1

What are the causes of nausea?
Meds and toxic substances
Labyrinthitis (inner ear infection)
Vestibular disorders
Motion sickness
Gut irritation
Metabolic disturbances
Bowel obstruction
Gastroparesis anxiety
anticipatory N/V"
Higher stimuli (sights, smells and emotions)
What causes nausea and vomting?
Nausea and vomting occurs when the vomiting centre
inside the brain is activated by input from the
chemoreceptor trigger zone (CTZ).
The chemoreceptor trigger zone is located in the
medulla oblongata of the brainstem and contains
dopamine, serotonin, histamine and muscarinic
receptors
How do antiemetics work?
Antagonising receptors in the CTZ
State the types of antiemetics
*Dopamine agonists*
Metoclopromide
Domperidone (drug of choice in Parkinson's disease)
*Prochlorperazine (as buccal tablet in migraine, post-
operative)
*Perphenazine, trifluoperazine, chlorpromazine (post-
operative)
*Haloperidol, Levopromazine (palliative care)
Droperidol (post-operative)
*Antipsychotics
*Anthistamines*
For vertigo & motion sickness: Cinnarizine,
cyclizine, promethazine teoclate (preferred if sedative
effect required)
*Antimuscarinics*
Hyoscine hydrobromide (most effective in motion
sickness)
*5HT3 antagonists*
For chemotherapy or PONV:
Granisetron, ondansetron, palonosetron
*Others*
Dexamethasone (cancer chemotherapy, post
operative)
Nabilone (synthetic cannabinoid, used in
chemotherapy unresponsive to other anti-emetics)
Aprepitant fosaprepitant rolapitant (chemotherapy.
Given with dexamethasone and 5HT3)
Which antipsychotic antiemetics are the most
sedating?
Levomepromazine and chlorpromazine
Which drugs can cause severe acute dystonic
reactions, especially in children?
Group 3 phenothiazines antipsychotics-antiemetics:
Perphenazine, trifluoperazine, prochlorperazine
How is nausea in pregnancy treated?
1st trimester: mild - no drug treatment required
Severe vomiting - short term antihistamine e.g. 1.
promethazine
Prochlorperazine, metoclopramide
If symptoms do not settle after 24-38hrs seek
specialist options
What is hyperemesis gravidarum?
Excessive vomiting during pregnancy
How is hyperemesis agravidarum treated?
Regular antiemetics
IV fluids and electrolyte replacement
Sometimes supplements are needed e.g. thiamine to
reduce the risk of wernickes encephalopathy
What are the risk factors for PONV?
Anaesthetic used, type and duration of surgery,
females, non-smokers, previous history, motion
sickness, opioid use
What is the treatment for post operative nausea and
vomiting?
Antiemetic prevention: 5HT3 receptor antagonists,
droperidol, dexamethasone, phenothiazine,
antipsychotics e.g. prochlorperazine and
antihistamine e.g. cyclizine
High risk of PONV or if PONV poses danger:
Combination of 2 or more antiemetics with from
different drug classes
What is the mechanism of action of metoclopromide?
Antagonises D2 receptors in chemoreceptor trigger
zone. Also acts directly on the gut to promote gastric
emptying; pro kinetic effect.
What is the indication for use of metoclopramide?
Prevention of nausea and vomiting:
Post-operation, radiotherapy-induced, delay
chemotherapy
Symptomatic treatment of nausea and vomting:
e.g. acute migraine, also used to improve absorption
of oral analgesics

