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Applied Pharmacology > GI > Flashcards

GI Flashcards

1
Q

What are the indications for Proton Pump Inhibitors?

A
  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.
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2
Q

What is the MOA for PPIs?

A
  • 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.
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3
Q

What are the side effects of PPIs?

A
  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
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4
Q

What are contraindications of PPIs?

A
  1. Osteoporosis as prolonged courses can increase risk of fracture in elderly people.
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5
Q

What must we do before initiating PPIs?

A

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

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6
Q

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

A
  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.

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7
Q

What are examples of PPIs?

A

Omeprazole
Lansoprazole
Pantoprazole

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8
Q

What are the indications of H2-receptor antagonists?

A
  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.
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9
Q

What is MOA for H2-receptor antagonists?

A

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.

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10
Q

Why are PPIs considered better than H2-receptors?

A

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

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11
Q

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

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

Generally well tolerated - few side effects.

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12
Q

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

A

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

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13
Q

What do H2-receptor antagonists interact with?

A

No major drug interactions

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14
Q

What is an example of a H2-receptor antagonist?

A

Ranitidine

Fomatidine

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15
Q

What are the indications for antacids and alginates?

A
  1. GORD = for symptomatic relief of heartburn

2. Dyspepsia = for short-term relief of indigestion

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16
Q

What is the MOA for antacids?

A

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

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17
Q

What is the MOA for alginates?

A

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.

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18
Q

What are the side effects of compound alginates/antacids?

A

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

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19
Q

What are the contraindications/cautions of alginates and antacids?

A
  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
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20
Q

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

A

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.

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21
Q

Give examples of antacids and alginates

A 
Alginate = gaviscon
Antacids = peptac, calcium carbonate, magnesium or aluminium salts.
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22
Q

What are the indications for bulk-forming laxatives?

A
  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
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23
Q

What is the MOA for bulk-forming laxatives?

A

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.

24
Q

What are the side effects of bulk-forming laxatives?

A

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

25
Q

What are contraindications of bulk-forming laxatives

A
  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).
26
Q

Are there any interactions with bulk-forming laxatives?

A

No clinically significant drug interference with bulk-forming laxatives.

27
Q

What are examples of bulk-forming laxatives?

A

Isphagula husk
Methylcellulose
Sterculia

28
Q

What are indications for osmotic laxatives?

A
  1. Constipation and faecal impaction
  2. Bowel preparation prior to surgery or endoscopy
  3. Hepatic encephalopathy
29
Q

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

A

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.

30
Q

What are the MOA for osmotic laxatives in hepatic encephalopathy?

A

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.

31
Q

What are the side effects of osmotic laxatives?

A
  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.
32
Q

What are the interactions of osmotic laxatives?

A
  1. No significant interactions

2. Effect of warfarin may be slightly increased

33
Q

What are the contraindications of osmotic laxatives?

A
  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.
34
Q

What are examples of osmotic laxatives?

A

Lactulose
Macrogrel
phosphate enema

35
Q

How are phosphate enemas administered?

A

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.

36
Q

What are the indications for Stimulant laxatives?

A
  1. Constipation

2. As suppositories for faecal impaction

37
Q

What is the MOA for stimulant laxatives?

A

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.

38
Q

How do stimulant laxatives such as suppositories work ?

A

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

39
Q

What are the side effects of stimulant laxatives?

A
  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)
40
Q

What are the contraindications of Stimulant laxatives?

A
  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
41
Q

Are there any interactions with stimulant laxatives?

A

No clinically significant adverse drug interactions

42
Q

Examples of stimulant laxatives include?

A

Senna
Bisacodyl
glycerol suppositories
docusate sodium.

43
Q

How are suppositories administered?

A

Rectally - treating faecal impact

44
Q

What are the indications of metronidazole?

A
  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.
45
Q

What is the spectrum of activity of metrinadazole?

A

Anaerobic bacteria and protozoa

46
Q

What is the MOA for metronidazole?

A

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).

47
Q

What is resistance in metronidazole like?

A

Resistance is generally low but is increasing in prevelance.

mechanisms include reduced uptake of metronidazole and reduced geenration of nitroso free radicals.

48
Q

What are the side effects of metronidazole?

A
  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.
49
Q

What are contraindications of metronidazole?

A
  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.
50
Q

What are the important interactions of metronidazole?

A

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

51
Q

What are the indications for antimotility drugs?

A

Symptomatic treatment for diarrhoea usually for IBS or viral gastroenteritis

52
Q

What is the MOA of anti-motility drugs?

A

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

53
Q

What are the contraindications of anti-motility drugs?

A
  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
54
Q

What are the side effects of anti-motility drugs?

A 
Most GI effects
- constipation
- abdominal cramping
- flatulence
if other CNS-penetrating opioids are used they may risk opioid toxicity and dependence.
55
Q

Give examples of antimotility drugs?

A

loperamide and codeine phosphate

Applied Pharmacology (11 decks)

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