Enzyme inducers / inhibitors and Management of constipation (laxatives - bulk forming, stimulant, faecal softeners, osmotics), drugs to be stopped before surgery

Question 1

Brief talking about at the beginning of this flashcard set - enzyme inducers and enzyme inhibitors

It is important to know the most common enzyme inhibitors and inducers

What is the enzyme which we are discussing here?

Answer 1

We are dicussing the cytochrome P450 enzyme system in the liver - most drugs are metabolised to inactivte metabolites by this system

Question 2

useful acronym for remembering the common enzyme inducers is PC BRAS

What effect do the enzyme inducers have on the drug concentration?

What are the PC BRAS enzyme inducers?

Answer 2

Enzyme inducers will increase P450 enzyme activity, hastening metabolism of other drugs with the result that they exert a reduced effect (and hence a patient will require more of some other drugs in the presence of an enzyme inducer)

• Phenyotin
• Carbamezapine
• Barbituates
• Rifampicin
• Alcohol (chronic excess)
• Sulphonylureas

Question 3

useful acronym for remembering the common enzyme inhibitors is AODEVICES

What effect do the enzyme inhibitors have on the drug concentration?

What are the AODEVICES enzyme inhibitors?

Answer 3

Enzyme inhibitors will decrease P450 enzyme activity and subsequently there will be increases levels of other drugs

• Allopurinol
• Omeprazole
• Disilfiram
• Erythromycin
• Valproate
• Isoniazid
• Ciprofloxacin
• Ethanol (acute intoxification)
• Sulphonamides

Question 4

Give the name of another enzyme inhibitor? (clue care home residents cant drink it if on warfarin)

Answer 4

This would be grapefruit juice - inhibits cytP450 causing increased levels of eg warfarin

Question 5

MANAGEMENT OF CONSTIPATION

Constipation is defaecation that is unsatisfactory because of infrequent stools, difficult stool passage, or seemingly incomplete defaecation. It can occur at any age and is commonly seen in women, the elderly, and during pregnancy.

What are the non-pharmacological options that are advised in all patients with constipation?

Answer 5

In all patinets with constipation, an increase in dietary fibre, adequate fluid intake and exercise is advised (fibre should be increased gradually to minimise flatulence and bloating)

The effects of a high-fibre diet may be seen in a few days although it can take as long as 4 weeks

Question 6

BULK FORMING LAXATIVES
Laxatives are a type of medication used to treat constipation

There are many different types of laxative

• Bulk forming
• Stimulant
• Faecal Softeners
• Osmotic
• Other

How do bulk-forming laxatives work? And therefore what must they be taken with?

Answer 6

Bulk forming laxatives work by increasing faecal mass

• They are not digested but instead asborb liquids in the intestines and swell to form a soft bulky stool - they must be taken with plenty of water
• The bowel is then stimulated normally by the presence of the bulky mass

Question 7

When are bulking agents of particular value?

When are bulking agents contrainidcated?

Answer 7

Bulk forming laxatives are of particular value in adults with small hard stools if fibre cannot be increased in the diet.

Bulking agents are contraidindicated in patients who have difficulty swallowing, GI obstruction, colonic atony and faecal impaction

Question 8

How long do bulk forming laxatives take to work and what may be side effects?

Answer 8

Onset of action is up to 72 hours. Symptoms of flatulence, bloating, and cramping may be exacerbated

Question 9

What are different examples of bulk forming laxatives? (try and give brand name as well just because patients always say these names)

Answer 9

Bulk-forming laxatives include

• bran
• ispaghula husk - fybogel
• methylcellulose - celevac (also acts as a faecal softener)
• sterculia - normacol

Remember to take all these with adequaste fluid intake

Question 10

STIMULANT LAXATIVES

How do stimulant laxatives work?

When are they contraindicated?

Answer 10

Stimulant laxatives increase intestinal motility to increase bowel movements

They are contraindicated in intestinal obstruction or acute colitis

Question 11

Why should prolonged use of stimulant laxatives be avoidded?

