gastrointestinal pharmacology - upper gi tract Flashcards
(120 cards)
1
Q
gastrointestinal system
A
facilitates absorption of nutrients from food
responsible for egestion of waste (undigested food substances and dead cells) as faeces
2
Q
digesting food uses around __% of our energy
A
10
3
Q
main organs of GI system - 4
A
mouth
esophagus
small/ large intestines
anus
4
Q
accessory organs of GI system - 3
A
liver
pancreas
gall bladder
5
Q
what takes most energy to digest
A
protein
6
Q
structure of gi tract walls - 5
A
smooth muscle
blood vessels
glands (exocrine, endocrine, paracrine)
epithelium facing lumen
circular muscle and longitudinal muscle in outer layer to help propel food along intestin
7
Q
what mechanisms are the GI tract controlled by - 2
A
neuronal
hormonal
8
Q
neuronal control of GI tract is via
A
enteric nervous system (not CNS)
9
Q
enteric nervous system role
A
secrete pharmacologically active peptides and send messengers to our gut
10
Q
hormonal control function is via
A
exocrine and endocrine control - substances released into bloodstream
paracrine - regulatory peptides released, more localised effect
11
Q
exocrine and endocrine control
A
substances released into bloodstream
exocrine = via duct
endocrine = directly into bloodstream
12
Q
paracrine control
A
regulatory peptides released, more localised hormone effect
13
Q
peristalsis
A
propels food bolus along GI tract
involuntary involving smooth muscle in GI tract
circular muscle and longitudinal muscle in outer layer to help propel food along intestin
14
Q
pertistalsis takes place where
A
esophagus to colon
15
Q
___ administered drugs absorb best in the GI tract
A
orally
16
Q
pharmacologically relevant functions of GI tract - 4
A
gastric secretion
nausea/ vomiting
gut motility/ defaecation
bile formation/ excretion
17
Q
stomach is part of the
A
upper GI tract
18
Q
cell types found in the stomach lining - 6
A
mucous neck cell
parietal cells
enterochromaffin-like cell
chief cells
D cells
G cells
19
Q
mucous neck cells secrete - 2
A
mucus to protect lining
bicarbonate
20
Q
parietal cells secrete - 2
A
gastric acid
intrinsic factor for calcium ion absorption
21
Q
enterochromaffin-like cell secrete
A
histamine to stimulate acid via Gs signalling
22
Q
chief cells secrete - 2
A
pepsinogen and proenzymes
gastric lipase
23
Q
D cells secrete
A
somatostatin which inhibits acid
24
Q
G cells secrete
A
gastrin which stimulates acid via Gq signalling
25
cell turnover in stomach time
2-9 days
26
we secrete ___L of gastric juice a day
approx 2.5
27
pH of gastric juice
1-2
28
phases of gastric juice - 3
cephalic - involved in taste and smell
gastric - has chemical and mechanical effects
intestinal
29
why is gastric juice acidic - 3
for proteolytic digestion
iron absorption
killing pathogens
30
proenzymes like prorennin and pepsinogen are coverted by ___ for ___
gastric acid
digestion
31
mucous role
protects stomach lining
32
prostaglandins role
inhibiting acid secretion
maintain mucous layer by inducing mucous secretion and bicarbonate
Gi signalling
33
bicarbonate ion function
maintain cell pH at 6-7
34
acid secretion is regulated by __ cells
parietal
35
what is gastric acid
hydrochloric acid
secreted as isotonic solution of 150mM at pH 1 by parietal cells
36
how do parietal cells secrete acid
carbonic anhydrase enzyme combines CO2 and H2O
forms carbonic acid
leads to release of H+ ions/ protons into cytoplasm of parietal cell
then pumped out into stomach lumen by proton pumps - ATP dependent (via H+K+ATPase)
37
antiport
passive change of two equally charged ions
in stomach context, Cl- into parietal cell, bicarbonate ions out of parietal cell into plasma
38
mediators of parietal cell output/ homeostasis - 5
histamine
gastrin
acetylcholine
prostaglandins E2 and I2
somatostatin
39
histamine
stimulatory local hormone
40
gastrin
stimulatory peptide hormone, stimulates acid secretion via action at CCK2 receptors
41
acetylcholine
stimulatory neurotransmitter, stimulates M3 receptors via Gq signalling
42
