L21. Pharmacology of the GIT Flashcards Preview

04. Gastrointestinal > L21. Pharmacology of the GIT > Flashcards

Flashcards in L21. Pharmacology of the GIT Deck (43):
1

Antacids Mechanism of Action

Neutralises gastric acid content in the lumen without impacting production or secretion of acid
- often in combination with PPI or H2 antagonists

2

Antacid example 1

ANTACID

Magnesium hydroxide
Magnesium salts have a laxative effect (non-absorbable ion)

3

Antacid example 2

ANTACID

Gaviscon
Mixture with sodium bicarbonate to make it fizzy
Can cause alkalosis
Risk of the rebound hyperacidity effect due to feedback pathways

4

Antidiarrhoeal major class

ANTI-DIARRHOEAL

Opioid Anti-diarrhoeals

Activate mu opioid receptors in the gut wall leading to decreased motility and increased fluid absorption (inhibit ACh release)
Very potent
Traveller's diarrhoea

Adverse effect: abdominal pain, bloating, vomiting and nausea, constipation

5

Example of antidiarrhoeal

Loperamide
- last derivation of morphine

Most commonly used and doesn't cross the BBB doesn't have the the analgesic effects of opioids.

6

Two other less commonly used antidiarrhoeals

Direct spasmolytics: mebeverine
Muscarinic receptor antagonists: hyoscine butylbromide

7

What are the two broad classes of anti-emetics?

Anti-nausea and vomiting:
Target the Vomiting centre: H2 and M receptor antagonists

Reflex anti-emetics:
Target the Chemoreceptor Trigger Zone: D2 and 5HT3 and NK1 receptor antagonists

8

Mechanism of action of the anti-histamines (H1)?

ANTI-EMETIC

First generation anti-histamines (cross the blood brain barrier and thus have sedative effects)

Blocks H1 receptors in the brain and prevents signalling pathways from the vomiting centre

Adverse effects: psychomotor impairment, dizziness, confusion, headache, blurred vision, dry eyes, constipation

9

Example of anti-histamine

Promethazine

10

Mechanism of action of the muscarine receptor antagonists

ANTI-EMETIC

Inhibits muscarinic signalling from the vomiting centre
May cause tachycardia
Adverse effects (inhibition of SLUD) - dry mouth, dry eyes, urinary retention and constipation, confusion

11

Example of muscarinic antagonist

Hyoscine hydrobromide

12

Dopamine D2 receptor antagonist mechanism of action

ANTI-EMETIC

Blockage of dopamine receptors in the CNS, basal ganglia and in the gut (facilitate gastric emptying)

However leads to severe extra-parametal side effects including dysphonia and parkinson's-like symptoms

13

Example of D2 receptor antagonist that enter the CNS

Metoclopromide
Prochloroperazine

14

Examples of D2 receptor antagonists that don't enter the CNS

Domperidone

15

Mechanism of action of Serotonin 5HT3 receptor antagonists

ANTI-EMETICS

Very effective especially with cytotoxic drug and chemotherapy related nausea and vomiting

Inhibit serotonin receptors in the CTZ and has less side effects as the dopamine receptors: constipation, headaches

Often used in combination with the D2 and NK1 antagonists

16

Example of serotonin 5HT3 receptor antagonist

ANTI-EMETIC

Ondasetron

17

Mechanism of action of neurokinin 1 antagonists

Prevents the neurokinin-1 receptor (receptor for substance P) at the CTZ

Never used alone, always in combination

18

Example of NK1 receptor antagonist

ANTI-EMETIC (add on drug)

Aprepitant

19

Mechanism of action of anti flatulence drugs

Defoaming polymers that alters surface tension on small air bubbles allowing them to coalesce into larger bubbles that are easier to pass

Used in mixtures with antacids

20

Example of drugs targeting flatulence

Simethicone

21

Mechanism of action of the proton pump inhibitors (PPI)

GASTRIC ULCERS

Irreversible inactive that pump system suppressing acid secretion (restoration only occurs upon synthesis of new pumps)

Headache, nausea, vomiting, diarrhoea, abdominal pain, constipation and flatulence

22

Indications of PPIs

Peptic ulcer disease, GORD, dyspepsia, H.pylori infection, NSAID adverse effects

23

Examples of PPIs [3]

Esomeprazole
Omperazole
Pantomeprazole

24

Mechanism of action of histamine D2 receptor antagonists

GASTRIC ULCERS

Competitive blockage of H2 receptor antagonists in the gut (basal membrane of parietal cells)
Leads to decreased activation of cAMP and decreased activity of the pump leading to decreased acid secretion

Often used in combination with PPI and anti-inflammatory drugs

Low side effects: hypotension, headache, confusion, diarrhoea or constipation

25

What are examples of histamine D2 receptor antagonists? [2]

Ranitidine
Cimetidine

26

What are the different types of laxatives? [5]

1. Bulking agents
2. Stool softeners
3. Osmotic laxatives
4. Stimulant laxatives
5. Glycerol

27

Mechanism of action of bulking agents

LAXATIVE

Increase fibre content and increases water retention of intestinal contents increasing reflex bowel action for peristaltic activity

Must be taken with lots of fluid
Adverse: flatulence, bloating, abdominal discomfort, intestinal obstruction, hypersensitivity reactions (rare)

28

Examples of bulking agents

LAXATIVE

Bran
Psyllium

29

Mechanism of action of stool softeners

LAXATIVE

Detergent action to enhance the mixing of water into the faeces (emulsifying effect)
Can increase intestinal fluid secretion

abdominal cramps, diarrhoea, nausea, rash

30

Example of stool softener

Docusate
(liquid paraffin)

31

What is docusate often combined with for treatment with opioid drugs to prevent constipation

Docusate + Senna (stimulant laxative)

32

What are the different classes of osmotic laxatives? [5]

1. Saline laxatives
2. Disaccharide
3. Polyols
4. Macrogols
5. Glycerol

33

General mechanism of action of the osmotic laxatives?

Most contain an non-absorbable component (metal ions, sugars, large macropolymers) that exert an osmotic effect on the gut to force water out

All are contraindicated in intestinal obstruction

34

Saline laxative example

Magnesium sulphate (epsom salts)

35

Disaccharide example

Lactulose

36

Polyols example

Sorbitol (artificial sweetener in confectionary)

37

Macrogol uses

Bowel preparations - often combined with electrolytes

38

Mechanism of action of stimulant laxatives

LAXATIVE

Direct stimulation of nerve endings in colonic mucosa to increase intestinal motility
can also cause accumulation of water and electrolytes in the lumen by reduction of net reabsorption

39

Example of a stimulant laxative

SENNA

40

Example of another laxative class (acts on mu opioid receptors)

Methylnaltrexone

Peripherally acts on mu opioid receptors to block action in the gut

41

Cytoprotective drug for ulcers

Sucralfate
Forms protective barrier at the ulcer site resistant to acid, pepsin and bile

42

Use of spasmolytics in ulcers: MOA and example

MUSCARINIC RECEPTOR ANTAGONIST
Hyoscine butylbromide
Reduces gut motility (anti-slud) = buscopam
Not absorbed so only has periperal effects

43

Use of prostaglandin E analogues in ulcers: MOA and example

Mimics endogenous PG
Increases mucosal secretion, mucosal blood flow and decreases acid secretion

Misoprostol