Pharmacy Clinic
Treatment of Heart Burn


VI-         Proton Pump Inhibitors "PPIs"

Facts about Lansoprazole

1)        Inhibition of acid release regardless primary stimuli
2)        24 - hour PH monitoring:
       at the morning or at the evening, PPI suppress acid secretion with PH  3.
3) The antibacterial activity
Antisecretory effect of PPI does not appear to correlate with serum concentrations. Some times antisecretory effect
seen when the drug is in conc. below detectable limits
-Degraded by protonation

Lansoprazole given as enteric coated capsules because of the:
1)        Acid lability
2)        Discolored
So they produce it as granules to avoid the discoloration, magnesium carbonate added as a stabilizing agent. And to
increase the stability manufactured in the form of capsule.

-Lansoprazole absorbed from the intestine and then goes to the blood stream then back to its site of action, which is
the parietal cells, in which the active forms released to do their effect.
-When Lansoprazole given with food it will stay in the stomach for long period, and exposed to acidity and then
decomposed.

-Lansoprazole by protonation in the canaliculi of the parietal cell catalyzed to produce sulfenic acid and sulfenamide,
the sulfenamide interact covalently with the sulfhydryl groups at the critical sites in the extracellular domain of the
membrane spanning H, K ATPase.

-Full inhibition occurs with two molecules of inhibitor bound per molecule of enzyme.

-Lansoprazole induces full inhibition of enzyme activity and it is permanent, secretion of acids resumes only after
insertion of new molecules of H, K ATPase into the luminal membrane.

-Lansoprazole produces only small and inconsistent changes in the volume of gastric juice and in the secretion of
pepsin and intrinsic factor and do not affect gastric motility.

-Lansoprazole has a dose related inhibition of gastric acid secretion that persists after the drug disappears from the
plasma, and this action because the irreversible inhibition of H, K ATPase enzyme.

-If the patient opens capsule and swallows the granules, the neutral pH in the mouth breakdown the
microencapsulation and the product exposed to gastric acid and degraded in the stomach.

-Not all H, K ATPase enzymes are inhibited by Lansoprazole, but it is dose dependent
-Lansoprazole produces the inhibitory effect also in small doses (no need for the loading dose)
Duodenal ulcer and reflux esophagitis lansoprazole 30mg, omeprazole 20 mg /day before meals in the morning or in
the evening, preferable in the morning, for 2 to 4 weeks or until endoscopic healing is observed.

Gastric ulcer lansoprazole 30mg, omeprazole 20 mg /day before meals in the morning or in the evening, preferable in
the morning, for 4 to 8 weeks or until endoscopic healing is observed.
The dose increased in case no response to the above dose up to 60 mg / day.
In patients not responding to H2 receptor antagonists, 30 to 60 mg / day for 8 to 12 weeks has been effective.

Zollinger Ellison syndrome the dose should be individualized, up to 120 mg / day has been given for this indication, for
elderly 30 mg /day may be used.
In case of this disease basal acid out put must be between 0 and 10 mmol / h in the hour prior to the next dose.

Missed dose — If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your
next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Safety of PPI

I.        Effect of PPI on serum gastrin and gastric mucosal cell:
Gastrin hormone secreted from G cells of gastric mucosa, pancreatic islets in fetal life.
The main action is the stimulation of gastric acid and pepsin secretion, stimulation of the growth of gastric mucosa,
stimulation of gastric motility, stimulate insulin and glucagon secretion but only after protein meal.

Gastrin release affected by:

1)        The contents of the stomach
2)        Stimulation of the nerve
3)        Presence of amino acids in the stomach
4)        Increase hormone release, increases gastric release but by the feedback of increasing acidity this response
inhibited.
Increasing level of serum gastrin for long period, in rats produce carcinoid.
Presence of acidity in the antrum suppress the feedback release of gastrin.

Serum gastrin level elevated during treatment with PPI, but were normalized 3 months after discontinuation of the
administration.
PPI increases serum gastrin level in the long treatment, but the increase is not more than 4 folds of the normal base
line.
The increase in serum gastrin is due to -ve feedback mechanism of decreasing the acidity which stimulate G cells to
release gastrin.

Contraindications of   (PPI)

Delayed-Release Capsules is contraindicated in patients with known hypersensitivity to any component of the
formulation.

Warnings

When gastric ulcer is suspected, the possibility of malignancy should be excluded before starting therapy with  * (PPI)
Delayed-Release Capsules is instituted, as treatment with this drug may alleviate symptoms and delay diagnosis of
malignancy.

Use in Pregnancy:

There are no adequate or well-controlled studies in pregnant women. Therefore, should be used during pregnancy
only if the potential benefit justifies the potential risk to the fetus. Reproductive studies conducted in pregnant rats
and rabbits at oral doses up to 300 and 30 mg/kg/day, respectively, did not disclose(show) any evidence of a
teratogenic effect.

Use in Nursing Mothers:

Because drugs are excreted in human milk,   should not be given to nursing mothers unless its use is considered
essential.

Use in Children:
Safety and effectiveness in children have not been established.

Use in Hepatically Impaired Patients:

It is recommended that the initial dosing regimen need not be altered for patients with mild or moderate liver disease,
but for patients with moderate impairment, doses higher than 30 mg per day should not be administered unless there
are compelling clinical indications.

Use in Renally Impaired Patients:

No dosage modification of PPI is required in patients with renal insufficiency.

Use in Elderly Patients:

Ulcer healing rates in elderly patients are similar to those in younger age groups.
The incidence rates of adverse events and laboratory test abnormalities are also similar to those seen in other age
groups. The initial dosing regimen need not be altered for elderly patients, but subsequent doses higher than 30 mg
per day should not be administered unless additional gastric acid suppression is necessary.

Drug Interactions:

PPI is metabolized through the cytochrome P450 system. Studies have shown that PPI does not have clinically
significant interactions with warfarin, antipyrine, indomethacin, aspirin, ibuprofen, phenytoin, prednisone, antacids or
diazepam in healthy subjects.

When PPI was administered concomitantly with theophylline, a minor increase (10%) in the clearance of theophylline
was seen, which is unlikely to be of clinical concern. Individual patients may require adjustment of their theophylline
dosage when PPI is started or stopped to ensure clinically effective blood levels.

Coadministration of PPI with sucralfate delayed absorption and reduced PPI bioavailability by approximately 30%,
however administration of sucralfate 30 minutes after PPI resulted in no significant difference in bioavailability.
Therefore, PPI should be taken at least 30 minutes prior to sucralfate.

Adverse reactions:
  • Abdominal Pain
  • Headache
  • Diarrhea
  • Nausea
  • Vomiting
  • Liver Function Test Abnormal
  • Dizziness