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SA Clinical Pharmacology & Therapeutics > 19 - Antiemetics > Flashcards

19 - Antiemetics Flashcards

1
Q

What are the physiological steps of vomiting?

A
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2
Q

What are the inputs on the chemoreceptor trigger zone that can activate it and therefore cause vomiting?

A

CTZ is found on the floor of the fourth ventricle main site for sensing emetic stimuli on the blood side of the BBB so can interact with toxins and things in the blood

Part of medulla

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3
Q

How can we stop nausea and vomiting?

A

Avoid the triggers or use drugs to target different triggers

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4
Q

What are the two classes of drug that act on the vestibular nuclei as antiemetics?

A
  • Muscarinic receptor antagonists
  • H1 receptor antagonists
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5
Q

How do muscarinic receptor antagonists act as anti-emetics and what are some examples of this class of drug?

A

Hyoscine Hydrobromide (oral or patch) → works centrally just inside the brain

  • Competitive blockage of muscarinic receptors in the vestibular nuclei and CTZ
  • Antispasmodic
  • Good for people who cannot take tablets, motion sickness and bowel obstruction
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6
Q

What are the side effects of hyoscine hydrobromide?

A
  • Classic anticholinergic side effects:
    sedation, consitpation, dizziness and dry mouth
  • Can exploit side effects, e.g long flight motion sickness and sedation for sleep
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7
Q

what are people who should avoid using muscarinic antagonists

A

elderly, glaucoma and people taking anti-psychotic meds

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8
Q

How do H1 receptor antagonists work as an antiemetic and what are some examples of this type of drug?

A
  • Act centrally on the vestibular nuclei and inhibit histaminergic signals from vestibular system to the CTZ in medulla

→ first generation of anti-histamines so act more centrally on Ash receptors

  • Good for motion sickness on long journeys
  • Promethazine used for morning sickness
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9
Q

What are the side effects of the class of antiemetic drugs containing cyclizine?

A

H1 receptor antagonist!

  • Cyclizine is the most common antiemetic but cannot be used in old women and children as they are affected most by excitation side effects

→ levomepromazine, prochlorperazirne

→ has less of a sedating effect as it dissent cross blood-brain barrier as they don’t use Ace receptors

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10
Q

What are some classes of antiemetics that work by blocking visceral aferents in the gut?

A

- 5HT3 receptor antagonists

- D2 receptor antagonists

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11
Q

What is the normal function of serotonin in the gut?

A
  • Produced by enterochromaffin cells in response to parasympathetic stimulation
  • Regulates appetite, causes smooth muscle contraction so increased motility and increased gut secretions

→ peripherally reduces GI motility, centrally acts to inhibit CTZ

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12
Q

How do 5HT3 receptor antagonists work as antiemetics and what are some examples of this type of drug?

A

Ondansetron

  • Acts on visceral afferents in the gut so peripherally reduces GI motility and GI secretions
  • Centrally inhibits the CTZ

- OFTEN FIRST LINE TREATMENT

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13
Q

What are some of the side effects of Ondansetrons and other serotonin receptor antagonists?

A

avoid giving to people with subacute abdominal obstruction, susceptible to long QT

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14
Q

How do D2 receptor antagonists work as antiemetics (by targeting visceral afferents of the gut) and what are some examples of this type of drug?

A

Domperidone and Metoclopramide (also 5HT3 antagonist)

  • Increases Ach at muscarinic receptors in the gut
  • Promotes gastric emptying by increasing tone of LOS and decreasing tone of pylorus so it opens. Also increased tone of gastric contractions
  • Increases peristalsis
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15
Q

Apart from emesis, what are metoclopramide and domperidone used for?

A

Metoclopramide: GORD and ileus

Domperidone: improving lactation in breastfeeding mothers

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16
Q

What are some side effects of antiemetics from the D2 receptor antagonist class?

A

Metoclopramide: galactorrhoea due to prolactin release, extra-pyramidal effects (e.g dystonia and parkinsonianism), drowsy

Domperidone: sudden cardiac death (long QT and VT) so not used very often, galactorrhea

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17
Q

which receptors are found in the gut

A
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18
Q

who should you avoid giving D2 receptor antagonists to? (Metocloprmide)

A
  1. post GI surgery, GI obstruction, GI perforation
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19
Q

What are some classes of drugs that act directly on the CTZ to prevent/stop vomiting?

A
20
Q

What are some D2 receptor antagonists that act on the CTZ as antiemetics, how do they work and what vomiting situations are they used in?

A

ANTIPSYCHOTICS: chlorpromazine and haloperidol

21
Q

What are some side effects of antipsychotics being used as antiemetics?

A

D2 receptor antagonists

→ dry mouth, long QT and VT, galactorrhea

22
Q

How do corticosteroids act as antiemetics and what are the side effects of these?

A

Dexamethasone and Methylprednisolone

Not used long term so don’t get side effects like skin changes and Cushing’s

23
Q

How do cannabinoids act as antiemetics and what are the side effects of these?

