Macrogol

Last updated

Macrogol
Poly(ethylene glycol) alternate.svg
Clinical data
Trade names MiraLax, ClearLax, Golytely, others
Other namesPolyethylene glycol (PEG), PEG 3350, PEG 4000, PEG 6000
AHFS/Drugs.com Professional Drug Facts
MedlinePlus a603032
License data
Pregnancy
category
  • AU:B1
Routes of
administration 		By mouth
Drug class Osmotic laxative
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability None
Excretion Feces (100%)
Identifiers
  • Poly(oxyethylene)
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula H–(OCH2CH2)n–OH
Molar mass Varies
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Macrogol, also known as polyethylene glycol (PEG), is used as a medication to treat constipation in children and adults. [1] It is taken by mouth. [1] Benefits usually occur within three days. [2] Generally it is only recommended for up to two weeks. [3] It is also used as an excipient. [4] It is also used to clear the bowels (known as "bowel prep") before a colonoscopy, [1] when the onset of the laxative effect is more rapid, typically within an hour [5] .

Contents

Side effects may include increased bowel gas, abdominal pain, and nausea. [1] Rare but serious side effects may include an abnormal heartbeat, seizures, and kidney problems. [6] Use appears to be safe during pregnancy. [7] [1] It is classified as an osmotic laxative. [2] It works by increasing the amount of water in the stool. [3]

Macrogol came into use as a bowel prep in 1980 and was approved for medical use in the United States in 1999. [8] [9] [10] It is available as a generic medication and over the counter. [1] [11] In 2020, it was the 226th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [12] [13] Typically it is formulated together with electrolytes. [14]

Medical uses

A polyethylene glycol (PEG) and electrolytes solution used as a laxative used to cleanse the colon before colonoscopy, lower gastrointestinal series, or colon surgery. GaviLyte G.jpg
A polyethylene glycol (PEG) and electrolytes solution used as a laxative used to cleanse the colon before colonoscopy, lower gastrointestinal series, or colon surgery.

Constipation

Macrogol 4000, pharmaceutical quality Polyethylene glycol 4000.jpg
Macrogol 4000, pharmaceutical quality

Macrogol 3350, often in combination with electrolytes, is used for short-term relief of constipation as well as for long-term use in constipation of various causes, including in multiple sclerosis and Parkinson's disease patients (an often-overlooked non-motor symptom) as well as constipation caused by pharmaceutical drugs such as opioids and anticholinergics. Whole bowel irrigation with macrogol is part of the bowel preparation before surgery or colonoscopy. Limited data also support its use for the treatment of fecal impaction. [15]

In those with chronic constipation it works better than lactulose. [16]

A 2007 comparison showed that people with constipation had a better response to macrogol than to tegaserod. [17] Popular types include: macrogol 3350, [18] macrogol 4000, and macrogol 6000. [19] The number represents the average molecular mass.[ citation needed ] Combining different molecular masses provides some control over the consistency. [20]

Excipient

Macrogol is used as an excipient in pharmaceutical products. [4] Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as ointment bases, tablet binders, film coatings, and lubricants. [20]

For example, PEG-2000 is one of the excipients in the Moderna COVID-19 vaccine. [21] [22]

PEGylation

Macrogols are also attached to biopharmaceutical drugs to slow down their degradation in the human body and increase their duration of action, as well as to reduce immunogenicity. This process is called PEGylation. [23] [24]

Contraindications

Contraindications for macrogol taken orally as a laxative are intestinal perforation, bowel obstruction, ileus, inflammatory bowel diseases, and toxic megacolon. [15]

The doses of macrogol as an excipient are too low to have relevant contraindications. [25]

Allergy to macrogol is rare, and usually appears as an allergy to an increasing number of seemingly unrelated products, including cosmetics, drugs that use it as an excipient, and peri-procedural substances such as ultrasound gel. [26]

Adverse effects

Oral macrogol is generally well tolerated. Possible side effects include headache, bloating, nausea, allergies, and electrolyte imbalance, mainly hypokalaemia (low blood potassium levels) and hyperkalaemia (high blood potassium levels). Hyperkalaemia is not an effect of macrogol itself but of potassium salts which are usually part of macrogol formulations. [15] With excessive use, it can cause diarrhea.

