Pharm of Hypothalamic, Anterior, and Posterior Pituitary Hormones Flashcards
1
Q
Hypothalamic vs Pituitary Agents
A
- Hypothalamic:
- Growth Hormone releasing hormone (GHRH)
- Thyrotropic releasing hormone (TRH)
- Corticotropin releasing hormone (CRH)
- Gonadotropin releasing hormone (GnRH)
- Dopamine (DA)
- Somatostatin (SST)
- Anterior Pituitary–> Endocrine glands/Liver/Bone/other–>target
- Growth Hormone (GH)
- Thyroid Stimulating Hormone (TSH)
- Adrenocorticotropin (ACTH)
- Luteinizing hormone (LH)
- Follicle Stimulating hormone (FSH)
- Prolactin (PRL)
- Posterior Pituitary–>Target Tissues
- Antidiuretic hormone (ADH)
- Oxytocin
2
Q
Drugs that mimic or block the effects of hypothalamic & Pituitary Hormones
A
- Anterior Pituitary
- Growth Hormone:
- Agonist Action
- Somatropin
- Mecasermin
- Antagnoist Action
- Octreotide
- Pegvisomant
- Agonist Action
- Gonadotropins:
- Agonist Action
- Mixed LH & FSH
- Menotropins
- LH
- Lutropin
- hCG
- FSH
- Follitropin
- Mixed LH & FSH
- Agonist Action
- Prolactin
- Antagonist Action
- D2 dopamine agonists
- bromocriptine
- D2 dopamine agonists
- Antagonist Action
- Growth Hormone:
- Hypothalamus
- GnRH
- Agonist Action
- Gonadorelin
- Antagonist Action
- GnRH receptor agonist-leuprolide
- GnRH receptor antagonist-ganirelix
- Agonist Action
- GnRH
- Posterior Pituitary:
- Oxytocin
- Agonist action
- Oxytocin
- Antagonist Action
- Atosiban (not FDA approved)
- Agonist action
- Vasopressin:
- Agonist Action
- Desmopressin
- Antagonist Action
- Conivaptan
- Agonist Action
- Oxytocin
3
Q
Growth Hormone Axis:
Stimulatory vs inhibitory inputs and hormones
A
- Stimulatory inputs:
- genetics
- exercise
- Increased:
- grhelin
- amino acids
- Decreased
- blood sugar
- fatty acids
- Stimulatory hormones:
- Hypothalamus-GH releasing Hormone (GHRH)
- Anterior Pituitary- Growth Hormone (GH)
- Liver-Insulin-like growth factor 1 (IGF-1)
- Inhibitory inputs: Negative feedback
- Genetics
- lethargy, stress, disease
- Decreased
- ghrelin
- amino acids
- Increased
- blood sugar
- fatty acids
- Inhibitory hormones:
- hypothalamus-Somatostatin (SST)
- direct downregulation
- hypothalamus-Somatostatin (SST)
4
Q
clinical presentation of low GH
A
- affects growth and development of jaws and teeth
- Children
- short stature:
- Delayed dental age
- Delayed replacement of deciduous teeth by permanent teeth
- Newly erupted permanent teeth often require ortho tx
- low age-adjusted growth velocity
- hypoglycemia due to unopposed action of insulin
- IGF-1 expression and postnala growth are GH-dependent during 1st year
- Subnormal serum GH after stimulation
- short stature:
- Adults:
- Decreased:
- muscle mass
- exercise capacity
- bone density
- Generalized obesity
- weak/lack of energy
- Dyslipidemia
- Reduced cardiac output
- Decreased:
5
Q
Pharmacological management of low GH
A
- Tesamorelin
- Somatotropin
- Mecarsermin
- patients that do not respond to GH or somatotropin
- mutations in receptor
- antibodies against hormone
- IGF-1 deficiency
- patients that do not respond to GH or somatotropin
6
Q
Tesamorelin
A
- Synthetic GHRH
- Mechanism=GHRH agonist
- used clinically to diagnose GH and GHRH sufficiency
- not used in disorders of GHRH or GH/IGF-1 secretion
- used to reduce excess abdomina fat in adult patients with HIV
- No side effects
- no contraindications
7
Q
Somatotropin
A
- Recombinant form of GH
- Mechanism: GH agonist
- Used in both adults and children
- additional symptoms
- Given to:
- children
- during active growth (before epiphyseal fusion)
- older children
- higher dosesae
- may be extended past puberty and into adulthood
- children
- Side effects:
- Children: Well tolerated
- can have rare but serious side effects:
- pseudotumor cerebri
- slipped capital femoral epiphysis
- scoliosis progression
- edema
- hyperglycemia
- can have rare but serious side effects:
- Adults: Less tolerated
- Children: Well tolerated
8
Q
Mecasermin
A
- recombinant IGF-1
- mechanism: IGF-1 agonist
- Used in children with growth failure and unresponsive to GH therapy
- Side effect:
- Hypoglycemia
- high carb meal or snack 20 minutes before administration limits
- Hypoglycemia
9
Q
clinical presentation of High GH
A
- Presentation: highly dependent on age
- Excess growth hormone can affect jaws and teeth:
- Gigantism- GH excess before fusion of growth plates
- prognathic mandible
- malocclusion
- hypercementosis
- Acromegaly- GH excess in adults
- change in occlusion
- prognathism
- jaw thickening
- Gigantism- GH excess before fusion of growth plates
- Test=GH supression test (Not Tesamorelin)
- blood levels measured before and after sugar consumed
- glucose decreases levels of GH
10
Q
Pharmacological management of High GH
A
- Pegvisomant
- Octreotide or Lanreotide
- Bromocriptine or cabergoline
11
Q
Pegvisomant
A
- mutant GH derivative
- Mechanism=GH Antagonist
- cross-link GH receptors
- does not induce conformation change so no activation of receptor
- prevents GH from activating GH signaling pathways
- Does not reduce GH secretion
- May elevate liver enzymes and induce lipodystrophy
12
Q
Octreotide
A
- or Lanreotide
- Synthetic SST analogs
- Mechanism: SST agonist
- longer half lives than SST (SST=1-3 min)
- Tx: Acromegaly and gigantism
- reduce GH and IGF-1
- Octreotide is the Most widely used SST analog
- Side effects:
- GI disturbances
- Gallstones
- abnormal cardiac conduciton
13
Q
Bromocriptine
A
- or cabergoline
- Dopaine Agonist with high affinity for DA D2 receptors (prolactin)
- but can reduce GH release at high doses in patients with acromegaly
- mechanism: unclear
- only 70% of patients respond
- can increase GH in patients without acromegaly
- Only affects GH and prolactin
14
Q
Dopamine pathway
A
- Positive feedback control=Prolactin
- Dopamine inhibits prolactin release from anterior pituitary
15
Q
Clinial Presentation: Low Prolactin
A
- Not a medical problem
- Problem for women who want to breastfeed and cannot due to low prolactin
- no approved treatments in US