Anti-emetics

Question 1

Metoclopramide drug class

Met/ Domperidone Clinical indications?

Answer 1

Dopamine D2 receptor antagonist- Antiemetic

Prophylaxis and treatment of N+V esp in the context of reduced gut motility
Delayed (but not acute) chemotherapy-induced nausea and vomiting,
Radiotherapy-induced nausea and vomiting,
Prevention of postoperative nausea and vomiting

Question 2

Metoclopramide/ Domperidone MOA

Elimination?

Answer 2

D2 receptor is the main receptor in the
chemoreceptor trigger zone (CTZ: area responsible for sensing emetogenic substances e.g. drugs

Dopamine is an important neurotransmitter in the gut, where it promotes relaxation of the stomach and lower oesophageal sphincter and inhibits gastroduodenal coordination

Metaclopramide blocks the D2 receptors > has a prokinetic effect > promotes gastric emptying > contributes to anti-emetic action

Effective in N+V due to CTZ stimulation with drugs and reduced gut motility due to opiods or diabetic gastroparesis

Elimination: occurs via the kidneys

Question 3

Metoclopramide SEs

Domperidone SEs?

Answer 3

Diarrhoea
Extrapyramidal syndromes (same mechanism as antipsychotics)
Acute dystonic reaction: oculogyric crisis: dystonic, conjugate and typically upward deviation of the eyes lasting from seconds to hours

These occur because metoclopramide crosses the BBB

Same but exclude extrapyramidal side effects: domperidone does not cross the BBB

Question 4

Metoclopramide/ Domperidone contraindications/ cautions

Answer 4

Extrapyramidal side effects are more common in young adults and children so should be avoided in these populations

Contraindicated in pts with obstruction or perforation (due to prokinetic effect)

Question 5

Metoclopramide / Domperidone interactions

Answer 5

M+ antipsychotics= risk of extrapyramidal side effects is greater
M + dopaminergic agents for parkinson’s= will antagonise their effect

Question 6

Metoclopramide dose

Answer 6

N+V, palliative care: PO, 10 mg 3 times a day
By subcutaneous infusion: 30–100 mg/24 hours

Chemo induced/ radio-induced N+V : Body-weight up to 60 kg: Up to 500 micrograms/kg daily in 3 divided doses, when administered by slow intravenous injection, to be given over at least 3 minutes.

Body weight 60 kg and above: 10 mg up to 3 times a day, when administered by slow intravenous injection, to be given over at least 3 minutes

Question 7

Communication/ monitoring requirements

Answer 7

Explain to patients you are prescribing an anti-sickness medicine. Safety-net for extra-pyramidal side effects

Monitor patients for extra-pyramidal features

Metoclopramide can also be used for patients with GORD who aren’t responding to conventional treatment as it opens the LOS and promotes gastric emptying

Question 8

Cyclizine drug class?

Clinical indications?

Answer 8

Anti-emetic- histamine H1 receptor antagonist

Prophylaxis and treatment of N+V esp in the context of motion sickness or vertigo

Question 9

Cyclizine MOA ?

Elimination?

Answer 9

Histamine (H1) and acetylcholine (muscarinic)
receptors predominate in the vomiting centre and in its communication with the vestibular system

Drugs such as cyclizine block both of
these receptors. This makes them useful treatments for nausea and
vomiting in a wide range of conditions (e.g. drug-induced, postoperative, radiotherapy)

Question 10

Cyclizine side-effect

Answer 10

Drowsiness
Dry throat and mouth (due to anti-cholinergic effect)
After IV injection, may cause transient tachycardia/ palpitations

Question 11

Cyclizine contraindications/ warnings

Answer 11

Hepatic encephalopathy pts: due to their sedating effect

Prostatic hypertrophy pts: may develop urinary retention- they are susceptible to anticholinegric side effects

Question 12

Cyclizine interactions

Answer 12

Sedation may be greater when combined with other sedative drugs (e.g. benzodiazepines, opioids)

Anticholinergic effects may be more
pronounced in patients taking ipratropium or tiotropium

Question 13

Cyclizine dose

Answer 13

For Adult

150 mg, dose to be given over 24 hours: SC infusion

Question 14

Haloperidol drug class and clinical indications

Answer 14

First-gen, typical, anti-psychotic medication

Nausea and vomiting, palliative care
Also licensed for intractable hiccups

Question 15

Haloperidol MOA

Elimination?

