GIT Pharmacology Flashcards
How many thick muscles does the stomach have and name them
Oblique muscle layer
Circular muscle layer
Longitudinal muscle layer
From inside to outside
They’re involved in the peristaltic action
Name the parts of the stomach
The sphincters
Pyloric sphincter
Oesophageal sphincter
Rugae (where the secretory cells of the stomach are)
When you cut a section through the stomach name the layers of the stomach coming from the outside and name the layers of cells that line the stomach in the rugae
Submucosa
mucosa
Muscularis
Cells that line the stomach internally: The mucous surface cell Mucous neck cell Parietal cell Chief cell Enteroendocrine cells
What are the functions of the cells that line the stomach
Mucous surface cell:
Secrete mucus
Mucous neck cell:
Secrete mucus
Parietal cell:
Secretes HCL
And intrinsic factor
Chief cell:
Secretes pepsinogen and gastric lipase
Enteroendocrine cell:
Secretes gastrin
Another name for chief cell and enteroendocrine cells are called respectively?
Zymogenic cells
G cells
What is the pH of HCL
1-2
Importance of the stomach secretions
The mucus forms a protective barrier against corrosive secretions
Hydrochloric acid converts pepsinogen from chief cell to pepsin(pepsin is involved in digestion)
–
Intrinsic factor-absorption of vitamin B12 for RBC production (even if you eat lots of vit b12 foods without the intrinsic factor it won’t be absorbed)
–
The acid and enzyme converts food into a thick semi-solid paste called chyme
–
Gastrin hormone (G cell)
»release more gastric juice
»increase gastric motility
-relax pyloric sphincter
»constrict oesophageal sphincter preventing re-entry
(When food enters the oesophageal sphincter is constricted to prevent reflux and pyloric is relaxed for food to move into the small intestine)
What is the mucosal defense against acid and enzyme attack:
- The mucus barrier (500 m thick),
- a mucus matrix into which bicarbonate ions are secreted to produce a buffering gradient.(acts as a buffer as in base acid reaction to neutralize HCL)
3.The surface epithelium, which requires prostaglandins E2 and I2 synthesized by the gastric mucosa,
a.stimulate mucus and bicarbonate secretion,
b.decrease acid secretion and cause vasodilatation,
• all of which serve to protect the stomach against damage.(the prostaglandins do that)
NSAIDS which inhibit prostaglandin (PG) synthesis will
decrease the protective barrier
True or false and why
True
They inhibit cyclooxygenase (Cox)
In case of tissue injury membrane phospholipids are acted on by phospholipase
This converts membrane phospholipids toarachnid onset acid and these are converted to prostaglandins by Cox 2
This causes pain ,inflammation. This only comes when you’re injured
In the system there’s constitutive prostaglandins secreted in the absence of injury by Cox 1
NSAIDS usually inhibit Cox cuz the NSAIDS used are non selective and inhibit both Cox 1 and Cox 2 and causes ulcer when used for a long time so the selective Cox inhibitors are to be used(celecoxib)(check spelling)
What is peptic ulcer and what can it lead to if care is not taken
Peptic ulceration results from a breach in the mucosa lining of the alimentary tract caused by acid and enzyme attack.
•Unprotected mucosa rapidly undergoes auto-digestion(pepsin will digest the proteins in the surface lining of the stomach (enzyme attack))leading to a range of damage:
–Inflammation or gastritis
–Necrosis
–Haemorrhage
–Perforation as the erosion deepens(can cause leaking from stomach into peritoneum and that section of the stomach affected could be taken off causing a short transit time for food)
Note: Gastric and duodenal ulcers differ in their location but
present with similar symptoms and are treated on similar
principles.
What happens in GERD or GORD
When food is eaten and gets into the stomach there’s so much intrabdominal pressure so the food tries to come out. The lower oesophageal sphincter (los)closed to prevent food from coming out.
