CPT21 - Antiemetics and Laxatives Flashcards
Mechanism of vomiting (6 steps)
1.) Nausea, salivation, sweating
2.) Retrograde peristalsis of the gut
3.) Deep Inspiration
4.) Closure of the glottis - protects the airways
5.) Abdominal muscles contract
6.) Lower oesophageal sphincter (LOS) relaxes
3 features of the chemoreceptor trigger zone (CTZ)
Function
Location
Triggers x4
1.) Function - receives inputs from blood-borne drugs/hormones, and communicates with other structures in the vomiting centre to initiate vomiting.
2.) Location - floor of the 4th ventricle in the medulla
3.) Triggers - 4 types
- direct triggers: drugs and hormones
- sensory afferents: unpleasant visual stimulation
- visceral afferents from gut: vagus nerve
- vestibular nuclei: inner ear –> motion sickness
2 drugs acting on the vestibular nuclei
Anti-Muscarinics
H1 Receptor Antagonists
1.) Anti-Muscarinics - hyoscine hydrobromide
- inhibits the parasympathetics nervous system
- side effects: ↓parasympathetics (sedation, memory, glaucoma, dry mouth, constipation)
2.) H1 Receptor Antagonists - cyclizine, promethazine, cinnirazine
- inhibits histaminergic signals from the vestibular system to the CTZ
- side effects: sedation, anti-muscarinic effects, cardiotoxicity (long QT interval), excitation
2 types of drugs acting on visceral afferents in the gut
5HT3 (serotonin) Receptor Antagonists
D2 (dopamine) Receptor Antagonist
1.) 5HT3 Receptor Antagonists - ondansetron (IV) (1st line)
- prevents serotonin exciting enteric neurones which ↓GI motility/peristalsis and ↓GI secretions
- side effects: constipation, headache, ↑LFTs, long QT syndrome, extra-pyramidal effects
- avoid in migraines as triptans use HT3 receptors
2.) D2 Receptor Antagonists
- metoclopramide, domperidone, prochlorperazine
- ↑ACh in the gut which ↑gastric emptying (↑tone at LOS and ↓tone at pyloric sphincter)
- domperidone less used due to significant cardiac side effects, good for ↑lactation in breastfeeding mothers
- metoclopramide is contraindicated in Parkinson’s
7 drugs acting directly on the CTZ
Corticosteroids
Cannabinoids
Neurokinin 1 (NK1) Receptor Antagonists
5HT3 Receptor Antagonists
D2 Receptor Antagonists
Muscarinic Receptor Antagonists
H1 Receptor Antagonists
1.) Corticosteroids - dexamethasone, prednisolone
- good for PONV, chemotherapy, palliation
- short-term usage means no long term steroid effects
- side effects: insomnia, ↑appetite, ↑blood sugar
2.) Cannabinoids - nabilone
- used as last line in chemotherapy
- side effects: dizziness, drowsiness
3.) Neurokinin 1 Receptor Antagonists - aprepitant
- ↓action of substance P at CTZ –> ↓excitation of CTZ
- ↑effects of 5HT3 receptor antagonists
- also has anxiolytic and antidepressant properties
- used only during chemotherapy
4.) 5HT3 Receptor Antagonists
- also act on visceral afferents in the gut
5.) D2 Receptor Antagonists
- also act on visceral afferents in the gut
6.) Muscarinic Receptor Antagonists
- also acts on the vestibular nuclei
7.) H1 Receptor Antagonists
- also acts on the vestibular nuclei
General management of a regular patient with N/V
First Line
Additional
1.) First Line - Ondansetron (5HT3) and/or Cyclizine (H1)
2.) Additional - Dexamethasone (corticosteroid)
4 treatments/prevention for motion sickness
Hyoscine Hydrobromide
Cyclizine
Cinnirazine
Promethazine
1.) Hyoscine Hydrobromide - 1st line
- can come in patch form so useful for people who can’t take tablets or have bowel obstruction
2.) Cyclizine
- sedation effects makes it ideal for plane journeys
3.) Cinnirazine
- has fewer sedative effects so is better for driving
4.) Promethazine
- used for morning sickness during pregnancy
