pituitary hypothalamus pharmacology

Question 1

Growth hormone replacements

Answer 1

Somatropin (native GH aa sequence), somatrem (additional methionine)

Question 2

Somatropin pharmacokinetics

Answer 2

Canbe given daily at bedtime via SC (more effective) or IM 3X per week. Active levels persist 36hrs.

Question 3

Somatropin uses

Answer 3

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

Question 4

GH insensitive deficiency

Answer 4

GH receptor mutation- Laron dwarf

Question 5

Mecasermin- MOA and uses

Answer 5

Recombinant IGF-1 used in GH insensitive deficiency

Question 6

Mecasermin- concerns

Answer 6

concern with hypoglycemia, so carb intake prior to SC injection

Question 7

What increases release of GH

Answer 7

GHRH, exercise, hypoglycemia, dopamine, arginine, Ghrelin

Question 8

What decreases release of GH

Answer 8

somatostatin and paradoxically decreased by dopamine agonists in acromegaly

Question 9

Off label uses of somatriptin

Answer 9

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)

Question 10

GHRH pharmacokinetics

Answer 10

Given IV, intranasally or subQ.

Question 11

GHRH adverse effects

Answer 11

rare, facial flushing, Ab formation with continued use

Question 12

Tesamorelin- MOA and uses

Answer 12

GHRH analog- usd in HIV patients with lipodystrophy scondary to use of highly active retroviral therapy. Reduces excess abdominal fat

Question 13

Uses of GHRH

Answer 13

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

Question 14

Functions of somatostatin

Answer 14

Inhibits GH release (Gi/o), decreased secretion of gastric acid and enzymes, reduces insulin and glucagon release

Question 15

List somatostatin agents with method of administration

Answer 15

Octreotide- SC or IM, lanreotide- SC. Note lanreotide is converted into octreotide which then inhibis the anterior pituitary release of GH

Question 16

Pegvisomant

Answer 16

GH receptor antagonist- mutated GH molecule administered SQ

Question 17

Treatment of excess GH

Answer 17

1. surgery. 2. Long acting lanreotide. 3. dopamine agonists (cabergoline, bromocriptine). 4. GH receptor antagonist: Pegvisomant

Question 18

Non-pituitary uses of somatostatin

Answer 18

Octreotide is used for control of bleeding from esophageal varices and GI hemorrhage- constriction of vascular smooth muscle,

Question 19

Somatostatin adverse reactions

Answer 19

Hyperglycemia, abd cramps, loose stools, cardiac effects

Question 20

Tuberoinfundibular pathway

Answer 20

hypothalamic dopamine inhibits pituitary release of prolactin. This explains why use of dopamine blocking antipsychotics can produce hyperprolactinemia - also poikilothermia and weight gain

Question 21

Prolactin regulation

Answer 21

Inhibitory control by dopamine, stimulated by suckling,

Question 22

PRL functions

Answer 22

Milk production, proliferation and differentiation of mammary tissue during pregnancy, Inhibits FSH/LH release and inhibits GnRH release

Question 23

Treatment of hyperprolactinemia

Answer 23

Dopamine agonists- decrease secretion and reduce tumor size

Question 24

List dopamine agonists

Answer 24

Bromocriptine and cabergoline (preferred agent)

Question 25

Pharmacokinetics of dopamine agonists

Answer 25

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)

Question 26

ADH analog

Answer 26

desmopressin- more stable to degradation

Question 27

Uses of desmopressin

Answer 27

diabetes insipidus, nocturnal enuresis, vonWillbrands disease, moderate hemophilia A

Question 28

ADH regulation

Answer 28

Released when blood osmolality increases and/or circulating blood volume decreases. Inhibited by ethanol

Question 29

Where does ADH exert its effects

Answer 29

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

Question 30

Treatment of diabetes insipidus

Answer 30

desmopressin (primary), chlorpropamide (1st gen sulfonylurea potentiates residual ADH for pts intolerant to desmopressin)

Question 31

Desmopressin route of administration and SE

Answer 31

1. nasally- irritation. 2. orally- GI upset, asthenia, elevation of LFTs. Systemic SE: hedache, nausea, abd cramps, allergic rxn, water intoxication

Question 32

Causes of nephrogenic Diabettes insipidus

Answer 32

Congenital mutations in aquaporins or receptors, drug induced by lithium or tetracycline Abx

Question 33

Lithium side effects

Answer 33

DI, hypothyroidism (anti-TSH), polyuria-polydipsia (anti-ADH)

Question 34

Treatment of nephrogenic diabetes insipidus

Answer 34

fluids, low salt/protein diet, thiazide diuretics, NSAIDs

Question 35

how are thiazide diuretics used in nephrogenic diabetes insipidus

Answer 35

Paradoxically reduces polyuria. antidiuretic effect parallels ability to cause natriuresis

Question 36

How are NSAIDs used in nephrogenic DI

Answer 36

indomethacin- : PGs attenuate ADH-induced antidiuresis - inhibition of PG synthesis may relate to the antidiuretic response seen

Question 37

Causes of SIADH

Answer 37

drugs: psychotropic (SSRIs, haloperidol, TCA), sulfonylureas, vinca alkaloid chemo, MDMA

Question 38

Treatment of SIADH

Answer 38

V2 receptor antagonists (Tolvaptan, conivaptan), Demeclocyline inhibits ADH effect on distal tubule, restriction of water intake,

Question 39

V2 receptor antagonists pharmacokinetics, toxicity

Answer 39

Tolvaptan: oral route, expensive, hepatotoxicity, increase in thirst. Conivaptan: IV, given with hypertonic saline if severe hyponatremia