Treatment of Vomiting and Gut Motility Disorders Flashcards

1
Q

Define emesis.

A

Vomiting, defense responsive mechanism to get rid of neurotoxins, irritant etc.

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2
Q

Which parts of the brain are involved in the control of vomiting?

A

Central neural regulation of vomiting is controlled by two separate units both in the medulla:

1) Vomiting (emetic) center
2) Chemoreceptor Trigger Zone (CTZ)

Pain, repulsive sights and smells and emotional factors from higher cortical centers are sent to the vomiting centers.

Enterochromaffin cells sense toxic chemicals or toxins in the gut. Signals are then sent through vagal afferents from the gut to the vomiting centers. Signals from vagal afferents also sent to the CTZ (main site for sensing emetic stimuli) which sends the impulse to the vomiting center.

The vomiting centers integrate incoming signals and coordinate emesis.

Signals about motion sickness from vestibular labyrinth → Vestibular nuclei (brain stem) → CTZ (main site for sensing emetic stimuli) → Vomiting centers

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3
Q

Which circumstances do we want to avoid vomiting in ?

A

Pregnancy (could be harmful to the fetus), cases of dehydration

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4
Q

Identify the location of vomiting center and CTZ.

A

1) Vomiting center: in the medullary and pontile reticular formation, also extending into spinal cord
2) Chemoreceptor trigger zone: in the area postrema in the floor of the 4th ventricle

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5
Q

Where does the vomiting center, and the CTZ receive impulses from ?

A

1) Vomiting center: Receive nerve impulses from both vagal and sympathetic afferent nerve fibres, and responds to the incoming signals to coordinate emesis
2) CTZ: sensitive to chemical stimuli and is the main site of action of drugs which stimulate vomiting. Also concerned with the mediation of motion sickness.

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6
Q

Are the vomiting center, and CTZ discrete areas ?

A

Vomiting center is not: collection of multiple sensory, motor and control nuclei

CTZ is: more discrete, in the area postrema in the floor of the 4th ventricle.

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7
Q

Explain how vomiting occurs in motion sickness.

A

Motion sickness is caused by certain kinds of movement and the origin of the stimuli is primarily the vestibular apparatus:

Vestibular labyrinth → Vestibular nuclei (brain stem) → cerebellum → CTZ → vomiting centre → vomit

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8
Q

Identify possible triggers of nausea/vomiting.

A
  • Stimulation of the sensory nerve endings in the stomach and duodenum.
  • Stimulation of the vagal sensory endings in the pharynx.
  • Drugs or endogenous emetic substances.
  • Disturbances of the vestibular apparatus.
  • Various stimuli of the sensory nerves of the heart and viscera.
  • A rise in intracranial pressure.
  • Nauseating smells, repulsive sights, emotional factors.
  • Endocrine factors
  • Migraine
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9
Q

Identify neurotransmitters involved in the vomiting pathway. What is their general function ?

A

ACh, Histamine, Dopamine, substance P, 5HT, make the pathway move forward.

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10
Q

Identify and describe the main stages of vomiting.

A

1) Nausea
- Feeling of wanting to vomit
- Associated with autonomic effects: salivation / pallor / sweating
- Often pro-drome of vomiting

2) Retching
- Strong involuntary effort to vomit
- Unproductive

3) Vomiting
- Expulsion of gastric contents through the mouth

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11
Q

Identify some types of vomiting, and state the possible conditions associated with each.

A
  • Projectile vomiting (hypertrophic pyloric stenosis in neonates, upper GI obstruction due to malignancy at older ages)
  • Haematemesis (e.g. oesophageal varices, bleeding gastric ulcer)
  • Early morning (e.g. pregnancy, alcohol dependence, some metabolic disorders (uraemia))
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12
Q

How can we determine where the bleeding occurs, in haematemesis.

A

Determine if vomiting fresh or altered blood (“coffee- grounds”)
Fresh implies bleeding has occurred nearer the exit (in this case, nearer the mouth)

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13
Q

What is the main aim of anti-emetic drugs ? Can you prescribe those when the cause is unknown ?

A

To stop nausea/vomiting.
Only prescribe when the cause of vomiting is known (in which case treat the cause if possible). If indicated, pick drug according to the aetiology of vomiting

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14
Q

Identify possible indications for anti-emetics.

