Download Gastroparesis

NOVEMBER 2013
G
GASTROPARESIS
astroparesis is a condition characterised by delayed
gastric emptying. It is often seen in people with longstanding diabetes mellitus (diabetic gastroparesis),
commonly with other evidence of autonomic neuropathy.
Coexisting anxiety and depression increase the prevalence
of gastrointestinal symptoms in people with diabetes.
Other conditions associated with gastroparesis include
hypothyroidism, chronic kidney disease, reflux oesophagitis,
Parkinson’s disease, stroke, multiple sclerosis, scleroderma,
dermatomyositis, polymyositis, myotonic dystrophy,
Crohn’s disease and functional bowel disorders. Some
people report a sudden onset of symptoms of gastroparesis
after an acute viral illness. Gastroparesis may also occur
after surgery.
Signs and symptoms
Symptoms of gastroparesis include:
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Nausea
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Vomiting
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Early satiety
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Postprandial fullness
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Loss of appetite
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Bloating
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Upper abdominal pain
Around 10% of people with diabetes will have symptoms of
gastroparesis. This is largely due to diabetic neuropathy in the
stomach. They may also show postprandial hypoglycaemia
or deterioration in diabetic control. Uncontrolled blood
glucose levels may aggravate symptoms of gastroparesis
and delay gastric emptying.
Pain occurs in about 20% of patients with gastroparesis and
impairs quality of life.
Medication-related causes
A number of medications can delay gastric emptying
including opioids (morphine, oxycodone, tramadol),
anticholinergic agents, calcium channel blockers, clonidine
(Catapres) and glucagon like peptide-1 (GLP-1) agents
used in diabetes.
GLP-1 analogues or incretins include exenatide (Byetta)
and liraglutide (Victoza). This class of medications for the
© Manrex Pty Ltd (ABN: 63 074 388 088) t/as Webstercare - 2013
treatment of type 2 diabetes increases glucose-dependent
insulin secretion, and suppresses inappropriate glucagon
secretion. The delay gastric emptying slows glucose
absorption, and decreases appetite. Another new class of
medications for type 2 diabetes, DPP-4 inhibitors or gliptins,
do not delay gastric emptying. This includes linagliptin
(Trajenta), saxagliptin (Onglyza), sitagliptin (Januvia) and
vildagliptin (Galvus).
Management
Management of gastroparesis should include assessment
and correction of nutritional state, relief of symptoms,
improvement of gastric emptying and, in diabetes, control
of blood glucose levels.
Nutrition and hydration
Frequent small volume nutrient meals that are low in fat
and soluble fibre are recommended. Hard-to-digest foods
like apples with their skin on, or high-fibre foods like
oranges and broccoli should be avoided. Liquids may be
easier to digest.
For residents unable to tolerate solid food, the next step
is to trial homogenised or liquid nutrient meals. For those
with severe disease unable to tolerate oral intake, enteral
alimentation (nasojejunal feeding) and parenteral nutrition
are options.
Medications
Drug treatment of gastroparesis includes the use of
prokinetic and antiemetic medications.
Prokinetic agents include
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domperidone (Motilium) 10 to 20 mg orally, 3 to 4
times daily before meals
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metoclopramide (Maxolon) 5 to 10 mg orally, 3 to
4 times daily before meals
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erythromycin 250mg orally, 3 to 4 times a day 30
minutes before meals
Prokinetic drugs can potentially improve glycaemic control
in diabetic gastroparesis by allowing a more predictable
absorption of nutrients. Combinations of prokinetic drugs
could be more effective than a single agent.
GASTROPARESIS
Domperidone
Domperidone is considered first-line therapy for the
treatment of gastroparesis. It has equal efficacy to
metoclopramide, but with lower side effects. The main
benefit is seen with a reduction in nausea and vomiting.
Domperidone does not cause central side effects such as
confusion, sedation and movement disorders, as it does
not cross the blood brain barrier.
A TGA alert in December 2012 highlighted concerns about
an increased risk of serious ventricular arrhythmias or
sudden cardiac death with domperidone. This is especially
evident in people older than 60 years of age and with
higher doses (daily doses greater than 30mg daily). Signs
and symptoms of abnormal heart rate or rhythm include
dizziness, palpitations, syncope and seizures.
Domperidone should not be administered with
ketoconazole, erythromycin or other potent CYP3A4
inhibitors which prolong QTc interval such as fluconazole,
voriconazole, clarithromycin and amiodarone. Itraconazole
and verapamil can also significantly increase the blood
levels of domperidone.
Domperidone is the preferred prokinetic agent in people
with Parkinson’s disease.
Metoclopramide
Erythromycin also has many drug-drug interactions and can
cause QT prolongation, increasing the risk of arrhythmias.
Others
Other medications used off-label include most antiemetic
drugs (e.g. prochlorperazine) and antihistamines (e.g.
promethazine). Ondansetron (Zofran) is no more effective
than metoclopramide and promethazine (Phenergan).
Tricyclic antidepressants (TCAs) in low doses can be
considered for nausea and vomiting in gastroparesis
not controlled by first-line therapies. TCAs with strong
anticholinergic properties such as amitriptyline (Endep)
should be avoided, and nortriptyline (Allegron) is
the preferred choice. A single report has shown that
mirtazapine (Avanza, Remeron, Milivin) is effective.
Pain relief is sometimes required. Preferred agents are lowdose tricyclic antidepressants, duloxetine (Cymbalta) and
pregabalin (Lyrica). NSAIDs should be avoided because
of the potential to worsen kidney function in people with
diabetes. Tramadol and opioids should also be avoided as
they reduce gastric motility.
Other treatments
Gastric electrical stimulation may control symptoms
of gastroparesis. Some benefit may be obtained with
acupuncture and pyloric botulinum toxin injection.
Metoclopramide is also considered first-line therapy for the
treatment of gastroparesis, although for no longer than 12
weeks. Tardive dyskinesia affects mainly older women after
one and a half to two years of therapy. Most common side
effects include acute dystonias, so metoclopramide should
be stopped if involuntary movements occur. As prolonged
reactions are more common in older people, the dose
should be commenced at 5mg three times daily before
meals.
Summary
Many drug-drug
metoclopramide.
References
Am J Gastroenterol 2013;108:18-37.
Curr Opin Gastroenterol 2012;28(6):621-8.
Australian Prescriber 2012;3(6):199.
Therapeutic Guidelines 2013.
interactions
can
occur
with
Erythromycin
The antibiotic erythromycin also has prokinetic properties
when administered IV or orally. IV injection is usually
reserved by acute conditions. Erythromycin stimulates
gastrointestinal contractions and results in increased GI
motility.
Tachyphylaxis develops rapidly during chronic oral use.
The clinical response drops after 4 weeks of oral therapy,
however some may continue to experience benefit. It may
make upper gastrointestinal symptoms worse, especially
at higher doses. An added benefit to erythromycin is its
availability in a liquid form, which may be more effective
than a tablet.
© Manrex Pty Ltd (ABN: 63 074 388 088) t/as Webstercare - 2013
Gastroparesis may cause severe symptoms and result
in nutritional deficiencies, impaired glucose control and
poor quality of life. Management is usually tailored to
the severity of the condition. Mild gastroparesis may be
controlled with lifestyle and dietary modifications. The
choice of prokinetic agents in more troublesome forms
of the condition is often guided by the potential for drug
interactions and the predominant symptom.