Anti-emetics, constipation, antidiarrhoea and prokinetics - Pharmacology

Question 1

What are the potential causes of vomiting

Answer 1

Stimulation of higher centers
Labyrinth impulses: motion sickness
Centrally acting emetics
Drug induced
Metabolic causes
Post op vomiting
Chemo and radiotherapy

Question 2

What are the major efferent pathways and receptors of the vomiting center

Answer 2

Major efferent pathways:
- Phrenic nerve
- Vagus nerve
- Spinal nerves

Receptors
- Ach M
- H1
- 5HT2

Question 3

What are the main receptors of the chemoreceptor trigger zone and what stimuli is it sensitive to

Answer 3

Receptors
- D2
- NK1: Neurokinin 1
- 3HT3

Stimuli
- Radiation
- Bacterial toxins
- Uraema

Question 4

What are the main receptors of the vestibular system

Answer 4

H1
Ach M

Question 5

What are the major efferent pathways and receptors of the peripheral pathways

Answer 5

Major efferent pathways:
- Phrenic nerve
- Vagus nerve
- Spinal nerves

Receptors:
- 5HT3

Question 6

What are the Anti-emetic drug groups

Answer 6

Antihistamines
Dopamine agonists
Benzodiaziapines
Neurokinin antagonists
Corticosteroids
Cannabinoids
Serotonin antagonists (5HT3)
Anticholinergic agents

Question 7

What are examples of antihistamines (H1 blockers)

Answer 7

• Promethazine (Phenergan, Avomine) - most effective, markedly sedating
• Cyclizine (Valoid) - safe in pregnancy, caution in children <6years: extrapyramidal effects
• Betahistine (Serc) - used in association with Meniere’s disease
• Cinnarizine (Stugeron)
• Hydroxyzine (Aterax)
• Diphenhydramine
• Flunarizine (Sibelium)

Question 8

What are antihistamines indicated for, where do they act and what are the limitations of use

Answer 8

Most effective drugs in preventing motion sickness
May be used for post operative emesis

Act on vestibular efferents and within brainstem at vomiting center

Limitations of use:
- Modest efficacy
- Dose related adverse effects
- Antimuscarinic effects

Question 9

What are examples of dopamine antagonists

Answer 9

Phenothiazines:
* Prochlorperazine (Stemetil)
* Trifluoperazine
* Perphenazine
* Chlorpromazine (Largactil)

Benzamides:
* Metoclopramide (Maxolon)

Butyrophenones:
* Haloperidol (Serenace)
* Domperidone (Motilium)

Question 10

What are the indications and side effects of dopamine antagonists: Phenothiazines

Answer 10

Most commonly used general purpose anti-emetics: prochlorperazine
Helpful in hiccups
Opiod and radiation induced vomiting

Side effects:
- Hypotension
- Restlessness
- Extra-pyramidal side effects
- Sedation

Question 11

What are the indications for dopamine antagonists: Butyrophenones

Answer 11

Domperidone:
- Increases gastro-intestinal peristalsis
- Nausea associated with migraine
- Gastroparesis in diabetics: not in mechanical obstruction
- May prolong QT interval
- Causes hyperprolactonaemia

Haloperidol
- Mainly used as antipsychotic agent in schizophrenia
- Used for sedation in endoscopy & surgery incombo with opiates & benzo’s
- Used for intractable hiccups

Question 12

What are the moa, indications and side effects of dopamine antagonist: Metoclopramide

Answer 12

Promotes gatsric emptying

Indications:
- Post op period
- Infection
- Uraemia
- Drug/toxin induced
- Radiation sickness

Side effects:
- Sedation, diarrhoea
- Extra-pyramidal symptoms
- Hyperprolactinemia

Question 13

What are examples of 5HT3 receptor antagonists

Answer 13

• Ondansetron
• Granisetron
• Palonsetron
• Dolasetron
• Tropisetron

Question 14

What are the indications and adverse effects of 5HT3 receptor antagoists

Answer 14

Indications:
- Chemo induced emesis
- Post op nausea and vomiting

Adverse effects
- Headache
- Constipation
- QT interval prolonged
- Expensive

Question 15

What is an example of neurokinin antagonists and whata re the indications and adverse effects

Answer 15

Aprepitant (Emend)
Administered orally with dexamethasone & palonosetron: increases activity

Indications:
- Prevention of acute and delayed chemotherapy induced nausea and vomiting
- Prevention of post op nausea and vomiting

Adverse effects:
- Extensive CYP3A4 metabolism: shorten t1/2 of Warfarin
- Constipation
- Fatigue

Question 16

What are examples of Cannabinoids, the MOA and side effects thereof

Answer 16

Dronabinol & Nabilone
- Major constituent D-9-tetrahydrocannabinol (THC)

