Pharm endocrine (hypothalamus/pit) Drugs

Question 1

Somatropin (ant. Pit) - GH+

Answer 1

• MOA:
• Recomb forms of Human growth hormone
• Acts GH receptors to increase IGF-1 (liver)
• Net Effect:
• Promotes protein deposition (lean body mass)
• Enhances fat use
• Decrease carb use
• Stimulates growth of cartilage & bone
• Pharmokinetics(body does to drug):
• Subcutneous admin (1/2 life short) 6-7x a week
• Therapy stopped until adequate height reached, epiphyses close or reponse stops

Question 2

Somatropin (ant. Pit) - GH+

Answer 2

• Clinical Use: (Replacement therapy)
• Replace in GH def - Turner’s syndrome, prader-willi, chronic kidney disease
• Adverse effects:
• More prominent in adults
• Scoliosis, edema, gynecomastia(benign growth of breast tissue), intracranial hypertension, carpal tunnel, Increased CYP450 activity
• Contraindications:
• Closed epiphysis, underlying intracranial lesion, active malignancy, diabetic retinopathy

Question 3

Pegvisomant (ant. pit) - GH(-)

Answer 3

• MOA:
• Blocks GH receptors = GH antagonist
• PK:
• Daily subcutaneous admin
• Clinical applications:
• Acromegaly - Or for pts who are NOT responsive to somatostatin analogs (natural inhibitor of GH)
• Adverse effects:
• Elevated liver enzymes
• Hypertension, peripheral edema, Paresthesias (tingling), dizziness
• Due to 2x GH
• MRI to check on enlarging adenoma

Question 4

Mecasermin (ant.pit) - IGF +

Answer 4

• MOA:
• Recombo form of IGF-1 stims IGF-1 receptors
• PK:
• SC injection 2x/daily Given right after snack
• Clinical uses:
• Laron dwarfism (insensitive to GH)
• GH-def w/neutralizing antibodies
• IGF-1 def that is NOT responsive to GH
• Adverse effects:
• Hypoglycemia, intracranial hypertension, INCREASED liver enzymes
• Contraindicated: in pts w/closed epiphyses or with suspected active neoplasm (tumor)

Question 5

Sermorelin (GHRH)-hypothalamus

Answer 5

• Shortest Pharm active analogue
• Used in diagnostic purposes
• Specific drug (orphan) = GH def & weight loss in Aids pts
• Used in athletic doping & youthful rejuvenation spas

Question 6

Octreotide (hypothalamus)

Answer 6

• Somatostatin VERY short 1/2 life 1-3 minutes - used for theraputic purpose
• MOA:
• Somatostatin receptor agonist +
• Clinical uses:
• Acromegaly
• Diarrhea from carcinoid tumors (GI)
• TSH-producing adenomas
• Diarrhea from vasoactive GI-peptide secreting tumors
• PK:
• 45 X more potent than somatostatin
• 1/2 life 80 min
• SC 3xday or IM 1x day
• Adverse effects:
• Ab pain, constipation, nausea, arrythmias, bradycardia, hypoglycemia, gallstones

Question 7

Gonadorelin (Hypothalamus)

Answer 7

• GnRH analogue
• Clinical uses:
• Diagnosis of hypogonadism
• stimulate ovulation (pulsatile form)
• Adverse effects:
• Anaphylaxis w/multiple doses
• Headache, flushin, lightheaded

Question 8

Leuprolide (Hypothalamus) GnRH +

Answer 8

• MOA: GnRH agonist +
• PK:
• IV, SC, IM or intranasaly (nafarelin)
• Depot forms = decrease gonadal steroid production
• Clinical uses:
• Ovarian suppression (ovarian hyperstim)
• Endometriosis, uterine fibroids
• Porphyria (skin & blood)
• Percocious puberty (early puberty)
• Advanced breat/prostate cancer (androgen dependent)
• Adverse effects:
• Hot flashes, Gynecomastia (irreversible), osteoporosis, sex dysfunction
• DVT w/Goserelin & leuprolide

Question 9

Ovulation Induction

Answer 9

• Major side effects:
• multiple pregers
• Ovarian hyperstim syndrome (direct use of drugs) = enlarged ovary, ascites, shock
• 3 steps to induction:
• Inhibit endogenous gonadotropin production - using GnRH agonist (continuous) or antagonist
• Induce follicle development: Daily injections menotropins, FSH or analogue
• Induce oocyte maturation: LH or analogue injection, OR use GnRH agonist (less risk for OHSS)

Question 10

Ganirelix (hypothalamus) GnRH(-)

