Lecture 11 - GI Flashcards
(115 cards)
1
Q
Where is gastric mucosa secreted from?
A
mucosal epithelial cells
2
Q
Why is the gastric mucous layer important?
A
This mucous layer protects from the cells of the stomach from the acid and enzymes in the lumen of the stomach (otherwise the stomach would eat itself)
3
Q
What can loss of the mucous layer lead to?
A
It can allow acid to reach the cells and cause an ulcer
4
Q
Parietal cells in the stomach make _____ (one of the strong acids known)
A
HCl
5
Q
What is the purpose of HCl in the stomach?
A
This acid is primarily to kill bacteria, viruses and other parasites, not for digestion
6
Q
What can overproduction of the acid (hyperacidity) lead to?
A
It can overwhelm the mucous layer and buffer systems and lead to ulcers
7
Q
What is a systemic antacid?
A
NaHCO3
8
Q
NaHCO3 dissociates into?
A
Na+ and HCO3- (bicarbonate)
9
Q
What effect does the bicarbonate ion have on the stomach?
A
The bicarbonate ion isn absorbed into the blood and slightly increases pH (alkalosis)
10
Q
NaHCO3 is quick, easy, and effective in the ____ term to reduce stomach acid
A
short
11
Q
Problems with NaHCO3 antacids?
A
- Alkalotic urine can increase the deposition of calcium and phosphate to form a kidney stone (cranberry juice does the opposite)
- This increases blood sodium, thus exacerbating HTN
- Acid rebound due to feedback regulation
12
Q
List some non-systemic antacids
A
CaCO3
Al(OH)3
Mg(OH)2
13
Q
Do non-systemic antacids affect extracellular or blood pH?
A
No
14
Q
Aluminum and calcium antacids are _______, thus they are often combined with magnesium
A
constipating
15
Q
______ ____ receptors in parietal cells stimulate HCl secretion from these cells
A
Muscarinic Ach
16
Q
Inhibiton of Muscarinic Ach receptors reduces ____ _______
A
acid secretion (but not by much)
17
Q
List an example of a Muscarinic type 1 ACh Receptor blocker
A
Pirenzipine
*can reduce acid by up to 40%
18
Q
SE of anticholinergics?
A
dry mouth, dry eyes, sedation, etc.
19
Q
Are anticholinergics a good choice?
A
Not really
-Since they are very non-selective and therefore will cause lots of side effects and limited acid reduction
20
Q
What are Cytoprotectives?
A
Drugs which protect cells from acidic damage, either directly or through stimulation of mucous
21
Q
What are two major Cytoprotective drugs?
A
- Sucralfate
- Misoprotol
22
Q
Sucralfate is an ______-based salt
A
aluminum
23
Q
Describe Sucralfate
A
Aluminum base salt:
- Binds to hydrogen ions to form a gooey paste, increasing pH (decreasing acidity)
- Also binds to degenerating cells, forming a protective layer
- “Artificial” mucous
- It is not absorbed into the bloodstream, but can inhibit absorption of other drugs
- Works for 8-12 hours, specifically protects damaged tissue as well as reducing acidity
24
Q
Describe Misoprostol
A
Misoprostol is a prostaglandin analogue which stimulates production of the mucosal layer
*Often given with Diclofenac (NSAID) to counteract stomach issues
25
What does stimulation of H2 receptors in parietal cells cause?
increases HCl production
26
______ of H2 receptors are highly effective in a number of acid-related disorders
Inhibition
27
H2 blockers are very _____ to the organ, to the receptor type (do not cross to PGE) and no adverse effect on mucosa
specific
28
List 3 H2 blockers
- Cimetidine
- Ranitidine
- Famotidine
29
Cimetidine (H2 blocker):
| Causes ____% reduction in acidity
50-60 (moderate)
30
Cimetidine (H2 blocker):
| Binds to Cyt ___ to cause DI
P450
31
Cimetidine (H2 blocker):
| Binds to androgen receptors - so what adverse effects can it cause?
- gynecomastia
- reduced libido
- impotence
32
Ranitidine (H2 blocker):
| Causes _____% reduction in acidity
65-70 (more effective than cimetidine)
33
Ranitidine (H2 blocker):
| Why does it cause less drug interactions than cimetidine?
Only binds P450 at high doses
34
Ranitidine (H2 blocker):
| Does it bind to androgen receptors?
No
| **Therefore less side effects
35
Brand name of Cimetidine?
Tagamet
36
Brand name of Ranitidine?
Zantac
37
Brand name of Famotidine?
Pepcid
38
Famotidine (H2 blocker):
| Why is it the most effective?