Mechanism:
- Block decending pathways in cortical centers

Side effects
- Dysphoria
- Hallucinations
- Sedation
- Vertigo
- Disorientation

Question 17

What are the indications for Anticholinergic agents

Answer 17

Used as adjunct therapy in management of:
➢Peptic ulcer disease
➢Zollinger-Ellison syndrome
➢(mostly patients who are refractory to standard therapies)
➢(to relief smooth muscle spasm)
➢Intestinal spasms
➢Biliary spasms
➢Genitourinary spasm
➢(Propantheline for hyperhydrosis)

Question 18

What are examples of Anti-cholinergic agents

Answer 18

• Dicyclomine: Relief of biliary, intestinal, genitourinary spasm
• Hyoscine Butyl-Bromide: Antispasmodic action on biliary,intestinal, genitourinary tract
• Mebeverine: Selective spasmolytic on GI smooth muscle (irritable colon)
• Propantheline: Adjunctive therapy in peptic ulcer disease

Question 19

What are the side effects and contra indications of Anti-cholenergic agents

Answer 19

Side effects:
- Cardiac arrhythmias
- Dry mouth
- Constipation
- Urinary retention
- Respiratory collapse / apnoea (Dicyclomine)

Contra-indications:
– Closed angle glaucoma
– Myasthenia gravis
– Paralytic ileus
– Pyloric stenosis
– Prostatic enlargement

Question 20

What are examples of anti-diarrheal agents: Anti-motility agents

Answer 20

Loperamide
Diphenoxylate
Codeine

Question 21

What are the MOA, indications, adverse effects and contraindications of anti-diarrheal agents: Anti-motility agents

Answer 21

MOA:
- Activate presynaptic opiod receptors -> inhibit ach release -> decreased peristalsis

Indications:
- Travelers diarrhoea
- Adjunct treatment in chronic diarrhoea

Adverse effects:
- Minimal

Contra-indications:
- Avoid in patients with suspected inflammatory diarrhoea

Question 22

What are examples, Indications and side effects of Anti-diarrheal agents: Modify fluid and electrolyte transport

Answer 22

Bismuth subsalicylate

Indications:
- Travellers diarrhoea
- Episodic diarrhoea
- Acute gastroenteritis
- H. Pylori eradication

Side-effects
- Black discoloration of mucous membranes

Question 23

What are examples of and MOA of anti-diarrheal agents: Adsorbents

Answer 23

Examples:
- Bile acid Sequestrants (cholestiramine)
- Kaolin and pectin
- Methylcellulose (fermented fibre)
- Aluminium hydroxide

MOA:
- Absorb intestinal toxins and micro-organisms
- Coat/protect intestinal mucosa
- Interferes with absorption of other drugs

Question 24

What are the indications of Anti-diarrheal agents: Probiotics

Answer 24

Acute diarrheal conditions
Antibiotic associated diarrhoea
Infectious diarrhoea

Limited evidence of efficacy
Used as space filler to prevent overgrowth of bad bacteria after antibiotic regimen

Question 25

What are the different types of laxatives

Answer 25

Dietary and fibre supplements
Osmotic laxatives
Stool-wetting agents and emolients
Stimulant laxatives

Question 26

What are the indications, MOA, contra-indications and side effects of laxatives: Dietary fibre

Answer 26

Indications:
- Fermented fibre: Used in darrhoea (not applicable to rest of card)
- Unfermented fibre: Used in constipation

MOA:
- Forms gell that retains water and distends intestine increasing peristalsis

Contraindications:
- Patients with obstructive symptoms
- Megacolon, megarectum

Side effects
- Bloating

Question 27

What are examplles, MOA, indications of laxatives: Osmotic active agents

Answer 27

Saline laxatives: Magnesium citrate, MAgnesium sulphate, Sodium phosphate
- MOA: Non absorbable salts keep water in the intestine

Electrolyte solution laxatives: Polyethylene glycol (PEG)
- Colonic lavage
- Radiologic or endoscopic procedures

Non digestible sugars and alcohols: Lactulose
- Degraded in lactic, formic and acetic acids -> increases osmotic pressure -> increasing fluid

Question 28

What are examples, MOA of laxatives: stool wetting agents

Answer 28

Docsate sodium/calcium/potassium
- Lowers surface tension of stools to allow mixing of aqueous and fatty substances

Mineral oil
- Penetrates and softens the stool and interfere with resorption of water
- Can cause anal leakage

Question 29

What are examples, MOA of laxatives: stimulant agents

Answer 29

Have direct effects on enterocytes, enteric neurons, GI smooth muscle
Induces limited low-grade inflammation in small and large bowel to promote accumulation of water and electrolytes

Senna:
- Water and electrolyte secretion into bowel

Bisacodyl:
- Acts on nerve fibres

Castror oil:
- Acts on small intestine to stimulate secretion of fluid and electrolytes and speed intestinal transit