GI pharmacology Flashcards
H2 antagonists
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
Ranitidine
Common indications
- Peptic ulcer disease
- GORD and dypspepsia
Mechanisms of action
- Inhibit H2 proton pump in parietal cell-> prevent gastric acid secretion
important adverse effects
- Diarrhoea/constipation
- Headaches etc.
Proton pump inhibitors
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
Omeprazole, pantoprazole, lanzoprazole
Common indications
- Peptic ulcer disease
- GORD and dyspepsia
- Used in treatment for H. pylori
Mechanisms of action
- Inhibits irreversibly H+/K+ ATPAse channel in parietal cells
important adverse effects
- Constipation/diarrhoea
- Headaches
- Increased risk of fractures-> should not be used in people with osteoporosis
- Can cause hyponatraemia
A 56-year-old gentleman presents with vomiting, severe crampy abdominal pain, loss of appetite. Patient has not had a bowel movement or passed gas in the last three days. On examination the abdomen is distended and generalised tenderness is present.
Which medication should be avoided in this patient?
- cyclizine
- metoclopramide
- morphine
- ondansetron
- phosphate enema
- metoclopramide (pro-kinetic) should be avoided in people w bowel obstruction due to the risk of perforation
Bulk forming laxatives
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
- isphagula husk, methylcellulose, sterculia
Common indications
- Constipation
Mechanisms of action
- Contain hydrophilic substance like cellulose/polysaccharide that attracts water to form bulk in colon-> peristalsis
important adverse effects
- Abdominal distention/flatulence
- Faecal impaction/intestinal obstruction (rarely)
warnings
- Cannot be used with those with poor motility like faecal impaction/obstruction/terminal ileus
Loperamide, codeine phosphate
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
Common indications
- Diarrhoea
Mechanisms of action
- Opioid agonist-> slows down peristalsis and slow down colonic transition time
important adverse effects
- constipation, flatulence, colicky abdominal pain
- codeine phosphate can enter CNS and cause opiod toxicity in high amounts
warnings
- Do not give in ulcerative colitis-> cause toxic megacolon
- Do not give in c diff infection-> patients develop diarrhoea
important interactions
A 24-year-old woman is vomiting following an evacuation of retained products of conception (ERPC), performed under general anaesthesia. She was given cyclizine 50 mg IV 30 minutes ago but this has not improved her symptoms.
Her past medical history is notable for a severe illness involving fever and muscles spasms, which was thought to have been precipitated by a prochlorperazine injection.
What is the most appropriate treatment for her nausea and vomiting?
A.Chlorpromazine
B.Cyclizine
C.Haloperidol
D.Metoclopramide
E. Ondansetron
E. Ondansetron. Predicting which antiemetic will work in which patient is not easy. In practice, drug selection is often based on pragmatic considerations such as familiarity and availability, and then adjusted according to the patient’s response. With her having already had cyclizine (an antiemetic that acts by histamine H1-receptor antagonism), it would now be best to offer a drug from a different class. This choice is influenced by her past reaction to prochlorperazine, which sounds like neuroleptic malignant syndrome (NMS). NMS is a serious condition that may be precipitated by drugs that have an anti-dopaminergic effect, including phenothiazine antiemetics (e.g. prochlorperazine, chlorpromazine), dopamine antagonist antiemetics (e.g. metoclopramide) and antipsychotics (including haloperidol, which is sometimes also used as an antiemetic). The risk of recurrence of NMS with re-exposure is unclear, but it would be prudent to avoid these drug classes where suitable alternatives exist. Ondansetron is an antiemetic that works by serotonin 5-HT3-receptor antagonism; it is not associated with NMS.
A 48-year-old woman who has peptic ulcers caused by Helicobacter pylori infection presents to her GP to commence treatment. She is allergic to benzylpenicillin, which caused an anaphylactic reaction.
What is the most appropriate 1-week oral treatment regimen?
A. Lansoprazole 30 mg 12-hourly, amoxicillin 1 g 12-hourly and clarithromycin 500 mg 12-hourly
B. Lansoprazole 30 mg 12-hourly, amoxicillin 1 g 12-hourly and metronidazole 400 mg 12-hourly
C. Omeprazole 20 mg 12-hourly and clarithromycin 500 mg 12-hourly
D. Omeprazole 20 mg 12-hourly and metronidazole 400 mg 8-hourly
E. Omeprazole 20 mg 12-hourly, clarithromycin 250 mg 12-hourly and metronidazole 400 mg 12-hourly
E. Omeprazole 20 mg 12-hourly, clarithromycin 250 mg 12-hourly and metronidazole 400 mg 12-hourly. Helicobacter pylori is a Gram-negative bacterium which causes peptic ulcer disease. Effective treatment requires combination therapy with two antibiotics and a proton pump inhibitor for 1 week. Treatment with a single antibiotic may be ineffective and may cause the bacteria to develop resistance.
The various regimens considered acceptable for H. pylori eradication, including recommended drug doses, are set out in a helpful table in the British National Formulary. Options for proton pump inhibition include lansoprazole, omeprazole and pantoprazole. The antibiotics are selected from amoxicillin (a broad-spectrum penicillin), clarithromycin (a macrolide) and metronidazole. As this patient has previously had an anaphylactic reaction to benzylpenicillin, amoxicillin is contraindicated and clarithromycin with metronidazole should be used. You should note that the doses recommended for antibiotics when used in H. pylori eradication may differ from those used in other indications.
An 86-year-old woman has been taking codeine phosphate to treat a sprained wrist. Co-incidentally, she has noticed that this improved the diarrhoea she usually suffers from as a result of diverticular disease.
