Laxatives are a group of diverse medications used in the pharmacological management of constipation. In this article, we shall look at the pharmacology of laxatives – their class, mechanism of action and routes of administration. Non-Pharmacological Measures Non-pharmacological measures are usually first-line in the management of constipation. This includes lifestyle modifications to increase dietary fibre, fluid intake and exercise. The Bristol stool chart can be referred to when discussing stool types. In addition, it is important to consider any newly started medications that may be causative. Such medications include: Ondansetron Loperamide Diuretics such as furosemide Antimuscarinic medications such as amitriptyline or oxybutynin Iron supplements Opioids Adobe stock, licensed to Teachmeseries Ltd Fig 1Bristol stool chart Classes of Laxatives The major drug classes used in the pharmacological management of constipation are bulk forming laxatives, stimulant laxatives and osmotic laxatives. Bulk-forming Laxatives Bulk-forming laxatives increase faecal mass by absorbing water – this increases peristalsis via mechanical stimulation of the gut wall. A lubricating layer is also formed, which makes the stool easier to pass. Examples of bulk-forming laxatives include ispaghula husk (Fybogel) and methylcellulose. They typically act within 12-24 hours, with maximum effect taking 2-3 days. They are available via the oral route only. Patients should be advised to stay hydrated during treatment, so there is adequate fluid available in the stool (ispaghula husk is capable of absorbing up to 40 times its own weight in water). Bulk forming laxatives are contraindicated for use in cases of bowel obstruction, faecal impaction or opioid induced constipation. Created in BioRender. Jones, O. (2025) https://BioRender.com/0dkcp13 Fig 2: Bulk forming laxatives Osmotic laxatives Osmotic laxatives, such as macrogol and lactulose, increase stool volume via osmosis which triggers colon motility via neuromuscular pathways, in a similar way to bulk forming laxatives. Macrogol and lactulose are poorly absorbed from the GI tract and act locally in the colon. Lactulose is also indicated for patients with hepatic encephalopathy as it reduces ammonia levels in the blood by the following mechanisms: Decreases intestinal production and absorption of ammonia Draws ammonia from the blood into the colon, where the body excretes it. Stimulant Laxatives Stimulant laxatives activate colonic and/or rectal nerves which leads to peristalsis. Examples include senna, bisacodyl, docusate sodium and sodium picosulfate. Senna has an onset of action between 8-12 hours and works by stimulating motility of the large intestine. This results in accelerated colonic transit and stimulation of water and electrolyte secretion into the lumen of the colon (this can cause electrolyte depletion and dehydration with prolonged use). Senna acts locally at the colon and is not dependent upon systemic absorption; sennosides are converted by bacteria of the large intestine into active metabolites. Bisacodyl has a similar mechanism of action to senna. Oral administration with bisacodyl causes an effect within 6-12 hours and after 20 minutes following rectal administration with a suppository. Bisacodyl acts locally in the colon, and tablets for oral administration are enteric coated to avoid release of drug in the stomach and small intestine. Docusate sodium acts as a faecal softener and allows penetration of faecal matter by water and salts. It also possesses stimulant activity. Its therapeutic effect occurs locally in the GI tract but there is some evidence of systemic absorption and excretion through bile. Oral administration of docusate causes an effect within 1-2 days, whereas rectal administration usually causes an effect within 20 minutes. Sodium picosulfate is metabolised by bacteria in the colon to form an active compound that stimulates the mucosa of the large intestine and rectum. The onset of action is 6-12 hours. Picolax contains sodium picosulfate and magnesium citrate; magnesium citrate acts as an osmotic laxative by retaining moisture in the colon. Picolax acts locally in the colon and components are not absorbed in any detectable amounts. Created in BioRender. Jones, O. (2025) https://BioRender.com/0dkcp13 Fig 2: Stimulant laxatives Softeners Laxatives that soften stools are particularly useful for patients experiencing hard stools. Many laxatives act as faecal softeners alongside other mechanisms of action. Arachis oil enemas lubricate and soften faeces thereby promoting bowel movement. Glycerol suppositories increase water absorption in the intestines leading to a softening effect on the stool. Docusate sodium is a surface-wetting agent which reduces the surface tension of the stool, allowing water to penetrate and soften it. Bulk forming laxatives and osmotic laxatives also have stool softening properties. Opioid Antagonists Opioid antagonist laxatives are used for patients with opioid induced constipation. Opioids prevent the colon responding with propulsive action through