Anti-emetics, constipation, antidiarrhoea and prokinetics - Pharmacology Flashcards
What are the potential causes of vomiting
Stimulation of higher centers
Labyrinth impulses: motion sickness
Centrally acting emetics
Drug induced
Metabolic causes
Post op vomiting
Chemo and radiotherapy
What are the major efferent pathways and receptors of the vomiting center
Major efferent pathways:
- Phrenic nerve
- Vagus nerve
- Spinal nerves
Receptors
- Ach M
- H1
- 5HT2
What are the main receptors of the chemoreceptor trigger zone and what stimuli is it sensitive to
Receptors
- D2
- NK1: Neurokinin 1
- 3HT3
Stimuli
- Radiation
- Bacterial toxins
- Uraema
What are the main receptors of the vestibular system
H1
Ach M
What are the major efferent pathways and receptors of the peripheral pathways
Major efferent pathways:
- Phrenic nerve
- Vagus nerve
- Spinal nerves
Receptors:
- 5HT3
What are the Anti-emetic drug groups
Antihistamines
Dopamine agonists
Benzodiaziapines
Neurokinin antagonists
Corticosteroids
Cannabinoids
Serotonin antagonists (5HT3)
Anticholinergic agents
What are examples of antihistamines (H1 blockers)
- 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)
What are antihistamines indicated for, where do they act and what are the limitations of use
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
What are examples of dopamine antagonists
Phenothiazines:
* Prochlorperazine (Stemetil)
* Trifluoperazine
* Perphenazine
* Chlorpromazine (Largactil)
Benzamides:
* Metoclopramide (Maxolon)
Butyrophenones:
* Haloperidol (Serenace)
* Domperidone (Motilium)
What are the indications and side effects of dopamine antagonists: Phenothiazines
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
What are the indications for dopamine antagonists: Butyrophenones
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
What are the moa, indications and side effects of dopamine antagonist: Metoclopramide
Promotes gatsric emptying
Indications:
- Post op period
- Infection
- Uraemia
- Drug/toxin induced
- Radiation sickness
Side effects:
- Sedation, diarrhoea
- Extra-pyramidal symptoms
- Hyperprolactinemia
What are examples of 5HT3 receptor antagonists
- Ondansetron
- Granisetron
- Palonsetron
- Dolasetron
- Tropisetron
What are the indications and adverse effects of 5HT3 receptor antagoists
Indications:
- Chemo induced emesis
- Post op nausea and vomiting
Adverse effects
- Headache
- Constipation
- QT interval prolonged
- Expensive
What is an example of neurokinin antagonists and whata re the indications and adverse effects
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
What are examples of Cannabinoids, the MOA and side effects thereof
Dronabinol & Nabilone
- Major constituent D-9-tetrahydrocannabinol (THC)
Mechanism:
- Block decending pathways in cortical centers
Side effects
- Dysphoria
- Hallucinations
- Sedation
- Vertigo
- Disorientation
What are the indications for Anticholinergic agents
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)
What are examples of Anti-cholinergic agents
- 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
What are the side effects and contra indications of Anti-cholenergic agents
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
What are examples of anti-diarrheal agents: Anti-motility agents
Loperamide
Diphenoxylate
Codeine
What are the MOA, indications, adverse effects and contraindications of anti-diarrheal agents: Anti-motility agents
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
What are examples, Indications and side effects of Anti-diarrheal agents: Modify fluid and electrolyte transport
Bismuth subsalicylate
Indications:
- Travellers diarrhoea
- Episodic diarrhoea
- Acute gastroenteritis
- H. Pylori eradication
Side-effects
- Black discoloration of mucous membranes
What are examples of and MOA of anti-diarrheal agents: Adsorbents
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
What are the indications of Anti-diarrheal agents: Probiotics
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
What are the different types of laxatives
Dietary and fibre supplements
Osmotic laxatives
Stool-wetting agents and emolients
Stimulant laxatives
What are the indications, MOA, contra-indications and side effects of laxatives: Dietary fibre
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
What are examplles, MOA, indications of laxatives: Osmotic active agents
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
What are examples, MOA of laxatives: stool wetting agents
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
What are examples, MOA of laxatives: stimulant agents
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