Treatments for common gut problems
Infective Gastroenteritis
GORD, Ileus
Nasogastric Tube
1.) Infective Gastroenteritis - doesn’t need anti-emetics
- vomiting helps remove the toxins
2.) GORD, Ileus - prokinetics (D2-R antagonists)
- ↑gut motility –> ↑gastric emptying
- not used in bowel obstruction or ischemic gut due to risk of perforation
3.) Nasogastric Tube - alternative to medication
- mechanically decompress the bowel, preventing N/V
4 features hyperemesis gravidarum
Definition
Mechanism
Other Symptoms x5
Medication x4
1.) Definition - severe N/V during pregnancy
2.) Mechanism - rapid rise in beta-hCG triggers the CTZ
- typically between weeks 4-16
3.) Other Symptoms
- dehydration, weight loss, electrolyte imbalance, ketonuria, orthostatic hypotenstion
4.) Medication - must use pregnancy safe drugs
- promethazine or prochlorperazine
- then add metoclopramide, then add ondansetron
- ondansetron can ↑risk of cleft palate in 1st trimester
4 features of post-operative nausea and vomiting (PONV)
Patient Risk Factors x5
Anaesthetic Risk Factors x3
Surgical Risk Factors x2
Medications
1.) Patient Risk Factors
- female, younger age, non-smoker
- history of PONV or motion sickness
2.) Anaesthetic Risk Factors
- general > regional, volatile anaesthetic gases or N2O, postoperative opioids
3.) Surgical Risk Factors - length of operation, laproscropic surgery (CO2) in abdominal surgery
4.) Medication - dependent on risk
- low: wait and see, moderate: 1/2 antiemetic agents
- high risk: >2 antiemetic agents
Management of N/V during chemotherapy (dependent on risk of vomiting)
Low Risk x2
Moderate Risk x3
High Risk x4
1.) Low Risk - dexamethasone
- metoclopramide as backup
2.) Moderate Risk - dexamethasone + ondansetron
- metoclopramide as backup
3.) High Risk
- dexamethasone + ondansetron + aprepitant
- metoclopramide as backup
Management of diarrhoea
Infective Gastroenteritis
Medication
Medication Mechanism of Action
Diet
1.) Infective Gastroenteritis - often toxin mediated
- requires rehydration as diarrhoea removes toxins
- antibiotics can be given if bacterial
2.) Medication - opioid receptor agonists
- loperamide, codeine and morphine
- loperamide is specific to the gut
- side effects: N/V, sedation, paralytic ileus, addiction
3.) Medication Mechanism of Action
- suppresses the gastrocolic reflex
-↓tone of SM, ↓peristalsis but ↑segmental contractions
4.) Diet - for patients with long term loose stools
- foods low in fibre, limit fruits (laxatives)
- avoid: caffeine, fatty or spicy foods and fizzy drinks
- consider probiotics to rebalance gut flora
Management of constipation
Diet and Lifestyle
Laxatives
Enemas (stool softeners)
1.) Diet and Lifestyle
- drink water, ↑fibre intake, regular exercise
2.) Laxatives - if diet and lifestyle is ineffective
- osmotic (macrogol) is first line
- stimulant is second line
3.) Enemas (stool softeners) - last line
- introduce fluid into the intestines
- can be osmotic or stimulants
4 types of laxatives
Osmotic x2
Stimulant x3
Bulk Forming x2
Stool Softeners x2
1.) Osmotic - draw fluid in (lactulose) or retain the fluid they came with (macrogols)
- macrogol is taken w/ fluid and you increase the amount of satchets daily (prevents vomiting)
- glycerine suppositories can be given PR
2.) Stimulant - bisacodyl, docusate sodium, senna
- ↑gut motility and ↑water and electrolyte transfer into the lower gut
3.) Bulk Forming - methylcellulose, ispaghula husk
- medicinal fibre which increases faecal bulk
4.) Stool Softeners - docusate sodium, liquid paraffin, phosphate enemas
- ↓surface tension of stool
- ↑penetration of fluid into stool
