Tocolytics Flashcards
Define Tocolytic Drug :
Any drug use to suppress premature labor
Most Common tocolytics
1) Beta agonist (Ritrodrine or Terbutaline ) but use has declined due to maternal side effects
2) Magnesium
Maternal (6)side effects of tocolytics: ( TRHAMM)
- Tachycardia
- Rarely Pulmonary edema
- Hyperglycemia + Hypokalemia
- Arrhythmia
- Myocardial Ischemia
- Mild hypotension
Why use caution when using ephedrine and /or Ketamine ?
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Premature labor is inhibited until ___________and ___________. What medication is given , and a minimum of _________hours is required.
Until lung mature And Sufficient surfactant is produced . Give steroids to induce production of surfactant A minimum of 24- 48 hrs is required
When Tocolytic therapy fails , what becomes necessary
Anesthesia ( for delivery )
Terbutaline : routes, rapid route, duration of effects and MOA of that duration .
Routes: PO, SQ, Inhalation
Rapidly effective by SQ and Inhalation.
Effects persists 3-6 hrs partly bc its structure w/ a RESORCINOL ring preventing COMT action.
Bc of this ring , terbutaline cannot be methylated by COMT
When are the tocolytics Terbutaline and Ritodrine used and how is Ritodrine administered ?
used to manage premature labor contractions through relaxation of myometrium via their B2 effect .
Ritodrine started IV and continued PO if tocolysis is achieved
How is ritodrone metabolized
Liver
To inactive conjugated
1/2 is excreted unchanged on the urine
Continuous use of beta agonist prayer has been associated with:
hypokalemia and tachyphylaxis
What is the mechanism of hypokalemia in beta 2 agonists ?
Insulin mediated increase in uptake of extra cellular K+
or
Increased Na+/K+/ATPase activity .
Pulmonary edema with normal PCWP have been attributed to what medications?
Terbutaline and Ritodrine
All beta adrenergic Tocolytic drugs only have B2 receptor effects . True or False ?
False .
Both B1 and B2 receptor effects
Where are B2 receptors found ? ( PALSSS)
Pancreas Adipose Tissue Liver Smooth muscle : Uterus, blood vessels , bronchi , intestine , detrusor , spleen Skeletal muscle Salivary glands
B2 Smooth muscles : name organs/locations
Uterus Blood vessels Bronchi Intestine Detrusor Spleen
Ritrodrine and Terbutaline are relatively selective B2 and stimulation of B2 in the myometrium =
Relaxation of the uterine smooth muscle
Other B2 effects such as vasodilation occur as well ( can be undesired ) + some B1 effects
Where are Beta 1 receptors located ?
Predominantly: Heart and adipose tissue .
This results in increased maternal HR and CO ( can be undesired )
MOA Beta Adrenergic Tocolytic Drugs
Agonist» Beta 2 site on outer membrane of uterine myometrail cells»_space;activate the enzyme adenyl Cyclase»_space; adenyl cyclase catalyzes conversion of ATP to cAMP» rise in intracellular concentration of cAMP = high cAMP concentration»_space;decrease in available intracellular concentration of calcium + inhibits myosin light chain kinase (MLCK)»_space; inhibition of MLCK= decrease interaction between actin and myosin = myometrial relaxation
A delay of ____minutes often results in slowing of maternal HR after administration of Tocolytic drug . However ,______, ______and ________ often require anesthesia
15 minutes ;
Advanced labor , non reassuring FH status, and abnormal presentation often require anesthesia
Theoretically, what are the effects of epidural analgesia/anesthesia after beta adrenergic agonist when compared to spinal anesthesia ? And why ?
May cause less hemodynamic compromise than spinal anesthesia
Because of slowe onset of sympathetic blockade .
However this theory remains UNPROVEN
Aggressive hydration in patients on Tocolytic therapy . Any thought ?
Avoid aggressive hydration before and during induction of anesthesia in these patients
Due to :
Risk of pulmonary edema
GA is required in a patient who has recently received beta-adrenergic tocolysis , what agents will you avoid in order to prevent exacerbation of maternal tachycardia
Atropine
Glycopyrrolate
Pancuronium
- Maternal tachycardia may make it difficult to asses volume status and depth of anesthesia
Why is it a bad idea to use Halothane on patients on tocolysis ?