What is an important side effect of stimulant laxatives?

Answer 11

Avoid prolonged use of stimulatnt laxatives as it may cause colonic atony

Important side effect of stimulant laxatives are abdominal cramps

Question 12

Give examples of stimulant laxatives?

Answer 12

• Bisacodyl tablets or suppositories
• Sodium picosulfate tablets
• Docusate sodium and glycerol have stimulant and softener properties
• Members of anthraquinone group - senna, co-danthramer and co-danthrusate

Question 13

Why are both co-danthrama and co-danthrusate limited in their use? (these are both members of the anthraquinone group)

Answer 13

The use of co-danthramer and co-danthrusate is limited to constipation in terminally ill patients because of potential carcinogenicity (based on animal studies) and evidence of genotoxicity.

Question 14

FAECAL SOFTENERS

How are faecal softeners meant to work and when are they particularly useful?

Answer 14

Faecal softeners are claimed to act by decreasing surface tension and increasing penetration of intestinal fluid into the faecal mass

They are particulary useful when managing painful anal conditions eg fissure

Question 15

What are examples of faecal softeners?

Answer 15

Docusate sodium

Glycerol

Arachis oil enemas

Liquid paraffin

Question 16

What are the side effects associated with liquid paraffin for constipation?

Answer 16

• Anal seepage
• Lipid pneumonia - when oil or fat enters the lungs
• Malabsorption of fat soluble vitamins

Question 17

OSMOTIC LAXATIVES

How do osmotic laxatives work?

Answer 17

Osmotic laxatives increase the amount of water in the large bowel, either by drawing fluid from the body into the bowel or by retaining the fluid they were administered with.

The water increases stoool volume and stretches the bowel wall so defecation can happen through the normal defecation reflex

Question 18

Give example of osmotic laxatives?

Answer 18

Lactulose

Macrogols (such as macrogol 3350 with potassium chloride, sodium bicarbonate and sodium chloride) are inert polymers of ethylene glycol which sequester fluid in the bowel; giving fluid with macrogols may reduce the dehydrating effect sometimes seen with osmotic laxatives.

Question 19

How does lactulose work and what other condition is it useful in treating first line? (clue - ammonia)

Answer 19

Lactulose is a semi-synthetic disaccharide which is not absorbed from the gastro-intestinal tract. It produces an osmotic diarrhoea of low faecal pH, and discourages the proliferation of ammonia-producing organisms. It is therefore useful in the treatment of hepatic encephalopathy.

Question 20

What condition would make you avoid the use of lactulose?

Answer 20

It’s not a good idea for people with irritable bowel syndrome (IBS) to take lactulose. Lactulose increases gas and bloating in the stomach, which can make IBS worse. Other types of laxative may be more suitable if you have IBS.

Question 21

In the management of short duration constipation, where dietary measures are ineffective, what is the recommended agent to treat the constipation? (give an example the laxative type)

Answer 21

If these measures are ineffective, or symptoms do not respond adequately, offer treatment with oral laxatives using a stepped approach:

Offer a bulk-forming laxative first-line, such as ispaghula. Note: it is important for the person to drink an adequate fluid intake.

Question 22

• If stools remain hard or difficult to pass in a patient with short-term constipation, what can be added to treat the condition?
• If stools are soft but difficult to pass or the person complains of inadequate emptying, what can be added?

Answer 22

If stools remain hard or difficult to pass, add or switch to an osmotic laxative, such as a macrogol.

• If a macrogol is ineffective or not tolerated, offer treatment with lactulose second-line.

If stools are soft but difficult to pass, or there is a sensation of inadequate emptying, add a stimulant laxative ev bisacodyl, senna, sodium picosulfate

Question 23

What is the recommended first line treatment of opioid induced constipation?

What usual first line agent should be avoided?

Answer 23

In patients with opioid-induced constipation, an osmotic laxative (or docusate sodium to soften the stools) and a stimulant laxative is recommended.

