|
Prescribed Medications for Treatment of GERD
Sometimes the self help measures do not provide adequate symptom relief. The
treating physician may start you on prescription strength H2-RA
Blockers or an even stronger acid reducing group of medications called Proton
Pump Inhibitors (PPI). These medications are relatively safe when taken
under the supervision of a physician, and their effect is somewhat dose dependent.,
i.e. if one tablet or capsule is not strong enough two or more will reduce
symptoms.
Prokinetic drugs like metoclopramide and cisapride are used in conjunction
with other measures in patients who are suffering from nausea or bloating in
addition to heartburn.
Cisapride (Propulsid) causes less diarrhea and extra-pyramidal side effects
than Metoclopropamide (Reglan). However, Cisapride can cause life threatening
cardiac arrhythmias, especially in patients with cardiac or renal diseases,
those with prolonged QT interval on their EKG, patients who are on anti-fungal,
anti-viral and Mycin types of antibiotics like erythromycin and clarithromycin. (Beacause
of this side-effect, Cisapride is no longer availabe in the US.)
PROTON PUMP INHIBITORS (PPI)
PPI class of drugs, i.e. Prilosec, Nexium and
Prevacid are the agents of choice in achieving symptom relief, improving
quality of life, healing, and prevention of mucosal injury in GERD patients.
As a class, these drugs are extremely safe.
PPIs have been used extensively for the treatment of GERD.
The currently available PPIs are Prilosec (omeprazole) 10, 20 and 40mg capsules,
Protonix (pantoprazole) 40mg tablet, AcipHex ( rabeprazole sodium) 20mg tablets,
Nexium (esomeprazole) 20 and 40mg capsules, and Prevacid (lansoprazole)15 and
30mg capsules. Except for AcipHex the rest of them are taken 30-60 minutes
before breakfast with a glass of water. For children and those unable to take
the capsules, the capsules can be opened, the content mixed with a tablespoonful
of applesauce and taken immediately. The most common reported adverse events
associated with PPIs include headache, diarrhea, abdominal pain, and nausea
and constipation and bloating. PPIs may interact with other medications by
affecting the absorption of drugs for which bio-availability is dependent upon
gastric pH (e.g. iron, ampicillin, and ketokonazole). PPIs may also inhibit
cytochrome P-450 metabolism to various degrees. However dose adjustment is
rarely necessary in the elderly, patients with renal insufficiency, or those
who have mild to moderate hepatic impairment.
Protonix , the currently least expensive, and in my
clinical experience the least effective of PPIs, is reported to have the least
effect on other drugs metabolized by the cytochromeP-450. Protonix is available
in IV form. Please refer to What's New section.
Dexlansoprazole/ Dexilant 60 mg is the strongest PPIs based on its dosage
per capsule.
Recommended Strategy for Using PPIs for treatment
of GERD
(Omeprazole = Prilosec, Esomeprazole = Nexium, Lansoprazole = Prevacid,
Pantoprazole = Protonix, and Rabeprazole = Aciphex):
-
Take twice daily for the
first 2-3 days of therapy.
-
First dose should be 30-60
minutes before breakfast with a glass of water.
-
Second dose, if necessary,
should be before dinner.
-
Not effective when taken
at time of heartburn.
-
Should not be administered
with H2-RA and somatostatins concurrently.
They will put arietal cells into a nonsecretory state, markedly reducing
PPI effect.
Points to Remember about PPIs (Omeprazole = Prilosec,
Esomeprazole = Nexium, Lansoprazole = Prevacid, Pantoprazole = Protonix,
and Rabeprazole = Aciphex):
-
PPIs are pro drugs, which
are activated in the acidic canalicular space of the parietal cell, therefore
they should not be co-administered with H2-RAs.
-
PPIs block final pathway
of acid release and prevent stimulated acid secretion.
-
PPIs permanently inhibit
proton pump and suppress gastric acid for several days, not taking it daily
still effective.
-
Unlike H2-RAs (Ranitidine = Zantac, Cimetidine
= Tagamet, Nizatidine = Axid, Famotidine=Pepcid), PPIs are not effected
by increasing Histamine release, so tolerance will not develop.