Because halothane sensitizes the myocardium to catecholamine-induced-arrhythmias
It should not be used
Why should hyperventilation avoided ?
It will exacerbate the hypokalemia = hyperpolarization of the cell membrane will be potentiated
A study found what effects of terbutaline pretreatment in non-pregnant patients on Succs neuromuscular blockage ?
The terbutaline pretreatment shortened BOTH onset time and recovery time of succs- induced-NMB. Therefore :
May be pro dent to use a nerve stimulator during GA
What are the MOA of Magnesium :
- Extra cellular Mag = competitive antagonist of calcium either at the motor end plate or cell membrane» reducing calcium influx into the myocyte .
- Competes with Ca++ for low affinity calcium-binding sites on outside of the sarcoplasmic reticulum and prevents the rise in free intracellular calcium concentration.
To sum it up : - Reduce calcium influx into the myocyte
- Prevent rise in free intracellular calcium concentration
Hypermagnesemia result in
1) Abnormal neuromuscular function
2) Decrease the release of acetylcholine at the NMJ + decrease the sensitivity of the end plate to acetylcholine
True or False . Per studies , Mag Sulfate results more frequent and more severe CV side effects than beta adrenergic tocolytic agents
No !
Mag Sulfate = less severe and less frequent CV side effects than Tocolytic
Magnesium can have similar effects of beta adrenergic tocolytic agents .what side effects have been reported ?
- Chest Pain And Tightness
- Palpitations
- Nausea
- Transient hypotension
- Blurred vision
- Sedation
- Pulmonary edema
- May lessen normal compensatory responses to hemorrhage in the mother AND fetus
How is Magnesium is eliminated
Almost entirely by renal excretion
Do you give Mag in patients with abnormal renal function ?
Monitor carefully if they receive Mag sulfate
Should you D/C magnesium before administering an epidural ? Why or why not ?
Yes, D/C it because Mag will increased the likehood of hypotension through its generalized vasodilation properties
This electrolyte potentiates the action of both depolarizing and non-depolarizing muscle relaxants
Magnesium
In hypermagnesemic women, what should not be given prior to administration of Succinylcholine?
A defasiculating dose of NDMB
-a standard dose of muscle relaxant (ie Succ 1mg/kg) should be used b/c the extent of potentiation by mag sulfate is variable
During the maintenance of anesthesia, in a hypermagnesemic woman, how would you adjust muscle relaxant?
Lower doses
Parturients receiving mag sulfate often appear
Sedated
It is recommended that severely pre-eclampsia woman undergoing c/s should receive mag sulfate on what scheduling?
- at least 2 hours BEFORE procedure
- during surgery
- 12 hours postpartum
Treatment for mag toxicity
- immediate d/c of infusion
- IV admin of calcium gluconate 1gm over 10mins
Primary anesthetic considerations for women receiving magnesium sulfate are: (3)
- Interaction with NDMDs
- Effects on uterine tone
- Interaction with calcium entry -blocking agents
Magnesium sulfate increases the potency and duration of:
Mevacurium
Rocuronium
Vecuronium
Why do many practitioners avoid use of depolarizing drugs in parturient?
Concern for residual post op NMB — which can lead to respiratory complications
Why is NMB rarely required to facilitate surgical closure after c/s?
Abdominal wall distention in the term parturient
What patient populations are at a greater risk for awareness?
- emergent c/s
- CABG
This drug stimulates uterine muscle and is administered to induce labor, reduce/prevent uterine atony, and decrease hemorrhage in the postpartum period
Oxytocin
Oxytocin preparations are all naturally occurring or synthetic?
Potency is measured in?
Synthetic
Potency described in units
The synthetic preparations of oxytocin are identical to the hormone normally released from the ______ ______ but devoid of contamination by other ________ _______ & ______ found in natural proteins.
Posterior pituitary
Contamination by other polypeptide hormones and proteins found in natural proteins
The sensitivity of the uterus to oxytocin increases as
Pregnancy progresses
Oxytocin for the induction of labor:
Dilute solution of 10mU/mL
Continuous gtt beginning at 1-2mU/min. Increased 1-2mU q 15-30mins until optimal response of uterine contraction q 2-3 mins
Average dose of oxytocin to induce labor is?
