Hyperemesis Gravidarum

Question 1

What is the mechanism of action of cyclizine?

Answer 1

Histamine H1 receptor antagonist.

Cyclizine acts on the chemoreceptor trigger zone (CTZ) of the brain. It can be given per oral (PO), intramuscular injection (IM) or intravenous (IV). Like other antihistamine medications, the most common side effect is drowsiness. Cyclizine also has some antimuscarinic properties with less common side effects, including dry mouth, constipation and urinary retention.

Question 2

What is the mechanism of action of metaclopramide?

Answer 2

Dopamine receptor antagonist.

Metoclopramide has its dominant effect on increasing gastric emptying, thereby reducing the volume of food in the stomach and leading to less regurgitation. It also increases the tone of the lower oesophageal sphincter and has some effect on the CTZ. Rare but important side effects of metoclopramide are focal dystonias and oculogyric crisis. These are most common in women under the age of 25, so in this age group, it is sensible to use alternative antiemetics where possible.

Question 3

What is the mechanism of action of metaclopramide?

Answer 3

Dopamine receptor antagonist.

Metoclopramide has its dominant effect on increasing gastric emptying, thereby reducing the volume of food in the stomach and leading to less regurgitation. It also increases the tone of the lower oesophageal sphincter and has some effect on the CTZ. Rare but important side effects of metoclopramide are focal dystonias and oculogyric crisis. These are most common in women under the age of 25, so in this age group, it is sensible to use alternative antiemetics where possible.

Question 4

How does omeprazole act to manage nausea and vomiting in pregnancy?

Answer 4

Omeprazole inhibits the hydrogen ion (H+) active transport mechanism of the H+/K+ ATPase (proton pump), thereby reducing acid secretion by up to 90%. It is a very well-tolerated medication, with only mild side effects.

Often gastro-oesophageal reflux and the symptom of water brash can complicate hyperemesis. A proton pump inhibitor, such as omeprazole, can relieve these symptoms.

Question 5

What is the mechanism of action of ondansetron?

Answer 5

Serotonin 5-HT3 receptor antagonist.

Ondansetron is highly selective for the 5-HT3 receptors. As a result, there are few side effects associated with it, the most common being constipation and headaches. Its mechanism of action in hyperemesis is primarily on the serotonin receptors of the CTZ. In response to the ingestion of toxic substances, the small intestine releases serotonin, which activates the afferent nerve fibres of the vomiting reflex. Ondansetron also blocks these peripheral receptors, and it is thought these may play a key role in its mechanism of action in controlling vomiting following chemotherapy.

Question 6

What is the mechanism of action of prochlorperazine?

Answer 6

Dopamine receptor antagonist.

Prochlorperazine is a centrally acting dopamine receptor antagonist that primarily reduces nausea and vomiting by acting on the CTZ. It is also commonly used as a treatment of vertigo in labyrinthitis, and can also be used as an antipsychotic. Dopamine antagonists can worsen Parkinson’s symptoms and rarely can cause pseudoparkinsonism and other extrapyramidal side effects in healthy individuals. Dopamine receptor antagonists can also raise prolactin levels and rarely induce lactation by blocking the normal inhibition of dopamine on the anterior pituitary.

Question 7

What is the mechanism of action of promethazine?

Answer 7

Histamine H1 receptor antagonist.

Promethazine has a similar mechanism of action to cyclizine. It also has some anticholinergic effects and has some antagonist effect on dopamine receptors. It has similar side effects to cyclizine but is more likely to cause confusion in an elderly patient and sedation. In pregnancy, NICE also support its use as a sedative for short-term use for patients with difficulty sleeping.

Question 8

What percentage of women experience vomiting in pregnancy?

Answer 8

> 50%

Vomiting in pregnancy is common (>50% of women).

Question 9

What is the triad of symptoms that must be present to ‘diagnose’ hyperemesis gravidarum?

based on RCOG

Answer 9

• > 5% weight loss
• dehydration
• electrolyte imbalance.

Question 10

What quantification tool is used to diagnose hyperemesis gravidarum?

Answer 10

Pregnancy-Unique Quantification of
Emesis

Question 11

What PUQE score indicates hyperemesis gravidarum requiring treatment?

Answer 11

> or equal to 13

greater than or equal to 13 indicates grave hyperemesis gravidarum

Question 12

When would you admit a patient experiencing hyperemesis gravidarum?

Answer 12

If they are not tolerating fluids.

Question 13

What are the first-line drugs used to treat hyperemesis gravidarum?

Answer 13

cyclizine and promethazine

Question 14

What are the second-line drugs used to treat hyperemesis gravidarum?

Answer 14

prochlorperazine and metoclopramide

Question 15

What is the third-line used to treat hyperemesis gravidarum?

Answer 15

Ondansetron

suspected to cause orofacial malformation
including cleft lip and palate

Question 16

What are the maternal risks of hyperemesis gravidarum?

Answer 16

• liver and renal failure in severe cases.
• central pontine myelinolysis.
• Wernicke’s encephalopathy.

Hyponatraemia and rapid reversal of hyponatraemia → central pontine myelinolysis
Thiamine deficiency may lead to Wernicke’s encephalopathy.

Question 17

What are the fetal risks of hyperemesis gravidarum?

Answer 17

• fetal growth restriction
• fetal death

• FGR is theoretically possible though most fetal outcome is normal.
• Fetal death may ensue in cases with Wernicke’s encephalopathy.