Pharmacology

Question 1

Groups of drugs that reduce acid secretions and an example of each?

Answer 1

Proton pump inhibitors (omeprazole)
H2 histamine receptor antagonists (ranitidine)
Muscarinic antagonists (pirenzepine)

Question 2

Describe the effect of NSAIDs on stomach acid secretions and problems that can arise from this

Answer 2

Increase acid secretion as they block cyclo-oxygenase blocking prostaglandin E2. Aspirin blocks irreversibly, ibuprofen blocks reversibly. In chronic usage predispose to formation of ulcers

Question 3

Proton pump inhibitors inhibit the active (i.e. membrane inserted) ________1________
They are basic prodrugs that are ____2___ at neutral pH, but which change conformation in a strongly acidic environment (i.e. the canaliculus)
They are absorbed from the GI tract and delivered via the ___3____ circulation to the secretory canaliculi of the stomach

Answer 3

1) H+/K+-dependent ATPase
2) inactive
3) systemic

Question 4

Why is timing of dose of proton pump inhibitors important in treatment to reduce acid secretions?

Answer 4

You need to catch actively secreting proton pumps. So need to take a certain time before eating.

Question 5

Difference between laxatives and purgatives? When should neither be used?

Answer 5

Laxatives are agents that are used to treat constipation
Purgatives are agents that cause purging, or cleansing, of the bowels by promoting evacuation
Neither should be used when there is physical obstruction to the bowel

Question 6

Medically sound uses of laxatives/purgatives include…

Answer 6

when ‘straining’ is potentially damaging to health (e.g. patients with angina), or when defaecation is painful (e.g. haemorrhoids) predisposing to constipation
to purge the bowel before surgery, or endoscopy
to treat drug-induced constipation, or constipation in bedridden, or elderly patients

Question 7

Bulk laxatives mechanism of action? Examples?

Answer 7

Increase the volume of the intestinal contents stimulating peristalsis
methylcellulose - orally

Question 8

Osmotic laxatives mechanism of action? Examples?

Answer 8

These increase bulk in the bowel by retaining water by an osmotic effect. They include salts containing poorly absorbed ions.
magnesium sulphate or hydroxide – orally; sodium citrate – rectally

Question 9

Stimulant laxatives mechanism of action? Examples? Side effect?

Answer 9

Increase motility by acting on the mucosa or nerve plexuses which may be damaged by prolonged drug use. They often cause abdominal cramp
e.g. bisacodyl – orally, or suppository when rapidly acting

Question 10

Faecal softeners mechanism of action? Examples?

Answer 10

promote defection by softening and or lubricating faeces and assisting evacuation
e.g. docusate sodium – orally

Question 11

6 classes of drugs that can cause vomiting?

Answer 11

Cancer chemotherapy
Operations involving the administration of a general anaesthetic [post-operative nausea and vomiting (PONV)]
Agents with dopamine agonist properties (e.g. levodopa used in Parkinson’s disease)
Morphine and other opiate analgesics (tolerance develops
Cardiac glycosides (e.g. digoxin)
Drugs enhancing 5-HT function (e.g. SSRIs; 5-HT3 receptors are prevalent in the CTZ)

Question 12

5-HT3 receptor antagonists mechanism of action? What are they used for? Examples?

Answer 12

Used to suppress chemotherapy- and radiation-induced emesis and post-operative nausea and vomiting
Block peripheral and central 5-HT3 receptors so vomit signals cannot be transmitted to the brain
They all end in setron e.g. ondansetron, palonosetron)

Question 13

Muscarinic acetylcholine receptor antagonists mechanism of action? What are they used for? Examples?

Answer 13

Used for prophylaxis and treatment of motion sickness (can be delivered by transdermal patch)
Probably block muscarinic acetylcholine receptors at multiple sites (e.g. vestibular nuclei, NTS, vomiting centre)
Direct inhibition of G.I. movements and relaxation of the G.I. tract may contribute (modestly) to anti-emetic effects
They are non-specific though to GI so numerous unwanted side effects
Example is hyosine

Question 14

Histamine H1 receptor antagonists mechanism of action? What are they used for? Examples?

Answer 14

Used for prophylaxis and treatment of motion sickness and acute labyrinthitis and nausea and vomiting caused by irritants in the stomach. Less effective against substances that act directly on the CTZ
Action attributed to blockade of H1 receptors in vestibular nuclei and NTS
e.g. cyclizine, cinnarizine

Question 15

Dopamine receptor antagonists mechanism of action? What are they used for? Examples?

Answer 15

Used for drug-induced vomiting (e.g. cancer chemotherapy, treatment of Parkinson’s disease with agents stimulating dopaminergic transmission) and vomiting in gastrointestinal disorders
Centrally block dopamine receptors in CTZ
e.g. domperidone and metoclopramide

Question 16

NK1 receptor antagonists mechanism of action? What are they used for? Examples?

Answer 16

Used in combination with a 5-HT3 receptor antagonist and dexamethasone in the acute phase of highly emetogenic chemotherapy. In combination with dexamethasone in the delayed phase
Mode of action don’t know
e.g. aprepitant

Question 17

Cannabinoid (CB1) receptor agonists mechanism of action? What are they used for? Examples?

Answer 17

Used ideally in in-patient setting for treatment of cytotoxic chemotherapy that is unresponsive to other anti-emetics
Decreases vomiting induced by agents stimulating the CTZ.
e.g. nabilone

Question 18

Explain how rehydration therapies work

Answer 18

exploit the SGLT1 as if you give people solutions of sodium and glucose there will be accompanying absorption of H2O.

Question 19

How do morphine like drugs have anti-diarrhoea activity

Answer 19

o inhibition of enteric neurones (hyperpolarization via activation of -opioid receptors)
o decreased peristalis, increased segmentation (i.e. constipating)
o increased fluid absorption
o constriction of pyloric, ileocaecal and anal sphincters
o increased tone of large intestine

Question 20

3 examples of opioids used for anti diarrhoea activity

Answer 20

codeine, diphenoxylate and loperamide

Question 21

3 examples of bile acid binding resins/ sequestrants?

Answer 21

Colveselam, colestipol, colestyramine

Question 22

How do bile acid binding resins work? What are they used for?

Answer 22

o Not digested or absorbed by the gut and act by binding to bile acids, preventing their reabsorption so you’ll get less bile.
o This lowers cholesterol as the liver needs to make new bile so will use up the cholesterol indirecting lower LDL blood levels
o Other clinical uses include cholestatic jaundice (itch) and bile acid diarrhoea

Question 23

• In severe hepatic failure (e.g. fulminant liver failure), detoxification of ammonia (NH3), via the urea cycle, to urea (excreted by kidneys) fails
• Blood NH3 levels rise (hyperammonemia) exerting a toxic effect _______ ultimately leading _______

Answer 23

CNS

Coma

Question 24

Therapeutic options for hepatic coma? Explain how they work?

Answer 24

A widely used therapeutic option is to administer:
o lactulose – a semisynthetic disaccharide of fructose and lactose which
• is not digested or absorbed in the small intestine
• when broken down in the colon acidifies the stool (reduces pH)
• converts ammonia (NH3) to ammonium (NH4+) which is not absorbed

o	antibiotics (neomycin, rifamixin) -  that are minimally absorbed
•	suppress colonic flora and thus inhibit ammonia generation