8-10mU/min
Gtt up to 40mU/min may be necessary to tx uterine atony after delivery.
High and bolus doses of oxytocin are more likely to decrease ?
Via what MOA?
Decrease SBP and DBP
-via direct relaxant effect on vascular smooth muscles
With high dose oxytocin, what also accompanies the transient decrease in SBP?
Reflex tachycardia and
Increased CO
Hypotension after oxytocin administration is likely due to patients with: (2)
- Blunted compensatory reflex responses (may be produced by anesthesia)
Or
- Hypovolemia **
HD effects of second dose of oxytocin are diminished compared to initial dose
Hemabate: carboprost tromethamine
IM administration stimulates
Gravid uterus myometrial contractions similar to labor at end of full term pregnancy.
Evacuates products of conception from the uterus in most cases.
Hemabate also stimulates the smooth muscle of?
Produces?
The GIT.
Produces vomiting and diarrhea or both.
Contraindications for Hemabate administration?
- Hypersensitivity (anaphylaxis / angioedema)
- Acute PID
- Active cardiac, pulmonary, renal or hepatic disease
Hemabate adverse reactions at completion of therapy:
Transient and reversible
Most adverse reactions to hemabate are related to its
Contractile effect on smooth muscle
in studies, patients who had Hemabate, approx:
2/3 experienced this reaction:
1/3 experienced:
1/8th had:
1/14th experienced:
2/3 experienced this reaction: VOMITING & DIARRHEA
1/3 experienced: NAUSEA
1/8th had: TEMP INCREASE GREATER THAN 2DEGREES F
1/14th experienced:FLUSHING
Although rare, what are additional adverse reactions to hemabate?
- Vaso-vagal syndrome
- Faintness; light headed ness
- Pulmonary edema
- Endometritis from IUCD
- Uterine rupture
Hemabate dose:
250mcg/ml
Deep IM
Total dose of hemabate should not exceed:
2 mg’s (8 doses!)
250mcg x 8 = 2000mcg (/1000 = 2mg)
Hemabate must be refrigerated at
2 - 8 degrees Celsius
36-46*F
Methergine is a semi-synthetic ergot alkaloid used for the prevention and control of postpartum hemorrhage.
It’s available in what supply?
How may it be admin?
- 2mg/ml for IM or IV
0. 2mg tablets for PO
Methergine acts directly on
Smooth muscle of the uterus
Methergine effect on contractions?
Increases the tone, rate, and amplitude of rhythmic contractions
Methergine induces a rapid and sustained titanic uterotonic effect which shortens which stage of labor and reduces ___?
The third stage of labor
And reduces blood loss
Methergine onset:
IV:
IM:
PO:
IV : immediate
IM: 2-5 mins
PO: 5-10mins
Pharmacokinetics of IV methergine show rapid distribution from plasma to peripheral tissues within
2-3 mins or less
Methergine bioavailability after oral admin:
About 60%
No accumulation after repeat doses
Methergine IM bioavailability
Increased to 78%
Ergot alkaloids are mostly eliminated how?
The decreased bioavailability of PO admin is a result of?
Hepatic metabolism and excretion
First pass metabolism in the liver
Methergine indication and usage following delivery of the placent, routine mgmt of uterine atony, hemorrhage and subinvolution fo the uterus,
And for control of uterine hemorrhage in the second stage of labor follow the delivery of:
The ANTERIOR shoulder
Contraindications for methergine
HTN
Toxemia
Pregnancy
Hypersensitivity
Methergine should not be administered IV routine b/c of
Sudden HTN and CVA
If methergine is administered IV as an essential lifesaving measure, how should it be administered?
What else should be done?
Slowly over a minimum of 60seconds
With careful BP monitoring
Methergine administration should be exercised with caution in the presence of
Hepatic or renal impairment
Is intra-arterial or periarterial injection of methergine okay?
