Pharm Ii Exam Ii - Hypothalamic And Pituitary Hormones

Front 1

• Describe the hormonal feedback mechanism for the pituitary and hypothalamus

Back 1

o Key point duel negative feedback
• -----From pituitary back to hypothalamus
• -----From target tissue to pituitary and the hypothalamus

Front 2

• How do you determine if there is a pituitary problem or something else going on?

Back 2

o Give releasing hormone
• -----If no change in pituitary response then pituitary is jacked up
• -----If there is a response in the pituitary but not the target tissue then there is another problem

Front 3

• Describe the main difference between membrane hormone receptors and cytoplasmic hormone receptors

Back 3

o Membrane receptors elicit an immediate response
• -----Which can lead to protein phosphorilation and genomic response
• -----i.e. estrogen
o Binding to a cytoplasmic receptor…you have to synthesize new DNA before it has an effect

Front 4

• General use for Hypothalamus stimulating drug

Back 4

o Test function of the pituitary

Front 5

• General function of Pituitary stimulating drug

Back 5

o Test function of target organ
o Stimulate hormonal production of target organs
• -----constant dose = Inhibit
• -----Pulsitile dose = stimulating
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Front 6

• Analog means

Back 6

o Similar but not the same

Front 7

• Synthetic means

Back 7

o same amino acid sequence as human but made in lab

Front 8

• if the drug ends in –relin it tends to be a ________

Back 8

o Agonist

Front 9

• If the drug ends in –relix it tends to be a ___________

Back 9

o Antagonist

Front 10

• GnRH agonists

Back 10

o Gonadorelin, (synthetic, not a analog)
o Leuprolide,
o Nafarelin,
o Goserelin.

Front 11

• GnRH antagonist

Back 11

o Abarelix

Front 12

• GHRH agonist

Back 12

o Sermorelin

Front 13

• CRH agonist

Back 13

o Corticorelin ovine triflutate
• -----sheep derived corticotrophin releasing hormone

Front 14

• Thing to remember about somatostatin

Back 14

o It inhibits everything

Front 15

• Somatostatin Analog

Back 15

o Octreotide

Front 16

• Dopamine agonists

Back 16

o Bromocriptine
o Cabergoline

Front 17

• ACTH analogs

Back 17

o Porcine corticotropin
o Cosyntropin

Front 18

• Gonadotropin analogs

Back 18

o Human chorionic gonadotropin (LH)
o Menotropin (FSH/LH)
o Urofollitropin (FSH)

Front 19

• GH analogs

Back 19

o Somatropin,
o Somatrem

Front 20

• Vasopressin analogs

Back 20

o AVP,
o Desmopressin

Front 21

• Oxytocin analog

Back 21

o Pitocin

Front 22

• MOA of GnRH

Back 22

o Regulates secretion/release of LH and FSH
o Released in pulsatile manner (stimulate gonads)

Front 23

• MOA of GnRH analogs

Back 23

o Long-acting (analog is longer acting than human GnRH)
o Continuous administration leads to down-regulation of the GnRH receptor (duel negative feedback regulation)
o Results in decreased LH/FSH production
• -----Just like tollerence

Front 24

• Clinical use of Gonadorelin

Back 24

o Synthetic human GnRH (not a analog)
o Used for Replacement therapy (replacing the GnRH to restimulate the gonads)
• -----Central (hypothalamic) amenorrhea
• -----Idiopathic hypogonadotropic hypogonadism

Front 25

• Clinical use for Long acting GnRH agonists

Back 25

o suppress the gonadal system)
• -----Ovulation suppression
• -----Prostatic or breast cancer
• -----Idiopathic precocious puberty
• -----Endometriosis (nafarelin)
• (Nafarellin) Can also be used for short term to tx cryptorchism w/ no anatomical obstruction
o Long acting GnRH agonist include
• -----Leuprolide,
• -----Nafarelin,
• -----Goserelin

Front 26

• ROA for the synthetic GnRH and Long acting GnRH agonists

Back 26

o Gonadorelin – IV infusion
• -----Half life is to short for IV pump
o Nafarelin – intranasal
o Leuprolide & Goserelin -- SC or IM depot

