Pharmacology Flashcards
Describe the cyclical pattern of myometrial activity during labor
A switch in pattern of myometrial contractility between contractures (long-lasting, low-frequency) & contractions (frequent, high-intensity, high- frequency activity)
- results in effacement & dilatation of the cervix
Parturition: Phase 1
- What occurs & how long does it take?
- Uterine contractions of increasing strength and frequency
- Cervix dilates
Time = Variable # of hours
Parturition: Phase 2
- What occurs & how long does it take?
Expulsion of fetus
Time = ~1 hour
Parturition: Phase 3
- What occurs & how long does it take?
- Expulsion of placenta
- Aftercontractions of uterus (reduces bleeding)
Time = ~ 10 min
Oxytocin:
- Where is it synthesized?
Posterior Pituitary, Ovary, Endometrium, & Placenta
Oxytocin:
- MOA?
- Stimulates uterine smooth muscle
Near end of term (due to ↑ Estrogen):
- ↑ #’s of oxytocin receptors, Na+ channels, &
gap junctions
- Stimulates myoepithelial cells → lactation
Oxytocin - effects are dependent on what? What effects does this have
Its effects are dependent on Estrogen.
- Immature uterus is resistant to effects
- ↑ Uterine sensitivity near term (~36 wks)
- ↑ #’s of oxytocin receptors, Na+ channels, &
gap junctions
Oxytocin - uses?
- Induce labor (IV)
- Augment labor – ONLY in abnormal labor (IV)
- Contract uterus after labor - ↓ bleeding (IM)
- Promote milk release – (intranasal)
What 3 things must be monitored during labor induction?
- Fetal & maternal HR
- Maternal BP
- Frequency of contractions
Oxytocin - AEs?
- Uterine hyper-stimulation (tetany)
- Anti-diuretic actions
- Vasodilation → hypotension, tachycardia
- Trauma to mother = uterine rupture
- Trauma to fetus = hypoxia
Dinoprostone - uses?
– “Cervical ripening” (softening, effacement & dilation of cervix – prep labor)
– Produce midtrimester abortion
– Vaginal gel or suppository
Dinoprostone - type of drug?
Prostaglandin (PGE2)
Carboprost - type of drug?
Prostaglandin (15-methyl PGF2)
Carbaprost - uses?
– Used to produce midtrimester abortion
– Used to ↓ postpartum bleeding
– Administered IM
In what types of situations are Prostaglandins contraindicated?
Cardiac, renal, pulmonary disease, prior uterine surgery, fetal distress, etc.
Prostaglandins - AEs?
– Nausea, vomiting, abdominal pain, diarrhea, fever & bronchoconstriction
– Hypotension, hypertension, syncope, dizziness & flushing.
– Fetal cardiac bradycardia
IM ___a___ & local administration of ___b___ may limit systemic AE’s
a) Carbaprost
b) Dinoprostone
Misoprostol - type of drug?
PGE1 analog
typically used to prevent NSAID-induced ulcers
Mifepristone - type of drug?
RU-486, a progestin receptor partial agonist
Misoprostol - uses?
- Used 48 hr after Mifepristone to produce first trimester abortion
- typically used to prevent NSAID ulcers
Mifepristone - uses?
Used in combo w/ Misoprostol to produce first trimester abortion
Misoprostol & Mifepristone - AEs?
Vomiting, diarrhea, abdominal & pelvic pain
- Vaginal bleeding common!
- Infection – sepsis.
Misoprostol & Mifepristone - off-label use?
- Cervical ripening
- Labor induction
- Induce abortion in early pregnancy
Drug class derived from fungus that grows on rye, etc.?
Ergot Alkaloids
Ergot Alkaloids - MOA?
- Agonists and/or antagonists at 5-HT, dopamine & α-adrenergic receptors
Produce strong uterine contractions:
– Low doses – clonic contractions
– High doses – tonic contractions
Ergonovine - Drug class?
Ergot Alkaloid
Methylergonovine - Drug class?
Ergot Alkaloid
Methylergonovine - uses?
↓ bleeding postpartum or after abortion
IM or IV
Ergonovine - uses?
↓ bleeding postpartum or after abortion
IM or IV
Ergonovine - AEs?
NVD, vasospasm, bowel ischemia
Methylergonovine - AEs?
NVD, vasospasm, bowel ischemia
Tocolytic Agents - what are they used for?
Objective is to inhibit premature labor (< 36 weeks) to permit further fetal development
What types of drugs may function as Tocolytic agents?
- β-2 agonists
- MgSO4 & Calcium Entry Blockers (CEB)
- COX-inhibitors (NSAIDS)
- Atosiban – Oxytocin Receptor Antagonist
- (Hydroprogesterone or Progesterone)
Via what molecular mechanisms do myometrium cells contract & relax?
Contraction:
- ↑ intracellular Ca(2+) via Ca2+/calmodulin-dependent activation of myosin light chain kinase (MLCK)
Relaxation:
- ↑ of cyclic nucleotides (cAMP & cGMP) and their activation of protein kinases, which cause phosphorylation/inactivation of MLCK
Ritodrine - what is it?
- β-2 agonist, Tocolytic
Terbutaline - MOA?
β-2 agonist (Tocolytic) that should NOT be used in pregnant women more than 48-72 hrs
Albuterol - MOA?
β-2 agonist
- Tocolytic that should NOT be used as a tocolytic
β-2 agonists - AEs?
