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Pharmacology > Antiemetics and Antidiarrhoeals > Flashcards

Antiemetics and Antidiarrhoeals Flashcards

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1
Q

What is vomiting?

A

involuntary, forceful of gastric contents through the mouth

it is a protective mechanism

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2
Q

Why is vomiting different to regurgitation?

A

regurgitation is expulsion of contents from the oesophagus - lots of babies do this

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3
Q

How do we vomit?

A

1) nausea, salivation and sweating
2) retrograde peristalsis of the upper bowel and stomach
3) deep inspiration
4) closure of glottis to protect airways
5) abdominal muscles contract
6) lower oesophageal sphincter relaxes

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4
Q

Where is the vomiting centre?

A

in the medulla

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5
Q

What is CTZ and where is it?

A

the chemoreceptor trigger zone is an area of the medulla oblongata that receives inputs and communicates with other structures in the vomiting centre to initiate vomiting.

located on the base of the floor of the 4th ventricle

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6
Q

What are the inputs to the vomiting centre?

A
  • sensory afferents via the midbrain
  • vestibular nuclei (motion sickness - inner ear)
  • visceral afferents from the gut (vagus nerve - if problems with gut, CNX sends signals up to CTZ)
  • direct triggers (drugs)
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7
Q

What drug agents act on the vestibular nuclei?

A

H1 receptor antagonists

  • Cyclizine
  • Levomepromazine
  • Cinnarizine
  • Promethazine
  • Dihenhydramine

Muscarinc receptor antagonists
-Hyoscine hydrobromide

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8
Q

What is the MOA of Cyclizine, Levomepromazine, Cinnarizine, prometazine, dihenhydramine

A

Acts on vestibular nuclei, inhibits histaminergic signals from vestibular system to CTZ in medulla

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9
Q

What are the uses of Cyclizine, Levomepromazine, Cinnarizine, prometazine, dihenhydramine?

A

Cinnirazine - motion sickness, non drowsy

promethazine - morning sickness in pregnancy

DON’T GIVE CYCLIZINE TO LITTLE OLD LADIES OR CHILDREN - causes excitation

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10
Q

What is the MOA for Hyoscine hydrobromide?

A

Works on PSNS
competitive blockade of muscarinic ACh receptor in the vestibular nuclei but also in the CTZ

NOTE - these receptors are everywhere in the body so get side effects potentially everywhere

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11
Q

What are the side effects of H1 receptor antagonists?

A
  • sedation
  • excitation
  • antimuscarinic - dry mouth, constipation, urinary retention
  • cardiac toxicity (long QT interval)
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12
Q

What are the side effects of hyoscine hydrobromide?

A
  • sedation
  • memory problems
  • glaucoma
  • dry mouth and constipation
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13
Q

Who is hyoscine hydrobromide good for?

A
  • people who can’t take tablets (the behind the ear skin patches)
  • motion sickness
  • gut problems (PNS effect)
  • cancer therapy feeling sick
  • people with severe diarrhoea
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14
Q

What drug agents act on visceral afferents in the gut?

A
  • 5HT3 receptor antagonists

- D2 receptor antagonists

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15
Q

What is 5HT3 and what is its role and where is it produced?

A

serotonin
produced by enterochromaffin cells
it excites enteric neurones, increases smooth muscle contraction, motility and increases gut secretion so regulates apeptite

-stops retrograde peristalsis

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16
Q

What are the names of some 5HT3 receptor antagonists?

A
  • Ondansetron
  • Granesitron
  • Palonestron
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17
Q

What is the MOA of Ondansetron, Granesitron, Palonestron?

A

reduction of GI motility and GI secretions

-also inhibits CTZ

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18
Q

What is the use of Ondansetron, Granesitron, Palonestron?

A

good for everyon- often 1st line treatment

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19
Q

What are the side effects of Ondansetron, Granesitron, Palonestron?

A

UNCOMMON

  • constipation
  • headache
  • elevated liver enzymes
  • long QT syndrome
  • extra-pyramidal effects - dystonia, Parkinson’s
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20
Q

What are the names of some D2 receptor antagonists that act on visceral afferents in the gut?

A

Metoclopramide

Domperidone

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21
Q

Why is domperidone less commonly used now?

A

associated with significant cardiac side effects

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22
Q

What is the MOA of Metoclopramide?

