Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PED2006 Systems Pharmacology > 1. Gastrointestinal System > Flashcards

1. Gastrointestinal System Flashcards

1
Q

Why is the guinea pig ileum used as a pharmacological model?

A

-Its responsiveness to various substances (eg acetylcholine, histamine, serotonin)
-Possesses both smooth muscle and an intrinsic nervous system (allowing direct and indirect assessment of drug effects)
-Drug responses can be selectively antagonised to study receptor specific actions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the physiology of smooth muscle

A

-Capable of sustained contractions with low energy use
-Displays intrinsic tone and spontaneous contractions independent of nerve stimulation
-Innervated by the autonomic nervous system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the structure of smooth muscle

A

-Smaller and lack striations compared to skeletal muscle
-Rely on vesicular calcium stores near the membrane (instead of SR or T-tubule system)
-Connected via gap junctions (enabling synchronised contraction)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe the electrical basis of smooth muscle activity

A

-Resting potential oscillates between -60 and -30 mV as slow waves initiated by pacemaker ICCs
-Action potentials triggered involve calcium influx for depolarisation and potassium efflux for repolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does the Enteric Nervous System contain?

A

-108 neurones organised into the myenteric and sub mucous plexuses
-ENS provides local reflex control while receiving modifying inputs from the CNS, parasympathetic and sympathetic systems
-Neurotransmitters include serotonin, NO, Purines and peptides.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does the myenteric plexus in the ENS control?

A

Longitudinal and circular muscle layers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does the submucous plexus in the ENS control?

A

Secretion and communicates with the myenteric plexus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Give some receptors found in smooth muscle

A

-M3 (ACh)
-⍺1 and β2 (norepinephrine)
-H1 (histamine)
-5HT receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How do calcium channel blockers affect smooth muscle?

A

Inhibit contractions, potentially causing constipation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why is the GI system important?

A

-Has major metabolic and endocrine function
-Has a wide range of pathologies associated
-Is a site for major drug absorption
-Has significant costs associated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What GI issues may we treat using pharmacology?

A

-Gastric secretion
-Vomiting (emesis)
-Bowel motility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What aspect of the GI system contains the intrinsic primary afferent neurones?

A

Intramural plexuses (either myenteric or sub mucous plexus)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Where do extrinsic afferents of the GI system originate from?

A

-The brainstem (vagal nerve afferent originates from nodose ganglia)
-The spinal cord (pelvic nerve originates from dorsal roots ganglia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the GI system controlled by?

A

Both neural and hormonal innervations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Name the hormonal innervations in the GI system

A

-Endocrine secretions (Gastrin and Cholecystokinin)
-Paracrine secretions (Histamine and Acetylcholine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What cells make up the gastric gland?

A

Parietal and chief cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Where in the parietal cell is the site of hydrochloric acid production?

A

The Caniculus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the action of tubulovesicles in parietal cells?

A

-They transport H+/K+ ATPases to the caniculus
-Fusing with the canalicular membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe how the caniculus acts as an HCl secretor?

A

-Cl-/K+ cotransports both into gastric lumen
-H+/K+ ATPase transfers H+ into the lumen for K+ into the parietal cell
-This leads to a net isotonic HCl secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the hormones and their receptors that are involved in the secretion of HCl into the gut lumen

A

-Acetylcholine on M receptors (INCREASING)
-Histamine on H2 receptors (INCREASING)
-Gastrin on G receptors (INCREASING)
-PGE2 acts on PG (DECREASING)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe Gastrin as a chemical affecting acid secretion

A

-Peptide hormone
-Stimulates acid secretion, pepsinogen secretion, blood flow and increases gastric motility
-Increases cytosolic Ca2+
-INCREASES ACID SECRETION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe Acetylcholine as a chemical affecting acid secretion

A

-Neurotransmitter
-Released from vagal neurones
-Increases cytosolic Ca2+
-INCREASES ACID SECRETION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe histamine as a chemical affecting acid secretion

A

-Hormone
-Sub type specific action (acting on H2 receptors)
-Increases cAMP
-INCREASES ACID SECRETION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Give some diseases associated with stomach acid dysregulation

