Drugs acting on Uterus Flashcards
Prostaglandins used for cervical ripening?
dinoprostne and misoprostol
-they also stimulate uterine contractions
Dinoprostone?
Synthetic prep of PGE2
vaginal insert and cervical gel
AE - tachysystole, fever, chills, nausea, vomiting, diarrhea
Misoprostol?
PGE1 analog
intravaginally, orally, sublingually
AE - tachysystole, fever, chills, nausea, vomiting, diarrhea
Oxytocin?
Peptide hormone secreted by the post pituitary that elicits uterine contractions and mild ejection in lactating women.
Preferred pharmacological agent used to induce labor when cervix is favorable or ripe. Riping agent should be used before oxytocin. Body becomes more sensitive to oxytocin the later in pregnancy.
Oxytocin activates GPCR leading to PLC activation and calcium release from SR as well as VG Ca2+ channels. This elevation in calcium activates MLCK resulting in myometrial contraction.
Oxytocin also increases prostaglandin synthesis.
IV infusion - used in hypertensive emergencies to initiate delivery
AE - excessive stimulation of uterine contractions and high concentrations can activate vasopressin receptors thus causing excessive fluid retention
How do you manage postpartum hemorrhage?
Uterine massage as well as oxytocic drugs (Oxytocin, ergot alkaloids, prostaglandins)
[oxytocin is first line tx given IV or IM]
**uterine atony is the most common cause of postpartum hemorrhage
Methylergonovine?
Ergot alkaloid used to manage postpartum hemorrhage. It is a partial agonist at a-adrenergic receptors and some serotonin receptors.
AE - HTN, headache, nausea, vomiting, chest pain
Contraindications - angina pectoris, MI, pregnancy, CV accident, ischemic attack, HTN
Which prostaglandins can be used to manage postpartum hemorrhage?
Carboprost Tromethamine
- PGF2a analog (prostaglandin)
- given IM
Misoprostol
- PGE1 analog
- vaginal or oral admin
Tocolytics?
Uterine relaxants used in labor before 37 weeks to prevent preterm labor. Normal management of preterm labor includes bed rest, tocolytics and glucocorticoids. The role of tocolytics is to delay therapy and allow glucocorticoids to develop fetal lung development.
Most common tocolytics are: magnesium sulfate, indomethacin, nifedipine, Atosiban, B2-adrenoceptor agonists (there are no first choice tocolytics)
Magnesium sulfate?
Primary tocolytic agent that uncoupled excitation-contraction in myometrial cells through inhibition of cellular action potentials.
AE - monitor mother for toxic effects (resp depression or cardiac arrest) and does cross placenta so watch out for resp and motor depression in neonates
Indomethacin?
Prostaglandins stimulate uterine contractions during normal labor, therefore NSAIDs are used to delay preterm labor – indomethacin is the main NSAID for this.
AE - fetal side effects limit its use /c it crosses placenta and can cause oligohydramnios and premature closure of ductus arteriosus
Nifedipine?
Calcium channel blocker that blocks calcium entry into myometrial cells thereby inhibiting contractility. It is effective and safe and has longer prolongation compared to other tocolytics.
AE - maternal tachycardia, palpitations, flushing, headaches, dizziness, nausea
Atosiban?
Competitive antagonist at oxytocin receptors.
-not available in the US
B2-adrenoceptor agonists?
Activation of B2-adrenoceptors on myometrium activates adenylyl cyclase leading to a rise in cAMP which in turn activates PKA. PKA phosphorylates SmMLCK resulting in lower affinity of SmMLCK for the calcium-calmodulin complex. As a result SmMLCK does not phosphorylate myosin resulting in myometrial smooth muscle relaxation.
AE - palpitations, tremor, nausea, vomiting, nervousness, anxiety, chest pain, shortness of breath, hyperglycemia, hypokalameia, Hypotension
Serious AE - pulmonary edema, cardiac insufficiency, arrhythmias, MI, maternal death
BLACK BOX WARNING - risk of use for preterm labor due to increased death and serious adverse reactions
**oral terbutaline should not be used to tx or prevent preterm labor but injectable can be used but is limited to a maximum of 72 hours