prostaglandins E2 and I2
local hormones that inhibit acid secretion
43
somatostatin
inhibitory peptide hormone
Gi signalling
44
long term hyperacidity can cause erosive/ ulcerative diseases of the upper GI tract in the stomach, duodenum, distal oesophagus. examples - 2
gastro oesophageal reflux disease (GORD)
peptic ulcer (acute or chronic)
45
gastro oesophageal reflux disease (GORD) - 3
reflux of stomach contents into oesophagus
causes heartburn like, irritation symptom
abnormal functioning of lower oesophageal sphincter - a muscle that can become weakened
inc risk of barrett's metaplasia in epithelial lining ,and oesophageal cancers - cells in lower oesophagus become similar to intestinal cells in response to gastric acid, becomes darker
46
gastro oesophageal reflux disease (GORD) risk factors - 4
poor diet - e.g. chocolate
obesity - fat pressing on stomach
age
tight clothing
47
two possible causes of peptic ulcers in stomach lining
helicobacter pylori infection
imbalance in gastric secretion
48
helicobacter pylori
extremophile
gram neg
bacili
class I carcinogen aka impairs DNA repair causing carcinogenesis
49
heliobacter pylori infection cause
contanimated food, water, utensils
50
heliobacter pylori infection symptoms
chronic inflammation/ gastritis, leading to
stomach/ duodenal ulcers
51
heliobacter pylori infection treatments - 2
bismuth quadruple therapy
works for 90% of patients
concomitant therapy using PPI, clarithromycin, amoxicillin, metronidazole
52
heliobacter pylori (H. pylori) infection difficulty in treatment - 2
resistance to clarithromycin antibiotic-in some regions, pts are tested for resistance to decide what therapy is ideal
which can also be caused from macrolide use for respiratory treatment as select for mutant H. pylori strains
53
ulcer formation
imbalances caused by drugs entering stomach - if longer, chronic
e.g. NSAIDs, salicylates, alcohol, bile, steroids can form peptic ulcers
can potentially lead to GI bleeding needing endoscoping intervention or surgery
54
NSAIDs, salicylates, alcohol, bile, steroids can form ___
peptic ulcers
55
drugs like NSAIDs inhibit _____ which is responsible for the synthesis of protective prostaglandin, leading to reduced inhibition of acid secretion, ultimately forming ulcers
cyclo-oxygenase 1
56
approaches to treat hyperacidity, ulcer reoccurance avoidance and ulcer healing - 3
inhibiting acid secretion
neutralising gastric acid
inc resistance of gastric mucosa
57
inhibiting acid secretion treatment for hyperacidity example - 2
histamine receptor antagonists
proton pump inhibitors
58
neutralising gastric acid treatment for treating hyperacidity example
antacids
59
histamine H2 receptor antagonist mechanism of action
inhibits acid production
histamine promotes gastric acid secretion
competitively inhibits histamine actions at all H2 receptors
inhibits cAMP
inhibits 90% acid secretion as a result
promotes ulcer healing as no more irritant acid
60
histamine receptor antagonist side effects - 3
rare - diarrhoea
dizziness
muscle pain
61
histamine receptor H2 antagonist examples - 4
cimetidine
ranitidine
nizatidine
famotidine
62
betazole
relatively specific histamine H2 receptor agonist, stimulates acid secretion
63
proton pump inhibitor mechanism
irreversibly inhibits H+/K+-ATPase in parietal cells of stomach lining
dec H+ ions pumped out of parietal cells into lumen in exchange for K+ ions
PPIs are weak bases, inactive at pH7 so require activation in acidic environment - prodrug
parietal cells contain acidic canaliculi, in which PPIs convert to sulfenaminde derivative which can bind covalently to proton pumps
binding blocks hydrogen ion secretion into stomach lumen/ acid secretion into stomach
100% effective
64
proton pump inhibitor administration
1 dose a day = 100% effect
often as enteric capsules to inc efficacy as inactivated by gastric acid (if orally admin, will be inactivated)
65
PPI examples - 5
omeprazole
esomeprazole
lansoprazole
pantoprazole
rabeprazole
66
proton pump inhibitor side effects