A
  1. Severe vomiting during pregnancy / hyperemesis gravidarum
  2. Postoperative nausea and vomiting
  3. Motion sickness
  4. Other vestibular disorders
  5. N/V induced by cytotoxic chemotherapy
  6. Palliative care
  7. N/V associated with migraine
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15
Q

Identify the main types of anti-emetics. Give examples per class.

A
  • Antihistamines (H1 receptors)
  • Antimuscarinics (M1 receptors): Hyoscine
  • Dopamine antagonists( D2 receptors): Phenothiazines, Metoclopramide
  • 5HT3 antagonists: Graniestron, Ondansetron
  • Neurokinin 1 receptor antagonists: Aprepitant, fosaprepitant
  • Synthetic cannabinoids (CB1 receptors): Nabilone
  • Steroids
  • Other neuroleptics
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16
Q

Identify the site of action of:

  • Antihistamines (H1 receptors)
  • Antimuscarinics (M1 receptors)
  • Dopamine antagonists (D2 receptors)
  • Neurokinin 1 receptor antagonists
  • Synthetic cannabinoids (CB1 receptors)
  • 5HT3 antagonists
A
  • Antihistamines (H1 receptors) → higher cortical centers
  • Antimuscarinics (M1 receptors) → vestibular nuclei region

• Dopamine antagonists (D2 receptors) → CTZ zone or GI afferents

• Neurokinin 1 receptor antagonists →
GI afferents
• Synthetic cannabinoids (CB1 receptors) → → GI afferents

• 5HT3 antagonists → CTZ zone or GI afferents

17
Q

ANTIHISTAMINES

Receptor blocked
Indications
Side effects
Examples of antihistamines and conditions used for

A

ANTIHISTAMINES

• Receptor blocked: H1 histamine receptor
• Indications: numerous causes of nausea and vomiting, including motion sickness and vestibular disorders
• Side effects: drowsiness and anti-muscarinic effects
• Examples:
1. Cinnarizine; motion sickness, vestibular disorders
2. Cyclizine; motion sickness
3. Promethazine; severe morning sickness

18
Q

ANTIMUSCARINICS

  • Receptor blocked
  • Indications
  • Side effects
  • Examples
  • Method of administration
A

ANTIMUSCARINICS

• Receptor blocked: Muscarinic receptors
• Indications: muscarinic-mediated impulses from the labyrinth and from visceral afferents
• Side effects: constipation, transient bradycardia, dry mouth
• Examples:
Hyoscine hydrobromide- Useful in motion sickness
• Method of administration: patch and tablets

19
Q

DOPAMINE (D2 RECEPTOR) ANTAGONISTS

  • Receptor blocked
  • Indications
  • Side effects
  • Examples
A

DOPAMINE (D2 RECEPTOR) ANTAGONISTS

• Receptor blocked: D2 receptor
• Indications: CTZ-triggered vomiting but not stomach-induced vomiting.
• Examples:
1. The phenothiazines and related drugs
(these are also classed as neuroleptics/antipsychotics)
Chlorpromazine
Prochlorperazine
2. Domperidone
3. Metoclopramide
• Side effects: neuroleptics/antipsychotics associated with dystonic reactions and tardive dyskineasia

20
Q

5HT3 ANTAGONISTS

  • Receptor blocked
  • Indications
  • Examples
A

5HT3 ANTAGONISTS

  • Receptor blocked: 5HT3 receptors in GI tract and in the CNS
  • Indications: Particularly useful in managing N/V in patients receiving cytotoxics (e.g. chemo) and in postoperative N/V
  • Examples: 1. Ondansetron
21
Q

Neurokinin 1 receptor antagonists

  • Receptor blocked
  • Indications
  • Examples
A

Neurokinin 1 receptor antagonists

  • Receptor blocked: Neurokinin 1 receptor
  • Indications: Adjunct to dexamethasone and a 5HT3 antagonist in preventing N/V associated with chemotherapy (if first line does not work)
  • Examples: Aprepitant
22
Q

Synthetic cannabinoids

  • Receptor blocked
  • Indications
  • Examples
  • Side effects
A

Synthetic cannabinoids

  • Receptor blocked: CB1 receptors
  • Indications: Used for N/V caused by chemo unresponsive to conventional anti-emetics
  • Examples: Nabilone
  • Side effects: drowsiness/dizziness
23
Q

Steroids

  • Example of anti-emetic steroids
  • Indications of example
A

Steroids

  • Dexamethasone has anti-emetic effects
  • Can be used alone, to treat vomiting associated with cancer chemotherapy, or in conjunction with other antiemetics
24
Q

Briefly describe how constipation comes about.