What are the restrictions associated with use of
metoclopramide?
Maximum use 5 days 10mg TDS, (max
500mcg/kg/day)
18+
Only for the treatment of postoperative nausea and
vomiting, radio-therapy induced nausea and vomiting,
delayed (but not acute) chemotherapy-induced
nausea and vomiting, and symptomatic treatment of
nausea and vomiting, including that associated with
migraine (where it may also be used to improve
absorption of oral analgesics)
IV bolus doses should be administered slowly over at
least 3 minutes
All liquid formulations should be given via a syringe to
ensure dose accuracy
This advice does not apply to unlicensed uses of
metoclopramide e.g. palliative care
How does metoclopramide improve absorption of oral
analgesics during a migraine attack?
The small intestines are where drugs are primarily
absorbed into systemic circulation
During migraines gastric emptying in the small
intestine is delayed
Slows the rate of absorption of oral analgesics and
explains why they may not be as effective during a
migraine attack
The use of a pro kinetic drug e.g. metoclopramide
increases gastric emptying and improves absorption
of oral analgesics
What are the side effects of metoclopramide?
Risk of neurological adverse effects - restricted dose
and duration of use
Acute dystonic reactions
> Facial and skeletal muscle spasms and oculogyric
crises
> More common in young, especially girl and young
women and very old
> Procyclidine (anti-parkinsonian drug) aborts dystonic
attacks
What are the interactions with metoclopramide?
Antipsychotics: increased extrapyramidal side effects
Parkinson's disease: exacerbates condition
What is the mechanism of action of domperidone?
Antagonises D2 receptors in chemoreceptor trigger
zone. Also acts directly on gut to promote gastric
emptying; pro kinetic effect.
Does not cross the BBB therefore does not cause
EPSE/ or other central effects such as sedation
2
What is the indication for use of domperidone?
Symptomatic relief of nausea and vomiting
Choice antiemetic in Parkinson's disease;
domperidone does not cause extrapyramadial side
effect
What are the restrictions associated with use of
domperidone?
For symptomatic relief of nausea and vomitting
Lowest effective dose for shortest possible duration
(Usually max 1 week)
Recommended dose for Adult/12+ and over 35kg:
10mg up to TDS
Children under 35kg: 250mcg/kg up to TDS
Oral liquid formulations should be given via syringe to
ensure dose accuracy
This advise does not apply to unlicensed uses of
domperidone e.g. palliative care
What are the side effects of domperidone?
Risk of cardiac side effects (e.g. QT prolongation,
ventricular arrhythmias, sudden death) therefore
MHRA has restricted indication, new
contraindications, reduced dose and duration
> Report signs of arrhythmias: syncope, palpitations
What are the contra-indications for use of
domperidone?
Impaired cardiac conduction (or possible impaired
cardiac conduction), cardiac disease, severe liver
impairment, administered concomitantly with drugs
that prolong the QT interval or potent CYP3A4
inhibitors
(Domperidone is heavily metabolised by the liver so in
liver impairment less would be metabolised, leading
to an increased risk of QT prolongation)
What are the interactions for use of domperidone?
Potent CYP3A4 inhibitor which will prevent
domperidone metabolism and lead to increasing
concentrations and higher risk of QT prolongation e.g.
amiodarone, ketoconazole, erthromycin
Drugs causing QT prolongation e.g. amiodarone, SSRIs,
quinolone
What is mechanism of action of 5-HT3 receptor
antagonists?
Block 5-HT3 receptors in the chemoreceptor trigger
zone and GI tract. 5-HT is a key neurotransmitter
released by the gut in response to emetogenic stimuli
State examples of 5HT3 receptor antagonists
Granisetron
Ondansetron
Palonosetron
 3

What is the indication for use of 5HT-3 receptors? dopamine)