Bulk-forming laxatives should be avoided.

Question 24

What is recommended for the treatment of opioid induced constipation where response to other laxatives is inadequate?

Answer 24

Naloxegol is recommended for the treatment of opioid-induced constipation when response to other laxatives is inadequate.

Naloxegol is a peripherally acting opioid receptor antagonist - . It therefore decreases the constipating effects of opioids without altering their central analgesis effects

Question 25

The treatment of faecal impaction depends on the stool consistency

What is the treatment in patients with hard stools?

What is the treatment in patients with soft stools?

Answer 25

In patients with hard stools, a high dose of an oral macrogol (such as macrogol 3350 with potassium chloride, sodium bicarbonate and sodium chloride) may be considered.

In those with soft stools, or with hard stools after a few days treatment with a macrogol, an oral stimulant laxative should be started or added to the previous treatment.

Question 26

If the patient remains faecally impacted after treatment, a sodium phosphate enema can be given. How does this work?

Answer 26

• Phosphate enemas contain sodium acid phosphate and sodium phosphate. The osmotic activity of the former increases the water content of the stool so that rectal distension follows and it is thought that this induces defecation by stimulating rectal motility
• Usually works in roughly 5 minutes

Question 27

What should be started for the management of patients with chronic consitpation? (clue same as management of short-term constipation)

Answer 27

Offer initial treatment with a bulk-forming laxative such as ispaghula. Note: it is important for the person to drink an adequate fluid intake.

If stools remain hard or difficult to pass, add or switch to an osmotic laxative, such as a macrogol.

• If a macrogol is ineffective or not tolerated, offer treatment with lactulose second-line.

If stools are soft but difficult to pass or there is a sensation of inadequate emptying, add a stimulant laxative.

Question 28

If at least two laxatives (from different classes) have been tried at the highest tolerated recommended doses for at least 6 months, what drug can be offered as the treatment for chronic constipation?

How does this drug work?

Answer 28

Prucalopride can be tried - it is a selective serotonin 5HT4-receptor agonist with prokinetic properties that is used when other laxatives have failed - the prokinetic properties stimulate gastrointestinal motility

Question 29

There is a finite list of drugs to be stopped or given before surgery

Try and name the drugs that should be stopped prior to surgery?

What happens to diabetic treatment prior to surgery?

Answer 29

• ACE inhibitors / ARBs
• Potassium sparing diuretics - risks hyperkalaemia if renal hypoperfusion
• Diabetic treatment - alternative must be arranged (T2DM treatment and insulin usually converted to insulin sliding scale)
• Anti-platelets / anti-coagulants
• Lithium
• NSAIDs
• Drugs which are non essential in short term eg vitamins, iron, laxatives, osteoporosis treatment, liquid antacid medicines (eg gaviscon), HRT, anti- histamines, herbal remedies or homeopathic medicines.

Question 30

State why each of the following cannot be given in surgery

• ACE inhibitors / ARBs
• All diuretics
• Diabetic treatment - alternative must be arranged (T2DM treatment and insulin usually converted to insulin sliding scale)
• Anti-platelets / anti-coagulants
• Lithium
• NSAIDs

Answer 30

• ACEi/ARBs - Both these drugs may drop the blood pressure during an anaesthetic. Anaesthetists may request that these drugs are given before surgery but this will be requested on an individual basis. Please with-hold unless requested.
• Potassium sparing diuretics - risks hyperkalaemia if renal hypoperfusion
• Diabetic treatment - alternative must be arranged (T2DM treatment and insulin usually converted to insulin sliding scale)
• Anti-platelets/anti-coagulants - increased risk of bleeding
• Lithium - unsure why
• NSAIDs - approximately one week before elective surgery to decrease the risk of excessive bleeding.

Image says all diuretics but it is only potassium sparing diuretics - https://www.royalberkshire.nhs.uk/Downloads/GPs/GP%20protocols%20and%20guidelines/Perioperative%20medicines%20management%20-%20GL058%20-%20v6.pdf