Parturition and Obstetric Pharmacology - Menon Flashcards
What is a tocolytic drug? Name (7) classes of tocolytics.
Tocolytic = used to inhibit or arrest uterine contractions
- Progestins (prophylaxis)
- Andrenergic (beta-2) receptor agonists
- MgSO4
- Ca channel blockers
- COX inhibitors
- Oxytocin receptor antagonists
- NO donors
Which beta agonist is often used as a tocolytic agent? What are its main side effects?
About how long can it be used before it becomes ineffective?
Terbutaline
AE: tachycardia, hypotension, pulmonary edema
Only effective for 48 hours
What calcium channel blocker is commonly used as a tocolytic agent?
Nifedipine
What is the tocolytic mechanism of action of MgSO4?
Give a major contraindication (hint: calcium)
Calcium channel antagonist (probably)
Don’t use longer than 5-7 days. Hypocalcemia and fetal bone defects may occur if used longer than that
Which COX inhibitor might be used to arrest preterm labor?
Why is this generally considered a bad idea?
Indomethacin
It may decrease platelets and close the ductus arteriosus. Never use in a term pregnancy.
What is dinoprostone? Give indications and adverse effects.
What is misoprostol? Give indications and adverse effects.
Dinoprostone: PGE2 analog. Used to promote ripening and dilation of the cervix (induction of labor). AE: uterine hyperstimulation.
Misoprostol: PGE1 analog. Used for cervical ripening (labor induction) . Also used in the treatment of incomplete or missed abortion. AE: uterine hyperstimulation and rupture (rare)
What is the drug of choice for induction, augmentation, and resolution of labor?
What is its half-life?
What are its main side effects?
oxytocin - used for induction, augmentation of labor, and post-partum hemorrhage
12-15 minutes
Antidiuretic effects (structural similarity to ADH), hypotension, and reflex tachycardia
Name two drugs commonly used for the treatment of post-partum hemorrhage.
Oxytocin and Ergonovine
How is **ergonovine **used?
What is the mechanism of action of ergonovine?
What are its adverse effects?
Prevention and treatment of post-partum hemorrhage and post-abortion hemorrhage.
Produces sustained contractions of uterine smooth muscle
AE: naus/vom, increased blood pressure, decreased pain threshold
Uterine changes in pregnancy: hyperplastic or hypertrophic?
How much larger does the uterus become?
Both. Hyperplasia predominates early, hyperplasia predominates late.
Pre: 40-70 grams; Post: 1200 grams
What cell-cell interaction increases in the uterus during pregnancy?
Approximately what percentage of the maternal circulation is dedicated to the gravid uterus?
Increased gap junctions
17% of cardiac output
Are myometrial cells mainly under hormonal or nervous control?
Why are gap junctions important to the function of the gravid uterus?
Neither. They are capable of contracting spontaneously.
The myometrium needs to contract in synchrony. Gap junctions enable this.
Describe the development of the labor phenotype. Focus on the predominant hormone before and after labor phenotype development and the effect this has on uterine makeup and function.
Shift from progesterone dominance to estrogen dominance:
Progesterone dominance
- Inhibition of intracellular calcium entry
- Inhibition of calcium release from the sarcoplasmic reticulum
- Membrane hyperpolarization (potassium channels)
- Inhibits expression of contraction-associated protein genes
Estrogen dominance
- Increased gap junctions (contraction synchrony)
- Increased prostaglandin and oxytocin receptor expression in myometrium
List (4) contraction-associated-proteins (CAPs) that are upregulated in the labor phenotype
connexin-43 (gap junction protein)
oxytocin receptor
CRH receptor
COX-2
What triggers labor?
Nobody really knows for sure but (probably multifactorial)… some theories:
- fetal adrenal glad maturity (fetal signal)
- increased maternal estrogens
- increased prostaglandins
- increase in CAPs
Define labor
How many stages?
Regular contractions leading to cervical dilation over time
4 stages
Describe the first stage of labor
Divided into two parts: latent phase and active phase
Latent: contration with slow cervical dilation (early)
Active: contractions with active cervical dilation (later)
Describe the second stage of labor
Starts with completion of dilation. Ends with delivery of the fetus.
Describe the third stage of labor
Starts after delivery of the fetus. Ends with delivery of the placenta.
Most hemorrhage occurs here.
Describe the fourth stage of labor
Lasts for one hour following delivery of the placenta
Constant myometrial contraction limits blood loss
Define preterm labor
Discuss identifiable risk factors
delivery between 20-37 weeks gestation
Risks:
- Infections and periodontal disease
- Smoking
- Genetics (personal history, family history)
- Cervical shortening and decreased uterine space (multiple fetuses is a major risk)
- Low pre-pregnancy weight, ethnicity, socioeconomic disadvantage
Approximately how many weeks gestation is considered ‘viability’?
A child born at 22 weeks has approximately what chance of zero chronic morbidity?
24 weeks
0% (6% chance of survival overall)
What is the leading cause of maternal mortality?
Post-partum hemorrhage
Define post-partum hemorrhage in terms of blood loss
During what stage of (normal) labor does the majority of blood loss occur?
What causes the majority of hemorrhage during post-partum hemorrhage? How might we treat this?
>500mL blood loss after vaginal delivery
>1000mL blood loss after a cesarean delivery
Stage 3 (does staging apply during cesarean delivery?)
Stage 4: atony of the uterus leads to excessive blood loss. Rx: uterine massage (think less massage, more punching) and oxytocin/prostaglandins/ergot alkaloid. Like most problems in life, this can also be solved with drugs and violence.
Give several risk factors for post-partum hemorrhage
- precipitous labor
- large fetal weight
- multifetal gestation
- polyhydramnios prolonged labor
- retained placenta
- grand multiparity
- intrauterine infection
- uterine relaxation agents
What is the etiology of Sheehan Syndrome?
Hypovolemia from obstetrical blood loss leading to pituitary dysfunction and/or necrosis (due to hypoperfusion of the pituitary gland)
Symptoms vary and may be delayed - think of any/all signs of pituitary insufficiency