A

increases ACh at muscarinic receptors in the gut promoting gastric emptying

  • increaswes tone at lower oesophageal sphincter so it closes
  • increases tone and amplitude of gastric contractions
  • decreases tone of pylorus so it opens

ALOS increases peristalsis

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23
Q

What is Metoclopramide used for?

A

GORD and ileus

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24
Q

What is ileus?

A

where the gut goes to sleep so gut motility stopped - often occurs after surgery or severe infection

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25
What are the side effects of Metoclopramide and who are they most severe in?
most common in young people and children - galactorrhoea via prolactin release - extra-pyramidal effects - dystonia and parkinsonism
26
What is the MOA of Domperidone?
similar mechanism to metoclopramide
27
Who is Domperidone used for?
selective cases - good for babies with reflux - imporving lactation in breastfeeding mothers
28
What are the side effects of Domperidone?
- sudden cardiac death (long QT and VT) | - galactorrhea
29
What agents act on CTZ?
- 5HT3 receptor antagonists - H1 receptor antagonists - muscarinic receptor antagonists - D2 receptor antagonists - corticosteroids, - cannabinoids - NK1 receptor antagonists
30
What are the names of D2 receptor antagonists?
the zine's - metoclopramide - domperidone - prochloroperazine - chlorpromazine - levomepromazine - haloperidol
31
Which drugs are both antipsychotics and antiemetics?
- prochloroperazine - chlorpromazine - levomepromazine - haloperidol
32
What is the MOA of the zine's
Act on CTZ | -may also block H1 and muscarinic receptors
33
What is the MOA of haloperidol?
Act on CTZ
34
What are the zine's used for?
motion sickness, vertigo NOTE - prochlorperazine in pregnancy
35
What is haloperidol used for?
chemotherapy and palliation | -can also be good to relax anxious patients
36
What are the side effects of - metoclopramide - domperidone - prochloroperazine - chlorpromazine - levomepromazine - haloperidol
Extra-pyramidal effects - dystonia and parkinsonism - sedation - hypotension
37
What are the names of the corticosteroids used?
Dexametasone | Methylprednisolone
38
What is the MOA of Dexametasone | Methylprednisolone?
- act on CTZ | - may have action of D2 receptors as antagonists
39
What are Dexametasone and Methylprednisolone good for?
perioperative nausea and vomiting chemotherapy palliation where the patient doesn't want to eat or can't stay awake
40
What are the side effects of Dexametasone and Methylprednisolone?
- insomnia - increased appetite - increased blood sugar
41
What is the name of a cannabinoid?
Nabilone
42
What is the MOA of nabilone?
assumed to act on CTZ
43
When is nabilone used?
good for chemotherapy but used as last in line
44
What are the side effects of nabilone?
dizziness and drowsiness
45
What are the names of Neurokinin 1 receptor antagonists?
tant's Aprepitant Fosaprepitant Netupitant
46
What is the MOA of Aprepitant, Fosaprepitant, Netupitant?
Prevent the action of substance P at CTZ and in peripheral nerves -also boosts effects of 5HT3 receptor antagonists - anxiolytic and antidepressant properties - works better in the presence of these "tron's"
47
What is substance P?
a neurotransmitter causing excitation
48
What are Aprepitant, Fosaprepitant, Netupitant good for?
chemotherapy - particularly for delayed emesis
49
What are the side effects of Aprepitant, Fosaprepitant, Netupitant?
headache diarrhoea/constipation stevens-johnson syndrome
50
What is stevens-johnson syndrome?
rare but serious disorder that affects the skin, mucous membrane, genitals and eyes -The syndrome often begins with flu-like symptoms, followed by a red or purple rash that spreads and forms blisters. The affected skin eventually dies and peels off
51
How would you treat motion sickness?
TAKE BEFORE JOURNEY 1st line - hyoscine hydrobromide BUT cinnirazine typically has fewer side effects (better if need to concentrate e.g. you are driving" Go for favourite side effects
52
Would you give someone an anti-emetic if you have infective gastroenteritis?
no - need to get rid of the toxins needed more for other bowel pathologies e.g. reflux, cancers, Chron's, UC (acute flares), appendicitis decompressing bowel may be more comfortable e.g. giving NG tube
53
What are pro kinetics? and when are they good to use?
