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Clinical pharmacology and therapeutics > S10: GI pharmacology & antiemetics > Flashcards

S10: GI pharmacology & antiemetics Flashcards

1
Q

Describe the mechanism of action of alginates and antacids

A

Antacids – buffering stomach acid
Alginic acid – increase stomach content viscosity and reduce reflux
Often taken as compound preparations (alginic acid + antacid)
Eg. Gaviscon

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2
Q

What are the adverse effects, warnings, contraindications & important drug interactions of alginates and antacids?

A

Adverse effects: magnesium salts can cause diarrhoea & aluminium salts can cause constipation
Warnings, contraindications: Na+ and K+ containing preparations should be used with caution in renal failure, high [sucrose] in some preparations (hyperglycaemia in DM)
Important drug interactions: can reduce absorption of many drugs, increased urine alkalinity can increase aspirin excretion

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3
Q

Describe the mechanism of action of proton pump inhibitors

A

Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
Final stage in the pathway -> very significant reduction in acid secretion

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4
Q

List examples of PPIs

A

Lansoprazole

Omeprazole

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5
Q

What are the adverse effects, warnings, contraindications & important drug interactions of PPIs?

A

Adverse effects: GI disturbance (abdominal pain, constipation, diarrhoea), headache, dizziness, drowsiness/confusion
Warnings, contraindications: mask symptoms of gastro-oesophageal cancer, osteoporosis – fracture risk
Important drug interactions: omeprazole CYP inhibitor – reduced clopidogrel action, can increase effects of warfarin & phenytoin

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6
Q

Describe the mechanism of action of H2 receptor antagonists

A

Inhibition of H2 receptors – local histamine release contributes to proton pump activation
Only partial reduction in acid secretion

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7
Q

What are the adverse effects, warnings, contraindications & important drug interactions of H2 receptor antagonists?

A

Adverse effects: well tolerated – diarrhoea, headache
Warnings, contraindications: mask symptoms of gastro-oesophageal cancer, renal impairment
Important drug interactions: few common DDIs

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8
Q

List examples of H2 receptor antagonists

A

Ranitidine

Current large scale recall on most ranitidine containing products -> possible carcinogenic contaminant

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9
Q

Describe treatment for H. pylori infection

A

Confirm infection by urea breath test
One week triple therapy – PPI + two antibacterial agents
Lansoprazole + clarithromycin + amoxicillin
OR lansoprazole + clarithromycin + metronidazole (where allergic to amoxicillin)
Compliance with full course important for effectiveness & minimise risk of bacterial resistance

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10
Q

Describe mechanism of action of aminosalicylates

A

Release of 5-aminosalsylic acid
Topical action at the colon – enteric coated tablets limit gastric breakdown
Used as first line treatment in ulcerative colitis

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11
Q

What are the adverse effects, warnings, contraindications & important drug interactions of aminosalicylates?

A

Adverse effects: GI disturbance (nausea, dyspepsia), leukopenia – rare
Warnings, contraindications: similar hypersensitivity (like aspirin)
Important drug interactions: enteric coated tablets may break down quicker in presence of PPI (increased pH)

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12
Q

List triggers which cause the vomiting centre to go

A

Direct triggers
Sensory afferents via midbrain
Visceral afferents from gut
Vestibular nuclei

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13
Q

List agents which act on the vestibular nuclei

A

Muscarinic receptor antagonists

H1 receptor antagonists

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14
Q

Describe muscarinic receptor antagonists

A

Hyoscine hydrobromide
Competitive blockade of muscarinic acetylcholine receptors – in vestibular nuclei & at chemoreceptor trigger zone (CTZ)
Indications: people who can’t take tablets, motion sickness & bowel obstruction

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15
Q

List side effects of muscarinic receptor antagonists

A

Sedation
Memory problems
Glaucoma
Dry mouth and constipation

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16
Q

Describe H1 receptor antagonists

A

Cyclizine
Centrally – acts on vestibular nuclei, inhibits histaminergic signals from the vestibular system to CTZ in medulla
Indications: motion sickness
Not good for: old ladies & children

17
Q

List side effects of H1 receptor antagonists

A

Sedation
Excitation
Antimuscarinic – dry mouth, constipation, urinary retention
Cardiac toxicity – long QT interval

