Nausea%20-and-%20vomiting%20in%20pregnancy Treatment

• Carefully weigh the potential adverse effects, risks, benefits and cost of treatment 
• Exercise caution when using multiple antiemetic drugs simultaneously due to increased risk of adverse effects 

Pyridoxine with or without Doxylamine

• Pyridoxine can be used as monotherapy or in combination with Doxylamine
• Pyridoxine/Doxylamine combination is considered as the 1st-line of treatment based on evidence supporting its efficacy and safety
  • Improves mild to moderate nausea but does not significantly decrease vomiting
• Pyridoxine is a co-enzyme in the transamination of amino acids and plays an important role in protein metabolism
  • Pyridoxine’s mode of action in alleviating NVP is not known; no clear association has been found between pyridoxine status and NVP
• Pyridoxine has no known teratogenic effects and is less likely to cause adverse effects than antihistamine antiemetics; but evidence for its benefit in N/V in early pregnancy remains limited
  • Maximum dose is 200 mg/day in pregnant women but doses of up to 500 mg/day appear to be safe
• Doxylamine is an H₁ receptor antagonist that has been shown to be effective for NVP

Antihistamines

• Diphenhydramine, Dimenhydrinate, Hydroxyzine, Meclizine, Promethazine and Trimethobenzamide have been used to control NVP and have been shown to be more effective than placebo
• Directly inhibit the action of histamine at H₁ receptor and indirectly affect the vestibular system, thereby decreasing the stimulation of vomiting center; also promotes antiemetic action by inhibiting muscarinic receptors
• When used in therapeutic doses, these agents do not appear to be associated with an increased risk of congenital abnormalities

Phenothiazines

• Phenothiazines (eg, Chlorpromazine, Prochlorperazine) have demonstrated significant therapeutic effect for severe NVP
  • Chlorpromazine may be given in refractory cases
• Block postsynaptic mesolimbic dopamine receptors and depress the reticular activating system, thus affecting emesis
• Studies of pregnant women exposed to various phenothiazines have failed to demonstrate an increased risk of fetal malformation

Propulsive Agent

• Metoclopramide is a stimulant of upper gastrointestinal tract (GIT) motility
• Increases lower esophageal sphincter tone and decreases transit time through the upper GIT, also blocks dopamine receptors at the chemoreceptor trigger zone of CNS
• NVP is associated with gastric dysrhythmia and the use of motility agents is a common practice
• Effective and safe but used as 2nd-line agent due to risk of extrapyramidal effects
• Studies have confirmed the lack of association between Metoclopramide exposure during the 1st trimester and congenital malformation

Other Agents Considered for Refractory Cases

Corticosteroid

• Eg Methylprednisolone
• Rationale for use is based on the theory that NVP is partly due to corticotropin deficiency
• Reserved for treatment of refractory NVP or hyperemesis gravidarum
  • Only a few studies have shown some effectiveness in treating NVP
• A small but significantly increased risk of oral clefting was noted with 1st trimester exposure
  • Routine use during 1st trimester is not recommended

Serotonin (5-HT₃) Antagonist

• Ondansetron, a 5-HT₃ antagonist, has been tried for the treatment of hyperemesis gravidarum
• Evidence on its safety and efficacy for NVP remains limited
• Use may be considered in women with refractory NVP or hyperemesis gravidarum if other interventions have failed and preferably after the 1st trimester

Adjunctive Therapy

Ginger   

• Used in teas, preserves, ginger ale and pill form
• May be used in mild to moderate NVP
• Has been demonstrated to be more effective than placebo in improving nausea but did not significantly reduce emesis 
• Safety data is lacking though many cultures use ginger as a spice with amounts similar to commonly prescribed therapy 

Acid-suppressive Therapy 

• A study revealed that women with heartburn or acid reflux and NVP experienced significant improvement in symptoms after treatment with acid-reducing agents (eg antacids, H₂-receptor antagonists, proton pump inhibitors) and antiemetics

Acupuncture, Acupressure or Acustimulation

• Traditional Chinese medicine practice of stimulating the P6 acupressure point (Neiguan point) to relieve nausea
  • The point is located 3 fingerbreadths below the wrist on the volar surface
• Data on the benefit of acupressure are equivocal