Front 27

• Compare the half life of GnRH and Long acting GnRH agonists

Back 27

o GnRH (gonadorelin) = 2-9 minutes;
o GnRH analogs = 3-4 hours

Front 28

• Excretion of GnRH and Long acting GnRH agonists

Back 28

o Renal

Front 29

• Adverse effects of Gonadorelin

Back 29

o Ovarian hyperstimulation
o Anaphylaxis
• -----Gonadorelin is a synthetic GnRH

Front 30

• Adverse effects of Long acting GnRH agonists

Back 30

o Androgen-like effects (PRIMARY AND SECONDARY EFFECTS)
• -----Adrenals become more predominant…secreting testosterone and estrogen
o Long acting GnRH agonists include
• -----Leuprolide,
• -----Nafarelin,
• -----Goserelin

Front 31

• Contraindications to synthetic GnRH and long acting GnRH analogs

Back 31

o Pregnancy and lactation
o Osteoporosis

o Long acting GnRH agonists include
• -----Leuprolide,
• -----Nafarelin,
• -----Goserelin
o synthetic GnRH includes
• -----Gonadorelin

Front 32

• GnRH Antagonist

Back 32

o Abarelix

Front 33

• MOA of Abarelix

Back 33

o Synthetic decapeptide with antagonist activity at GnRH receptor
• -----Knocks Testosterone down to <50 ng/dL 4 weeks after IM administration
• -----About 75% of males are suppressed a year later.
• ----- After the supression occurs they stay on a maintenance dose

Front 34

• Clinical Use of Abarelix

Back 34

o Advance prostatic cancer

Front 35

• ROA for Abarelix

Back 35

o IM administration – day 1,15, and 29 and then 1/month

Front 36

• Half-life of Abarelix

Back 36

o 13 days
o Highly (>96%) bound to protein
• -----so sticks around in the system for a long period of time
o Little to no CYP metabolism

Front 37

• Adverse effects of Abarleix

Back 37

o Hot flashes,
o sleep disturbance,
o breast enlargement,
o breast pain or nipple tenderness,
o pain,
o back pain,
o constipation,
o peripheral edema,
o dizziness,
o headache

Front 38

• MOA of FSH

Back 38

o Stimulates the ovarian follicle and controls estrogen release from follicle.
o Stimulates spermatogenesis

Front 39

• MOA of LH

Back 39

o Promotes development and maintenance of corpus luteum.
o Controls testosterone production in Leydig cells

Front 40

• hCG is an analog to what hormone

Back 40

o LH

Front 41

• Menotropin is an analog to what hormone

Back 41

o FSH
o LH

Front 42

• Urofollitropin is an analog to what hormone

Back 42

o FSH

Front 43

• CLINICAL USE of hCG and Menotropin

Back 43

o Infertility - Induce ovulation
o Hypogonadism (males and females)
• -----hCG = LH
• -----Menotropin = FSH &LH

Front 44

• Clinical use of Urofollitropin

Back 44

o Induce ovulation in women with polycystic ovary syndrome
• -----B/c you are liminating the LH that would exacerbate the problem
o Urofollitropin = FSH

Front 45

• ROA for LH and FSH analogs

Back 45

o IM

Front 46

• Half Life for LH and FSH

Back 46

o LH 4 hours;
o FSH 70 hours
• -----metabolized in the liver

Front 47

• Adverse effects of LH and FSH analogs

Back 47

o Ovarian enlargement/hyperstimulation
o Thromboembolism

Front 48

• MOA of GH

Back 48

o Pulsatile release
o Binds to specific GH cell surface receptors in multiple tissues
o Direct effects-- Stimulates IGF(insulin like growth factor) production
o Indirect effects-- Anabolic and growth-promoting effects mediated by IG

Front 49

• Describe the duel negative feedback on GH

Back 49

o IGF-1 and SRIF
• -----IGF via feedback inhibition
• -----Also IGF stimulates SRIF
• -----SRIF is somatostatin…modulates the amount of growth hormone being released

Front 50

• MOA of Sermorelin

Back 50

o Synthetic GHRH agonist
o Initiates secretion of growth hormone (GH)
o Pulsatile release

