GI

Question 1

What are the indications for Proton Pump Inhibitors?

Answer 1

1. Peptic Ulcer Disease = used in the treatment and prevention, including NSAID-associated/induced ulcers
2. Symptomatic relief of dypepsia and GORD.
3. Eradication of Helicobacter Pylori infection = usually in an eradication treatment with antibiotics.

Question 2

What is the MOA for PPIs?

Answer 2

• The H+/K+ ATPase in gastric parietal cells usually acts as a proton pump and is responsible for secreting H+ into the stomach generating stomach acid.
• The PPIs act by irreversibly inhibiting this proton pump reducing the production of stomach acid and thus providing symptomatic relief.
  It is able to completely suppress acid production as it targets the final stage of gastric acid production.

Question 3

What are the side effects of PPIs?

Answer 3

1. GI disturbance = nausea, vomiting and diarrhoea.
2. headaches
3. Reduction of stomach acid pH, lowers the body’s defence system against infection such as C.diff.
4. Prolonged treatment may lead to hypomagnesaemia which can lead to tetany and severe ventricular arrhythmias

Question 4

What are contraindications of PPIs?

Answer 4

1. Osteoporosis as prolonged courses can increase risk of fracture in elderly people.

Question 5

What must we do before initiating PPIs?

Answer 5

Check for all red flags as it may disguise or mask symptoms of gastric cancer which cannot be treated with omeprazole alone.

Question 6

What interactions do PPIs have that you should be aware of?

Answer 6

1. Clopidogrel = omeprazole in particular is thought to reduce the anti-platelet effect by decreasing the activation of cytochrome P450 enzymes.

Lansoprazole and pantoprazole have lower propensity to interact with clopidogrel and so these are the preferred PPIs when a patient is on clopidogrel.

Question 7

What are examples of PPIs?

Answer 7

Omeprazole
Lansoprazole
Pantoprazole

Question 8

What are the indications of H2-receptor antagonists?

Answer 8

1. Peptic ulcer disease = used for the Tx and prevention of gastric and duodenal ulcers and NSAID-associated ulcers.
2. GORD and dyspepsia = relieving symptoms of dyspepsia.

Question 9

What is MOA for H2-receptor antagonists?

Answer 9

Usually, histamine is released by local paracrine cells which bind to H2-receptors on parietal cells. This binding stimulates the H+/K+ ATPase to secrete gastric acid.
Therefore, by blocking the H2 receptor it will prevent the ligation of Histamine and thus prevent gastric acid secretion.

Question 10

Why are PPIs considered better than H2-receptors?

Answer 10

H2-receptors cannot completely suppress acid production because there are other pathways which stimulate the H+/K+ proton pumps which the H2-receptor cannot block.
The PPI on the other hand is able to completely suppress acid secretion by acting on H+/K+ and blocking its effects

Question 11

What are the common side effects of H2-receptor antagonists?

Answer 11

1. GI disturbances = diarrhoea and less often constipation
2. headaches
3. dizziness

Generally well tolerated - few side effects.

Question 12

What are contraindications/cautions for using H2-receptor antagonists?

Answer 12

Renal impairment - give a reduced dose as the drug is excreted via the kidneys

Must check for red flags as it may mask Gastric cancer symptoms

Question 13

What do H2-receptor antagonists interact with?

Answer 13

No major drug interactions

Question 14

What is an example of a H2-receptor antagonist?

Answer 14

Ranitidine

Fomatidine

Question 15

What are the indications for antacids and alginates?

Answer 15

1. GORD = for symptomatic relief of heartburn

2. Dyspepsia = for short-term relief of indigestion

Question 16

What is the MOA for antacids?

Answer 16

Antacids work by buffering/neutralising the stomach acids. They are primarily used for short-term relief.

Question 17

What is the MOA for alginates?

Answer 17

Alginates work by increasing the viscosity of stomach contents. It forms a layer/raft which seperates the gastric contents from the gastro-oesophageal junction. This therefore reduces the reflux of stomach acid into the oesophagus.

Question 18

What are the side effects of compound alginates/antacids?

Answer 18

Few side effects which vary depending of the constituents and the dose taken.
magnesium salts can cause diarrhoea
aluminium salts can cause constipation

Question 19

What are the contraindications/cautions of alginates and antacids?

