-pituitary uses of somatostatin
Octreotide is used for control of bleeding from esophageal varices and GI hemorrhage- constriction of vascular smooth muscle,
Somatostatin adverse reactions
Hyperglycemia, abd cramps, loose stools, cardiac effects
Tuberoinfundibular pathway
hypothalamic dopamine inhibits pituitary release of prolactin. This explains why use of dopamine blocking antipsychotics can produce hyperprolactinemia - also poikilothermia and weight gain
Prolactin regulation
Inhibitory control by dopamine, stimulated by suckling,
PRL functions
Milk production, proliferation and differentiation of mammary tissue during pregnancy, Inhibits FSH/LH release and inhibits GnRH release
Treatment of hyperprolactinemia
Dopamine agonists- decrease secretion and reduce tumor size
List dopamine agonists
Bromocriptine and cabergoline (preferred agent)
Pharmacokinetics of dopamine agonists
Bromocriptine activates D1 and D2 receptors and has frequent side effects. Cabergoline is more selective for D2,more effective in reducing PRL secretion and better tolerated (less SE)
ADH analog
desmopressin- more stable to degradation
Uses of desmopressin
diabetes insipidus, nocturnal enuresis, vonWillbrands disease, moderate hemophilia A
ADH regulation
Released when blood osmolality increases and/or circulating blood volume decreases. Inhibited by ethanol
Where does ADH exert its effects
collecting tubules- V2 receptors (coupled to Gs) increase rate of insertion of water channels leading to increased water permeability. Vascular smooth muscle: V1 receptors (Gq) mediates vasoconstriction. Pressor responses at much highe Cp than needed for antidiuresis
Treatment of diabetes insipidus
desmopressin (primary), chlorpropamide (1st gen sulfonylurea potentiates residual ADH for pts intolerant to desmopressin)
Desmopressin route of administration and SE
- nasally- irritation. 2. orally- GI upset, asthenia, elevation of LFTs. Systemic SE: hedache, nausea, abd cramps, allergic rxn, water intoxication
Causes of nephrogenic Diabettes insipidus
Congenital mutations in aquaporins or receptors, drug induced by lithium or tetracycline Abx
Lithium side effects
DI, hypothyroidism (anti-TSH), polyuria-polydipsia (anti-ADH)
Treatment of nephrogenic diabetes insipidus
fluids, low salt/protein diet, thiazide diuretics, NSAIDs
how are thiazide diuretics used in nephrogenic diabetes insipidus
Paradoxically reduces polyuria. antidiuretic effect parallels ability to cause natriuresis
How are NSAIDs used in nephrogenic DI
indomethacin- : PGs attenuate ADH-induced antidiuresis - inhibition of PG synthesis may relate to the antidiuretic response seen
Causes of SIADH
drugs: psychotropic (SSRIs, haloperidol, TCA), sulfonylureas, vinca alkaloid chemo, MDMA
Treatment of SIADH
V2 receptor antagonists (Tolvaptan, conivaptan), Demeclocyline inhibits ADH effect on distal tubule, restriction of water intake,
V2 receptor antagonists pharmacokinetics, toxicity
Tolvaptan: oral route, expensive, hepatotoxicity, increase in thirst. Conivaptan: IV, given with hypertonic saline if severe hyponatremia