Front 51

• Clinical use of Sermorelin

Back 51

o Growth hormone deficiency
o Growth hormone deficiency diagnosis

Front 52

• ROA for Sermorelin

Back 52

o IV

Front 53

• Half-life of Sermorelin

Back 53

o 63 minutes
• -----Enzymatically degraded in plasma

Front 54

• ADVERSE EFFECTS of Sermorelin

Back 54

o ***Facial flushing,
o N/V

Front 55

• Drug Interactions of Sermorelin

Back 55

a lot more b/c it works through IGF
o Agents that inhibit secretion of GH
• -----Insulin,
• -----glucocorticoids,
• -----NSAIDS
o Agents that increase GH levels
• -----Clonidine,
• -----levodopa
o Agents that decrease response to GHRH
• -----Antimuscarinic drugs

Front 56

• MOA of Somatropin

Back 56

o Recombinant GH (pulsitile)

Front 57

• MOA of Somatrem

Back 57

o Recombinant GH analog (continuous)

Front 58

• Clinical use for GH and GH ANALOGS

Back 58

o Replacement therapy in GH deficiency
o Turner’s Syndrome in girls
o AIDS wasting or cachexia

• Somatropin and Somatrem

Front 59

• ROA for GH and GH ANALOGS
o Parenteral administration (IM or SC)

• Somatropin and Somatrem

Back 59

• Half life for GH and GH ANALOGS
o Short half-life (20-30 min)
o IGF levels peak at 20 hours (genomic mediated  lag time)
• -----Effects last much longer than half-life Due to slow induction and slow clearance of IGFs

• Somatropin and Somatrem

Front 60

• Adverse effects of GH and GH analogs

Back 60

o Headache,
• -----intracranial hypertension
o Muscle pain,
o mild hyperglycemia
o Antibody production to GH
• -----Switch spp the analog is made from and it will bypass the Ab
o Leukemia
o Contraindicated once epiphyses closed

• Somatropin and Somatrem

Front 61

• Drug interactions of GH and GH analogs

Back 61

o Corticosteroids,
o sex steroids

• Somatropin and Somatrem

Front 62

• MOA of Pegvisomant

Back 62

o Pegylated analog of GH (Antagonist)
• -----Pegylated – modified aa in the sequence…put side chains on it…still recognize receptor but does not initiate response
o Blocks action of GH on target tissue
• -----Decreases IGF levels

Front 63

• Clinical use for Pegvisomant

Back 63

o Used to treat acromegaly
• Especially those resistant to somatostatin analogs

Front 64

• MOA of Octreotide

Back 64

o Somatostatin Analog
o Inhibits secretion of pituitary and gastrointestinal hormones
• -----Growth hormone,
• -----TSH
• -----prolactin,
• -----Glucagon
• -----insulin,
• -----VIP,
• -----gastrin,
• -----secretin,
• -----motilin,
• -----pancreatic
• -----polypeptide

Front 65

• Clinical use of Octreotide

Back 65

• Acromegaly
• Hyperfunctioning endocrine tumors
• -----GH-secreting tumors
• -----Carcinoid syndrome,
• -----VIP-secreting tumors
• Non-FDA approved uses
• -----Insulinomas
• -----Orthostatic hypotension

Front 66

• Compare native somatostatin (SRIF) and its analog

Back 66

o Somatostatin analog = Octreotide
• Native SRIF
• -----Very short half-life, 1-3 minutes
• -----Not absorbed orally
• SRIF analog (Octreotide)
• -----Longer half-life (80-90 mins), IV, SC or IM administration
• -----More selective for inhibiting GH
• -----32% excreted unchanged in urine

Front 67

• Adverse effects of Octreotide

Back 67

o Octreotide is a somatostatin analog
o Suppression of insulin release
• -----This is the main adverse effect
• -----Leads to an increase in blood glucose
o Gallstone formation
o GI effects
• -----Abdominal pain, diarrhea, nausea/vomiting
• -----A lot of the GI effects is from ingibiting GI hormones

Front 68

• Drug interactions of Octreotide

Back 68

o Decreased bioavailability of cyclosporine
o *Additive effects: (could result in drop in BP)
• -----Beta-blockers and
• -----calcium channel blockers

