LUBIPROSTONE AND CONSTIPATION

Constipation is very common problem and has a great impact on the quality of life. Mostly with constipation, people go with life style modification, increase fluid intake, exercise and OTC medications like psyllium husk which improve the symptoms of problem. However, some patients have chronic constipation and persistent symptoms and require the prescription medicines. There are three types of prescription medication used for chronic constipation. Among them, lubiprostone is newer one. It is approved by FDA in 2006 and in 2014 in United Kingdom and in 2015 in Canada. FDA approved it, for IBS-C in 2008 and for OIC in chronic non-cancerous pain in 2013. It is approved for both men and women aged 18 years or over.

WHAT IS LUBIPROSTONE?

LUBIPROSTONE is an oral laxative which is selective chloride channel activator CCI-2 used in chronic constipation. Its chemical name is difluoropentyl-2-hydroxy-6 oxo octa hydro cyclo penta heptanoic acid. It is bicyclic fatty acid derivative of prostaglandinE1and has almost no effect on prostaglandin receptors of GIT and on smooth muscle of GIT. Its act locally so that why has a very quick onset of action.
INDICATION
It is available through the prescription only.
It has following indications,
• OIC (opioid induce constipation with chronic non cancer pain). Opioid analgesic is used to treat neuropathic pain or pain associated after trauma. Opioid analgesic after binding to peripheral opioid receptors of the gut causing the absorption of electrolytes particularly chloride which in turn reduces the volume of small intestine and ultimately decrease gut motility which results in constipation.
• IBS-C (irritable bowel syndrome is very common chronic gastrointestinal disorder which is characterized by altered bowel movements habits such as diarrhea or constipation with abdominal discomfort and pain. LUBIPROSTONE is used in IBS with constipation that is IBS-C).
• Chronic Idiopathic constipation (constipation without any reason. Constipation which is not caused by disease or medication and lasts for at least 3 months or longer)

DOSAGE FORM AND STRENGTH

It is available as liquid filled gelatin capsule and in 24 mcg and 8 mcg strength.

MECHANISM OF ACTION

There are approximately 9 chloride channels which are distributed to all types of cells in the body. They are considered as pore forming proteins (protein which interact with cellular membrane and cause perforation of cell membrane and forms pore). Through the chloride channels or the pores transportation of chloride ion take place which in turn show an important role in fluid transport across the cell membrane and has a critical role in maintaining the cellular volume and cellular PH.
Chloride-2 channels are locally and specifically activated by LUBIPROSTONE which are widely distributed in stomach, small intestine and colon. These channels after activation allow only transportation of chloride ion across cell membrane and not allowed transportation of larger anion or cations. Efflux of chloride ion into intestine increase fluid secretion which in turn soften the stool and increase GI motility and decreased GI transit time and show spontaneous bowel movement with in one day and relief bloating and abdominal discomfort with in one week.
Before arrival of lubiprostone, unresponsive patients to laxative treatment and with serious illness like Alzheimer disease, COPD and cancer methyl naltrexone bromide an opioid receptors antagonist was given subcutaneously.

DOSING

24 mcg twice daily is recommended for OIC and in chronic Idiopathic constipation with food and water to minimize risk of vomiting. 8mcg twice daily in IBS-C. Care must be taken with hepatic dysfunction and dose adjustment is required. Dose are also adjusted depending upon severity of adverse effects.

PHARMACOKINETICS

When lubiprostone is taken, it is metabolized locally through Carbonyl reductase via oxidation / reduction process with in stomach and jejunum. It is not metabolized by liver through cytochrome P450 pathway and has minimum drug interactions. Peak plasma concentration of lubiprostone is not observed in blood however, its active metabolite M3 which is approximately 10% of totally administered drug is present in the blood and bound to protein 94%which has half-life of 0.9 to 1.4 hours. It is eliminated as 60% in urine and 30 % in faces.

PRECAUTION

• Lubiprostone should be taken at around same time each day. Don’t take more or less dose of lubiprostone. Take according to your physician advice.
• Discuss your medical history with your physician if you have diarrhea, obstruction or liver problems or about your prescription or nonprescription medicines or any herbal products which you are taking. If you are pregnant or want to conceive.
• Counsel the patients about dyspnea that is feeling of chest tightness or difficulty in breathing after administration of first dose of drug within 1 hour which go away after 3 hours and may recur with repeating dose.
• There may be hypotension followed by syncope after the administration of lubiprostone within 30 or 60 minutes.
• Nausea and diarrhea also results in loss of body fluid and raise the chances of hypotension.

CONTRA INDICATIONS
• If you are allergic to it, then tell your doctor.
• If there is GI obstruction
• In IBS associated diarrhea or if patient have already diarrhea.
• It should not be given along with methadone (di phenyl heptane) which may reduce chloride channels activation.

ADVERSE EFFECTS OF LUBIPROSTONE
• Nausea
• Vomiting
• Headache
• Dizziness
•  Ischemic colitis
• Rash, malaise and swelling
• Dyspnea
• Hypotension or tachycardia
• Muscle cramps /spasm
• Gas, dry mouth and fever
• Chest discomfort but if patient experience shortness of breath or chest tightness immediately call doctor.
• Swelling of legs, hand and feet but if there is swelling of mouth, lip ,face and tongue then call doctor
• Heart burn
• Severe diarrhea …..contact doctor
• Fainting …….contact doctor

If someone experience other than above mentioned side effects then immediately contact physician and report it.

Safety and efficacy of lubiprostone has not been established in children, pregnant woman and with hepatic or renal dysfunction. In animal milk, lubiprostone is not excreted but no data is available about human milk. We can only suppose that human milk should not have lubiprostone. Despiteof it, if child experience diarrhea or any problem due to lubiprostone then consult the pharmacist or physician.