Granisetron and ondansetron for symptomatic relief Ergot derived, fibrotic reactions - NOT RECOMMENED:
of: Bromocriptine
Post-operative nausea vomiting Cabergoline
Chemotherapy-induced nausea vomiting Pergolide
Palonosetron: prevention of N&V associated with Non-ergot derived:
moderately or highly emetogenic cytotoxic Pramipexole
chemotherapy) Ropinirole
They are not useful in vestibular causes of vomiting Rotigotine
e.g. motion sickness because serotonin is not in Amantadine (weak dopamine agonist)
communication between vestibular system and Apomorphine (Advanced disease for unpredictable
vomiting centre "off periods")
MAO-B INHIBITORS (prevents degradation of
What are the side effects of 5HT3 receptor dopamine)
antagonists? Selegiline (drugs and driving - metabolised to
QT interval prolongation amphetamine)
Rasagiline
What are the interactions for 5HT3 receptor COMT INHIBITORS (prevents degradation of
antagonists? dopamine)
Increased risk of tornado de pointes with Used as an adjust to levodopa for end of dose motor
hypOkalaemia fluctuations
> Loop/thiazide diuretics, corticosteroid, beta-agonists Entacapone (colours urine)
e.g. salbutamol, theophylline, stimulant laxatives Tolcapone (hepatotoxic)
abuse amphoteracin B
Increased risk of QT interval prolongation: What is the treatment for Parkinson's disease?
Amiodarone, clarithromycin, quinine, sumatriptan, If motor symptoms decrease quality of life
lithium, antipsychotic 1: Levodopa (with benserazide/carbidopa)
Serotonin syndrome: 5HT1a agonists e.g. sumatriptan, If motor symptoms do not affect quality of life
MAOIs, SSRIs Levodopa (with carbidopa/benserazide)
Non-ergot derived dopamine receptor agonists
What is Parkinson's disease? MAO-B inhibitors
Movement disorder caused by the death of cells that Adjuvant therapy
generate dopamine in the basal ganglia and Dyskinesia & motor fluctuations with levodopa
substantial nigra (nigrostriatal pathway) Non-ergot derived dopamine receptor agonists
What are the symptoms of Parkinson's disease? MAO-B inhibitors
Motor symptoms: COMT inhibitors
Hypokinesia Ergot derived dopamine receptor agonist if
Bradykinesia inadequate response with non-ergot derived
Rigidity dopamine receptor agonists
Resting tremor Amantadine if dyskinesia not adequately managed by
Postural instability modifying therapy
Non-motor symptoms: Advanced Parkinson's disease:
Dementia > Apomorphine (SC intermittent injections/continuous
Depression infusion) for refractory motor fluctuations "OFF"
Sleep disturbances episodes
Speech and language change > Levodopa-carbidopa intestinal gel for advanced levodopa-
Swallowing problems responsive Parkinson's disease with severe motor
Weight loss fluctuations, hyperkinesia or dyskinesia)
> Deep brain stimulation only if symptoms are not
adequately controlled with the best drug treatment
State the dopaminergic drugs
Physiotherapy if patient has balance and motor function
LEVODOPA (dopamine precursor) difficulties
Co-beneldopa (levodopa + benserazide) SALT if patient had communication, swallowing difficulties,
Co-careldopa (levodopa + carbidopa) saliva problems
> Associated with more motor complications Occupational therapy if patient has problems with their day
DOPAMINE RECEPTOR AGONIST (mimics action of to days activities

