Uterine Drugs

Question 1

What can oxytocics be used for?

Answer 1

stimulate uterine smooth muscle contraxn to:

promote labor

OR

limit bleeding post-labor

Question 2

what are tocolytics used for?

Answer 2

reduce uterine smooth muscle contractility–>suppress labor

Question 3

how can smooth muscle contraction be stimulated?

Answer 3

^^intracellular Ca++

1. ligand-R cAMP, ligand gated [ligand binding depolarizes] & VG-Ca+ channels open–> Ca+ influx
2. Ca+ depolarizes membrane–> further influx of Ca++
3. GPCR’s:
   
   • phosphorylate MLC kinase [dependent on Ca+ & clmodulin]–>reacts w/ actin
   • activate PLC–> hydrolyzes PIP2 into IP3 & DAG
4. IP3 binds to sarcoplasmic reticulum–> releases stored Ca+
5. Ca+ actively pumped out by NA+/Ca+ exchanger
6. below Ca+ threshold, MLC’s are dephosphorylated by MLC-Pase ==> relax
7. Na/K+ gradient is maintained by NA+/K/atpase

Question 4

How does oxytocin relate to relationships?

what happens if OTR is inactive/ablated?

Answer 4

important in relationship bonding

• released in both sexes during orgasm
• if ablated: monogamous mammals fail to bond w/ mates

**note: ethanol inhibits OT release–> maybe why bar flings don’t work out???

Question 5

What are the PK’s of OT?

Answer 5

absorp/excrete: parenteral, subL, or nasal–> peptide H so can’t be given orally

• removed by liver or kidney
• degraded more readily at pregnancy term
  
  • enzyme activity ^^ [oxytocinase] –> made by uterus and placenta

Question 6

What is our drug of choice for labor indxn?

What else is it used for?

Answer 6

PITOCIN: synthetic OT

• works for post-due date, augment dysfxnal labor, speed up labor in risk situations [cHTN, preeclempsia]
• milk let down postpartum
• stimulates uterine motility postpartum to reduce bleeding

Question 7

What are contraindications to using pitocin?

Who should we use it on [specific group]?

Answer 7

• not intended for abortifacient use
• cephal-pelvic disproportion [baby head to big to fit thru pelvic canal]
  
  • abnormal fetal positions
• hypertonic uterine contrxns

USE ON: women doing a vBack [old Csxn ^^risk of uterine rupture]

Question 8

Quick, review how PG’s are made?

What are the important 2 PG’s that effects the uterus?

Answer 8

membrane–PLA2--> Arachadonic Acid–COX--> PGH2–> PGE2

PGE2: softens cervix, contrax uterus & produces hyperalgesia [^^sensitivity to pain…OUCH]

• PGER is GsPCR–> membrane depol–>ca+ influx–> MLC-PO4 –> contrxn

PGF2: uterine contrxns via PGFR [GqPCR–>IP3–>release Ca+ from SR–> contrxn]

Question 9

Where do PG’s act?

HOw are they related to physiology of labor?

Answer 9

Site of Axn: close to site of synthesis [local] and are deactiv8d b4 going in2 circulation

physio of labor:

• levels rise in amniotic fluid in labor
• induces local myometrial contrxns
• promotes cervical ripening
  
  • complex biochem process–> rearrangement of collagen molecules
  • cervix thins, softens, relaxes, & dilates in response to uterine contrxns

Question 10

What would the effect of Indomethacin be on labor?

[maybe other NSAIDs too, but this is the important guy]

USE?

Answer 10

blocks COX enzyme–> decreases PG’s–> reduces OT-induced contrxns

Actually makes it a tocolytic!!

Question 11

What are/is:

dinoPROSTone -

misoPROTol-

dinoPROST

carboPROST-

[uses too!!]

Answer 11

dinoPROSTone: natural PGE

• used to Tx hydatidiform mole

misoPROTol= synthetic PGE, given oral or vaginal, MUST b used w/ P R antagonist= Mifepristone

• used to ripen [dil8] cervix & promote labor
• used as abortifacient

dinoPROST: natural PGF2a

carboPROST: PGF2a used as IM injxn–> synthetic?

• used in any trimester as abortifacient–>induce labor
  
  • means it is not dependent on estrogen to prime uterus

Question 12

PG’s are responsible for inducing what physiologic Sx’s?

Thus what are the side-effects of many PG drugs?

Answer 12

HYperalgesia [pain]

inflammation

fever

vomiting

diarrhea

*****Thus; drugs cause flu-like Sx’s/SE’s

Question 13

What are Ergots?

What does poisoning w/ ergits result in?

Answer 13

ergots= alkaloids from a fungus that grows on cereal grasses [rye, wheat etc]

• potent sm. muscle stimulator/contractor
• ^^fetal mortality rate

poisoning: MC in grazing farm animals

• convulsion: CNS dysfxn–> contorting & twisting neck, muscle spasms, confusion, delusions
• gangrenous: vascular constrxn==>decreased BQ==>^^infxn ==>peripheral gangrene
  
  • could lose body parts

Question 14

What do we use ergots for?

(2)

Answer 14

1. contrxn of uterus = ergonovine/ergometrine
   
   • control bleeding postpartum
     
     • contrxn compresses BVs to reduce bleeding [^^Pressure >cap, vein, & arterial]
   • acts via a-adrenergic, dopaminergic & 5HT2 R’s
2. contrxn of BVs = ergotamine
   
   • Tx migraine HAs
   • Cafergot has both caffeine & ergotamine

Question 15

describe where tocolytics can act on a sm. muscle myometrial cell?

Answer 15

Question 16

What is terbutaline?

toco- or oxy- lytic?

SE’s?

Uses?

Answer 16

terbutaline= B2 agonist

• MOA: activate adenylyl cyclase–> ^^cAMP–>^^PKA–> phosphorylates & inactivates MLCK
  
  • inactive MLCK means MLC’s aren’t phosphyralted and thus cant interact with actin
  • NO CONTRXN= tocolytic
• USE: after 20 wks
• SE’s:
  
  • ^^HR & pulm. edema in moms
  • hyperglycemia
  • precipitate MI by ^^O2 demand [^^HR]

Question 17

WHat is Mg+ Sulfate?

USE?

Answer 17

Mg+ Sulfate= tocolytic

MOA: competes w/ Ca+ for R’s–> relaxation of Sm.M

USE: prevent seizure associated with eclampsia

Question 18

What is Atosiban?

USE?

Answer 18

Atosiban [tractocile] = OTR antagonist [only one approved]

MOA: inhibits OTR–> blocks IP3 activation–> relax Sm. M

USE: delays labor w/in mins

SEs: fewer maternal SEs than B2blockers, but less effective?

• ^^fetal mortality