Interactions

The interaction potential is low. Absorption of other pharmaceutical drugs can be reduced because oral macrogol accelerates intestinal passage, but this is seldom clinically relevant. For antiepileptic drugs, such a mechanism has been described in rare cases. [15]

Pharmacology

Mechanism of action as a laxative

Macrogol is an osmotically acting laxative; that is, an inert substance that passes through the gut without being absorbed into the body. It relieves constipation because it causes water to be retained in the bowel instead of being absorbed into the body. This increases the water content and volume of the stools in the bowel, making them softer and easier to pass, as well as improving gut motility. [15] [27] [28]

Chemistry

Available forms

When sold for gut cleansing (and as a laxative), it is usually in combination with salts such as sodium bicarbonate, sodium chloride and potassium chloride [29] to help mitigate the possibility of electrolyte imbalance and dehydration. Brand names include CosmoCol, Cololyt, Glycoprep, Laxido, MiraLax, Molaxole, Movicol, and Osmolax.

Polyethylene glycol-electrolyte solution is a fixed-dose combination medication sold under various brand names in the US, including Colyte, [30] Gavilyte, Golytely, [31] Nulytely, [32] Moviprep, [33] and Trilyte. [34] [35] Brand names available in the UK include CosmoCol, Klean-Prep, Laxido, Molaxole, Movicol, Plenvu, TransiSoft, and VistaPrep. [36] As of June 2023, polyethylene glycol 3350 is available in the US as a combination with sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride and sold under the brand name Suflave. [37] It is indicated for cleansing of the colon in preparation for colonoscopy in adults. [37]

Research

PEGylation

The protein uricase can be PEGylated to form pegloticase, which improves its solubility at physiological pH, increases serum half-life and reduces immunogenicity without compromising activity. Upper images show the whole tetramer, lower images show one of the lysines that is PEGylated. (PDB: 1uox PEG-uricase model from reference ) PegUricase.png
The protein uricase can be PEGylated to form pegloticase, which improves its solubility at physiological pH, increases serum half-life and reduces immunogenicity without compromising activity. Upper images show the whole tetramer, lower images show one of the lysines that is PEGylated. ( PDB: 1uox ​ PEG-uricase model from reference )

When attached to various biopharmaceutical medications (which are proteins), macrogol results in a slowed clearance of the carried protein from the blood. This makes for a longer-acting medicinal effect and reduces toxicity, and it allows for longer dosing intervals. It also reduces the proteins' immunogenicity. Examples for PEGylated proteins include peginterferon alfa-2a and -2b, which are used to treat hepatitis C, pegfilgrastim, which is used to treat neutropenia, and pegloticase for the treatment of gout. [15]

Nerves and spinal cords

There is evidence demonstrating PEG-induced repair of specific nerve cells in animal models:

Cancer prevention

Other

Related Research Articles

<span class="mw-page-title-main">Polyethylene glycol</span> Chemical compound

Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight. The structure of PEG is commonly expressed as H−(O−CH2−CH2)n−OH.

<span class="mw-page-title-main">Constipation</span> Bowel dysfunction

Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement. Complications from constipation may include hemorrhoids, anal fissure or fecal impaction. The normal frequency of bowel movements in adults is between three per day and three per week. Babies often have three to four bowel movements per day while young children typically have two to three per day.

<span class="mw-page-title-main">Laxative</span> Agents that relax and loosen the bowels and stools

Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation.

<span class="mw-page-title-main">Electrolyte imbalance</span> Medical condition

Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include calcium, chloride, magnesium, phosphate, potassium, and sodium.

An excipient is a substance formulated alongside the active ingredient of a medication. Excipients serve various purposes, including long-term stabilization, bulking up solid formulations containing potent active ingredients in small amounts, or enhancing the therapeutic properties of the active ingredient in the final dosage form. They can facilitate drug absorption, reduce viscosity, or enhance solubility. Excipients can also aid in the manufacturing process by improving the handling of active substances, facilitating powder flowability, or preventing denaturation and aggregation during the expected shelf life. The selection of excipients depends on factors such as the route of administration, dosage form, and active ingredient.

<span class="mw-page-title-main">Sodium phosphate</span> Sodium salts of phosphoric acid

A sodium phosphate is a generic variety of salts of sodium and phosphate. Phosphate also forms families or condensed anions including di-, tri-, tetra-, and polyphosphates. Most of these salts are known in both anhydrous (water-free) and hydrated forms. The hydrates are more common than the anhydrous forms.