Although her wrist has now healed, she is keen to continue taking the codeine, as not having to open her bowels so regularly has considerably improved her quality of life. However, the codeine does makes her feel a little ‘light headed’, which she finds unpleasant.
What alternative opioid would be better to treat her diarrhoea?
A.Loperamide
B. Morphine (immediate release)
C.Morphine (modified release)
D. Oxycodone (modified release)
E. Pethidine
A. Loperamide. Loperamide is an antimotility drug used in selected cases of diarrhoea. Pharmacologically, it is an opioid similar to pethidine, but unlike other opioids it does not cross the blood–brain barrier. This means it is devoid of central nervous system effects, including analgesia, but retains the peripheral effects such as reducing gut motility. The antimotility effects are mediated by opioid µ-receptor agonism in the myenteric plexus of the gastrointestinal tract.
While the other opioids in this list will have similar antimotility effects, they are likely also to cause central nervous system effects which, in this context, are undesirable.
A 62-year-old man with a background of alcoholic cirrhosis is admitted to the acute medical unit with confusion. A diagnosis of hepatic encephalopathy is made. His wife reports that he had been complaining of constipation in the days leading up to admission.
What laxative should be prescribed?
A. Docusate sodium
B. Ispaghula husk
C. Lactulose
D. Macrogol
E. Senna
C. Lactulose. One of the main substances involved in the pathogenesis of hepatic encephalopathy is ammonia. Lactulose is an osmotic laxative that reduces absorption of ammonia by increasing transit rate of colonic contents and by acidifying the stool, which inhibits the proliferation of ammonia-producing bacteria. This makes it an important treatment for patients with, or at risk of, hepatic encephalopathy, regardless of whether they are constipated. In these circumstances, the aim should be for patients to produce three loose stools each day. The other drugs are all laxatives that will treat his constipation but will not be as beneficial in treating his encephalopathy.
A 50-year-old man complains of severe itch. He has had this for several days and it affects his whole body. He was admitted yesterday with progressive ascites due to cirrhotic liver disease. He is taking furosemide 40 mg orally daily, spironolactone 200 mg orally daily, lactulose 30 mL orally 8-hourly and phosphate enema 128 mL rectally daily. He has no allergies.
On examination of his skin, there are multiple spider naevi over his upper body and excoriation marks over his arms, trunk and thighs.
What is the most appropriate initial pharmacological treatment?
A. Chlorphenamine orally
B. Codeine phosphate orally
C. Hydrocortisone topically
D. Loratadine orally
E. Prednisolone orally
D. Loratadine orally. Pruritus is a common problem in liver disease. Non-pharmacological measures such as warm baths may be helpful but are often insufficient. First-line pharmacological treatment is usually with an antihistamine. When prescribing for patients with advanced liver disease, it is important to avoid using sedating drugs wherever possible. This is because sedation can precipitate hepatic encephalopathy. Chlorphenamine is a first-generation antihistamine with pronounced sedative effects. By contrast, loratadine is a second-generation antihistamine which, by virtue of not crossing the blood–brain barrier, does not cause sedation.
Topical corticosteroids are sometimes used for inflammatory lesions associated with pruritus (e.g. eczema), but they are not an option for generalised pruritus. Systemic corticosteroids are not used for pruritus. As an opioid agonist, codeine phosphate may cause itch. Furthermore, its sedative effects may be problematic.
An 85-year-old woman is advised to take ranitidine for dyspepsia.
What best describes the mechanism of action of ranitidine?
A. Antagonism of histamine H1 receptors in gastric parietal cells
B. Antagonism of histamine H1 receptors in the vagus nerve
C. Antagonism of histamine H2 receptors in gastric parietal cells
D. Antagonism of histamine H2 receptors in gastric chief cells
E. Antagonism of histamine H2 receptors in the vagus nerve
C. Antagonism of histamine H2 receptors in gastric parietal cells. Ranitidine is a histamine H2-receptor blocker. Histamine is released from paracrine cells in the stomach and binds to H2-receptors on gastric parietal cell walls. Acting through second messenger systems, this activates the proton pumps that are responsible for gastric acid secretion. By blocking H2 receptors, ranitidine increases the pH of the stomach contents and thereby reduces symptoms of gastritis and gastro-oesophageal reflux.
A 55-year-old woman with psoriatic arthritis was admitted to hospital 12 days ago with severe cellulitis. On admission her liver function was normal, but she has now developed cholestatic jaundice.
Her medications are flucloxacillin, methotrexate, morphine, paracetamol and simvastatin.
Which drug is most likely to have caused her cholestatic jaundice?
A. Flucloxacillin
B. Methotrexate
C. Morphine
D. Paracetamol
E. Simvastatin
A. Flucloxacillin. Cholestatic jaundice is a rare, but potentially serious, adverse effect of flucloxacillin (a penicillinase-resistant penicillin). It can occur even when treatment has been completed and is a contraindication to future use of this drug.
Although paracetamol, methotrexate and simvastatin (a statin) can all cause liver toxicity, they do not generally cause cholestatic jaundice. Paracetamol in overdose causes hepatocellular necrosis, which can be fatal if untreated. Methotrexate can cause hepatitis as part of a hypersensitivity reaction or if taken in overdose. Chronic use of methotrexate can cause hepatic cirrhosis. Statins can cause a rise in liver enzymes (transaminases) and, less frequently, drug-induced hepatitis. Morphine does not cause hepatotoxicity, but it is metabolised in the liver so dose reduction is required in people with liver failure.