No. It should be avoided
Patient with CAD or RF for CAD may be more susceptible to developing this with methylergonovine-induced vasospasm
Myocardial ischemia/infarction
Inadvertent administration of what medication to newborn infants has occurred?
What s/s are seen as a result?
Methergine
S/S: respiratory depression, convulsions, cyanosis, oliguria
TX is symptomatic
Resp and CV support required in severe cases
Caution should be exercised with methergine and concurrent use of
Beta blockers
Concomitant admin of methergine and beta blockers may result in what?
Exchange the vasoconstrictive action of ergot alkaloids
Most common adverse reaction to Methergine
HTN
Some w/seizure and/or HA.
*hypotension has been reported
Dosing and indication for Methergine
IM 0.2mg/ml - after delivery of the anterior shoulder, after delivery of the placenta, or during the puerperium
May be repeated as required at intervals of 2-4hr
IV dosing of methergine
0.2mg/ml slowly over a period of no less than 60s
PO dose of methergine
0.2mg tablet 3-4 x day in puerperium for max of 1 wk
IV contrast medium reactions can be divided into:
Renal or general and the subdivided into acute and delayed
Contrast media induced renal impairment can be reducded with the use of
Low osmolarity contrast media and extracellular gold expansion
What can IV contrast medium do if extravasates from vein?
Local tissue sloughing and necrosis
ICM is typically a water soluble , iodine containing solution of two available types:
- Media that can dissociate into ions in solution
2. Media that will remain in a neutral state in solution
ICM is also formulated as high osmolarity contrast media (HOCM) which contains few dissolved particles and iodine atoms
and low osmolarity contrast media (LOCM) contains greater number of dissolved particle with iodine.
- HOCM causes fluid to shift from:
- LOCM induces
- HOCM - fluid shift from cell to the vein
2. LOCM induces less fluid shift from the cell ; it’s closely iso-osmolar
Reactions with ICM. occur with LOCM or HOCM? Most? Least?
Possible with either ICM.
Fewer with LOCM.
Some ICM reactions can occur how long after administration?
A half hour to a week after admin
ICM reaction theory is:
ICM molecules serve as an antigen and affix itself to either mast cells or basophils.
Release histamine mediators Inhibit coagulation Dilate vessels Release complement Or stimulate IgE reaction
ICM can stimulate what type of modulated immune reaction?
IgE
What is a new ICM undergoing testing?
Advantages over ICM: higher radiation absorption, yielding better images w/lower XR dose, lower allergic responses, longer imaging times
Gold nanoparticles
Preanesthetic assessment for a pt undergoing CT should include questions re:
Asthma
Allergies
Previous reactions to contrast media
What medication must be withheld b/c of risk of lactic acidosis observed in pts w/diabetic nephropathy?
Metformin
Patients with multiple medical problems (esp cardiac dx), preexisting azotemia, advanced age, being tx with nephrotoxic agents (aminoglycoside antimicrobials, gentamicin, tobramycin, streptomycin, amikcyin, kanamycin, and neomycin), NSAIDs
Are at risk for reactions to
IV contrast media
IV contrast media in pregnancy
Is contraindicated
Prevention of CM reactions can be taken by doing these interventions:
- Use smallest amount of contrast needed.
- Hyrdate to safeguard against renal failure (1hr before and 24hr after)
- Pretreat if at risk for anaphylactic
- Those with moderate or severe previous ICM reactions tx with Histamine blocker (diphenhydramine) and H2 blocker (cimetidine/ranitidine) IV or PO
Pretreatment for ICM anaphylactic reactions:
Corticosteroids such as methylprednisolone or prednisone PO or IV
The most frequent cause of anaphylactic reactions
ICM
ICM anaphylactoid reactions can be initiated with what amount of contrast medium?
As little as 1ml of contrast
Fluorescein and its metabolites are eliminated how?
Via renal elimination
Important educational component for patients who receive Fluroescein contrast agent?
The urine remains slightly fluorescent for 24-36hrs.
General caution is exercised in patient with a hx of allergy or bronchial asthma with the use of Fluorescite 10% injection to include:
An emergency tray should be available in the event of possible reaction
Indications and usage for Fluorescite injection 10%?
Diagnostic angiography/angioscopy of retina and iris vasculature