Answer 10

• MOA:
• Antagonist of GnRH receptors (-)
• PK: SC injections
• Clinical uses:
• Prevention of premature LH surges during controlled ovulation hyperstimulation
• Adverse effects:
• Headache, nausea
• OHSS
• Ectopic pregnancy, Thrombotic disorder, spontaneous abortion

Question 11

Cetrolix (hypothalamus) GnRH(-)

Answer 11

• NOT 1st line - potential for anaphylaxis
• Clinical uses:
• Controlled ovarian hyperstimulation
• hormone sensitive breast/prostate cancer
• endometriosis
• Degarelix - used only in ADVANCED prostate cancer

Question 12

Follitropin (rFSH) & Urofollitropin (FSH)

Answer 12

• MOA:
• Stimulate gonadal maturation & steroid production
• Clinical uses:
• Ovulation induction
• Male hypogonadotropic hypogonadism (GIVEN with Human chorionic gonad)
• Adverse effects:
• Multiple fetuses
• Ovarian cysts (hypertrophy)
• Upper resp infections
• Embolism & thrombosis
• OHSS

Question 13

Male hypogonadotropic hypogonadism

Answer 13

• Causes:
• Kallman syndrome (anosmia - inability to smell)
• Inflammatory disease
• HIV/AIDS
• Pituitary tumor
• Obesity
• Opiates

Question 14

hCG (LH receptor +)

Answer 14

• Types: Choriogonadotropin alfa (hCG), Lutropin alfo (form of LH)
• Menotropins (hMG) - extract of urine from postmenopausal women (FSH & LH)
• Clinical uses:
• Starting ovulation during controlled ovulation hyperstim
• Ovarian follicle development in women with hypogonadotropic hyogonadism
• And in MALES combo with FSH
• MOA: Agonist of LH receptor
• PK: IM injection 2-3x week
• Adverse effects:
• Headache, depression, edema
• OHSS in women and gynecomastia in men

Question 15

Bromocriptine (hypothalamus)

Answer 15

• Treatment: reduces prolactin & higher doses reduce GH
• MOA: Dopamine analog
• agonist @ dopamine receptors (D2)
• Other clinical uses:
• Parkinson’s (combo with L-dopa) -linked to valvular heart disease due to HIGH doses
• NOT to be used in women to stop lactation following stillbirth
• PK: Oral or vaginal admin (large oral dose absorbed in liver)
• Adverse effects:
• GI
• Orthostatic hypertension
• Psychiatric disturbance
• Cabergoline: similar effects (LESS GI)

Question 16

Oxytocin (post pit)

Answer 16

• MOA:
• Agonist (+) of oxytocin receptor
• PK:
• Administered IV (intranasally)
• Clinical uses:
• Induction & augmentation of labor
• Control hemorrhage after delivery
• Adverse effects:
• Fetal distress
• Placental abruption
• uterine rupture
• fluid retention
• hypotension

Question 17

Atosiban (post pit) (-)

Answer 17

• MOA:
• Oxytocin receptor antagonist (-)
• PK: IV admin
• _Clinical uses: _
• Tocolysis (labor repressents) **for preterm birth **
  *

Question 18

Vasopressin (Kidney)

Answer 18

• Effects:
• Decreases urine production = kidneys to return more to H20 to blood
• Decreases water lost through sweating & constriction of arterioles = INCREASE BP
• Clinical uses:
• Treatment of Nephrogenic Diabetes insipidus
• Control bleeding esophageal varices
• V1- mediated vasocontriction of splanchnic arterial vessels - reduce portal blood flow = reduces pressure & bleeding
• Advanced cardiac life support:
• In emergency situations to activate V1 pressor responses

Question 19

Desmopressin (post pit)

Answer 19

• MOA: agonist of vasopressin V2 receptors
• PK:
• Longer acting synthetic vasopressin
• Oral, IV, SC, intranasal
• Clinical uses:
• Pit diabetes insipudis (central)
• Hemo A
• vWD
• Nocturnal bed wetting
• Adverse effects:
• GI
• Headache
• Hyponatremia (low Na+ in serum)
• allergic rxn

Question 20

Conivaptan (ADH) (-)

Answer 20

• MOA:
• Antagonist (-) of vasopressin V1a & V2
• PK:
• IV infusion
• Clinical uses:
• Hyponatremia (caused by SIADH)
• Adverse effects
• Infusion site rxns
• Hypertension, orthostatic hypotension, hypokalemia, thrist, polyuria
• Contraindications:
• P450 3A4 substrate = cant use P450 3A4 inhibitors - Ketoconazole, ritonavie, clarithromycin