Lecture 2 - Gastric motility. Drugs affecting GI function

Question 1

What are the 2 gastric contraction controlls?

Answer 1

1. frequency
2. force

Question 2

Where are pacemaker cells located and what do they control?

Answer 2

• smooth muscle cells in UPPER FUNDUS
• rythmic, autonomous, partial depolarisation

Question 3

What rate do slow wave potentials sweep down stomach?

Answer 3

• rate of 3/min
• basic electrical rhythm (ber) of stomach

Question 4

When does a contraction occur?

Answer 4

when the
- slow wave exceeds resting membrane potential
- THREEEEEE peristalic waves / minute

Question 5

What are force (neural) increased and decreased by?

Answer 5

increased - VAGAL activity
decreased - ADRENERGIC activity

Question 6

what is force (hormonal) increased and decreased by?

Answer 6

increased- gastrin
decreased- secretion

Question 7

What is the response to intake of food? (4)

Answer 7

• waves of PERISTALTIC contraction through stomach
• force contractions and ^ pressure in antrum
• retropulsion of food against closed pylorus
• mixing + grinding of food

Question 8

describe response to intake of food (receptors) (4)?

Answer 8

• stretch receptors
• activation of vagal inhibitory neurones
• relaxation of smooth muscle
• little change in pressure
  (RECEPTIVE RELAXATION)

Question 9

Clinical term of vomiting and definition

Answer 9

EMESIS
- forceful evacuation of stomach contents

Question 10

Give 2 stimulus for emesis

Answer 10

• pain
• repulsive sights/smells
• emotional factors
• endogenous toxins / drugs
• stimuli from pharynx / stomach
• motion

Question 11

what are 2 centers controlling emesis?

Answer 11

• vomiting centre
• chemoreceptor trigger zone

Question 12

what are the neurotransmitter stimulus the control centres are sensitive to?

Answer 12

• ACh
• Histamine
• 5-HT
• Dopamine

Question 13

example of necessary to stimulate vomiting?

Answer 13

• toxin ingestion

Question 14

what is ipecacuanha

Answer 14

• locally acting in stomach
• irritant effects of alkaloids emetine and cephaeline

Question 15

Give 4 examples of Anti-emetics

Answer 15

1. H1 receptor antagonists
2. muscarinic antagonists
3. D2 receptor antagonists
4. 5-HT3 antagonists

Question 16

give examples of 5-Ht3 antagonists (3)

Answer 16

• cannabinoids
• antipsychotics
• steroid / neurokinin antagonists

Question 17

examples of H1 receptor antagonists

Answer 17

• cyclizine
• promethazine

Question 18

what are H1 receptors antagonists most effective for?

Answer 18

• motion sickness
• given before sickness

Question 19

what does h1 receptor antagonists act on?

Answer 19

vestibular nuclei not CTZ

Question 20

what are ADVS effects H1 rec. ant. ?

Answer 20

• mild
• drowsiness and sedation

Question 21

example of muscarinic antagonists

Answer 21

• hyoscine

Question 22

uses of Muscarinic antagonists

Answer 22

-motion sickness
- effective against vestibular apparatus stimuli and local gut stimuli

• INEFFECTIVE ON CTZ stimuli

Question 23

ADVS effects of Muscarinic ant.

Answer 23

mild
- dry mouth
- burred vision
- sedation
LESS THAN H1 ant.

Question 24

examples of D2 receptor antagonists

Answer 24

• metoclopramidine
• phenothiazines (prochlorparazine)

Question 25

uses of D2 receptor antagonists

Answer 25

- vomiting caused by renal failure - radiotherapy work centrally in the chemoreceptor trigger zone

Question 26

ADVS effects of D2 receptor antagonists

Answer 26

- CNS effects (motor movement disorders- twitching, restlessness) - prolactin stimulation > menstrual disorders

Question 27

examples of 5-HT3 antagonists ? (1)

Answer 27

Ondansetron

Question 28

uses of 5-HT3 antagonists

Answer 28

- antiemetic chemotherapy - post surgery - primarily act on CTZ

Question 29

when is 5-HT3 released in gut ?

