09-Drugs for pregnancy Flashcards
What are the two main categories of drugs used in the management of uterine contractions?
oxytocics and tocolytics
What are oxytocics? What are they used for?
- promote contraction of uterus
- used for the induction or augmentation of labour and to control postpartum hemorrhage
- *augmentation = increase intensity of labour
What are tocolytics? What are they used for?
- inhibit uterine contraction; induces relaxation of the uterine muscles
- slow down labour contractions
T or F: There are medications that can stop labour contractions
FALSE; there are no drugs that can STOP labour contractions. Tocolytics can only slow down contractions
The more release of calcium from the sarcoplasmic reticulum into the intracellular space, the greater the __________ contraction
uterine
How do Gi protein coupled receptors affect Ca+ (contraction)? Provide an example of drug that activate Gi proteins
- decreased cAMP concentration
- less cAMP = less phosphorylation of Ca+ sequestering proteins
- More Ca+ build up = CONTRACTION
- Ex: Misoprostol
How do Gq protein coupled receptors affect Ca+ (contraction)?
Provide an example of drug that activates Gq proteins
- increased inositol triphosphate
- IP3 binds to the sarcoplasmic reticulum and stimulates Ca+ release
- DAG binds to Ca+ ion channels increasing influx of Ca+
- build up of Ca+ = CONTRACTION
- Ex: Ergonovine
How do Gs protein coupled receptors affect Ca+(contraction)?
Provide an example of a drug that activates Gs protein
- increased cAMP concentration
- increased Ca+ sequestering proteins
- less Ca+ available
- INHIBIT CONTRACTION
- Ex: Salbutamol
What receptors does oxytocin bind to? (what G protein is associated)
Why would oxytocin be administered?
- oxytocin (endogenous hormone) binds to receptors associated with Gq protein coupled receptor
- increases frequency and force of uterine contractions
What are the two available exogenous oxytocin drugs?
pitocin and syntocinon
What type of drug is pitocin/syntocinon? What two ways can pitocin/syntocinon be administered?
- pitocin/syntocinon are agonist drugs (sometimes called oxytocin)
- IV infusion or IM injection
Why would pitocin/syntocinon be administered by IV?
- uterine response occurs almost immediately and subsides within one hour
- you can titrate up or down
- help with induction and augmentation
Why would pitocin/syntocinon be administered by IM?
- uterine response occurs within 3-5 minutes and persists for 2-4 hrs
- post-partum hemorrhage
T or F: There will be no biological effect until oxytocin receptors are present in the myometrium
True –> Oxytocin CAN NOT be used as an abortifacient for this reason
When do oxytocin receptors appear on the myometrium?
- oxytocin receptors do not appear on myometrium until 2nd half of gestation in order to prevent preterm labour
Does the oxytocin biological effect work off of positive or negative feedback?
positive feedback
Describe the positive feedback mechanism of oxytocin
- Estrogen release from ovaries
- Stretching of the myometrium promotes the oxytocin receptors to bind to the myometrium
- Oxytocin release from fetus and mother’s posterior pituitary
- Stimulates uterus to contract
- Stimulate placenta to make prostaglandins
- Prostaglandins stimulate more vigorous contractions of the uterus
- Increase in contraction releases more oxytocin
Why do we encourage mothers to breastfeed as soon as baby is born?
- breastfeeding increases oxyotcin release = increase uterine contractions
Describe the process of administering oxytocin for the induction of labour
- administer pitosin via IV route
- dose increased every 15-60min until normal labour pattern is established
What is one adverse effect of excessive oxytocin?
- oxytocin can bind to other receptors, specifically ADH receptor and produces an antidiuretic effect (water conservation)
- could lead to pulmonary edema, heart failure, and water intoxication
What is uterine hypertonus? Why is it a concern?
- single contraction lasting longer than 2 minutes
- oxytocin infusion should be terminated if contractions are less than 2 min apart, and last longer than 90 seconds
- uterus “seizes” which can rupture the uterus
- vasoconstriction can create a hypoxic environment for the baby
Which G proteins do prostaglandin agonists activate? What are 3 of the most common prostaglandin agonists?
- prostaglandin agonists bind to Gi and Gq protein coupled prostaglandin receptors
- dinoprostone
- carboprost
- misoprostol
What is dinoprostone used for? What are the administration options?
- helps with cervical ripening, initiation of labour
- available in tablet and gel form for intravaginal administration
When would carboprost be used?
- used to control postpartum hemorrhage (in cases that are not responding to oxytocin)
What is misoprotsol used for?
- may be used for cervical ripening (in gel product),
- the control of refractory cases of postpartum hemorrhage
- as an abortifacient
- cervical ripening = thinning and effacement of cervical
- cervical ripening induces labour
What are some adverse affects of prostaglandin agonists?
- nausea, vomiting, diarrhea, headache, HTN, bronchospasm due to stimulatory effect on smooth muscle
What are the two main Ergot Alkaloids? What are they used for and how are they administered?
