Repro Drugs Flashcards
Oxytocin
"CLASS: Oxytocic Agent MECHANISM: Stimulates uterine smooth muscle contraction (OXT / Gq receptor \>\> PLC \>\> IP3 \>\> increased Ca2+ \>\> Calmodulin \>\> phosphorylates / activates MLCK = uterine contraction), posterior pituitary hormone related to vasopressin (Pitocin), not absolutely receptor specific = some ADH receptor activity. Also made in ovary, endometrium, placenta. Effects depend on estrogen exposure: immature uterus is resistant, sensitivity increases near term ~36 weeks from increased oxytocin receptors, Na+ channels on smooth muscle, and gap junctions (when action potential propagates to smooth musce, myometrium contracts as a unit). Stimulates lactation via myoepithelial cells (milk letdown). INDICATION: Induce/augment labor (IV) if sluggish, decrease bleeding (IM) via uterine contraction post-labor, milk letdown (intranasal). AEs: With labor induction, must monitor: fetal & maternal HR, maternal BP, contraction frequency (overdose changes rhythmic contraction into tetany -- uterine hyperstimulation -- putting getus at risk of hypoxia from reduced blood flow through uterine arteries). Antidiuretic in large dose or given too rapidly = fluid retention, water intoxication, hyponatremia, heart failure, seizure, death. Vasodilation (if bolus IV) = hypotension, tachycardia. Uterine rupture (maternal trauma from strong contraction), hypoxia (fetal trauma)."
Dinoprostone
"CLASS: Oxytocic Agent MECHANISM: Prostaglandin, can produce strong uterine contraction (involved in male & female GU tracts, labor, dysmenorrhea). PGE2, used for ""cervical ripening"" (softening, effacement and dilation of cervix to prep labor), can produce midtrimester abortion. Vaginal gel or suppository. INDICATION: Cervical ripening, midtrimester abortion AEs: Contraindicated: cardiac, renal, pulmonary disease, prior uterine surgery, fetal distress. N/V/D, abdominal pain, fever, bonchoconstriction, hypotension, hypertension, syncope, dizziness, flushing, fetal cardiac bradycardia. Local administration (gel and suppository) limits systemic AE's"
Ergonovine
CLASS: Oxytocic Agent MECHANISM: Ergot alkaloid, derived from fungus grown on rye, agonist +/- antagonist at 5-HT, dopamine, a-adrenergic receptors. Produces strong uterine contractions (uncontrolled = not for labor induction). Low dose: clonic contraction (slow, infrequent), High dose: tonic contraction (contracutre). IV or IM. Decrease postpartum or post-abortion bleeding. INDICATION: Decrease postpartum or post-abortion bleeding AEs: N/V/D, vasospasm, bowel ischemia (especially local to IV or IM injection)
Carboprost
“CLASS: Oxytocic Agent MECHANISM: Prostaglandin, can produce strong uterine contraction (involved in male & female GU tracts, labor, dysmenorrhea). 15-methyl-PGF2, produces midtrimester abortion (expels fetus rapidly), decreases postpartum bleeding (post-placental expulsion contraction). IM. INDICATION: Midtrimester abortion, decrease postpartum bleeding AEs: Contraindicated: cardiac, renal, pulmonary disease, prior uterine surgery, fetal distress.
N/V/D, abdominal pain, fever, bonchoconstriction, hypotension, hypertension, syncope, dizziness, flushing, fetal cardiac bradycardia.
IM administration limits systemic AE’s”
Misoprostol
CLASS: Oxytocic Agent MECHANISM: PGE1 analog, used to prevent NSAID-induced ulcers, used 48 hours after mifepristone (“RU-486”), to produce first trimester abortion. Very similar to alprostadil (male sexual dysfunction agent, PGE1 analog) INDICATION: First trimester abortion following mifepristone administration, used off-label: intravaginally for cervical ripening and labor induction AEs: Vomiting, diarrhea, abdominal & pelvic pain, vaginal bleeding (lasting up to 2 weeks).
Mifepristone
CLASS: Abortifacient MECHANISM: Progestin receptor partial agonist, mechanism unclear: anti-glucocorticoid activity. Used prior to misoprostol to induce first trimester abortion. Methotrexate also used by some to terminate early pregnancies. INDICATION: First trimester abortion, 48 hours prior to misoprostol AEs: Uterine infections
Methylergonovine
CLASS: Oxytocic Agent MECHANISM: Ergot alkaloid, derived from fungus grown on rye, agonist +/- antagonist at 5-HT, dopamine, a-adrenergic receptors. Produces strong uterine contractions (uncontrolled = not for labor induction). Low dose: clonic contraction (slow, infrequent), High dose: tonic contraction (contracutre). IV or IM. Decrease postpartum or post-abortion bleeding. INDICATION: Decrease postpartum or post-abortion bleeding AEs: N/V/D, vasospasm, bowel ischemia (especially local to IV or IM injection)
Albuterol
CLASS: Tocolytic Agent MECHANISM: Inhibits uterine contraction in preterm labor to permit further fetal development (not for long-term use, e.g. a couple days to allow glucocorticoid administration to mother for lung maturation). Acts at b2, Gs receptor >> adenylyl cyclase >> cAMP >> PKA >> blocks MLCK phosphorylation / activity in myometrial cell = prevents uterine contraction. INDICATION: Off-label: inhibit uterine contraction (PO) AEs: Does not decrease fetal mortality (and may put mother at risk). Increased maternal & fetal HR, arrhythmia, hypokalemia (predisposes arrhythmia), maternal pulmonary edema, myocardial ischemia (if used chronically), skeletal muscle tremor (high dose acts on skeletal rather than smooth muscle cells), hyperglycemia.