- Doesn't bind to P450 at all
- Very few adverse side effects
- Famotidine is the most effective at reducing acid secretion and has the best safety profile
39
Proton Pump Inhibitors (PPI):
| MOA
Inhibit gastric H+/K+ ATPase Proton Pump
40
Proton Pump Inhibitors (PPI):
| Are especially good for ____ reduction of acid
rapid
41
Proton Pump Inhibitors (PPI):
| Where do they bind to?
Bind to H+ extrusion sites and block the release of H+ and Cl-
42
Proton Pump Inhibitors (PPI):
| _____ effective
fairly
43
Proton pump inhibitors all end in _____
prazole
44
List some PPI's
```
Omeprazole
Esomeprazole
Lansoprazole
Pantoprazole
Rabeprazole
```
45
PPI's are especially good for ____
GERD (as well as other acid-dependent disorders)
46
Proton Pump Inhibitors (PPI):
| Are generally ____ and ____
safe and cheap
47
Describe in detail the MOA of Proton Pump Inhibitors (PPI)
- PPI's enter the secretory canaliculus of the parietal cell which opens when acid secretion occurs
- The pro drug is converted to the active drug here
- PPI's bind very tightly to the channel, thus have a long half-life
*Rabeprazole also increases mucous secretion
48
In the early 1980's, what was found to be the major cause of ulcers?
H. Pylori infection
49
H.Pylori is present is ___% of duodenal ulcers and ____% of gastric ulcers
95
| 80
50
How does H. Pylori cause an ulcer?
- To escape gastric acid, H P burrows into the gastric mucosa
- HP then produces urease, the enzyme that converts urea to ammonia and CO2
- This kills mucosal epithelial cells, leaving the gut unprotected
51
List some ways that we can test for H. Pylori infection
- Breath test for urea
- Serological
- Culture
- Histology
52
What treatment do we recommend for H. Pylori infection?
Combination of anti secretory or antibiotic treatments as it is more effective than either alone
53
What is defined as triple therapy for an H. pylori infection?
-A PPI to control acid and 2 effective antibiotics to kill the HP
54
What is defined as quadruple therapy for an H. pylori infection?
- A PPI to control acid and 2 effective antibiotics to kill the HP
- Add bismuth
55
What is GERD?
Gastroesophageal Reflux Disease:
- The most prevalent type of ulceration-5X more common that gastric ulcers
- Lower esophageal sphincter (LES) defect allows acidic contents to contact the esophageal lining
56
What kind of drugs can contribute to GERD by reduces LES pressure and allowing reflux?
- B blockers
- Ca channel blockers
- Nicotine
57
Treatment of GERD?
Pharmacological treatments (PPI) are not nearly as effective as behavioural changes:
- Avoid fat, caffeine, chocolate, peppermint, and alcohol
- Avoid large meals, especially right before bed, stop smoking
58
What is Ulcerative Colitis?
- Inflammation of the submucosa
| - Ulcerations may cover the entire surface of the colon
59
Symptoms of Ulcerative Colitis?
-Diarrhea, bleeding, severe pain
60
What can Ulcerative Colitis cause?
- loss of nutrition
- anemia
- starvation is a risk
*can cause colon to be come "stiff" from scarring and burst, leading to peritonitis
61
What is Crohn's disease?
- Inflammatory disease which can cover the entire digestive system
- Tends to be separate, isolated regions of inflammation
- Unlike UC, fistulas may form
- Unlike UC, the intestinal wall may be breached
- CD may also be associated with severe skin inflammation
62
IBD = ??
Irritable Bowel Disease
63
IBD:
| Is there a cure ?
No - only treatments which are variably effective
64
Surgical removal of the colon can eliminate ______ ______
ulcerative colitis
*surgery cannot always eliminate CD
65
3 goals of treatment for these disorders (UC, CD, IBD)?
1 - Treat the acute outbreak
2 - Induce and retain remission
3 - Treat complications
66
UC:
| What is the first line treatment?
5-ASA
(5 - Amino Salycilic Acid)
(Mesalamine)
* It is effective for mild to moderate UC
* It is less useful in severe UC and in CD.
67
5-ASA for Ulcerative Colitis:
| MOA
- Unknown method of action
| - Does not work by COX inhibition (NSAIDs exacerbate the disease)
68
5-ASA for Ulcerative Colitis:
| Response rate:
60-80%
69
How is 5-ASA released in large intestine?
