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Flashcards in pituitary hypothalamus pharmacology Deck (39):
1

Growth hormone replacements

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

2

Somatropin pharmacokinetics

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

3

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

4

GH insensitive deficiency

GH receptor mutation- Laron dwarf

5

Mecasermin- MOA and uses

Recombinant IGF-1 used in GH insensitive deficiency

6

Mecasermin- concerns

concern with hypoglycemia, so carb intake prior to SC injection

7

What increases release of GH

GHRH, exercise, hypoglycemia, dopamine, arginine, Ghrelin

8

What decreases release of GH

somatostatin and paradoxically decreased by dopamine agonists in acromegaly

9

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)

10

GHRH pharmacokinetics

Given IV, intranasally or subQ.

11

GHRH adverse effects

rare, facial flushing, Ab formation with continued use

12

Tesamorelin- MOA and uses

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

13

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

14

Functions of somatostatin

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

15

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

16

Pegvisomant

GH receptor antagonist- mutated GH molecule administered SQ

17

Treatment of excess GH

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

18

Non-pituitary uses of somatostatin

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

19

Somatostatin adverse reactions

Hyperglycemia, abd cramps, loose stools, cardiac effects

20

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

21

Prolactin regulation

Inhibitory control by dopamine, stimulated by suckling,

22

PRL functions

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

23

Treatment of hyperprolactinemia

Dopamine agonists- decrease secretion and reduce tumor size

24

List dopamine agonists

Bromocriptine and cabergoline (preferred agent)

25

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)

26

ADH analog

desmopressin- more stable to degradation

27

Uses of desmopressin

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

28

ADH regulation

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

29

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

30

Treatment of diabetes insipidus

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

31

Desmopressin route of administration and SE

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

32

Causes of nephrogenic Diabettes insipidus

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

33

Lithium side effects

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

34

Treatment of nephrogenic diabetes insipidus

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

35

how are thiazide diuretics used in nephrogenic diabetes insipidus

Paradoxically reduces polyuria. antidiuretic effect parallels ability to cause natriuresis

36

How are NSAIDs used in nephrogenic DI

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

37

Causes of SIADH

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

38

Treatment of SIADH

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

39

V2 receptor antagonists pharmacokinetics, toxicity

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