-
Omeprazole (Prilosec), Esomeprazole
(Nexium) and Lansoprazole (Prevacid) are metabolized by CY P450 system.
13-23% Asians are slow metabolizers (CYP2 C19 gene polymorphism).
-
PPIs are potent agents, offer
ease of dosing with favorable drug interaction and extreme safety profile.
-
GERD
patients should be managed with appropriate therapy proportional to the frequency
and severity of their symptoms.
-
Symptom severity neither
predict severity of disease, nor Erosive Esophagitis.
-
Symptom relief and mucosal
healing are closely related to the dose and potency of the acid reducing
medication and the duration of therapy.
-
In uncomplicated GERD use
the least frequent dosing that provides adequate symptom relief.
-
H. Pylori is an unsafe
biological antisecretory agent with high morbidity and must be eradicated
whenever and wherever it is discovered.
Potential Side Effects of Long-Term PPI Therapy for
Treatment of GERD
(Omeprazole = Prilosec, Esomeprazole = Nexium, Lansoprazole = Prevacid,
Pantoprazole = Protonix, and Rabeprazole = Aciphex):
-
Gastric nodules and Fundic
type Polyps
-
Parietal cell hyperplasia
-
Antral Gastritis
-
Hypergastrinemia
-
Increased risk of community
acquired pneumonia (X 2.3)
-
Increased risk of clostridium
difficile Diarrhea in hospitalized patients on PPIs
-
NO increased risk of carcinoid
and adenocarcinoma of the stomach
WHO NEEDS PROTON PUMP INHIBITORS
-
Those with endoscopically proven Erosive Esophagitis
and Peptic Stricture.
-
Those with ENT symptoms of GERD, i.e. chronic
sore throat, frequent dry cough or throat clearing, and hoarseness of voice
(reflux laryngitis), require higher doses i.e. 40 mg of Omeprazole once
or twice daily for several months.
-
Those with severe symptoms that do not respond
to less intense measures.
-
All of the above for maintenance of healing
or symptoms.
-
A cost effective
approach for patients with moderate to severe symptoms of GERD and a
relatively normal
endoscopy is
to take PPIs on demand. However, in patients with erosive esophagitis the
healing dose is the maintenance dose (see selected reference No. 9).
SYMPTOMS WHILE ON PPIs
Patients who develop symptoms several hours after taking a PPI, require one
of several therapeutic approaches depending upon their symptoms.
If they develop heartburn while on PPIs, an adjustment
of the PPI dose (increasing strength or b.i.d dosing), or using a PPI with longer
half-life may be necessary. Most PPIs keep intra-gastric pH above 4 for about
10-12 hours except for esomeprazole (Nexium 40 mg capsule) that keeps pH above
4 for more than 16 hours. Occasionally
supplementation with H2-RA, i.e. over the counter Cimetidine or Ranitidine,
at bedtime may be all that is needed. 70% of normal subjects taking PPIs twice
daily have periods of gastric pH less than 4 for 60 minutes or longer during
the night.
This phenomenon, which is of potential clinical importance when accompanied by
reflux of acid into the esophagus is infrequent in normal subjects but it may
be seen in up to 50% of patients with Barrett’s esophagus and scleroderma. In
GERD patients with nocturnal acid breakthrough we add a bedtime H2-RA
to twice-a-day PPI or switch to esomeprazole
40 mg once or twice daily. If patient complains about nausea, bloating
or early satiety, a prokinetic agent will be the added drug of choice. If you
have increased the PPI dose and have added metoclopropamide and the patient still
complains about heartburn, burping or regurgitation, these symptoms may be due
to the bile reflux - as PPIs do not eliminate bile reflux. In these situation
antacids may be helpful in order to neutralize bile acids.
Occasional patients suffer from visceral hypersensitivity syndrome plus
GERD. Their symptoms fail to respond adequately to the above treatment
modalities. These rare patients may benefit from the additional prescription
of low dose tricyclic antidepressants like amitriptyline 10-50 mg daily.
Tricyclic antidepressants can help more than two-thirds of patients with
functional esophageal complaints resistant to antireflux therapy.
|