A

-Dyspepsia (indigestion) causing pain, bloating, nausea
-Peptic ulceration caused by prolonged excess acid secretion
-Reflux oesophagitis (damage to oesophagus by excess acid secretion)
-Zollinger Ellison syndrome (tumours in pancreas or SI create too much stomach acid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How may we decrease secretions of gastric acid?
-Reducing proton pump function -H2 receptor antagonism -Acid neutralisation
26
What is the target of Proton pump inhibitors?
(Irreversibly inhibit) H+/K+ ATPase in the canaliculus
27
Give some examples of proton pump inhibitors
-Omeprazole -Lansoprazole
28
What are proton pump inhibitors used in?
-Peptic ulcers -Reflux oesophagitis -Zollinger Ellison
29
Where do Proton pump inhibitors bind on their target enzyme?
Cysteine-813 on the 5 and 6 transmembrane loops, blocking this channel
30
Describe how proton pump inhibitors are absorbed and distributed
-Orally given -Weak bases and are enteric coated preventing stomach acid degradation -Absorbed in small intestine and transported via albumin to parietal cells
31
What is responsible for metabolising proton pump inhibitors?
CYP2C19 and CYP3A4
32
How long is the mechanism of action (including half life) of proton pump inhibitors?
Despite having a short half life of 1-2 hours, action lasts 24-48 hours as new proton pumps must be synthesised
33
Give some adverse effects associated with proton pump inhibitors
-Headache -Nausea, vomiting, diarrhoea, constipation -Abdominal pain and bloating -Vitamin deficiencies (B12 absorption) -Increased infections risks -Can mask symptoms of gastric cancer
34
Give some examples of histamine H2 receptor antagonists
-Cimetidine -Ranitidine
35
What are histamine H2 receptor antagonists used in?
-Peptic ulcer -Reflux oesophagitis
36
Describe the absorption and distribution of H2 receptor antagonists
-Orally given most frequently and well absorbed -Tmax is 1-3 hours -Widely distributed in body fluids, doesn't cross the BBB easily (except cimetidine) -Low binding to proteins
37
Describe the metabolism and excretion of H2 receptor antagonists
-Inhibits CYP450 -Therefore primarily eliminated via the kidneys by renal excretion
38
What clinical considerations should be given to the administration of H2 receptor antagonists?
-Some may cause gynecomastia and impotence due to anti androgenic effects -Inhibit CYP450s so polypharmacy must be regulated -Dose adjustment in renal impairment -May cause diarrhoea, dizziness and muscle pain
39
Describe antacids as a treatment for gastric acid secretions
-Weak bases that neutralise gastric acid -Short term relief -Do not reduce acid production but buffer existing acid
40
What are antacids used to treat?
-Dyspepsia -Gastroesophageal Reflux Disease (GERD)
41
Give some types of antacids
-Aluminium based -Magnesium based -Calcium based -Sodium based
42
Describe the distribution and metabolism of antacids
-Since most acids act locally in the stomach, systemic distribution is minimal, however absorbed antacids may affect serum electrolytes and acid base balance -No significant metabolism for most antacids as they act through chemical neutralisation -Carbonates and bicarbonates are converted to CO2 and water, leading to gas and belching
43
Describe the excretion of antacids
-Insoluble compounds (Al and Mg OH) -Absorbed antacids (NaHCO3, CaCO3) are excreted via the kidneys
44
Describe helicobacter pylori infections
-Important factor in peptic ulcer formation -Risk factor in gastric cancer
44
Give some adverse effects associated with antacids
-Diarrhea, constipation, belching -Acid rebound -Alkalosis -Sodium content may be increased
45
How are helicobacter pylori infections tested and treated?
-Urea breath test -Treated with combination triple therapy
46
What does the combination therapy for helicobacter pylori infections consist of?
-Proton pump inhibitors -Antibacterials -Cytoprotective agent
47
What is the purpose of cytoprotective agents in H pylori treatment?
-Helps protect gastric mucosa from acid damage and pepsin -Also binds enterotoxins -Also stimulates prostaglandin, mucus and bicarbonate secretion
48
Give examples of cytoprotective agents used in H pylori treatment?
-Bismuth chelate -Sucralfate -Misoprostol
49
Describe the mechanism of NSAID induced mucosal damage
-Inhibition of prostaglandin synthesis by COX inhibition -Direct mucosal irritation by penetrating gastric epithelial cells -Increased risk of mucosal erosion and ulcer formations
50
Do glucocorticosteroids induce mucosal damage?
YES, in a similar way to NSAIDs -They inhibit prostaglandin synthesis -May increased gastric acid secretion
51
What are the 4 key areas of the stomach?
-Cardia -Fundus -Body -Pylorus
52
Describe the cardia of the stomach
-Region closest to the oesophagus -Contains the cardiac sphincter, preventing gastric reflux by keeping stomach contents from moving back into oesophagus
53
Describe the fundus of the stomach
-Upper, dome shaped region -Stores undigested food and gases released during digestion
54
Describe the corpus body of the stomach
-Largest and main part of the stomach -Responsible for mixing and churning food
55
Describe the pylorus of the stomach
-Lower portion of stomach that connects to the duodenum -Contains the pyloric sphincter -Regulating the release of chyme into the small intestine
56
Describe what controls the frequency of gastric contractions
-Pacemaker cells, consisting of smooth muscle cells in upper fungus -Creating a rhythmic, autonomous and partial depolarisation which drives peristaltic movement -Slow wave potentials sweep down the stomach, creating the basic electrical rhythm of stomach (BER)