What is levodopa?
The amino acid precursor of dopamine and acts by
replenishing depleted dopamine levels in the brain
> Used for 1st line treatment in Parkinson's disease as
overall improvement in motor performance is more
noticeable with levodopa than with dopamine-
receptor agonists
Name the peripheral dopa-decarboxylase inhibitors
and why are they given with levodopa?
Carbidopa and benserazide - they are given with
levodopa to prevent its breakdown to dopamine in
the periphery. Once levodopa is broken down to
dopamine in the periphery it cannot enter the BBB as
it is too solubl. Levodopa enters the BBB through a
transporter. Also decreases side effects of nausea,
vomiting and cardiovascular effects and a lower dose
of carbidopa is required for therapeutic effect
Why is levodopa taken at specific times of the day?
To avoid "off" periods
What are the side effects of levodopa?
1. Impulse control disorders
e.g. compulsive gambling, hyper sexuality, binge
eating, obsessive shopping
2. Excessive sleepiness and sudden onset of sleep
> Warning: driving or operating machinery
3. Motor complications
Dyskinesia: involuntary muscle movements
Response fluctuation: large variations with "ON"
period = normal function and "OFF" period =
weakness and restricted mobility
4. End of dose deterioration with shorter length of
benefit (wearing off)
> Modified-release preparations may help
Name examples of dopamine receptor agonists
Non-ergot derived:
Pramipexole
Ropinirole
Rotigotine
Ergot-derived:
Bromocriptine
Carbergoline
Pergolide
Apomorphine
Amantadine
How do dopamine receptor agonists work?
(Parkinson's meds)
Direct action on dopamine D2 receptors in striatum
4
What is the indication for dopamine receptor
agonists?
Non-ergot derived dopamine receptor agonists are
one of the first-line option in patients with motor
symptoms that do not affect quality of life OR as an
adjunct to levodopa
What are the side effects of dopamine receptor
agonists?
Associated with more hallucinations, excessive
sleepiness and impulse control disorders than with
levodopa
Psychotic symptoms e.g. hallucinations, delusions
Can cause hypotensive reactions in the first few days
> Warning: driving or operating machinery, advise
patient to take at night
Ergot derived:
Fibrotic reactions
> Pulmonary (dyspnoea, persistent cough)
> Retroperitoneal (abdominal pain and tenderness)
> Pericardial (cardiac failure)
Name examples of MAOB inhibitors
Rasagiline
Selegiline (metabolises to amfetamine; driving
offence)
What is the mechanism of actions of MAOB
inhibitors?
Inhibits monoamine oxidase B enzymes which are
responsible for the breakdown of monoamines; e.g
dopamine
What is the indication for MAOB inhibitors?
Used alone in Parkinson's disease in patients with
motor symptoms that do not affect quality of life OR
as an adjunct to levodopa
What are the side effects of MAOB inhibitors?
Hypertensive crises
What are the interactions of MAOB inhibitors?
Hypertensive crises can occur with sympathomimetics
(drugs that increase blood pressure);
pseudoephedrine, phenylephrine, xylometazoline,
oxymetazoline, adrenaline, noradrenaline,
methylphenidate, amphetamines, B2 agonists (OTC
interactions: nasal decongestants)
Name examples of COMT inhibitors
Entacapone
 5

What is the mechanism of action of COMT inhibitors? How are non-motor symptoms of Parkinson's disease
Prevents the peripheral breakdown of levodopa, by managed?
inhibiting catechol-O-methyltransferase, allowing 1. Dementia
more levodopa to reach the brain. 2. Depression
Catechol-O-methyltransferase is one of the enzymes 3. Psychotic symptoms
that degrade catecholamines, dopamine, adrenaline 1. Reminence therapy, rivastigmine
and noradrenaline 2. CBT, SSRI
3. Review Parkinson's meds, atypical antipsychotics if
What is the indication for use of COMT inhibitors? needed
Used as an adjunct to levodopa

What are the side effects of COMT inhibitors?

Entacapone: colours urine reddish-brown
Tolcapone: hepatotoxicity
> Report signs of liver toxicity e.g. anorexia, nausea,
vomiting, abdominal pain, dark urine, pruritus

What are the interactions of COMT inhibitors?

Increased cardiovascular effects (sympathomimetic
effects)
Adrenaline, noradrenaline, MAOIs e.g.
tranycypromine (catecholamines)

What are the side effects associated with abrupt

withdrawal of antiparkinson meds?
Acute kinesia
Neuroleptic malignant syndrome

What are the DVLA requirements for Parkinson's

disease patient?
Notify DVLA and car insurer

What are the side effects of apomorphine?

Nausea, vomiting: Start domperidone two days before
apomorphine treatment and discontinue ASAP (both
cause QT prolongation = serious risk of arrhythmias )

QT interval prolongation, arrhythmias, postural

hypotension, hallucination, pronounced sleepiness

What are the monitoring requirements for

apomorphine?
ECG

What are the interactions for apomorphine?

Drugs that prolong the QT interval:
Macrolides, amiodarone, antipsychotics,

What are the options for treating nausea and

vomitting in Parkinson's disease patients?
Domperidone
DO NOT give metoclopramide - causes acute dystonia
and antagonises the effect of antiparkinsons meds