binding to enteric π opioid receptors. Opioid antagonists block the binding of opioids to enteric π receptors without altering the analgesic effect, as these laxatives are peripherally acting only and have minimal blood brain barrier (BBB) penetration. Examples include naloxegol, naldemedine and methylnaltrexone. Naloxegol is a PEGylated derivative of the π-opioid receptor antagonist naloxone. PEGylation reduces naloxegol’s passive permeability and also renders the compound a substrate for the P-glycoprotein (PGP) transporter, both of which may reduce BBB penetration. Naloxegol is a substrate for CYP3A4, therefore use is contraindicated with strong inhibitors of CYP3A4 and not recommended with strong inducers of CYP3A4. Naldemedine is a derivative of naltrexone which is also a π-opioid receptor antagonist, to which a side chain has been added that increases the molecular weight and the polar surface area, thereby reducing its ability to cross the BBB. Naldemedine is also a substrate for the P-gp transporter; therefore if naldemedine is used with strong P-gp inhibitors, monitoring should be put in place for adverse reactions. Caution should be taken with using naloxegol or naldemedine if patients have clinically significant alterations to the blood brain barrier (such as Parkinson’s or Alzheimer’s disease) as CNS penetration may be increased. Special Cases In pregnancy, 40% of patients experience constipation, due to progesterone mediated smooth muscle relaxation. Most laxatives have minimal systemic absorption and are commonly used during pregnancy without concerns about teratogenic effects. A bulk forming laxative should be considered as a first line option in pregnancy because there have been no reports of foetal adverse effects with their use. An osmotic laxative such as lactulose or macrogol can be used as second line treatment – there is less evidence on the use of osmotic laxatives in pregnancy compared to bulk forming laxatives. Stimulant laxatives such as senna may be used when a stimulant effect is required (i.e. if stool is soft but difficult to pass). For opioid induced constipation, stimulant laxatives alongside an osmotic laxative is often used first line, with opioid antagonists used as second/third/fourth line treatment. Bulk forming laxatives should not be used in opioid induced constipation as this can cause abdominal colic and rarely bowel obstruction. Summary Table Commonly used laxatives are described below characterised by class. Mode of action, examples, time to action, routes available, side effects and other important information is listed. A further table describes laxatives that are not characterised into a class. Doses can be accessed via the British national formulary (BNF) or electronic medicines compendium (EMC) via the summary of product characteristics (SPC). Class Mode of action Examples & time to act Route Side effects Notes Bulk forming laxatives Acts by keeping fluid within the stool and increasing faecal mass which stimulates peristalsis and also softens the stool Ispaghula husk (Fybogel) Acts within 12-24 hours but maximum effect takes 2- 3 days PO Flatulence, bloating, cramping Useful if unable to increase fibre in diet Must stay hydrated during treatment Avoid in possible obstruction, faecal impaction, opioid induced constipation Stimulant laxatives Stimulate colonic and or rectal nerves which leads to peristalsis Bisacodyl (6-12hrs) PO, PR Abdominal cramps Avoid in intestinal obstruction MHRA alert in 2020 following concerns of misuse and abuse (mostly concern over patients with eating disorders). Pack size restrictions put in place, only able to buy smaller packs via general sale, can buy up to 100 tablets from a pharmacy (under supervision of pharmacist). Need to be over 18 to buy unless from a pharmacy then under supervision of pharmacist can be sold to patients 12 years upwards. Sodium picosulfate (6-12hrs) – Dulcolax/Picolax PO Senna (8-12hrs) PO Docusate sodium (12-72hrs) PO, PR Osmotic laxatives Increase fluid in the large bowel which stimulates peristalsis and also soften stools Lactulose, macrogol Action 2-3 days PO Reactions related to the gastrointestinal tract occur most commonly: Abdominal pain, diarrhoea, flatulence, nausea and vomiting Must stay hydrated MHRA alert (2021) – mixing PEG based laxatives (macrogol/movicol/moviprep) with starch based thickeners may counteract the thickening action leading to risk of aspiration for patients with dysphagia Macrogol contains high amounts of sodium, caution with cardiovascular disease and those on a low salt diet Opioid antagonists Blocks the actions of opioids in the gut without altering analgesic effect as compounds do not cross the blood brain barrier NaloxegolΒ (where response to other laxatives is inadequate) Peak blood concentrations achieved in <2 hours PO Gastrointestinal disorders Opioid like withdrawal (naloxegol and methylnaltrexone) Naloxegol – caution in cardiovascular disease (QT interval over 500 milliseconds; recent history of myocardial infarction (within 6 months)) Naloxegol & naldemedine: If patients have clinically