5-ASA is only released in large intestine in sulfasalzine by bacteria (N=N)
??? WTF
70
5-ASA linked to _____
sulfapyridine
71
The non-therapeutic ______ causes most side effects (nausea, headaches)
sulfapyridine
72
If formulated with a pH coating, 5-ASA may be released through entire _____
intestine
73
Glucocorticoids:
| Describe "Steroid-responsive" patients
In these patients (~4-%) symptoms improve over 1-2 weeks, and the disease remains in remission as the steroids are tapered off
74
Glucocorticoids:
| Describe "Steroid-dependent" patients
These patients (30-40%) responds to steroids well, but experience relapse of the disease with tapering of the steroids
75
Glucocorticoids:
| Describe "Steroid-unresponsive" patients
As indicated, these patients (15-20%) do not respond to steroid treatment
76
What are Glucocorticoids used for?
Used for acute treatment of moderate to severe bowel issues
77
Are Glucocorticoids useful in maintaining remission?
No way jose
78
SE of Glucocorticoids?
- Weight gain, moon-face, stress and emotional responses
- Steroid-dependent diabetes
- Increased risk of infection
79
What are immunosuppressants?
Drugs usually developed for tissue rejection or cancer
80
Immunosuppressants are ____ derivatives: DNA synthesis inhibitors (used in cancer work)
thiopurine
81
List some immunosuppressants
- Mercaptopurine
| - Azothiopurine
82
How long may it take Immunosuppressants to work?
may take weeks to months (immune cell lifespan)
83
What kind of patients are thiopurines reserved for?
Steroid-resistant or steroid-dependent patients
84
What are thiopurines useful in?
Remission and reduction of relapse (UC and CD)
85
Are thiopurines useful in acute attacks?
NO - as they have a long onset time
86
Thiopurines have a small risk of major _____, especially in cotreatment with steroids.
infection
87
Methotrexate is a ?
Dihydrofolate reductase inhibitor
*Blocks DNA synthesis
88
What kind of patients is Methotrexate reserved for?
steroid-resistant or steroid-dependent patients
89
What is Cyclosporine?
Calcineurin inhibitor (tissue transplantation)
90
What is Cyclosporine used for?
Only used for the most serious cases of UC and CD as it has serious side-effects (severe immune suppression)
91
Cyclosporine is used right before ______
surgery
92
_____% of severe UC patients respond to cyclosporin
| **Levels must be constantly monitored **
50-80
93
What is TNF alpha?
a major pro-inflammatory ligand
94
What are TNF alpha inhibitors used for?
used to treat other inflammatory diseases, such as eczema and RA
95
Give an example of a TNF alpha inhibitor
Infliximab (Remicade)
96
Describe Infliximab (Remicade)
- It is an engineered antibody
- It may kill the cell to which it attaches
- Has very prolonged effects
97
________ also reduces TNF alpha but is NOT effective as a UC treatment
Etanercept
98
TNF alpha inhibitor:
| Prolonged effect may be due to the ??
long half life of the drug (8-10 days)
99
TNF alpha inhibitor:
| If this drug kills the immune cells, then _____ in the submucosa is required
repopulation
100
TNF alpha inhibitor:
| are very _____
expensive
101
TNF alpha inhibitor:
| Increases chances of serious ___ infection, especially tuberculosis
lung
102
UC and CD may be due to changes in ??
intestinal bacteria
103
______ and _______ are drugs that are investigated that may change the proportions of different bacteria
antibiotics
| probiotics
104
______ = frequent liquid stool due to an intestinal disorder
diarrhea
105
List some causes of diarrhea
```
foods
bacteria
virus
drug side effect
laxative abuse
malabsorption syndrome
stress
bowl tumor
```
*diarrhea can be very mild or cause life-threatening dehydration
106
Treatment for diarrhea
- clear liquids
- pedialyte
- BRAT diet (Bananas, Rice, Applesauce, Toast)
107
How do antidiarrheals work?
- Decrease hypermotility
| - Opiates, opiate-related agents, adsorbents antidiarrheal combos
108
Describe Opiates
- Decrease intestinal motility
| - Tincture of opium, paregoric, codeine
109
SE of Opiates
CNS depression
| constipation
110
Duration of opiates
2 hours
111
List some Opiate-Related Agents
diphenoxylate (Lomotil)
loperamide (Imodium)
*these are synthetic drugs chemically related to the opioid meperidine
112
SE of Opiate-Related Agents
drowsiness
| distention
113
Adsorbents are another type of _______
antidiarrheal
114
How do Adsorbents work?
coat the wall of the GI tract and adsorb the bacteria or toxins causing diarrhea (the substance takes in toxin)
115
List some examples of Adsorbents
- Kaopectate (kaoline and pectin)
| - Pepto-bismol adsorbs bacterial toxin & for GI discomfort