Answer 29

-following endogenous toxins and chemotherapy drugs

Question 30

ADVS effects 5-HT3 antagonoists ?

Answer 30

mild - headache , diarrhoea

Question 31

definition of diarrhoea

Answer 31

passage of loose or watery stools at lease 3 times in 24 hours

Question 32

On average an adult has just under ____ episode of diarrhoea per year

Answer 32

one

Question 33

give 4 causes of diarrhoea

Answer 33

- viral - rotavirus - bacterial - campylobacter - systemic disease- inflammatory bowel disease - drug- induced antibiotics e.g. ERYTHROMYCIN

Question 34

Describe mechanism of Anti-diarrhoeals (6)

Answer 34

- stim of OPIATE receptors in bowel - increase tone of smooth muscle - suppress propulsive peristalsis - raise sphincter tone at ileo-caecal value and anal sphincter - reduce sensitivity to rectal distension - resultant delay in passage of faeces through the gut / ^ water + electrolyte absorption in sml intest. + colon

Question 35

give example of anti-diarrhoeals 2

Answer 35

opiod agonists - codeine, morphine

Question 36

describe mechanism of action for opiod agonists (analgesiacs)

Answer 36

- activate mew receptors on myenteric neurons - causes hyperpolarisation > inhibition of ACh release - reduced bowel motility - tolerance + dependence

Question 37

give 2 examples of synthetic opioid analogues

Answer 37

1. Loperamide (imodium) 2. diphenoxylate

Question 38

mechanism of action for loperamide (imodium)

Answer 38

- binds to opiate receptors in gut wall - relatively free of CNS side effects

Question 39

what is diphenoxylate combined with to discourage abuse ?

Answer 39

atropine

Question 40

In Western populations ___% of people defaecate between 3 times a day and once every 3 days

Answer 40

90

Question 41

Up to ___% of elderly people are constipated

Answer 41

20

Question 42

> __ million prescriptions for laxatives written each year in UK In UK over __ medicines have constipation listed as a possible side effect

Answer 42

10 700

Question 43

give the 4 types of laxatives

Answer 43

1. bulk forming agents 2. osmotic laxatives 3. stimulants 4. faecal softeners

Question 44

how do osmotic laxatives work?

Answer 44

- act by osmosis to retail water in the bowel - softer bulkier poo

Question 45

onset of action for osmotic laxatives

Answer 45

30 mins - rectal prep 2-5 hrs - magnesium salts 48 hrs for lactulose

Question 46

side effects osomotic laxatives

Answer 46

- abdominal cramps - flatulence - electrolyte disturbance

Question 47

give an example of bulk forming agents and what they contain?

Answer 47

e.g. Ispaghula - contain polysaccharide + cellulose components

Question 48

what is Bulk forming agents onset of action? And what do they do?

Answer 48

12-36 hrs - must be taken with fluid - increase faecal bulk + stim peristalsis

Question 49

side effects of Bulk forming agents

Answer 49

- flatulence + bloating

Question 50

give an example of stimulant laxatives and the pathology

Answer 50

e.g. senna - directly stimulates colonic nerves reduces time of moving faecal mass

Question 51

what is the onset of action and side effects of stimulant laxatives ?

Answer 51

OFA- 8-12 hrs - abdominal cramps - colonic atony with long term use

Question 52

give an example of faecal softeners and what they are

Answer 52

e.g. Docusate sodium - non-ionic surfactant with stool sofening - reduces surface tension - ^ penetration of fluid into faecal mass - weak stimulant

Question 53

2 types of inflammatory bowel disease and the difference

Answer 53

1. crohn's disease - affects entire gut 2. ulcerative colitis - affects only large bowel

Question 54

characteristics of IBD

Answer 54

- cyclical bouts of diarrhoea constipation +/or abdominal pain

Question 55

treatments for IBD

Answer 55

Glucocorticoids - oral or local (antiinflam) Aminosalicylates sulfasalazine - mechanism unknown immunosuppression - INFLiximab