in 1.5-3% of patients- nausea, rashes, headache, abdominal pain
can cause bacterial overgrowth due to PPI-caused lack of acid - inc infection risk
DNA damage through further conversion of PPI metabolites in permanent high dose long term admin
67
antacids are often __ or __ salts
magnesium
potassium
68
antacids mechanism of action
neutralise gastric acid by inhibiting peptic enzymes by inc ph to over 5
alginates/ simeticone to inc mucous adherence and viscosity and form protective coating of oesophagus
69
antacids can heal ___ ulcers, but have less effect for ___ ulcers
duodenal
gastric
70
antacids can be combined with ___ and ___ to inc mucous adherence and viscosity and form protective coating of oesophagus
alginates
simeticone
71
antacids examples - 3
magnesium hydroxide
magnesium trisilicate
aluminium hydroxide gel
72
antacids side effects -magnesium salts
diarrhoea
so both salts given to preserve normal bowel function, cancel out
73
antacids side effects -aluminium salts
constipation
so both salts given to preserve normal bowel function, cancel out
74
cytoprotective agents
enhance endogenous mucosal protection mechanisms
75
cytoprotective agents enhance endogenous mucosal protection mechanisms. examples of mechanisms - 3
bismuth chelate
sucralfate
misoprostol
76
bismuth chelate
toxic to H. pylori, prevents its adherence to mucosa, inhibits its bacterial proteolytic enzymes
77
sucralfate
forms complex gels with mucous, decreases degradation of mucous by pepsin and limits diffusion of H+ avoiding hyperacidity
78
misoprostol
synthetic prostaglandin analog
reduces gastric secretion in stomach by stimulating prostaglandin receptors, thus reduced acid secretion
79
what is emesis
vomiting
80
emesis causes - 5
natural reflex to:
infection
early pregnancy
drugs
motion
neuronal input from GI tract e.g. anxiety
81
emesis is controlled by
medulla regions - signals sent to medulla
82
which medulla regions control emesis - 2
vomiting centre (if vom bc of fear, pain, originates here)
chemoreceptor trigger zone CTZ (toxins, drugs, )
83
emesis - seeing something repulsive is processed where
cortex
84
emesis - motion sickness is processed where
vestibular apparatus
85
neurotransmitters controlling vomiting that are released by the vomiting centre to CTZ chemoreceptor trigger zone - 2
acetylcholine
histamine
86
neurotransmitters controlling vomiting that released by CTZ chemoreceptor trigger zone - 2
5-hydroxytryptamine 5-HT
dopamine
87
neurotransmitters controlling vomiting released by vomiting centre
substance P
88
antiemetic drugs are drugs that are antagonists of - 5
H1 receptors
muscarinic receptors
5-HT3 receptors
dopamine receptors
NK1 receptors
89
other antiemetic drugs include synthetic cannabinoids like ___
nabilone, antagonised by naloxone
90
antiemetic drugs are often an adjunct to _______
cancer therapy
aka added on to prevent the nausea symptoms of therapy
91
antiemetic drugs - H1 recepor antagonist drug examples - 3
cinnarizine
cyclizine
promethazine
92
antiemetic drugs - H1 recepor antagonist drug side effect
drowsiness
93
antiemetic drugs - muscarinic receptor antagonist drug example
hyoscine for motion sickness
94
antiemetic drugs - muscarinic receptor antagonist side effects
dry mouth
blurry vision
drowsiness
95
antiemetic drugs - 5-HT3 receptor antagonist drug examples - 2
dolasetron
granisetron
act on CTZ to treat therapy induced nausea
96
antiemetic drugs - 5-HT3 receptor antagonist drug side effects
rare, GI upset, headaches
97
antiemetic drugs - dopamine receptor antagonist drugs example - 2
chlorpromazine
perphenazine
antipsychotic - d2 receptor antagonists
98
antiemetic drugs - NK1 receptor antagonist drug example
aprepitant
blocks substance P receptors in VC and CTZ
99
dolasetron mechanism of action
serotonin 5-HT3 receptor antagonist, highly selective, found in and acts on VC on brainstem
treats nausea and vomiting after chemotherapy and surgery - inhibits the signaling pathways responsible for chemotherapy-induced nausea and vomiting (CINV)
