Laxatives and cathartics

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Introduction0:00–0:50

Laxatives and cathartics are medications that increase the passage of stool. Laxatives ease the passage of fully formed fecal matter from the rectum; while cathartics have a stronger effect, and causes the evacuation of the entire colon, usually in the form of watery, unformed stool.
Some medications can function both as a laxative and a cathartic, depending on the dosage. Both types of medications are used to treat constipation, which is a decrease in frequency of the passage of small, hard stools, or difficulty with initiating bowel movements.
Normal stool frequency is usually at least 3 times per week for someone on a typical Western diet. Now, the small and large intestines are where most of the absorption happens in the GI tract.

Physiology0:50–2:11

The small intestine contains smooth muscles that perform peristalsis, which is a series of coordinated wave-like muscle contractions that help push the food bolus through the GI tract.
Lining the luminal surface of the intestine is a layer called the mucosa, which absorbs nutrients or secretes different molecules, like ions and water, into the lumen.
The undigested component of the food bolus eventually reaches the large intestine and becomes feces or stool. The large intestine mainly absorbs excess water from the stool and that helps condense it into a more solid form.
However, stool should still be 70-80% water by weight, so if the feces becomes too dry, it could condense into a large, hard mass that’s difficult to pass.
So instead of peristalsis, which only pushes the food bolus in one direction, the colon undergoes segmental contraction, which pushes the feces in both directions within the haustra to constantly mix it with water; kind of like how a cement truck keeps churning to keep the cement from drying.
Now, constipation can occur due to a poor diet or a malfunction within the GI tract itself, although, up to 60 percent of chronic constipation does not have a clear cause.

Pathology2:11–3:53

One of the most important dietary factors is the lack of fiber, which is the part of food that resists digestion and reaches the colon relatively unchanged.
Fiber usually comes from plants like fruits and vegetables. They get incorporated into the stool where they absorb water, causing the stool to swell and bulk up, which prevents it from hardening, while also making it easier to pass.
Another cause of constipation is due to decreased motility of the GI tract, which could be caused by disorders like irritable bowel syndrome, or medications like opioids.
In either case, it takes longer for the digested food to travel through the GI tract, so more water is absorbed, and the stool hardens.
When these hardened stool form a large mass that’s difficult to pass, it’s called a fecal impaction, and it could lead to large bowel obstructions.
A large colonic carcinoma or an inflamed and swollen diverticula can cause a blockage in the colon, which could lead to constipation.
Finally, problems like anal fissures and haemorrhoids can make defecation so painful that the person will voluntarily avoid passing stool.
The longer the stool stays in the colon, the harder it will become, ultimately making the situation worse. Medications that are used to manage constipation include: bulk forming agents, stimulant laxatives, osmotic laxatives, and stool softeners.
Let’s start with bulk forming agents, which include methylcellulose and psyllium. These fibrous compounds are composed of polysaccharide polymers from plants.

Bulk-Forming Agents3:53–5:03

They are taken perorally and can’t be digested by the enzymes in our GI tract. So these fibers end up getting incorporated into the stool, where they draw in more water, making the stool swell up into a softer, bulky mass, kind of like a stinky sponge.
This increase in size stimulates intestinal motility and the softer stool is also easier to pass. Bulking agents are great for long term treatment of constipation because they don’t have many side effects.
However, they are contraindicated in those with intestinal obstructive as the increased stool mass could worsen the blockage.
Next are the stool softeners like docusate, which can be taken peroral or as a suppository. Normally water and lipids don’t mix, so the fats in stool could prevent water from entering.
Docusate is an surfactant, which means it has a hydrophilic head that’s water soluble, and a hydrophobic tail that’s water insoluble, so it sticks out into the lipids.

Stool Softeners5:03–6:09

This disrupts the normal surface tension between water and fat, which allows the water to penetrate the stool and make it more viscous and softer.
Although docusate is widely used, it’s shown to have low efficacy for the treatment of constipation. However, it’s useful in children who have hard stool that’s painful to pass.
Next are the osmotic laxatives, which include ion forming compounds like magnesium sulfate, magnesium hydroxide, sodium phosphate, and indigestible alcohols and sugars, like polyethylene glycol and lactulose.
Both magnesium cations and phosphate anions are not well absorbed, so they draw more water out of the cells in the intestinal wall via osmosis and increase the amount of water in the lumen.
This increases intestinal motility which pushes the stool through the GI tract and also helps mix the stool with water. Besides treating constipation, these agents can be used to cleanse the bowels before procedures like colonoscopies or surgeries, kind of like using a drain cleaner to clean dirty pipes.

