Preterm labor is a multifactorial problem that current treatment options address only symptomatically rather than causally. Preventative treatment with progesterone can lower preterm birth rates in high-risk groups by over 30%. Tocolysis using beta-adrenergic agonists like terbutaline and fenoterol can be used to prevent premature labor by relaxing the uterus. However, these drugs often cause side effects from activating the sympathetic nervous system.

1. KLP IVKLP IV

2.  Preterm labor is a multifactorial problem. The current
treatment options are symptomatic, rather than
causally directed. Preventive treatment with
progesterone can lower the rate of preterm birth in
high-risk groups by more than 30%.
 TocolysisTocolysis –– thethe uterineuterine relaxantsrelaxants effecteffect ofof β2β2--
adrenoceptoradrenoceptor agonistsagonists (terbutaline,(terbutaline, fenoterol)fenoterol) cancan bebe
usedused toto preventprevent prematurepremature laborlabor
 Preterm labor is a multifactorial problem. The current
treatment options are symptomatic, rather than
causally directed. Preventive treatment with
progesterone can lower the rate of preterm birth in
high-risk groups by more than 30%.
 TocolysisTocolysis –– thethe uterineuterine relaxantsrelaxants effecteffect ofof β2β2--
adrenoceptoradrenoceptor agonistsagonists (terbutaline,(terbutaline, fenoterol)fenoterol) cancan bebe
usedused toto preventprevent prematurepremature laborlabor

3. Pathophysiology prematur Labor

4. Contraction Mechanism

5. Mechanisms of action of tocolytic drugs
Betamimetics are the best-studied tocolytic drugs; they inhibit myometrial
contractions by raising the intracellular concentration of cAMP. Fenoterol has
been approved for this purpose only in Germany and Austria, where it is used in
95% of hospitals. In other countries, ritodrine and terbutaline are used.

6.  There is no drug of first choice. The tocolytic agent
that is most effective and has the least side effects is
selected individually for each patient.
 Because these drugs activate the sympathetic nervous
system, nearly all patients who take them suffer from
tachycardia, sweating, tremulousness, nausea, or
headaches in the first few hours of use. Betamimetics
have the highest side-effect rates of all tocolytic drugs.
 There is no drug of first choice. The tocolytic agent
that is most effective and has the least side effects is
selected individually for each patient.
 Because these drugs activate the sympathetic nervous
system, nearly all patients who take them suffer from
tachycardia, sweating, tremulousness, nausea, or
headaches in the first few hours of use. Betamimetics
have the highest side-effect rates of all tocolytic drugs.

7.  Selective estrogen receptor modulators (SERMs)
exhibit a pharmacologic profile characterized by
estrogen agonist activity in some tissues with estrogen
antagonist activity in other tissues. These compounds
were initially called “antiestrogens”.
 Selective estrogen receptor modulators (SERMs)
exhibit a pharmacologic profile characterized by
estrogen agonist activity in some tissues with estrogen
antagonist activity in other tissues. These compounds
were initially called “antiestrogens”.

8. DHT
Androgen-receptor signaling in prostate cancer. Hormone-dependent androgen signaling takes place through DHT stimulation of the AR (left
panel). Hormone-refractory prostate cancer cells survive through stimulation of multiple signaling pathways, including the PI3K and the MAPK
pathways. These culminate in androgen-receptor signaling, or alternate pathways that lead to cell proliferation, migration and survival (right
panel). aHSP90-inhibitor-sensitive protein or pathway. Abbreviations: AKT, protein kinase B; GF, growth factor; IGF1, insulin-like growth
factor 1; IL-6, interleukin 6; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; MEK, upstream kinases of mitogen-activated protein
kinases, also known as MAP2Ks; P13K, phosphatidylinositol 3 kinase; mRNA, messenger RNA; STAT3, signal transducer and activator of transcription
3; TK, tyrosine kinase.