important disruptions to the blood brain barrier (BBB) then caution should be used. Methylnaltrexone (30-60 minutes) S/C injection Naldemedine (It can only be used if other laxatives have already been tried) Peak plasma concentrations in blood reached in 45 minutes in fasted patients PO Other Laxatives Laxative Mode of action Time to act Route Side effects Notes Glycerol suppositories Several modes of action: Osmotic laxative Promotes peristalsis and evacuation of the lower bowel by virtue of a mild irritant effect. Lubricating and faecal softening actions 15-30 minutes PR AbdominalΒ cramps Local irritation For occasional use only Prucalopride Serotonin 5ht4 receptor agonist with prokinetic properties stimulates intestinal motility Maximum plasma concentration reached in 2-3 hours. Treatment should be reviewed after 4 weeks if no response PO Gastrointestinal disorders Only for use when other laxatives fail (two laxatives from different classes have been used at highest recommended doses for at least 6 months) Side-effects generally occur at the start of treatment and are usually transient. For elderly start at half dose Linaclotide Linaclotide is a Guanylate Cyclase-C receptor agonist (GCCA) with visceral analgesic and secretory activities, action at this receptor leads toΒ increased intestinal fluid and accelerated transit. Acts locally in the GI tract – rarely detectable levels in plasma. Treatment should be reviewed if no response after 4 weeks PO Gastrointestinal disorders Licensed in moderate to severe IBS associated constipation (IBS-C) Should not be used in IBD Arachis oil enema Decrease surface tension and increase penetration of fluid into faecal mass 15-30 minutes PR Local irritation Contraindicated if hypersensitivity to peanut or soya References BNF summary constipation available from: Constipation | Treatment summaries | BNF | NICE accessed 12/8/24 MHRA alert:Stimulant laxatives (bisacodyl, senna and sennosides, sodium picosulfate) available over-the-counter: new measures to support safe use. Available from: Stimulant laxatives (bisacodyl, senna and sennosides, sodium picosulfate) available over-the-counter: new measures to support safe use – GOV.UK (www.gov.uk) Accessed 12/8/24 MHRA alert: Polyethylene glycol (PEG) laxatives and starch-based thickeners: potential interactive effect when mixed, leading to an increased risk of aspiration. Available from: https://www.gov.uk/drug-safety-update/polyethylene-glycol-peg-laxatives-and-starch-based-thickeners-potential-interactive-effect-when-mixed-leading-to-an-increased-risk-of-aspiration. Accessed 12/8/24 NICE CKS Constipation guideline. Available from: Constipation | Health topics A to Z | CKS | NICE. accessed 12/8/24 Online BNF Methylnaltrexone accessed 13/8/24 available from: Methylnaltrexone bromide | Drugs | BNF | NICE Online BNF Prucalopirde accessed 13/88/24 available from: Prucalopride | Drugs | BNF | NICE Online BNF Linaclotide accessed 13/8/24 available from: Linaclotide | Drugs | BNF | NICE SPC Fybogel Orange Granules.Β Last updated on emc: 07 Dec 2020. Available from: Fybogel Orange Granules – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk). Accessed 14/8/24. SPC Bisacodyl 5mg Tablets Last updated on emc: 12 Nov 2021 available from: Bisacodyl 5mg Tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 14/8/24 Β SPC Dulcolax Adult 5 mg Gastro-resistant Tablets Last updated on emc: 05 Jun 2024. Available from: Dulcolax Adult 5 mg Gastro-resistant Tablets (GSL) – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 14/8/24. SPC Senokot 7.5 mg Tablets 12 Years Plus Last updated on emc: 11 Dec 2020. Available from: https://www.medicines.org.uk/emc/product/11548/smpc. Accessed 14/8/24 SPC Dioctyl 100mg capsules. Last updated on emc: 23 Nov 2023. Available from: Dioctyl 100 mg Capsules – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk). Accessed 14/8/24 SPC Glycerol 4g suppositories. Last updated on emc: 02 Jan 2015. Available from: Glycerol 4g Suppositories – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk). Accessed 14/8/24 SPC Arachis Oil Enema. Last updated on emc: 09 Jun 2023. https://www.medicines.org.uk/emc/product/12901/smpc Accessed 14/8/24. BNF Lactulose available from https://bnf.nice.org.uk/drugs/lactulose/ accessed 15/8/24 SPC compound macrogol oral powder. Last updated on emc: 07 Dec 2021. Available from Compound Macrogol Oral Powder Sugar Free. – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) Accessed 15/8/24 BNF Naloxegol available from: Naloxegol | Drugs | BNF | NICE accessed 15/8/24 Constipation: treatment during pregnancy β SPS – Specialist Pharmacy Service β The first stop for professional medicines advice accessed 29/8/24 TREATMENT OF CONSTIPATION IN PREGNANCY β UKTIS Date of issue: July 2022, Version: 3. Accessed 29/8/24. SPC Moventig 12.5 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 31/8/24 SPC Rizmoic 200 micrograms film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 31/8/24 Do you think youβre ready? Take the quiz below Pro Feature - Quiz Laxatives Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article