Anti-emetics Flashcards
Metoclopramide drug class
Met/ Domperidone Clinical indications?
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
Metoclopramide/ Domperidone MOA
Elimination?
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
Metoclopramide SEs
Domperidone SEs?
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
Metoclopramide/ Domperidone contraindications/ cautions
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)
Metoclopramide / Domperidone interactions
M+ antipsychotics= risk of extrapyramidal side effects is greater
M + dopaminergic agents for parkinson’s= will antagonise their effect
Metoclopramide dose
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
Communication/ monitoring requirements
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
Cyclizine drug class?
Clinical indications?
Anti-emetic- histamine H1 receptor antagonist
Prophylaxis and treatment of N+V esp in the context of motion sickness or vertigo
Cyclizine MOA ?
Elimination?
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)
Cyclizine side-effect
Drowsiness
Dry throat and mouth (due to anti-cholinergic effect)
After IV injection, may cause transient tachycardia/ palpitations
Cyclizine contraindications/ warnings
Hepatic encephalopathy pts: due to their sedating effect
Prostatic hypertrophy pts: may develop urinary retention- they are susceptible to anticholinegric side effects
Cyclizine interactions
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
Cyclizine dose
For Adult
150 mg, dose to be given over 24 hours: SC infusion
Haloperidol drug class and clinical indications
First-gen, typical, anti-psychotic medication
Nausea and vomiting, palliative care
Also licensed for intractable hiccups
Haloperidol MOA
Elimination?
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
Haloperidol side effects?
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
Haloperidol warning
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
Haloperidol interactions
QT interval prolongation: amiodarone and macrolides
Haloperidol dose in context of palliation?
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.
Domperidone drug class
Dopamine receptor antagonist
Domperidone dose?
10mg TID before meals
PO
Dexamethasone drug class
Dex clinical indications?
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
Dexamethasone, mechanism of action
Dex elimination
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
Dex SEs?
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
Dex contraindications/ cautions
Should be prescribed in caution in people with infection and in children as it can suppress growth
Dex interactions
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
Dex Dose:?
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
Dex communication points
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