- ergonovine (IM)
- methylergonovine (IM, PO)
- IM administration: cause uterine contractions within 1-5 min that persist for 3 hrs (for post-partum hemorrhage)
- used only in developing countries
How do ergonovine and methylergonovine cause uterine contractions?
- they bind to Gq protein coupled prostaglandin E1 receptors and a-1 adrenoceptors
- causes contraction of smooth muscle in uterus and vasculature
Why are ergot alkaloids not used very much in Canada?
- they contract the uterus and the vasculature resulting in increased blood pressure
Should ergot alkaloids be used to induce labour?
NO! Due to the risk of uterine hypertonus, they should not be given to induce labour
What is the concern with uterine hypertonus?
- hypertonus can asphyxiate the fetus and cause uterine rupture
When should prostaglandins not be used for cervical ripening or post-partum hemorrhage?
If a client…
- has had previous C-section
- has had previous hx of uterine hypertonus
- has ruptured membranes
- has already taken another oxytocic (DO NOT COMBINE)
Oxytocin is the best for what 3 “conditions”
- post-partum hemorrhage, induction, augmentation
Ergot alkaloids should only be used for….
post-partum hemorrhage
NOT: induction or augmentation
Prostaglandins should only be used for…
post-partum hemorrhage, cervical ripening
NOT: augmentation or induction
What are tocolytic drugs?
any drug that decreases intracellular calcium levels and reduces the strength of uterine contraction
When would a tocolytic drug be used?
- preterm labour (to delay delivery by 48hrs) –> 24-34 wks
- cephalic version (not Canadian practice)
- uterine hypertonus (seizing)
- when patient is experiencing regular contractions that last longer than 45 seconds and occur 2-10 min apart
- cervix is dilated more than 2 cm and had begun to efface
Client needs to be in labour for you to administer tocolytic drugs
Why would you want to delay delivery up to 48hrs?
- administration of glucocorticoids (cortisol speeds up lung maturation; reduces strokes)
- delivery at a facility with NICU
- prolonged pregnancy when there are underlying self-limiting conditions that are unlikely to cause recurrent preterm labour (car accident –> mom needs surgery)
Tocolytic drugs should _________ be combined
NEVER
What is the purpose of glucocorticoid therapy?
- recommended for women 24-34 wks who are likely to deliver premature baby within 7 days
- steroids help speed the development of the lungs
- reduce risk of respiratory distress syndrome, bleeding in the brain, necrotizing enterocolitis, and specsis
What drug is administered for glucocorticoid therapy?
- betamethasone 12mg IM every 24hrs (two doses)
Does glucocorticoid therapy helps a fetus past 34 weeks?
No
What are prostaglandin inhibitors (NSAID)?
- indomethacin
- inhibits prostaglandin synthesis via inhibition of COX 1 and COX2 enzymes
How long do you give prostaglandin inhibitors for?
48 hrs
What are some maternal side effects of prostaglandin inhibitors?
- nausea, increased risk of post-partum hemorrhage
What are some things that need to be taken into consideration before prostagladin inhibitor is administered?
- women w/ platelet disorders (may lead to bleeding out)
- renal dysfunction
- NSAID-sensitive asthma
- PUD
What are the fetal side effects if prostaglandin inhibitors are administered after 32 weeks gestation?
- premature closure of the ductus arteriosis, causing pulmonary HTN, tricuspid regurgitation, and renal failure
What are calcium channel blockers? Example of drug
- calcium antagonist
- Nifedipine
- inhibits the action of calcium on myometrium
What are some side effects of nifedipine?
flushing, dizziness, headache, palpitations, reflex tachycardia
In what other condition can nifedipine be prescribed?
may also be used for pregnancy-induced HTN
What are Beta2 adrenergic agonists? Example of drug
- stimulate Gs protein coupled B2-adrenergic receptors
- increase intracellular cAMP via stimulation of adenylyl cyclase
- induces phosphorylation and sequestration of Ca
- ritodrine and terbutaline
Why are ritodrine and terbutaline not used very much?
- can cause tachycardia, tremors, palpitations, arrhythmias, hyperglycemia, myocardial ischemia
When is ritodrine or terbutaline used?
cephalic version
What is an oxytocin receptor antagonist? Example of drug
- inhibits the binding of oxytocin at its receptor site (on uterine and breast myoepithelial cells)
- atosiban (has few side effects)
Why isn’t atosiban used very much?
- only effective in later gestational stages
- not effective
- not available in north america
What is the order in which tocolytic drugs should be used?
- Indomethacin (prostaglandin antagonist)
- first line therapy for labour inhibition in women 24-32 wks of labour
- can have long term adverse effects when used at gestational age 32-34 wks - Nifedipine
- between 32-24 wks of gestation; recommneded for initial treatment of preterm labour
The whole reason why tocolytic drugs are administered is to relax the uterus to get glucocorticoid on board