Front 69

• MOA of Bromocriptine

Back 69

o Dopamine Agonists
• Agonist at D2 receptors on lactotrophs
• Inhibits prolactin release from anterior pituitary
• Results in:
• -----Normal ovulation/ovarian function in amenorrheic women
• -----Suppressed lactation

Front 70

• CLINICAL USE of Bromocriptine

Back 70

o Bromocriptine is a dopamine agonist

• Hyperprolactinemia
• Acromegaly
• Parkinson’s disease

Front 71

• Adverse effects of bromocriptine

Back 71

o During initiation of treatment
• -----Nausea, vomiting, dizziness
• -----ORTHOSTATIC HYPOTENSION
o Seizures, dysrhythmias, stroke (would have to have a high concentration to have these side effects)

Front 72

• Contraindications of bromocriptine

Back 72

o Severe ischemic disease,
o hypertension
o Toxemia of pregnancy

Front 73

• Drug interactions of bromocriptine

Back 73

o Drugs that increase prolactin (counteract the effects of bromocryptine)
• -----Phenothiazines (chlorpromazine)
• ---------------Potent antagonist of the D2 receptor
• -----Butyrophenones (haloperidol)
• ---------------Potent antagonist of the D2 receptor
• -----Monoamine oxidase inhibitors
o Antihypertensive agents
• -----Additive effect to anti hypotensive effects

Front 74

• AVP and AVP Analogs include

Back 74

o Arginine vasopressin (AVP)
o Desmopressin (synthetic analog)
• -----Long half life
• -----Can be given intranasally

Front 75

• MOA for AVP and AVP Analogs

Back 75

o Primary antidiuretic hormone
o Synthesized in hypothalamus, transported and released from posterior pituitary
o Increases reabsorption of water in the renal collecting ducts
o Stimulates contraction of vascular smooth muscle

Front 76

• Clinical use of AVP and AVP Analogs

Back 76

o Diabetes insipidus
o Hemophilia A
o von Willebrand’s disease
o Enuresis

Front 77

• Compare the pharmicokinetics of AVP and desmopressin

Back 77

o AVP
• -----Parenteral administration:
• ---------------IM
• ---------------SC
• -----Short half-life (10-20 min); biological activity lasts 2-8 hours
• -----Metabolized in liver and kidneys
o Desmopressin
• -----Administered
• ---------------SC,
• ---------------IV,
• ---------------oral
• ---------------intranasal
• -----Biological activity same as half-life (5-21 hours)
• ---------------Almost 100% bioavalability
• ---------------Not bound to proteins

Front 78

• Adverse effects, contraindications, and caution with AVP and AVP analog

Back 78

o ADVERSE EFFECTS
• -----WATER INTOXICATION
• -----Vasoconstriction
o Contraindicated in:
• -----Chronic nephritis
o Use with caution:
• -----coronary artery disease
• ---------------Desmopressin is drug of choice because it causes Minimal vasoconstriction

Front 79

• Drug interactions of AVP AND AVP Analogs

Back 79

o Potentiators of V1 and/or V2 effects
• -----Carbamazepine
• -----Chlorpropamide
• -----Tricyclic antidepressants
o Inhibitors of V1 and/or V2 effects
• -----Lithium,
• -----heparin
• -----Epinephrine,
• -----ethanol

Front 80

• MOA of oxytocin

Back 80

o 2nd posterior pituitary hormone
• -----Increases strength of uterine contraction
• -----Increases milk-letdown
o Released by reflex due to dilation or contraction of the uterus or suckling
o Increased uterine sensitivity in late-pregnancy

Front 81

• Clinical use of oxytocin

Back 81

o IV
• -----Induce/enhance uterine contractions
o IM
• -----Prevent post-partum hemorrhage
o Nasal
• -----Stimulate milk-letdown

Front 82

• ADVERSE EFFECTS of oxytocin

Back 82

o Uncommon, but may include:
• -----Arrhythmias,
• -----CNS stimulation,
• -----excessive uterine contraction
• -----hyponatremia

Front 83

• Contraindications of oxytocin

Back 83

o Fetal distress
o Abnormal fetal presentation
o Prematurity
o Cephalopelvic disproportion