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_Sem 4. CPT NOTES > S10 L2 Antiemetics > Flashcards

S10 L2 Antiemetics Flashcards

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1
Q

What is vomiting?

A

Involuntary, forceful, expulsion of gastric contents through the mouth

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2
Q

What is the difference between vomiting and regurgitation?

A

Regurgitation- mechanical problem (almost always)
Food or liquid won’t go into the stomach
Brought up effortlessly
e.g. babies- when they have had enough milk it overflows- regurgitation

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3
Q

What actually happens when we vomit?

A

Vomiting centre in the medulla signals to vomit

  1. Nausea, salivation and sweating
  2. Retrograde peristalsis
  3. Deep inspiration
  4. Closure of glottis
  5. Abdominal muscle contract
  6. LOS relaxes
  7. Expulsion out of mouth
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4
Q

What triggers the vomiting centre?

A

Different things trigger the chemoreceptor trigger zone

  1. Direct triggers- chemicals
  2. Visceral afferents from the gut → detect stretch caused by overload in the small bowel, take some of the pressure off by vomiting
  3. Vestibular nuclei → motion sickness
  4. Sensory afferent via midbrain
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5
Q

Where is the chemoreceptor trigger zone located?

A

Floor of the 4th ventricle
Blood side of BBB
Blood not too thick here so some substances can pass through

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6
Q

How can we stop vomiting?

A
  • Remove the triggers

- Inhibit the pathways via drugs

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7
Q

What drugs can be used?

A

Often antagonists- block the pathway
Different drugs work on the different triggering centres
Often work in multiple areas
- Vestibular nuclei → muscarinic receptor antagonist, H1 receptor antagonists
- Visceral afferent from gut → 5HT3 antagonists, D2 receptor antagonists
- Directly inhibit the trigger zone → D2 receptors, 5HT3 receptor antagonists, muscarinic receptor antagonists, H1 receptor antagonists, corticosteroids, cannabinoids and NK1 receptor antagonist

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8
Q

What drugs act on the vestibular nuclei?

A

Muscarinic receptor antagonists

H1 receptor antagonists

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9
Q

How do the muscarinic receptor antagonists work?

A

Competitive blockade of muscarinic acetylcholine receptors

→ receptor are found all over the parasympathetic NS

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10
Q

What is an example of a muscarinic receptor antagonist that work on the vestibular nuclei?

A

Hyoscine hydrobromide
- Patch
Ideal for people who can’t take tablets

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11
Q

What are the muscarinic receptor antagonists used for?

A

Motion sickness

Bowel obstruction

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12
Q

What are the side effects of muscarinic receptor antagonists?

A
  • Sedation
  • Memory problems
  • Glaucoma
  • Dry mouth
  • Constipation
    (block the parasympathetic functions)
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13
Q

What are H1 receptor antagonists?

A

Inhibits histaminergic signals from the vestibular system to the CTZ in medulla

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14
Q

What are the H1 receptor antagonists good for?

A

Motion sickness - long plane journeys

Morning sickness in pregnancy - promethazine

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15
Q

What are examples of the H1 receptor antagonists?

A

‘-zine’
- Cyclizine → not good for little elderly ladies or children - disorientated/confused
(-promethazine (morning sickness, cinnirazine, diphenhydramine)

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16
Q

What are the side effects of H1 receptor antagonists?

A
  • Sedation
  • Excitation
  • Antimuscarinics → dry mouth, constipation, urinary retention
  • Cardiac toxicity- long QT interval
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17
Q

What drugs act on the visceral afferents in the gut?

A

5HT(3) receptor antagonists → serotonin

D2 receptor antagonists

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18
Q

Where is serotonin produced?

A

95% produced in the gut
Produced by the enterochromaffin cells
Response to parasympathetic stimulation - excites enteric neurones
→ smooth muscles contraction increases motility (except in the stomach)
→ ↑gut secretions
Regulates appetite

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19
Q

How do the 5HT(3) receptor antagonists work?

A

Peripherally → Reduced GI motility, reduced GI secretion
Centrally → acts to inhibit the CTZ
Good for almost everyone

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20
Q

What is an examples of the 5HT(3) receptor antagonists?

A

‘-setron’

- Ondansetron

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21
Q

What are the side effects of 5HT(3) receptor antagonists?