57
What is the average basic electrical rhythm of stomach?
3 waves per minute
58
Describe what controls the force of gastric contractions
-Neurally (increased by vagal activity, decreased by adrenergic activity) -Hormonally (increased by gastrin, decreased by secretin
59
Describe the responses of the stomach to food intake
-Waves of peristaltic contraction throughout the stomach -Forceful contractions and increased pressure in antrum -Retropulsion of food against closed pylorus -Causing a mixing and grinding of food
60
What is receptive relaxation in the stomach?
A neurogenic reflex allowing the stomach to expand and accommodate food without a significant increase in intragastric pressure
61
Describe the steps of receptive relaxation in the stomach
-Stretch receptors are activated -Activating inhibitory vagal neurones -Causing relaxation of smooth muscle -Allowing expansion
62
What is emesis
Forceful evacuation of stomach contents
63
Give stimuli that may cause emesis
-Pain -Repulsive sights/smells -Emotional factors -Endogenous toxins/drugs -Stimuli from pharynx and stomach -Motion
64
What controls emesis?
-Vomiting centre -Chemoreceptor trigger zone (CTZ)
65
What neurotransmitters can be used to stimulate emesis?
-Acetylcholine -Histamine -5HT -Dopamine
66
What are emetics, and why aren't they used anymore?
-Substances used to stimulate vomiting -Not in use due to risk of aspiration of vomit into airways
67
Give some examples of classes of anti emetics
-H1 receptor antagonists -Muscarinic antagonists -D2 receptor antagonists -5HT3 antagonists
68
Describe H1 receptor antagonists as antiemetics, and give an example.
-Blocks histamine mediated signalling leading to emesis -Blocks in vestibular system, CTZ and vomiting centre -Can cause mild drowsiness and sedation -EG CYCLIZINE, PROMETHAZINE
69
Describe muscarinic antagonists as antiemetics, and give an example.
-Blocks acetylcholine at M1 receptors -In vestibular system, CTZ and vomiting centre -Can cause dry mouth, blurred vision and sedation -eg Hyoscine
70
Describe 5HT3 antagonists as antiemetics, and give an example
-Blocks serotonin receptors -In GI tract+vagus nerve, and CTZ and vomiting centre -Used in chemotherapy induced nausea, radiotherapy induced nausea -Can cause headache, constipation, serotonin syndrome -eg Ondansetron
71
Describe D2 antagonists as anti emetics, and give an example
-Blocks D2 dopamine receptors -In GI tract and CTZ -Used in postoperative, chemotherapy, and migraine induced nausea and vomiting -Can cause CNS effects (twitching, restlessness) and prolactin stimulation (menstrual disorders) -eg Metoclopramide
72
What is diarrhoea?
Passage of loose or watery stools at least 3 times in 24 hours
73
Give some examples of causes of diarrhoea
-Viral (rota or noro) -Bacterial (campylobacter) -Systemic disease (IBS) -Drug induced (antibiotic)
74
Describe the mechanism of action of antidiarrhoeal drugs
-Reduce intestinal motility, increasing water absorption -Increase tone of smooth muscle and raises sphincter tone at ileo-caecal valve and anal sphincter -Reduce sensitivity to rectal distension -Suppress propulsive peristalsis
75
Give an example of types of antidiarrhoeal medication
-Opioid agonists (eg codeine and morphine) -Synthetic opioid analogues (eg loperamide, diphenoxylate)
76
Describe opioid agonists as an anti diarrhoeal treatment
-Activate µ-receptors on myenteric neurones -Causing hyperpolarisation therefore inhibition of ACh release -Reduces bowel motility
77
What are the benefits of synthetic opioid analogues as antidiarrhoeal treatments
-Minimal CNS effects (lower addiction and abuse potential) -Stronger GI selectivity (more effective at reducing diarrhoea) -Longer duration of action -Fewer systemic side effects
78
What is diphenoxylate coupled with to reduce abuse?
Atropine
79
What is constipation?
Passage of hard stools less frequently than the patient's normal pattern
80
What are the types of laxatives?
-Bulk forming agents -Osmotic laxatives -Stimulants -Faecal softeners
81
Describe the mechanism of action of bulk forming agent laxatives, and give an example
-Absorb water into the stool, increasing bulk and stimulating peristalsis -Mimic the dietary fibre effect, promoting regular bowel movements -Slow onset (12-72 hours) -Side effects include flatulence and bloating -eg Methylcellulose
82
Describe the mechanism of action of osmotic laxatives, and give an example
-Draw water into the bowel via osmosis, softening stools and increasing motility -Fast onset (2-48 hours) -Side effects include abdominal cramps, flatulence, electrolyte disturbance -eg Lactulose
83
Describe the mechanism of action of stimulant laxatives, and give an example
-Directly stimulate enteric nerves in the colon, increasing peristalsis -Promoting fluid and electrolyte secretion, softening stools -Side effects include abdominal cramps and colonic atony -eg Senna
84
Describe the mechanism of action of faecal softener laxatives, and give an example
-Act as surfactants, lowering stool surface tension, meaning more water enters stool softening it -Lubricant laxatives coat stools, preventing water loss and easing passage -Side effects include leakage and anal irritations -eg Docusate sodium
85
What is irritable bowel syndrome
-Chronic functional GI disorder -Characterised by abdominal pain and altered habits -Relief after defecation, bloating and gas
86
Give some inflammatory bowel diseases
-Crohn's disease -Ulcerative colitis

PED2006 Systems Pharmacology (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions