1- pharmacology of intestinal motility

Question 1

what are causes of nausea?

Answer 1

anxiety, motion sickness, migraine, pregnancy, side effects of drug

Question 2

what triggers of vomiting?

Answer 2

it’s a defence mechanism triggered by emetic centre located in brain stem

Question 3

what is detected in higher cortical centres?

Answer 3

pain, repulsive sights, smells, emotional factors

Question 4

what is function of vomiting centre?

Answer 4

integrate incoming signals: coordinates emesis (vomiting)

Question 5

what is chemoreceptor trigger zone in brain?

Answer 5

main site for sensing emetic stimuli - express 5HT3 receptors and D2 receptors

Question 6

what do enterochromaffin cells sense?

Answer 6

sense toxic chemicals or toxins in gut (also secrete histamine)

Question 7

what is classical conditioning for vomiting?

Answer 7

pair 2 stimuli together (stimuli that normally wont cause nausea with stimuli that usually does) - following repeated paring, previously innocuous stimuli would produce stimulations of nausea

Question 8

what are the main neurotransmitter systems involved in nausea/vominiting?

Answer 8

5-HT, dopamine and ACh

Question 9

what are the different classes of anti-emetic drugs?

Answer 9

• anti-histamines
• antimuscarinics
• 5-Ht3 receptor antagonists
• dopamine receptor antagonists
• neurokinin-1 receptor antagonists

Question 10

what are examples of anti-histamines?

Answer 10

cyclizine, promethazine, diphenydramine

Question 11

what are examples of antimuscuranics?

Answer 11

scopolamine (hyoscine)

Question 12

what are examples of 5-Ht3 antagonists?

Answer 12

ondansetron, granisetron, palonesetron

Question 13

what are examples of dopamine receptor antagonists?

Answer 13

chlorpromazine, droperidol, haloperidol, metoclopramide

Question 14

what are examples of neurokinin-1 receptor antagonists?

Answer 14

fosaprepitant, aprepitant

Question 15

antihistamines
1. what is mechanism
2. when are they indicated
3. what are side effects

Answer 15

1. act as antagonists at H1 receptors in brain
2. indicated for motion sickness
3. sedation because they act at H1 receptors that are involved in sleep response

Question 16

antimuscarinics
1. what is mechanism
2. when are they indicated
3. what are side effects

Answer 16

1. act as antagonist at M1 muscarinic acetylcholine
2. indicated for motion sickness
3. antimuscarinic side effects (act everywhere in body) so range from dry mouth, tachycardia, constipation (because stimulates peristaltic reflex)

Question 17

for 5-HT3 receptor antagonists
1. what is mechanism
2. when are they indicated
3. what are side effects

Answer 17

1. act as antagonists, act in gut and brain (chemoreceptor trigger zone in medulla where there’s high density of 5HT)
2. used to counteract nausea
3. constipation, diarrhoea and headache

Question 18

how does 5-HT3 receptor antagonists lead to constipation?

Answer 18

in gut 5HT3 receptor on presynaptic afferents of parasympathetic innervation to gut so when activated by 5HT they stimulate Ach release which binds to Ach receptors = peristaltic reflex. therefore when block no peristaltic reflex hence no peristalsis so constipation

Question 19

for dopamine receptor antagonist
1. what is mechanism
2. when are they indicated
3. what are side effects

Answer 19

1. act as antagonists, on D2 receptors in chemoreceptor trigger zone of medulla in hindbrain - also D2 in GI tract
2. were originally used as antipsychotic but now low dose antiemetic
3. diarrhoea + extrapyramidal side effects (group of symptoms for people taking antipsychotic medications = inability to sit still, involuntary muscle contraction, tremors, stiff muscles, and involuntary facial movements)

Question 20

for neurokinin-1 receptor antagonists
1. what is mechanism
2. what is side effects?

Answer 20

1. act as antagonists at NK1 receptors in GI tract and chemoreceptor trigger zone of medulla in hindbrain blocking effects of substance P (which evokes vomit)
2. constipation + headache

Question 21

what are drug classes that affect GI motility?

Answer 21

• antidiarrhoeal drugs
• drugs that reduce constipation
• laxatives
• faecal softeners

Question 22

what are examples of antidiarrhoeal drugs?

Answer 22

Loperamide, diphenoxylate

Question 23

what are examples of drugs that reduce constipation?

Answer 23

Naloxegol, Prucalopride, Lubiprostone

Question 24

what are examples of laxatives?

Answer 24

Bulk laxatives, Osmotic laxatives, Stimulant laxatives

Question 25

what are examples of faecal softeners?

Answer 25

Docusate sodium

Question 26

what is mechanism of antidiarrhoeal drugs?

Answer 26

opiate agonist (loperamide) that will bind to mu opiate receptor that will have reduced effect on brain over other opiates (opiates can be addictive so can lead to drug abuse)

Question 27

what are some treatments that can be given alongside anti-diarrhoeal drugs for treatment for diarrhoea?

Answer 27

1st line = electrolytes replacement
then atropine (muscarinic acetylcholine receptor antagonist)

Question 28

what are side effects of anti-diarrhoeal drugs?

Answer 28

constipation, sedation, respiratory depression (common for opiates)

Question 29

for bulk laxatives
1. what are examples
2. what is mechanism

Answer 29

1. Ispaghula husk, methylcellulose, bran
2. bulk formed from polysaccharides that are not digested→ the bulk leads to a triggering of peristaltic reflexes (promoting passage of stool)

Question 30

for osmotic laxatives
1. what are examples
2. what is mechanism

Answer 30

1. Saline purgatives (magnesium sulfate, magnesium hydroxide), Lactulose
2. osmotic load leads to increased fluid in the bowel promoting movement of the contents of the gut.

Question 31

for stimulant laxatives what are examples and their mechanism? (2 examples - each with different mechanism)

Answer 31

examples = senna + glycerol suppositories

• senna mechanism = stimulant purgative- increases electrolyte then water secretion from the rectal mucosa as well as stimulation of the myenteric plexus(nerve fibres in intestinal wall)→ peristaltic reflex. Used in bowel obstruction.
• glycerol suppositories = stimulates the rectal mucosa →promotes defecation by inducing reflex contraction of rectal muscles + relaxation of anal sphincter