A

Uncommon

  • Constipation
  • Headache
  • Elevated liver enzymes
  • Long QT syndrome
  • Extra-pyramidal effects → dystonia, parkinsonism
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22
Q

How do the D2 receptor antagonists work?

A

↑ACh at muscarinic receptors in the gut
Promotes gastric emptying
- ↑tone at lower oesophageal sphincter so it closes
- ↑tone and amplitude of gastric contractions
- ↓tone of pylorus so it opens
↑peristalsis

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23
Q

What are examples of the D2 receptor antagonists?

A

Metoclopramide

Domperidone

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24
Q

What can D2 receptor antagonists be used to treat?

A 
Metoclopramide: Vomiting caused by:
- GORD
- Ileus → inability of the intestines to contract normally leading to a build up of food material  
Domperidone 
- Lactation in breastfeeding mothers
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25
What are the side effects of metoclopramide?
- Galactorrhoea via prolactin release | - Extra-pyramidal effects → Dystonia, parkinsonism
26
What are the side effect of domperidone?
- Sudden cardiac death (long QT and VT) | - Galactorrhoea
27
What drugs act on the CTZ?
``` 5HT(3) receptor antagonists H1 receptor antagonists Muscarinic receptor antagonists D2 receptor antagonists Corticosteroids Cannabinoids NK1 receptor antagonists ```
28
What are examples of the D2 receptor antagonists that work on the CTZ?
'-zines' - Chlorpromazine* - Haloperidol* * antipsychotics - Metoclopramide - Domperidone
29
How do the D2 receptor antagonists work on the CTZ?
Block the H1 and muscarinic receptors Good for motion sickness, vertigo Prochlorperazine in pregnancy Haloperidol - act on CTZ, good for chemotherapy and palliation
30
What are the side effects of D2 receptor antagonists?
- Extra-pyramidal effects → dystonia and parkinsonism - Sedation - Hypotension
31
What are the corticosteroids used to prevent vomiting by acting on the CTZ?
Dexamethasone | Methylprednisolone
32
What are the corticosteroids good for?
Perioperative nausea and vomiting Chemotherapy Palliation
33
What are the side effects of the corticosteroids used for vomiting?
Insomnia ↑appetite ↑ blood sugar
34
What is the cannabinoids used to prevent vomiting by acting on the CTZ?
Nabilone is 9-THC Assumed to act on the CTZ Good for chemotherapy - used a last line (other drugs used before)
35
What are the side effects of the cannabinoids?
Dizziness | Drowsiness
36
What are the neurokinin 1 receptors antgonists?
- Prevent the action of substance P at the CTZ and in peripheral nerves - Boost effects of 5HT(3) receptor antagonists - Anxiolytic and antidepressant properties
37
What is an example of the Neurokinin 1 receptor antagonists?
Aprepitant
38
What are the neurokinin 1 receptor antagonists good for?
Chemotherapy
39
What are the side effects of neurokinin 1 receptor antagonists?
Headache Diarrhoea/constipation Stevens-Johnson syndrome
40
What drugs should be used for motion sickness?
Prevention is better than cure in the case of motion sickness Drug depends on who is taking it - Hyoscine hydrobromide -1st line → sedative, good for children and passengers but NOT driver - Cinnirazine - fewer side effect
41
What drugs should be used for sickness caused by gut problems?
- Dependent on the causes - Sometimes vomiting is a protective mechanism in the gut - Nasogastric tube should be considered before medication - Prokinetics → ↑gut motility → useful for GORD, ileus, NOT for obstruction or risk of perforation
42
What is the best approach for treating sickness caused by gut problems?
1. 5HT(3) receptor antagonist- blocks visceral afferents and CTZ - ↓serotonin → Ondansetron 2. H1 receptor antagonist- CTZ - ↓histamine → Cyclizine 3. Corticosteroid - CTS- → Dexamethaosne
43
What can cause direct stimulation of the CTZ?
- Hormones → Bhcg in hyperemesis gravidarum - Drugs → Chemotherapy → Anaesthetics → Opiates etc....
44
What is hyperemesis gravidarum?
Rapid rise in Bhcg stimulates the CTZ Typically weeks 4-16 but many continue beyond Higher risk with multiple pregnancies e.g. twins... More than morning sickness → dehydration, 5% weight loss, electrolyte imbalance and urinary ketones
45
What is the treatment for hyperemesis gravidarum?