Answer 15

This antipsychotic drug works by blocking post-synaptic dopamine D2 receptors which are found in the CTZ

Blockage here contributes to elimination of N+v

Biliary excretion via faeces and urine

Question 16

Haloperidol side effects?

Answer 16

Extrapyramidal effects
Acute dystonic reactions: back of
first-generation antipsychotics. They take several forms: acute dystonic
reactions are involuntary parkinsonian movements or muscle spasms
Akathisia is a state of inner restlessness
Neuroleptic malignant : syndrome is rare but life-threatening side effect characterised by rigidity,
confusion, autonomic dysregulation and pyrexia
Drowsiness
Hypotension
Prolonged QT interval
Erectile dysfunction
Hyperprolactinaemia symptoms: menstrual disturbance, galactorrhoea, breast pain

Question 17

Haloperidol warning

Answer 17

Start with lower doses in the elderly
Avoid in dementia: may increase the risk of death and stoke
Avoid in Parkinson’s due to extrapyramidal effects

Question 18

Haloperidol interactions

Answer 18

QT interval prolongation: amiodarone and macrolides

Question 19

Haloperidol dose in context of palliation?

Answer 19

By mouth: For Adult
Initially 1.5 mg 1–2 times a day, increased if necessary to 5–10 mg daily in divided doses.

By subcutaneous infusion: For Adult
2.5–10 mg/24 hours.

Question 20

Domperidone drug class

Answer 20

Dopamine receptor antagonist

Question 21

Domperidone dose?

Answer 21

10mg TID before meals

PO

Question 22

Dexamethasone drug class

Dex clinical indications?

Answer 22

Systemic corticosteroids (glucocorticoids)

To treat allergic or inflammatory disorders, e.g. anaphylaxis, asthma.
Suppression of autoimmune disease, e.g. inflammatory bowel
disease, inflammatory arthritis.
In the treatment of some cancers as part of chemotherapy or to
reduce tumour-associated swelling.
Hormone replacement in adrenal insufficiency or hypopituitarism

Question 23

Dexamethasone, mechanism of action

Dex elimination

Answer 23

Corticosteroids are most commonly prescribed to modify the immune response- dex exerts mainly glucocorticoid effects on the cytosolic glucocorticoid receptors

They upregulate anti-inflammatory genes
and downregulate pro-inflammatory genes (e.g. cytokines, tumour
necrosis factor alpha). Metabolic
effects include increased gluconeogenesis from increased circulating
amino and fatty acids

Metabolised by liver, excreted in urine

Question 24

Dex SEs?

Answer 24

Immunosuppression increases the risk and severity of infection and
alters the host response. Metabolic effects include diabetes mellitus
and osteoporosis. Increased catabolism causes proximal muscle
weakness, skin thinning with easy bruising and gastritis. Mood and
behavioural changes include insomnia, confusion, psychosis and
suicidal ideas. Hypertension, hypokalaemia and oedema can result from
mineralocorticoid actions.

Prolonged treatment with dex causes adrenal atorphy

Question 25

Dex contraindications/ cautions

Answer 25

Should be prescribed in caution in people with infection and in children as it can suppress growth

Question 26

Dex interactions

Answer 26

Corticosteroids increase the risk of peptic ulceration and gastrointestinal
bleeding when used with NSAIDs
Eenhance hypokalaemia in patients
taking β2-agonists, theophylline, loop or thiazide diuretics.
Efficacy
may be reduced by cytochrome P450 inducers (e.g. phenytoin,
carbamazepine, rifampicin). Corticosteroids reduce the immune
response to vaccines

Question 27

Dex Dose:?

Answer 27

In emergencies (e.g. treatment of cerebral
oedema caused by cancer or MSCC), dexamethasone is prescribed at a high
dose (e.g. 8 mg twice daily orally or IV), then weaned slowly as
symptoms improve

Question 28

Dex communication points

Answer 28

Advise pts who are taking dex in prolonged treatment to not stop suddenly as it will case an addisonian crisis and make them very unwell

In prolonged treatment, monitor for adverse effects by, for
example, measuring glucose and HbA1c or performing a dual-energy
X-ray absorptiometry (DEXA) scan to look for osteoporosis