drugs to help increase drug motility e.g. domperidone and metroclopramide good to use in GORD and ileus ALSO chewing gum activates gut to increase motility
54
When would you not use metoclopramide and domperidone?
with obstruction of the bowels !!! or ischaemic bowel | increased risk of perforation as increase gut motility on dead/obstructed bowel
55
What is the typical treatment for gut problems?
1st line Ondansetron and/or cyclizine ADD dexamethasone is struggling Try different classes of drugs if they don't work
56
What are the direct triggers of CTZ?
``` Hormones (BHCG in pregnancy) DRUGS -chemo -anaesthetics -opiates etc ```
57
What is hyperemesis gravidarum, when does it happen and in what circumstance is it more likely?
severe vomiting, dehydration, weight loss, electrolyte imbalances and urinary ketones in pregnancy where there is a rapid rise in BHCG which stimulates the CTZ -typically occurs 4-16 weeks but may continue beyond this and there is a higher risk with multiple pregnancies like twins
58
What is the treatment for hyperemesis gravidarum?
Promethazine/prochlorperazine then add metoclopramide (but this works on the gut which isn't the actual problem) then add ondansetron (but there is a increased risk of cleft lip and palate if you use this in 1st trimester of pregnancy
59
What is the typical treatment for Chemotherapy sickness?
start with dexamethasone moderate risk - add ondansetron high risk - add ondansetron and aprepitant too For rescue use metoclopramide
60
What are the risk factors for post-operative nausea and vomiting?
- female - history of motion sickness - younger - non-smoker - general anaesthetic - laproscopic surgery - duration of operation
61
What is the treatment plan for post operative nausea and vomiting?
Low risk - wait and see Moderate risk - pick 1/2 antiemetic agents High risk - pick more than 2 if prophylaxis doesn't work try a different class
62
What is diarrhoea?
depends on the patient!! -ask about consistency, frequency and compare to their normal bowel habit REMEBER - diarrhoea can be osmotic or secretory
63
How can you treat diarrhoea?
TREAT THE CAUSE !! - increase transit time (if the stools are in contact with the enterocytes for longer, you will get better absorption - comfort - prevent incontinence
64
What are the drug classes that are used to treat diarrhoea?
- opioid receptor agonists - osmotic laxatives - stimulant laxatives - bulk forming laxative - stool softeners
65
What are the names of the opioid receptor agonists?
Loperamide Codeine Morphine
66
What is the MOA of loperamide?
- immodium - specific to *mu* receptors in the myenteric plexus - decreases tone of longitudinal and circular smooth muscle - reduces peristalsis but increases segmental contractions - decreases colonic mass movement by suppressing gastrocolic reflex
67
What is the MOA of codeine and morphine?
acts on *mu* and *delta* receptors but not specific to the gut -can be used for pain too e.g. with appendicitis with pain and diarrhoea
68
What are the side effects of Loperamide Codeine Morphine?
- paralytic ileus - nausea and vomiting - sedation and addiction
69
What are some osmotic laxatives?
Lactulose Movicol Cosmocol
70
What is the MOA of Lactulose Movicol Cosmocol?
Lactulose -laxatives draw fluid in to gut lumen Macrogels (M and C) -retain the fluid they came with
71
What are the names of stimulant laxatives?
``` Bisacodyl Sodium pico sulphate Senna Co-danthromer Docusate Sodium ```
72
What is the MOA of stimulantt laxatives?
increase the intestinal motility NOTE - docusate sodium acts as a stool softener too given orally or per rectum (glycerin suppositories help to lubricate too)
73
What are the names of bulk forming laxatives?
Ispaghula husk | Methylcellulose
74
What is the MOA of bulk forming laxatives?
- helps bulk the stool | - medicinal fibre
75
What are the names of some stool softeners?
Docusate sodium Glycerin suppository Arachis oil Liquid paraffin
76
What is the MOA for stool softeners?
Decrease surface tension of stool | increase penetration of fluid into stool
77
What is the constipating diet?
used for those with long term loose stools -IBS, IBS, short bowel, hyper motility includes eating bananas, white rice/bread low fibre less fruit (3 portions) avoiding caffeine and fizzy drinks consider probiotics to reinstate balanced intestinal flora
78
What helps with constipation?
drinking more water increased fibre intake regular exercise toilet routine and positioning

Pharmacology (5 decks)

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