1. H1 receptor antagonist- CTZ - ↓histamine → promethazine OR D2 receptor antagonist- CTZ- ↑ACh in gut → prochlorperazine 2.D2 receptor antagonist- CTZ- ↑ACh in gut → Metoclopramide 3. 5HT(3) receptor antagonist- CTZ - ↓serotonin- (↓enteric response to PNS stimulation) → Ondansetron
46
How does chemotherapy cause emesis?
Directly triggers the CTZ Different drugs have different effects Different doses of the same drug have different effects
47
What drugs are used to treat low risk emesis caused by chemotherapy?
Dexamethasone | For rescue- metoclopramide
48
What drugs are used to treat moderate risk emesis caused by chemotherapy?
Dexamethosone and Ondansetron | For rescue- metoclopramide
49
What drugs are used to treat high risk emesis caused by chemotherapy?
Dexamethosone (corticosteroid) and Ondansetron (5HT(3) receptor antagonist) and Aprepitant (NK1 antagonist) For rescue- metoclopramide
50
What are the risk factors for post operative nausea and vomiting?
``` Patient - Female - History of PON+V or motion sickness - Younger age - Non smoker Anaesthetic - General >regional - Use of volatile anaesthetic gases or NO - Post-operative opioids Surgery - Duration of operation - Laparoscopic surgery ```
51
What is the management plan for post operative nausea and vomiting?
Prevention is better than cure Low risk → wait and see Moderate risk → Pick 1 or 2 antiemetic agents High risk → Pick more than 2 antiemetic agents If prophylaxis fails use an antiemetic from another class
52
What drugs are used for post operative nausea and vomiting?
1. 5HT(3) receptor antagonist → Ondansetron 2. H1 receptor antagonist → Cyclizine 3. Corticosteroid → Dexamethasone
53
What is diarrhoea?
Change in consistency and frequency of defecation compared to normal
54
What is infective gastroenteritis?
``` Caused by bacteria, virus or protazoa Causes diarrhoea and vomiting Maybe toxin mediated Osmotic or secretory Shouldn't stop vomiting or diarrhoea in this case as it is a protective mechanism ```
55
When should you stop diarrhoea?
1. ↑transit time means not enough absorption of nutrients and electrolytes 2. Comfort 3. Prevent incontinence → slow transit more water reabsorbed less liquidy stools easier to hold onto
56
What is important to remember when treating diarrhoea?
Treat the underlying cause
57
What are the opioid receptor antagonists?
Loperamide, codeine and morphine Bind to the µ and δ receptors (Loperamide- µ receptor) → ↓tone of longitudinal and circular smooth muscle → ↓peristalsis but ↑segmental contractions → ↓colonic mass movement by supressing gastrocolic reflex
58
What are the side effects of opioid receptor antagonists?
Paralytic ileus → paralysis of the intestine Nausea and vomiting Sedation and addiction
59
What is the constipating diet?
For those with long term loose stools (IBD, IBS, short bowel, hypermobility, drug side effects) - Bananas, white rice and white bread/pasta→ slow it down - Avoid food high in potassium and fibre → speeds it up - Limit fruit to 3 portions per day - Avoid caffeine, sorbitol, fatty or spicy food and fizzy drinks - Consider probiotics and re-instate a balanced intestinal flora
60
What diet and lifestyle changes can be made to avoid constipation?
14% population prevalence of chronic idiopathic constipation - Drink more water - Increase fibre intake- wholegrain foods, fruit and veg, nuts, pulses - Regular exercise - Toilet routine and positions → go when you need, don't hold on as body then gets used to holding on, relax, squat position
61
What medicine are there for constipation?
Laxatives→ osmotic 'mush', stimulants 'push', bulk forming, stool softeners Enemas→ osmotic, stimulants
62
What are osmotic laxatives?
Increase the amount of water in the large bowel - Draw fluid in → lactulose - Retain the fluid they came with → Macrogols - Movicol
63
What are the stimulant laxatives?
Increase intestinal motility → orally or per rectum Docusate sodium - stimulant and stool softener Glycerin suppositories cause rectal irritation and lubrication
64
What are the bulk forming laxatives?
Medicinal fibre - builds stools up a bit and softens them Ispaghula husk, methylcellulose
65
What are stool softners?
↓surface tension of stools ↑penetration of fluid into stool Docusate sodium Glycerin suppository

_Sem 4. CPT NOTES (26 decks)

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