Answer 19

1. Compound alginates should NOT be given alongside thickened milk preparations. This is because it may excessively thicken stomach contents which may lead to bloating and abdominal discomfort.
2. Hyperkalaemia - potassium containing preparation should be used with caution
3. Fluid overload - sodium containing preparation should be used with caution
4. Renal failure - pt at increased risk of hyperkalaemia and fluid overload.
5. some sucrose containing preparations can worsen hyperglycaemia in people with Diabetes

Question 20

What interactions of antacids/alginates should you be aware of?

Answer 20

Compound alginates can bind to other drugs reducing their absorption.

Antacids can reduce serum concentration of many drugs and so doses should be taken 2 hours apart. This applies to ACEi, Antibiotics (cephalosporins, cirprofloxacin and tetracyclines), bisphosphonate, digoxin, levothyroxine, PPIs.

Question 21

Give examples of antacids and alginates

Answer 21

Alginate = gaviscon
Antacids = peptac, calcium carbonate, magnesium or aluminium salts.

Question 22

What are the indications for bulk-forming laxatives?

Answer 22

1. Constipation = esp in pts who cannot increase their dietary fibre intake.
2. Mild chronic diarrhoea = associated with diverticular disease or IBS or managing stoma output

Question 23

What is the MOA for bulk-forming laxatives?

Answer 23

Bulk-forming laxatives contain a hydrophillic substance such as a polysaccharide or cellulose which isn’t absorbed/broken down in the gut.
Similar to dietary fibre, this attracts water into the stool increasing stool mass.
Increased stool bulk stimulates peristalsis and helps to relieve constipation.
It can also help chronic diarrhoea caused by diarrhoea or IBS by increasing the bulk of stool.

Question 24

What are the side effects of bulk-forming laxatives?

Answer 24

They are well tolerated but can commonly lead to mild abdomen distension and flatulence.
Rarely, they may cause faecal impaction and GI obstruction

Question 25

What are contraindications of bulk-forming laxatives

Answer 25

1. Patients who have sub-acute or established GI obstruction or Faecal impaction. 2. Patients who have ileus (area with lack of movement in the intestines which can have increased risk of obstruction).

Question 26

Are there any interactions with bulk-forming laxatives?

Answer 26

No clinically significant drug interference with bulk-forming laxatives.

Question 27

What are examples of bulk-forming laxatives?

Answer 27

Isphagula husk Methylcellulose Sterculia

Question 28

What are indications for osmotic laxatives?

Answer 28

1. Constipation and faecal impaction 2. Bowel preparation prior to surgery or endoscopy 3. Hepatic encephalopathy

Question 29

What are the MOA for osmotic laxatives in constipation and bowel preparation?

Answer 29

They are based on osmotically active substances such as sugars or alcohols which means they aren't digested or absorbed and therefore remain in the gut lumen. They hold water in the stool maintaining its volume and stimulating peristalsis and thus defecation.

Question 30

What are the MOA for osmotic laxatives in hepatic encephalopathy?

Answer 30

Lactulose (osmotic laxative) reduces ammonia absorption and does this by increasing gut transit rate and acidifying the stool which inhibits the proliferation of ammonia-producing bacteria.

Question 31

What are the side effects of osmotic laxatives?

Answer 31

1. Flatulence, abdo cramps and nausea are common but usually wear off with time 2. Diarrhoea is also a possible complication 3. Phosphate enemas can cause local irritation and electrolyte disturbance.

Question 32

What are the interactions of osmotic laxatives?

Answer 32

1. No significant interactions | 2. Effect of warfarin may be slightly increased

Question 33

What are the contraindications of osmotic laxatives?

Answer 33

1. DON'T use in intestinal obstruction as there is a risk of perforation 2. Phosphate enemas shouldn't be given to those with heart failure ascites or when the electrolyte disturbances can cause quite significant fluid shifts.

Question 34

What are examples of osmotic laxatives?

Answer 34

Lactulose Macrogrel phosphate enema

Question 35

How are phosphate enemas administered?

Answer 35

With the patient lying on their side as for a rectal examination they should stay in this position until they need to pass/open their bowels.

Question 36

What are the indications for Stimulant laxatives?

Answer 36

1. Constipation | 2. As suppositories for faecal impaction

Question 37

What is the MOA for stimulant laxatives?