<span class="mw-page-title-main">Fecal impaction</span> Medical condition

A fecal impaction or an impacted bowel is a solid, immobile bulk of feces that can develop in the rectum as a result of chronic constipation. Fecal impaction is a common result of neurogenic bowel dysfunction and causes immense discomfort and pain. Its treatment includes laxatives, enemas, and pulsed irrigation evacuation (PIE) as well as digital removal. It is not a condition that resolves without direct treatment.

Phospho soda was an over the counter saline laxative produced by the C.B. Fleet Company in Lynchburg, Va. Phospho soda consisted mostly of monobasic sodium phosphate monohydrate and dibasic sodium phosphate heptahydrate. Phospho soda is often taken in a double dose, to prepare for colonoscopy. It is still used outside the US.

<span class="mw-page-title-main">Bristol stool scale</span> Medical system for classifying human faeces

The Bristol stool scale is a diagnostic medical tool designed to classify the form of human faeces into seven categories. It is used in both clinical and experimental fields.

Phosphate nephropathy or nephrocalcinosis is an adverse renal condition that arises with a formation of phosphate crystals within the kidney's tubules. This renal insufficiency is associated with the use of oral sodium phosphate (OSP) such as C.B. Fleet's Phospho soda and Salix's Visocol, for bowel cleansing prior to a colonoscopy.   

<span class="mw-page-title-main">Bisacodyl</span> Laxative

Bisacodyl (INN) is an organic compound that is used as a stimulant laxative drug. It works directly on the colon to produce a bowel movement. It is typically prescribed for relief of episodic and chronic constipation and for the management of neurogenic bowel dysfunction, as well as part of bowel preparation before medical examinations, such as for a colonoscopy.

<span class="mw-page-title-main">Whole bowel irrigation</span> Medical process

Whole bowel irrigation (WBI) is a medical process involving the rapid administration of large volumes of an osmotically balanced macrogol solution, either orally or via a nasogastric tube, to flush out the entire gastrointestinal tract.

<span class="mw-page-title-main">Lubiprostone</span> Medication used for constipation

Lubiprostone, sold under the brand name Amitiza among others, is a medication used in the management of chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation. The drug is owned by Mallinckrodt and is marketed by Takeda Pharmaceutical Company.

<span class="mw-page-title-main">Disodium phosphate</span> Chemical compound

Disodium phosphate (DSP), or disodium hydrogen phosphate, or sodium phosphate dibasic, is an inorganic compound with the chemical formula Na2HPO4. It is one of several sodium phosphates. The salt is known in anhydrous form as well as hydrates Na2HPO4·nH2O, where n is 2, 7, 8, and 12. All are water-soluble white powders. The anhydrous salt is hygroscopic.

<span class="mw-page-title-main">Sodium picosulfate</span> Chemical compound

Sodium picosulfate is a contact stimulant laxative used as a treatment for constipation or to prepare the large bowel before colonoscopy or surgery.

<span class="mw-page-title-main">PEGylation</span> Chemical reaction

PEGylation is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol polymer chains to molecules and macrostructures, such as a drug, therapeutic protein or vesicle, which is then described as PEGylated. PEGylation affects the resulting derivatives or aggregates interactions, which typically slows down their coalescence and degradation as well as elimination in vivo.

<span class="mw-page-title-main">Polycarbophil calcium</span> Pharmaceutical drug

Polycarbophil calcium (INN) is a drug used as a stool stabilizer. Chemically, it is a synthetic polymer of polyacrylic acid cross-linked with divinyl glycol, with calcium as a counter-ion.

<span class="mw-page-title-main">Senna glycoside</span> Constipation and surgery medication

Senna glycoside, also known as sennoside or senna, is a medication used to treat constipation and empty the large intestine before surgery. The medication is taken by mouth or via the rectum. It typically begins working in around 30 minutes when given by rectum and within twelve hours when given by mouth. It is a weaker laxative than bisacodyl and castor oil.

<span class="mw-page-title-main">Naloxegol</span> Medication used in the treatment for Opioid-Induced Constipation

Naloxegol is a peripherally acting μ-opioid receptor antagonist developed by AstraZeneca, licensed from Nektar Therapeutics, for the treatment of opioid-induced constipation. It was approved in 2014 in adult patients with chronic, non-cancer pain. Doses of 25 mg were found safe and well tolerated for 52 weeks. When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.

Constipation in children refers to the medical condition of constipation in children. It is a functional gastrointestinal disorder.

References

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