Pharm- Hypothalamic, Pituitary, And Thyroid Drugs

Front 1

anterior pituitary

Back 1

Hypothalamic neurons secrete releasing/inhibiting factors into a portal vessel system that carries the factors to the cells of the anterior pituitary via Growth-Hormone Releasing Hormone (GHRH), Somatostatin (SST), and Dopamine (DA).
The pituicytes of the anterior pituitary produce various hormone products:Growth Hormone (GH) and Prolactin (PRL), Thyroid-Stimulating Hormone (TSH), etc

Front 2

posterior pituitary

Back 2

Hypothalamic neurons from the Supraoptic Nucleus and the Paraventricular Nucleus project directly into the posterior pituitary

secrete Arginine Vasopressin (ADH) and Oxytocin directly into the bloodstream

Front 3

Growth Hormone (GH)

Back 3

large peptide hormone (anterior pituitary)
physiological effects include:
1. Increasing the growth and metabolic activity of all tissue
2. Stimulating protein synthesis in muscle and adipose tissue
3. Stimulating lipolysis in adipose tissue
* often via Insulin-like Growth Factor-1 (aka IGF-1, aka Somatomedin)
*negative feedback.
Mechanism: stimulating the JAK/STAT kinase pathway, while IGF-1 acts mainly by stimulating the MAP kinase pathway.

Front 4

Prolactin (PRL)

Back 4

peptide hormone(anterior pituitary)
tonically inhibited by dopamine from the hypothalamus
- to be lifted during pregnancy to increase milk production in breast lobules
Mechanism: activating the JAK/STAT kinase pathway

Front 5

Arginine Vasopressin (AVP)

Back 5

posterior pituitary
plasma osmoregulation and BP Regulated by:
1. Serum osmolarity (salt concentration)-osmoreceptors
2. Systemic blood pressure- baroreceptors

Mechanism: G-protein receptors
1. V1 receptors- on vascular smooth muscle. They utilize Gq/Calcium – Protein Kinase C to stimulate vasoconstriction.
2. V2 receptors- renal tubules Use Gs/cAMP – Protein Kinase A to allow for increased renal water resorption. *major action

Front 6

Oxytocin

Back 6

small peptide hormone (posterior pituitary)
Uterine contractions during labor, infants’ suckling stimulates oxytocin

Oxytocin causes contraction of the uterine myometrium and the myoepithelium of mammary glands
Mechanism: via a G protein- the Gq/Calcium – Protein Kinase C pathway

Front 7

GH drugs

Back 7

1. Somatropin (Humatrope)- recombinant human GH
2. Somatrem (Protropin)- recombinant human GH with an extra methionine group added

given 3X weekly via IM or SC injection for dwarfism, Turner’s Syndrome, chronic renal failure
* Normal adults and children- increase muscle mass and reduce adipose tissue
Side Effects- autoimmune anti-GH antibodies

3. Growth Hormone Releasing Hormone (GHRH)- recombinant peptide Sermorelin acetate, or GHRH-29
*no clinical use and is only used for investigation

Front 8

Somatostatin drugs

Back 8

Octreotide (Sandostatin)- selective SST2R agonist
45 times more effective than SST at inhibiting GH release

uses: GH secreting tumors (acromegaly)
Side effects: GI distress, gallstones, and hyperglycemia
Given by SC injection 3X/day

Front 9

Prolactin inhibiting drugs

Back 9

dopamine (DA) receptor agonists- selective for D2

1. Bromocriptine (Parlodel)- a semi-selective D2 agonist, given orally 2-3X a day
2. Pergolide (Permax)- a cheap, long-lasting D2 agonist, given orally once a day
3. Cabergoline (Dostinex)- newer, more potent, and more selective than the previous two drugs. It shows fewer side effects and is only administered once every 2-3 days.
Uses: hyperprolactinemia by a prolactin-secreting pituitary tumor, pregnancy, or lactation
Side effects: nausea, orthostatic hypotension, and dyskinesia

Front 10

Oxytocin drugs

Back 10

Pitocin and Syntocin
Uses: Induce uterine contractions and maintain labor, Control postpartum bleeding, Stimulate milk letdown
Given IV, IM, or as a vaginal suppository during labor- short half-life (1-6 min)
Side effects: uterine hypertonus or rupture at high doses, fetal hypoxia

Front 11

vasopressin drugs

Back 11

1. Pitressin- natural 9 amino acid AVP peptide- activity at both V1 and V2 receptors *limited clinical use: temporarily control GI bleeding (vasoconstrictor) given IM and SC with a 10 min half-life
Side effects: skin blanching, abdominal cramps, and hypertension

2. Desmopressin acetate (DDAVP)- a synthetic AVP analogue- selective for V2 receptors
Uses: Diabetes Insipidus, and von Willebrand’s Disease (V2 stimulation of Factor VIII synthesis)
Given orally, IV, SC, or intranasally
Side effects: water retention

Front 12

Hypothyroidism drugs

Back 12

underproduction of thyroid hormones- Hashimoto or dietary iodine deficiency, goiter (myxedema in adults), cretinism (infants)

Tx= simple replacement
1. Levothyroxine (Synthroid, L-T4) * drug of choice (body can regulate T3 levels)
2. Liothyroxine (Cytomel, L-T3) *myxedema coma only (severe/acute)
3. Liotrix (Euthroid, Thyrola) - mixture of T4 and T3 ratio (4:1)
4. Thyroid (USP) and Thyroglobulin (Proloid)- extracts of animal thyroid glands- *first used drugs not recommended for use now

Front 13

Hyperthyroidism drugs

Back 13

overproduction of thyroid hormones- - Graves’ Disease, goiter, tumor
Treatments include:
1. Blocking iodide uptake at the membrane of follicular epithelial cells- Thiocyanate, Perchlorate * drugs of choice
2. Blocking iodination of tyrosine residues on Tg- Thiourelyenes
2. Blocking coupling of MIT/DIT- Thiourelyenes, Iodide
3. Blocking peripheral conversion of T4 to T3- Propylthiouracil
4. Blocking sympathetic pathways by blocking beta-adrenergic receptors- Propanolol- used for "thyroid storm" Sx
5. Iodide or KI (Lugol’s) solution/tablets- replace deficiency or if radioactive (Iodine-131) used for tumor destruction

Side Effects- esp sythesis blockers- agranulocytosis, aplastic anemia