Terbutaline
“CLASS: Tocolytic Agent MECHANISM: Inhibits uterine contraction in preterm labor to permit further fetal development (not for long-term use, e.g. a couple days to allow glucocorticoid administration to mother for lung maturation). Acts at b2, Gs receptor >> adenylyl cyclase >> cAMP >> PKA >> blocks MLCK phosphorylation / activity in myometrial cell = prevents uterine contraction. INDICATION: Off-label: inhibit uterine contraction (IV, SQ, PO) AEs: Does not decrease fetal mortality (and may put mother at risk). Increased maternal & fetal HR, arrhythmia, hypokalemia (predisposes arrhythmia), maternal pulmonary edema, myocardial ischemia (if used chronically), skeletal muscle tremor (high dose acts on skeletal rather than smooth muscle cells), hyperglycemia.
Should not use oral form, not for injectable use >48-72 hours. Cardiac AE’s & death.”
Nifedipine
CLASS: Tocolytic Agent MECHANISM: Calcium channel blocker, effectiveness ~ritodrine with fewer maternal AE’s and lower neonatal morbidity INDICATION: Not approved in US for preterm labor AEs: Dizziness, lightheadedness, nervousness, flushing, HA, nausea, muscle cramps, tremors, hypotension (decreased blood to placenta can lead to fetal hypoxia).
Atosiban
CLASS: Tocolytic Agent MECHANISM: Synthetic oxytocin analog, oxytocin receptor antagonist. Specific for uterine smooth muscle (**NOT general smooth muscle relaxant**). IV INDICATION: Not available in US (available in 30 countries) AEs: N/V, HA, dizziness, flushing, tachycardia, hypotension, hyperglycemia
Ritodrine
CLASS: Tocolytic Agent MECHANISM: Inhibits uterine contraction in preterm labor to permit further fetal development (not for long-term use, e.g. a couple days to allow glucocorticoid administration to mother for lung maturation). Acts at b2, Gs receptor >> adenylyl cyclase >> cAMP >> PKA >> blocks MLCK phosphorylation / activity in myometrial cell = prevents uterine contraction. [NO LONGER USED IN U.S.]. INDICATION: [WITHDRAWN] AEs:
COX Inhibitors
CLASS: Tocolytic Agent MECHANISM: Inhibits uterine contraction in preterm labor to permit further fetal development (not for long-term use, e.g. a couple days to allow glucocorticoid administration to mother for lung maturation). Blocks PGF2a formation (from arachidonic acid) >> inhibits FP / Gq receptor activation >> PLC >> IP3 >> increased Ca2+ >> calmodulin >> phosphorylates / activates MLCK in myometrial cell = prevents uterine contraction. COX-2 shown to be efficacious INDICATION: [Use is discouraged] Prolong gestation / slow labor (synergistic with other tocolytics). Following birth, may use (e.g. indomethacin) to close patent ductus arteriosus. AEs: Discouraged because of fetal development AE’s: closure of ductus arteriosus.
Pseudoephedrine
CLASS: Stress Incontinence MECHANISM: a1-agonist = Increases bladder sphincter contraction. INDICATION: For priapism and stress incontince = involuntary loss of urine with physical activity, e.g. coughing, laughing. Common in older or pregnant women. Due to increased intraabdominal pressure, weakened pelvic muscles, especially after multiple pregnancies.
AEs: May be contraindicated (?hypertension)
Oxybutynin
CLASS: Muscarinic antagonist MECHANISM: Muscarinic antagonist = decreased detrusor instability / inhibit aberrant bladder contractions. May have antispasmodic actions (?CCB-like). Immediate and sustained release formulas (PO), transdermal patch for women = decreased peak plasma concentration to reduce systemic AE’s. INDICATION: For urge incontinence = loss of urine with strong urge to void due to involuntary detrusor contraction. Empties at inappropriate volume (aka detrusor instability, irritable bladder, spasmodic bladder). Cause is unclear (?myogenic vs. neurogenic) AEs: Relatively nonselective (may be reduced with sustained release and transdermal patch formulatioins): dry mouth, blurred vision, dizziness, constipation, urinary retention, sedation. Many patients won’t tolerate AE’s >> stop taking after ~6 months in favor of adult diapers.