Answer 37

By increasing the water and electrolyte secretions from the colonic mucosa it increases the volume of colonic content stimulating peristalsis. They also have a direct pro-peristaltic action through the bacterial metabolism of senna in the intestine produces metabolites that have a direct action on the enteric nervous system, stimulating peristalsis.

Question 38

How do stimulant laxatives such as suppositories work ?

Answer 38

Rectal administrations such as glycerol suppositories, provokes a more localised effect and useful in treating faecal impaction.

Question 39

What are the side effects of stimulant laxatives?

Answer 39

1. Abdo pain and cramping and diarrhoea may occur as an obvious side effect. 2. Prolonged use may cause some stimulants to cause melanosis coli (reversible pigmentation)

Question 40

What are the contraindications of Stimulant laxatives?

Answer 40

1. Avoid giving to patients with suspected intestinal obstruction as there is a risk that it could induce perforation. 2. Rectal preparations should not be used in patients with haemorrhoids or anal fissures

Question 41

Are there any interactions with stimulant laxatives?

Answer 41

No clinically significant adverse drug interactions

Question 42

Examples of stimulant laxatives include?

Answer 42

Senna Bisacodyl glycerol suppositories docusate sodium.

Question 43

How are suppositories administered?

Answer 43

Rectally - treating faecal impact

Question 44

What are the indications of metronidazole?

Answer 44

1. Antibiotic associated colitis = caused by gram positive C.diff 2. Oral infections (dental abscess) or aspiration pneumonia (gram negative anaerobes) 3. Surgical and gynaecological infections caused by gram negative anaerobes from the colon 4. Protozoal infections including trichomonal vaginalis, amoebic dysentry and giardiasis.

Question 45

What is the spectrum of activity of metrinadazole?

Answer 45

Anaerobic bacteria and protozoa

Question 46

What is the MOA for metronidazole?

Answer 46

Metronidazole enters bacterial cells by cell diffusion and the reduction of metronidazole in anaerobic bacteria generates nitroso free radical. these nitroso free radicals bind to DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death (bacteriocidal).

Question 47

What is resistance in metronidazole like?

Answer 47

Resistance is generally low but is increasing in prevelance. | mechanisms include reduced uptake of metronidazole and reduced geenration of nitroso free radicals.

Question 48

What are the side effects of metronidazole?

Answer 48

1. GI upset (nausea&vomiting) 2. Immediate/delayed hypersensitivity 3. Prolonged course can cause neurological adverse effects including peripheral and optic neuropathy, seizures and encephalopathy.

Question 49

What are contraindications of metronidazole?

Answer 49

1. Severe liver disease - metabolised by hepatic CYP enzymes 2. Alcohol - inhibits acetyladehyde dehydrogenase respsonible for clearing meabolite acetylaldehyde from the body can cause nausea and vomiting, flushing and headaches.

Question 50

What are the important interactions of metronidazole?

Answer 50

Inhibitory effect on CYP enzymes reduces metabolsim of warfarin = increased risk of bleeding CYP inducers are more readily metabolised which results in reduced plasma concentrations Increases risk of lithium toxicity

Question 51

What are the indications for antimotility drugs?

Answer 51

Symptomatic treatment for diarrhoea usually for IBS or viral gastroenteritis

Question 52

What is the MOA of anti-motility drugs?

Answer 52

Loperamide is an agonist of the opioid u-receptors in the gut. the increases non-propulsive contractions of gut smooth muscle but reduces propulsive (peristaltic) contractions. resulting in the transit of bowel contents to be slowed and anal sphincter tone to be increased. slower gut transit allows more time for water to be absorbed hardens the stool

Question 53

What are the contraindications of anti-motility drugs?

Answer 53

1. Acute ulcerative colitis where inhibition of peristalsis increases risk of megacolon and perforation 2. c.diff colitis 3. acute bloody diarrhoea (dysentry) because this may signify bacterial infection 4. use of antimotility may increase the risk of haemolytic-uraemic syndrome

Question 54

What are the side effects of anti-motility drugs?

Answer 54

``` Most GI effects - constipation - abdominal cramping - flatulence if other CNS-penetrating opioids are used they may risk opioid toxicity and dependence. ```

Question 55

Give examples of antimotility drugs?

Answer 55

loperamide and codeine phosphate