18
Q

List agents acting on visceral afferents in the gut

A

5HT3 receptor antagonists

D2 receptor antagonists

19
Q

Describe 5HT3 receptor antagonists

A

Ondansetron
Peripherally – reduces gut motility, reduces GI secretions
Centrally – acts to inhibit CTZ
Indications: almost everyone – 1st line treatment

20
Q

List side effects of 5HT3 receptor antagonists

A 
Uncommon 
Constipation
Headache 
Elevated liver enzymes
Long QT syndrome 
Extra-pyramidal effects – dystonia, parkinsonism
21
Q

Describe D2 receptor antagonists (acting on visceral afferents in gut)

A

Metoclopramide, domperidone
Increases acetylcholine at muscarinic receptors in gut
Promotes gastric emptying – increases tone at LOS, increases tone and amplitude of gastric contractions, decreases tone of pylorus so it opens
Increases peristalsis
Indications:
- Metoclopramide: GORD, ileus
- Domperidone: improving lactation in breastfeeding mothers

22
Q

List side effects of D2 receptor antagonists

A

Metoclopramide: galactorrhoea, extra pyramidal effects
Domperidone: sudden cardiac death (long QT and VT), galactorrhoea

23
Q

List agents acting on the CTZ

A 
5HT3 receptor antagonists 
H1 receptor antagonists 
Muscarinic receptor antagonists 
D2 receptor antagonists 
Corticosteroids 
Cannabinoids 
NK1 receptor antagonists
24
Q

Describe D2 receptor antagonists (acting on CTZ)

A

Metoclopramide, domperidone, chlorpromazine, haloperidol
Act on the CTZ, may also block H1 and muscarinic receptors
Indications: motion sickness, vertigo, pregnancy
Haloperidol – chemotherapy & palliation
Side effects: extra-pyramidal effects, sedation, hypotension

25
Q

Describe corticosteroids

A

Dexamethasone, methylprednisolone
Assumed to act on the CTZ, may also have properties of D2 receptor antagonists
Indications: perioperative nausea & vomiting, chemotherapy, palliation

26
Q

List side effects of corticosteroids

A

Insomnia
Increased appetite
Increased blood sugar

27
Q

Describe neurokinin-1 receptor antagonists

A

Aprepitant
Prevent the action of substance P at CTZ & in peripheral nerves
Boosts effects of 5HT3 receptor antagonists
Anxiolytic & antidepressant properties
Good for chemotherapy – particularly for delayed emesis

28
Q

List side effects of neurokinin-1 receptor antagonists

A

Headache
Diarrhoea/constipation
Stevens-Johnson syndrome

29
Q

Describe treatment for motion sickness

A

Hyoscine hydrobromide is 1st line

Cinnirazine has fewer side effects

30
Q

What is hyperemesis gravidarum? What is the treatment for it?

A

Rapid rise in B-hCG stimulates the CTZ
More than just ‘morning sickness’ – dehydration, weight loss, electrolyte imbalance, urinary ketones
1st line: promethazine, prochlorperazine

31
Q

Outline treatment for post-operative nausea

A

Ondansetron and/or cyclizine

Then add dexamethasone

32
Q

Describe opioid receptor agonists (specific for intestine)

A

Loperamide, codeine phopshate
Specific to u receptors in myenteric plexus
Decreases tone of longitudinal and circular smooth muscle
Reduces peristalsis but increases segmental contractions
Decreases colonic mass movement by supressing gastrocolic reflex

33
Q

List side effects of opioid receptor agonists

A

Paralytic ileus
Nausea and vomiting
Sedation and addiction (codeine & morphine)

34
Q

Describe osmotic laxatives

A

Lactulose, Movicol
Increase the amount of water in the large bowel
Lactulose – draws fluid in
Movicol – retain the fluid they came with

35
Q

Describe stimulant laxatives

A

Bisacodyl, senna, docusate sodium

Increase intestinal motility, may be given orally or per rectum

36
Q

Describe bulk forming laxatives

A

Ispaghula husk, methylcellulose

Medicinal fibre

37
Q

Describe stool softeners

A

Docusate sodium, glycerin suppository
Decrease surface tension of stool
Increase penetration of fluid into stool

Clinical pharmacology and therapeutics (14 decks)

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