A

Used for chemotherapy last line when everything else has failed!

avoid in people with psychiatric disorder

24
Q

How do neurokinin 1 receptor antagonists act as antiemetic, what else can they be used for and what are some examples of this class of drug?

A

Aprepitant

  • Prevent the excitatory action of substance P at CTZ and in peripheral nerves so can be used as pain killers
  • Good anxiolytic and antidepressant properties
  • Boost effects of serotonin agonists and 5HT3 receptor antagonists (used to reduce nausea and vomiting) → chemo

– anxiolytic and antidepressant properties

- Good for chemotherapy delayed emesis

25
Q

What are some side effects of neurokinin 1 receptor antagonists?

A
  • Headache
  • Diarrhoea/Constipation
  • Stevens-Johnson syndrome
26
Q

What drugs are used for motion sickness?

A
  • Trial and error to see what is best and what side effects the patient prefers
  • Take before journey
27
Q

what is the first line drug to use in bowel obstruction

A

cyclizine

28
Q

what are the receptors found at the Bottom of the brainstem

A

faecal softener: docusate sodium, liquid paraffin

29
Q

What are some gut problems that can cause nausea and vomiting, and how should we treat this acutely before treating the underlying cause?

A
  • Infective gastroenteritis is supportive treatment as toxin needs to get out
  • Consider a nasogastric tube to decompress
  • Give antiemetic
30
Q

What are prokinetic drugs?

A
  • Drugs that increase gut motility, e.g domperidone and metoclopramide (D2 antagonists)
  • Useful for ileus and GORD
  • Do not use for obstructions as risk of perforation
31
Q

What are the first line anti-emetics?

A

If one not working don’t choose another drug in the same class

32
Q

What is hyperemesis gravidarum and how do we treat it?

A

- Rapid rise in b-hCG stimulates CTZ so severe N+V

  • Higher risk with multiple pregnancies
  • Can cause dehydration, weight loss, electrolyte imbalance
  • May require admission to replace fluids
33
Q

What antiemetics are used for nausea caused by chemotherapy?

A

Patients are risk stratified depending on their chemo drug and dose and then this decides their antiemetic

34
Q

What are some risk factors that increase your chance of post operative nausea and vomiting?

A
35
Q

What antiemetics are used for postoperative nausea?

A
  • Can alter the risk factors, e.g use a different anaesthesia
  • If patient is motion sick use drugs that act on vestibular nuclei e.g H1 receptor antagonists
  • If patient is having gut surgery use drugs that act on visceral afferents from the gut e.g 5HT3 antagonists and D2 receptor anatagonists
36
Q

What drugs can we use to treat diarrhoea?

A
  • Antimotility drugs (opioid agonists)

- Loperamide (u) and Codeine Phosphate (u and d) (opioids)

  • Loperamide is 1st line as gut specific, decreases tone of longitudinal and circular muscle, reduce peristalsis, and colonic mass movement

→ domperidone, metoclopramide, naloxegol.

37
Q

order for treating diarrhoea

A

→ treat complications: oral rehydration, IV fluid

→ treat cause: salmonella, travellers diarrhoea

→ reduce bowel motility: opioids, muscarinic receptor antagonists

38
Q

What are the side effects of using u opioid agonists to treat diarrhoea?

A
  • Paralytic ileus
  • Nausea and Vomiting
  • Sedation
  • Addiction (codeine)

– impaired response function, Aden-cortical function

39
Q

What diet can you recommend to someone with long term loose stools, e.g IBS, short bowel, drug side effects?

A

CONSTIPATING DIET

40
Q

What lifetsyle changes can you recommend to someone with constipation?

A
  • Drink more water
  • Increase fibre intake e.g fruit, veg, nuts
  • Regular exercise
  • Toilet routine and positioning
41
Q

What are some different drugs used for constipation?

A
42
Q

What are some examples of osmotic laxatives and what is their mechanism of action?

A

- Lactulose: draws fluid in from outside the gut

- Macrogol (really good - up to 12 sachets a day): retain the fluid they came with

  • MOVICOL FIRST LINE: both increasing amount of water in large bowel

→ flatulence, cramps, diarrhoea

43
Q

What are some examples of stimulant laxatives and how do they work?

A

- Bisacodyl, Docusate Sodium, Glycerol Suppository, Senna

- Enhance gut motility and increase water and electrolyte transfer into the lower gut

  • Given orally or rectally when osmotics haven’t worked
44
Q

What are some examples of bulk-forming laxatives and how do they work?

A

- Ispaghula Husk and Methylcellulose

  • Stimulation through increase faecal bulk, hydrophillic action causing gut lumen water retention
45
Q

How do stool softeners work to relieve constipation and what are some examples?

A

Like washing up liquid changing the surface tension!!!

46
Q

vomiting centres diagram

A
47
Q

where are the H1 and M1 receptors found in the brain

A

SA Clinical Pharmacology & Therapeutics (36 decks)

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