inhibits stimulation of GI tract, diaphragm, abdominal muscles
100
dolasetron side effects - 4
headache
fatigue
heartburn
less frequent urination
101
nabilone mechanism of action
synthetic cannabinoid - THC analogue
agonist for CBR1/2 GPCRs, which are highly expressed in vomiting centre and CTZ
inhibits serotonin binding and this chemotherapy induced nausea and vom
102
nabilone side effects
dizziness
drowsiness
euphoria
headache
memory issues
103
the biliary system
consists of liver
excess cholesterol is converted to bile acids, helps emulsify fats and aids digestion
104
bile consists of - 5
bile acid
electrolytes
cholesterol
lipids
bile pigments
105
what do drugs affecting the biliary tend to prevent
formation of gallstones with high cholesterol content
aka cholesterol cholelithiasis
106
cholesterol cholelithiasis
formation of gallstones with high cholesterol content
linked to high alcohol consumption and sickle cell anemia
diagnosed via ultrasound scan
107
cholesterol cholelithiasis treatment - 2
surgery
or
dissolvable by drugs like urodeoxycholic acid
108
urodeoxycholic acid
dissolves gallstones
naturally occuring so well tolerated
109
biliary colic
pain produced by passage of gallstones through bile duct
110
drugs that are used in biliary colic - 3
morphine - but constricts sphincter of Oddi, raising pressure in bile duct
buprenorphine
pethidine - opioid, relaxes smooth muscle
111
ppi side effect and stat
ppi users are 2.3x more likely to develop acute kidney injury due to inflammation than non ppi users
112
what are the main 3 focuses in the lower gi tract that we aim to treat
constipation
diarrhoea
chronic bowel disorder
113
what are the main 3 focuses in the upper gi tract that we aim to treat
hyperacidity
nausea/vom
biliary disease
114
cimetidine (histamine H2 antag) side effects
sexual dysfunction
inhibits p450 so causes drug interactions
115
what antacid is less used and why - 3
aluminium hydroxide gel - not well absorbed, could contribute to renal toxicity and alzheimer's
116
chemotherapy induced vomiting
chemotherapy causes gi tract degeneration causing inc release of serotonin from enterochromaffin cells
serotonin binds to 5-HT₃ receptors located on vagal afferent nerve endings in the GI tract
projects signals to VC in medulla to initiate vomiting
117
case study - efficacy of nabilone
Superiority over Prochlorperazine (anti-psychotic)
A double-blind crossover trial involving patients receiving cancer chemotherapy found that 80% responded to nabilone therapy, compared to 32% for prochlorperazine.
Both nausea and vomiting episodes were significantly lower in patients given nabilone, and patients favored nabilone for continued use
118
treatments current of upper GI tract disease - will basically fix them all mayne
PPIs - inhibit acid production
H2 receptor antag - dec acid secretion
antacids- neutralize stomach acid
abx - target H. pylori to dec ulcer
119
clinical shit we gaf about
hyperacidity - can cause gastro oesophageal reflux disease (GORD), peptic ulcer (acute or chronic)
peptic ulcers due to helicobacter pylori infection or imbalance in gastric secretion
emesis
cholesterol cholelithiasis - gall stones
biliary colic - pain produced by passage of gallstones through bile duct
120
examples of drugs we gaf
abx for heliobacter pylori - bismuth quadruple therapy (cytoprotective) or concomitant therapy using PPI, clarithromycin, amoxicillin, metronidazole
peptic ulcers - histamine 2 receptor antagonists cimetidine, ranitidine, nizatidine, famotidine , proton pump inhibitors omeprazole, lansoprazole (inhibit gastric acid secretion) antacids magnesium hydroxide, magnesium trisilicate alongside alginates or simeticone (neutralise gastric acid)
anti emetic drugs - H1 receptor antagonist promethazine, muscarinic receptor antagonist hycosine, 5-HT3 receptor antagonist dolasetron, dopamine receptor antagonist chlopromazine or dopamine d2 antipsychotics
cholesterol cholelithiasis - surgery or dissolvable urodeoxycholic acid
biliary colic - literally opioids yk this