– ↑ maternal & fetal HR – Arrhythmias – Hypokalemia – Maternal pulmonary edema – Myocardial ischemia – Skeletal muscle tremor – Hyperglycemia
Magnesium Sulfate (Mg2SO4) - MOA?
- ↓ Ca(2+) for contraction (causing relaxation)
Tocolytic agent that shouldn’t actually be used as a tocolytic
Magnesium Sulfate (MgSO4) - AEs?
– Hypermagnesemia, Hypocalcemia – Flushing, nausea, vomiting – Headaches, visual disturbances – Muscle paralysis – Cardiac electrical disturbances – Pulmonary edema
- Use is discouraged!
Nifedipine - MOA?
Calcium-channel blocker
- yet another Tocolytic drug that is not approved in the USA
Name the Tocolytic agent that is as effective as ritodrine but has fewer maternal AE’s and lower neonatal morbidity. It is also not approved in the USA for use as a tocolytic.
Nifedipine
Nifedipine - AEs?
– Dizziness, lightheadedness, nervousness – Flushing, headache, nausea – Muscle cramps or tremors – Hypotension – ↓ fetal blood supply
NSAIDS - MOA as Tocolytics?
(COX-inhibitors) inhibit uterine contractions, prolonging gestation and/or slowing labor
Combination of _____ with other tocolytics provides enhanced tocolysis
NSAIDs
NSAID use as tocolytic agent - encouraged or discouraged?
Use is discouraged because of potential adverse effects on fetal development – closure of ductus arteriosus
Atosiban - MOA?
- Synthetic peptide analog of oxytocin
- Oxytocin Receptor Antagonist
- Specific for uterine smooth muscle – (not a general smooth muscle relaxant)
• Not available in US
Atosiban - used in USA as Tocolytic?
No, it’s available in 30 countries but NOT the USA due to efficacy/safety concerns
Atosiban - AEs?
Nausea & vomiting, headache, dizziness, flushing, tachycardia, hypotension, hyperglycemia
a) What is the only FDA-approved Tocolytic drug that we learned about?
a) Hydroxyprogesterone
Hydroxyprogesterone - uses?
to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth
- Reduced # of preterm births, but no effect on infant mortality
What is the benefit on infant mortality from Hydroxyprogesterone in a woman w/ a Hx of preterm births?
Hydroxyprogesterone causes reduced # of preterm births, but has NO EFFECT on infant mortality
Hydroxyprogesterone - MOA?
Progesterone (Tocolytic)
Hydroxyprogesterone - AEs?
Nausea & vomiting, headache, dizziness, flushing, tachycardia, hypotension, diarrhea, hyperglycemia, depression
Stress urinary incontinence - Cause?
- ↑ intra-abdominal pressure
- weakened pelvic muscles
Stress urinary incontinence - Tx?
↑ sphinctor contraction – α1-adrenergic agonist (pseudoephedrine) – estrogens (?) – TCA (imipramine) – exercise, surgery, implants
What is Urge urinary incontinence?
Sudden involuntary bladder contraction
– Bladder contracts at inappropriate volume
– Also called detrusor instability, irritable bladder, spasmodic bladder, etc.
What is Stress urinary incontinence?
Involuntary loss of urine with physical activity (coughing, laughing, etc.)
- Common in women – ↑ age, pregnancy
- Cause: intra-abdominal pressure
weakened pelvic muscles
Urge urinary incontinence - Tx?
↓ detrusor instability
– Muscarinic antagonists/ antispasmodics
— Oxybutynin, Tolterodine
AEs of antimuscarinics used for Urge Incontinence?
– Dry mouth – Blurred vision – Dizziness – Constipation – Urinary retention – Sedation
Many patients may not tolerate AE’s – use adult diapers
Urge incontinence drug available as SR & patch, which may ↓ peak plasma concentrations – reducing systemic AE’s
Oxybutynin
Newer agent used for Urge Incontinence claimed to be bladder selective (M3 receptors)?
– less dry mouth
Tolterodine
Tolterodine - MOA?
M3-selective (supposedly) anticholinergic
- less AEs, like dry mouth
Tolterodine - uses?
Urge incontinence
Urinary Retention - Tx?
Relax sphincter, ↓ prostate size
– α1-selective adrenergic antagonists
– 5 α-reductase inhibitors
– PDE5-inhibitor – Tadalafil (Cialis®)
Female Sexual Dysfunction - Tx?
- Oral or vaginal estrogen used to treat vaginal atrophy, dryness & dyspareunia.
- Low dose transdermal testosterone appears to improve lack of sexual desire and arousal, but was rejected by FDA because long-term safety is unknown
- Bupropion may increase sexual desire & arousal
- Sildenafil - not likely useful, but “some patients do benefit”
- Topical alprostadil cream applied to the genitalia for sexual arousal – mixed results.
- Zestra – an OTC herbal massage oil is claimed to increase desire and arousal in one manufacturer funded study
Sildenafil - efficacy in female sexual dysfunction?
In clinical studies, Sildenafil had little or no efficacy in treating female sexual dysfunction.
But “some patients do benefit”
OTC herbal massage oil that is claimed to increase desire and arousal?
Zestra
What drug?
Topical cream applied to the genitalia for sexual arousal – mixed results.
Alprostadil
_____ may increase sexual desire & arousal in females.
Bupropion