Osmotic Laxatives6:09–9:38

The downside is this could cause a lot of fluid loss, leading to dehydration. As a result, they should not be used in people with cardiac diseases, pre-existing electrolyte abnormalities, and those at risk for renal failure.
Lactulose, on the other hand, is a synthetic disaccharide of galactose and fructose, which does not get broken down by intestinal enzymes, so it can’t be absorbed.
Like the other osmotic laxatives, it also causes an increase in luminal water through osmosis. Now, once in the small intestine, lactulose is broken down by bacteria into lactic acid and acetic acid, which further stimulates peristalsis.
Furthermore, lactulose is used to treat hepatic encephalitis, which is caused by liver dysfunction. The liver normally breaks down ammonia (NH3,) which is toxic to brain cells.
So when the liver fails, these toxins can build up in the body. However, when lactulose is broken down into lactic acid, it decreases the pH in the lumen.
This promotes the conversion of ammonia into ammonium ions (NH3 into NH4+, ) which can’t be reabsorbed, so it gets excreted in the stool.
The main side effect of lactulose includes bloating and flatulence, due to the production of methane by the bacteria that feeds on this medication.
Finally, we have the stimulant laxatives like bisacodyl and senna. These medications are taken peroral or as a suppository, and work by causing mild inflammations that irritate the small and large intestinal walls.
This stimulates smooth muscle contraction, which increases intestinal motility. The inflammation also increases electrolyte secretion from the cells of the intestinal walls, which draws more water into the lumen.
Overdose of these medications can lead to cramping, diarrhea, and fluid and electrolyte deficits. Since they are irritants, long term use could cause damage to the walls of the colon and cause atonic, or lazy colon, which means there’s decreased muscle tone.
Senna could also cause a benign side effect called melanosis coli, which is a dark discoloration of the colon wall. This does not cause any symptoms and is reversible when the medication is stopped.
Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts! So let’s start by looking at the laxatives that increase the water content in stool and we’ll put these guys in a swampy area.
On one side, is a bale of hay for the bulking agents that mainly come from plant fibers, and on the other side is a soft, fluffy pillow for the stool softeners.
The hay is blocked off by a traffic barrier to help you remember bulking agents should not be used when there’s an intestinal obstruction.
Next, a tired doctor sat on the soft pillow, which represents docusate. He’s doing an experiment where he’s mixing some olive oil with a bottle of water to help you remember docusate’s mechanism of action.
Next, let’s look at the stimulant laxatives. So next to the swamp is a sauna for senna, and sitting in it is a bison with the head of a crocodile for bisacodyl.
There’s a little fire heating the sauna to help you remember these medications irritate the intestinal wall and cause inflammation of the GI tract.

Stimulant Laxatives9:38–11:07

For side effects, there’s a large intestine relaxing lazily for atonic colon. It’s been roasting by the fire too long and there’s black spots all over him, to represent melanosis coli.
Okay, let’s move onto the osmotic laxatives which will be hanging out in a kiddie pool. The pool represents the colon and it’s filling with water, which represents the mechanism of these medications.
Floating on one side of the pool is a magnet and a phosphorescent glow stick, and they represent magnesium hydroxide and sodium phosphate.
A large leak is on this side of the pool, which represents fluid loss and dehydration. A heart and a kidney got washed out from this leak to help you remember these medications should not be used by people with cardiac diseases or those at risk for renal failure.
At the other end of the pool is a baby drinking from a milk bottle for lactulose. His tummy is bloated and he’s passing gas, which are the main side effects.
Floating next to him, is a brain inside a fertilizer bag full of ammonia, since lactulose is used to treat hepatic encephalopathy.
Ok, as a quick recap, laxatives and cathartics are medications used to treat constipation, which can be caused by a variety of factors including: low fiber, decreased motility, physical obstructions, and pain during defecation.

Memory Palace11:07–13:40

Stool softeners and bulking agents increase the water content of the stool while osmotic laxatives increase the water content inside the lumen.
Stimulant laxatives irritate the intestinal wall which causes smooth muscle contractions and increases water secretion. But wait, there’s more: Here’s a mind map with all of the mnemonics.
Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers after the credits.

Review13:40–14:14

Mind Map14:14–11:51