A

Hard stool, dilating the rectum, bowel movement is wider.

Chronically, softer stool is suck behind it, becomes harder, so patients get liquid on the sides .

25
Q

Which type of stool are we aiming for in the Bristol Stools Chart ?

A

Type 4

26
Q

Identify the main treatment for constipation.

A

1) Reversing cause, including diet/lifestyle diet, such as:
- increased water intake
- prune juice
- fuits/veggies

2) Laxatives (but before prescribing them, make SURE the problem is constipation, checking the patient’s norm, e.g. could be completely normal to go to the bathroom only once a week as long as they’ve done that all their life)
Only prescribe if natural ones don’t work (because these have side effects)

27
Q

Identify the main types of laxatives.

A
  1. Bulk-forming laxatives (this increases bulk of stool, which triggers peristalsis. Sometimes makes it worse)
  2. Stimulant laxatives (directly promotes lumen, by acting on wall)
  3. Faecal softeners (cause it to disperse)
  4. Osmotic laxatives (pulls water in, triggering peristalsis)
  5. Peripheral opioid-receptor antagonists (only for opioid induced constipation)
28
Q

Identify an example of each main kind of laxative.

A
  • Bulk: ispaghula husk
  • Stimulant: senna
  • Softener: docusate
  • Osmotic: lactulose
  • Peripheral opioid receptor antagonist: methylnaltrexone bromide
29
Q

What are the main clinical pathological features of diarrhea ?

A

1) increase in the motility of the GI tract

2) decrease in the absorption of fluid and thus a loss of electrolyte

30
Q

Describe the management of acute diarrhea.

A
  1. Maintenance of fluid and electrolyte balance e.g. ORT/ORS
  2. Anti-motility drugs (e.g. loperamide (imodium)
  3. Anti-spasmodics (reduce smooth muscle tone, and used for pain) e.g. hyoscine butylbromide (buscopan), mebeverine
  4. Occasionally anti-bacterial agent is indicated (e.g. systemic bacterial infection, campylobacter enteritis, shigellosis and salmonellosis)
31
Q

Describe the management of chronic diarrhea. What kind of condition may we see chronic diarrhea in ?

A
  • Antimotility agents e.g. loperamide (imodium)
  • Adsorbents (NB not for acute diarrhoea) e.g. kaolin, light
  • Bulk forming drugs (useful in controlling diarrhoea assoc. with diverticular disease) e.g. ispaghula (may have converse effect, too much of a bulk, decreases motility)

Chronic diarrhea is seen in inflammatory bowel disease patients.

32
Q

What are the main contents of bile ? Which of these is usually in excess in gall stones ?

A
  1. Bilesalts
  2. Bilirubin
  3. Cholesterol
  4. Lecithin
  5. Plasma electrolytes

Majority of stones in gall bladder are excess cholesterol in bile- related stones

33
Q

Which hormone promotes gall bladder emptying ?

A

CCK

34
Q

What is a possible complication of gall stone ?

A

Body will naturally try to expel them, which

can lead to stone being stuck in bile duct, which can cause an infection (acute cholecytitis)

35
Q

Describe the treatment of gall stones.

A
  • The use of lap chole and modern endoscopic techniques has limited the place of medication to treat gallstones
  • Ursodeoxycholic acid is still used to dissolve gallstones – mainly if mild symptoms and not amenable to other treatment.
36
Q

Describe the treatment of biliary colic and acute cholecystitis

A

Not trying to treat stone, trying to treat pain, and infection if there is one.

1) Pain: Biliary colic is v painful–may require an opioid, such as morphine or pethidine, given parenterally and/or diclofenac (NSAID) by suppository.
→ Parenteral/rectal route chosen as overcomes difficulties in absorption caused by vomiting.

2) Pain continuing for over 24 hours or accompanied by fever usually necessitates hospital admission (iv antibiotics may be required).

37
Q

Identify an example of bile acid sequestrants. What is its mechanism of action, and what are its main indications ?

A
  • Colestyramine is an anion-exchange resin, it forms an insoluble complex with bile acids in the intestine
  • Indications:
  • Relieves pruritus associated with partial biliary obstruction and primary biliary cirrhosis
  • Can also be used in some instances of diarrhoea e.g. Crohn’s disease related
  • Can be used in hypercholesterolaemia
38
Q

Identify the main drugs which affect bile flow.

A

1) Bile acid sequestrants

2) Ursodeoxycholic acid is still used to dissolve gallstones