9.  Growth factors that are ligands for receptor tyrosine
kinases including epidermal growth factor (EGF),
insulin-like growth factor (IGF), vascular endothelial
growth factor (VEGF) and transforming growth
factor (TGFB), can initiate a signaling cascade that
culminates in AR activation. While the initiating
signaling event differs, all of these mechanisms
employ a phosphorylation cascade, including the
well known AKT and MAPK path- ways
 Growth factors that are ligands for receptor tyrosine
kinases including epidermal growth factor (EGF),
insulin-like growth factor (IGF), vascular endothelial
growth factor (VEGF) and transforming growth
factor (TGFB), can initiate a signaling cascade that
culminates in AR activation. While the initiating
signaling event differs, all of these mechanisms
employ a phosphorylation cascade, including the
well known AKT and MAPK path- ways

10. Dutasterid
 DHT, the primary prostatic androgen, is
transformed from T by types 1 and 2 5 -reductase. The
predominant isoenzyme in normal prostate is type 2 5
-reductase.
 The two 5 -reductase inhibitors currently available for
clinical use are finasteride and dutasteride
 DHT and other androgens are hypothesized to con-
tribute to the maintenance of homeostasis between
the processes of cell proliferation and (penurunan) cell
death (ie, apoptosis)
 DHT, the primary prostatic androgen, is
transformed from T by types 1 and 2 5 -reductase. The
predominant isoenzyme in normal prostate is type 2 5
-reductase.
 The two 5 -reductase inhibitors currently available for
clinical use are finasteride and dutasteride
 DHT and other androgens are hypothesized to con-
tribute to the maintenance of homeostasis between
the processes of cell proliferation and (penurunan) cell
death (ie, apoptosis)

11.  Cell proliferation and apoptosis are androgen-
dependent mechanisms affected by intermediaries set
in motion by the binding of DHT to the androgen
receptor. DHT indirectly mediates expression of
genes that control cellular proliferation and death by
controlling the expression and secretion of growth
factors
 Androgen receptor (AR) is a member of the super-
family of nuclear hormone receptors which acts
as a ligand- activated transcription factor
 Cell proliferation and apoptosis are androgen-
dependent mechanisms affected by intermediaries set
in motion by the binding of DHT to the androgen
receptor. DHT indirectly mediates expression of
genes that control cellular proliferation and death by
controlling the expression and secretion of growth
factors
 Androgen receptor (AR) is a member of the super-
family of nuclear hormone receptors which acts
as a ligand- activated transcription factor

12. ). Ligand-binding positively or negatively controls gene expressions of target genes by
AR through switching of co-regulators; most of them form histone-modifying enzyme
complexes, together with histone remodeling by ATP-dependent chromatin remodelling
complexes

13. Diagrammatic representation of factors involved in maintaining homeostasis between cellular proliferation
and cellular death in the prostate. DHT dihydrotestosterone; EGF epidermal growth factor; IGFs insulin
like growth factors; KGF keratinocyte growth factor; TGF- transforming growth factor– .

14. Raloxifene
 SERMs also have differing effects on the female genital
tract. Raloxifene acts as a complete estrogen antagonist
in its effects on uterine wet weight in estrogen replete
ovariectomized rats. In human studies, raloxifene does
not cause any increase in vaginal bleeding nor does it
significantly increase endometrial thickness as
assessed by transvaginal ultrasonography.
 The effects of raloxifene on bone and the determinants
of bone strength (turnover, quantity, and quality)
 SERMs also have differing effects on the female genital
tract. Raloxifene acts as a complete estrogen antagonist
in its effects on uterine wet weight in estrogen replete
ovariectomized rats. In human studies, raloxifene does
not cause any increase in vaginal bleeding nor does it
significantly increase endometrial thickness as
assessed by transvaginal ultrasonography.
 The effects of raloxifene on bone and the determinants
of bone strength (turnover, quantity, and quality)

15.  . The first, which depends on the activation of its
binding to the ligand, appears to indicate that this
drug is capable of decreasing osteoclastic resorptive
activity by up to 50%, interleukin-6 (IL-6)
production, and up to 30% of the pro- duction of
tumor necrosis factor (TNF- ) at 6 months in vitro
as well as in vivo . Both of these latter sub- stances
constitute important mediators of bone resorption
 The second, which depends in this case on the
activation of the RRE, suggests that raloxifene is
capable of increasing the production of
transforming growth factor 3 (TGF- 3), thereby
decreasing the number of osteoclasts as well as their
resorptive activity
 . The first, which depends on the activation of its
binding to the ligand, appears to indicate that this
drug is capable of decreasing osteoclastic resorptive
activity by up to 50%, interleukin-6 (IL-6)
production, and up to 30% of the pro- duction of
tumor necrosis factor (TNF- ) at 6 months in vitro
as well as in vivo . Both of these latter sub- stances
constitute important mediators of bone resorption
 The second, which depends in this case on the
activation of the RRE, suggests that raloxifene is
capable of increasing the production of
transforming growth factor 3 (TGF- 3), thereby
decreasing the number of osteoclasts as well as their
resorptive activity