Uterine Drugs

Question 1

Drugs that induce labor / Prevent Post-partum Hemorrhage

Answer 1

1. Oxytocin
2. Prostaglandins
3. Ergot Alkaloids

Question 2

Oxytocin

Answer 2

Use:

• inducing labor
• Controlling postpartum hemorrhage

Mech:

• Binds to receptor and alters transmembrane ion currents in myometrium muscle
• Leads to sustained contraction uterus and contraction of myoepithelial cells in mammary gland

Pharmacokinetics:
- UTERINE SENSITIVITY to oxytocin increases during GESTATION; Sensitivity greatly increases during LABOR
– # of receptors increase in uterus at 20 weeks
- T ½ = 5 min
– Adm as a nasal spray to induce lactation

Toxicities
– Maternal death (hypertensive episodes)
– UTERINE RUPTURE
– WATER INTOXICATION/HYPONATREMIA (stimulates Na+ excretion)
– Fetal death

Question 3

Prostaglandins

- Misoprostol (PGE1)

Answer 3

Biological use:

• Causes uterine stimulation throughout all of gestation
• Sensitivity highest in early phases, “RIPENS CERVIX”

Clinical Use: to induce contractions during THERAPEUTIC ABORTION
– Misoprostol used in combo with mifepristone (an anti-progestin)

Toxicities:
– Uterine Bleeding
– GI smooth muscle contraction = nausea, vomiting, diarrhea (common)

Question 4

Ergot Alkaloids

- e.g., Ergonovine

Answer 4

Use: to prevent postpartum hemorrhage and prolonged uterine contraction (after abortion), in COMBO WITH OXYTOCIN

Pharmacokinetics/Mech:

• Gravid uterus is very sensitive
• Mech (messy): Partial agonist/antagonist at ALPHA, DA and 5‐HT RECEPTORS.
• Vasoconstrictive
• Increases uterine motor activity (force and frequency)
• high doses leads to sustained contraction (specific receptor not clear)

Toxicities/Contraindications:
– Many (e.g., limb weakness/numbness)
– Elevated BP (do not use if patient is hypertensive)
– Nausea, vomiting common
- Similar to LSD (effects at high doses)

Question 5

Tocolytic Agents

Answer 5

Cause uterine relaxation to prevent pre-term labor

1. Magnesium Sulfate
2. Beta-2 Agonists

Question 6

Magnesium Sulfate

Answer 6

Mech:
- Calcium channel blockade (tricks the cell into taking Magnesium instead of Calcium), thereby decreasing freq/strength of smooth muscle cell contractions
– Uncouples excitation and contraction

Use:
- Cause uterine relaxation to prevent pre-term labor
- helps w/ PRE-ECLAMPSIA & ECLAMPSIA
– Might be neuroprotective in neonates

Toxicity:
- Hypermagnesemia

Question 7

Beta-2 Agonists

- e.g., Terbutaline

Answer 7

Mech: DECREASES INTRACELLULAR CALCIUM, thereby relaxing uterine smooth muscles

Use:
- Cause uterine relaxation to prevent pre-term labor

Admin: I.V. initially; then oral for
maintenance)

Toxicities:
- Reflex tachycardia, high doses lead to beta 1 effects
- Studies indicated these agents may prolong delivery (24‐48 h)
– Maternal complications may increase

Question 8

Anti-Progestin Mech (Generally)

Answer 8

• Bind to and inhibits Progesterone Receptors (also glucocorticoid receptor (GR))
  • When adm in mid‐luteal (secretory) phase: luteolytic

Question 9

Mifepristone

Answer 9

Use:
- In combination with PGE1 (Misoprostal) for termination of early pregnancies (Emergency contraception)
- Endometriosis (lesions are receptor‐positive)
– Excess adrenal cortisol secretion (Cushing’s Syndrome)
– Breast cancer/other cancers = PR/GR positive

Mech:
– Progesterone‐Receptor Modulator (PRM): Competitive antagonist
• Blocks uterine progesterone receptors = decidual breakdown = blastocyst
detachment (decreases hCG)
• Increases sensitivity of myometrium to prostaglandins = contractile, softens cervix
- Glucocorticoid (Androgen) receptor antagonist

Toxicities:
– Contraindicated with glucocorticoids
– Can cause SERIOUS BLEEDING in 5% of patients
– Infection (anti‐glucocorticoid effect)
– Drug interactions (CYP3A4)