In some people the los is not strong enough to prevent the food from coming out.the stomach is lined w mucus to oreotect it from the corrosive substances but the oesophagus is not lined w that mucus so when the food mixed with HCL and enzymes is refluxed or comes up there is inflammation of the oesophageal lining and is felt as heartburn
It is not to be mistaken with a cardiovascular problem or cardio chest pain
What are the main causes of GORD
Loss of tone
Intraabdominal pressure caused by weight gain
Drug management of GORD is similar to that of acid-related disorders
True or false
•
True
Name three conservative treatment options of GORD
Conservative treatment options:
–Weight loss
–Raising the head of the patients bed
–Excessive smoking should be avoided
In three short sentences name the pathogenesis of PUD
-Increased hydrochloric acid secretion
●Inadequate mucosal defence against gastric acid
●Infection with gram-negative Helicobacter pylori
NB- know the cause of the PUD before you treat it
What are the four aims of treating PUD ,how is gastric acid secretion neutralized, how is mucosal resistance increased ?
To reduce gastric acid secretion with
Neutralizing secreted gastric acid secretion with Antacids such as
•
Increase mucosal resistance to acid-pepsin attacks with
Misoprostol or chelates(Bismuth chelate reduces mucosal damage or strengthens or repairs the mucosal layer)
•Eradicating H.pylori
How does gastric acid secretion occur and how is it reduced
Gastrin is released by G cells and this activates gastrin receptors on the mast cells to activate histamine and histamine activated histamine receptors on the parietal cells to cause Hplus release and the gastrin also activated gastrin receptors on the parietal cells to cause the HPlus release
Proton pump inhibitors to stop the release of Hplus
»H2 antagonists
»Muscarinic receptor antagonists
How does H pylori cause PUD and how is it eradicated
H pylori causes increased gastrin release by the G cells
Gastrin can directly activate the gastrin receptors on parietal cells and can also activate gastrin receptors on mast cells causing release of histamine causing the activation of histamine receptors on parietal cells causing release of Protons and chlorides
When the test is done is Hpylori is involved
Triple therapy is used :
One proton pump inhibitor and two antibiotics namely metronidazole and amoxicillin or metronidazole and clarithromycin or amoxicillin and clarithromycin. Takes a week or two to work
Or Quadruple therapy:
One proton pump inhibitor ,two antibiotics and bismuth chelate
More effective than triple therapy and takes shorter time to work like three days or one week
What system does the parietal cell use to cause the release of H plus and what drugs inhibits it,what’s the mechanism of action , route of administration,indications ,adverse effects ,contraindications and the function of clopidogrel
Proton pump or Hydrogen potassium ATPase
It pumps protons
Omeprazole,Iansoprazole ,Esomeprazole,Rabeprazole,Lansoprazole
They are proton pump inhibitors
Mechanism of action: They inactivate the ATPase
And cause irreversible inhibition of the hydrogen /potassium ATPAse
Route of administration- oral and Occasionally Iv
Indications-Indications: short term treatment of peptic ulcers, eradication of H. pylori
- Adverse effects: GI upsets, nausea, headaches, PPIs may increase the risk of fractures, particularly if the duration of use is 1 year or greater
- Contraindications: PPIs(proton pump inhibitors may decrease the effectiveness of clopidogrel (used in place of aspirin at a low dose of 75 milligram for its anti platelet activity and is given to people at risk of stroke or thrombosis also in case some people can’t take aspirin due to some disease they take clopidogrel)because they inhibit CYP2C19 and prevent the conversion of clopidogrel to its active metabolite.
When a certain mechanism is used and brings in Chloride what does it take out and later chloride is taken out with what
Bicarbonate
It’s taken out with potassium
Name the receptors on the parietal cell
Gastrin receptors(G receptors)
Histamine H2 receptors
Muscarinic receptors
Prostaglandin receptors(PGE2)(the prostaglandins inhibit the release of H plus from the parietal cell or decrease the release of Hplus and Chloride
Where is histamine released from and which drugs inhibit histamine receptors ,mechanism of action,route of administration,indications,adverse effects,contraindications
Mast cells
Cimetidine (Tagamet)(it is a hepatic enzyme inhibitor meaning it stops the metabolism or inactivation of warfarin ,phenytoin)
Ranitidine (Zantac)
Famotidine
Nizatidine
They are histamine H2 receptor antagonists
Mechanism of Action: Competitively block the action of histamine on the parietal cells by antagonizing H2 receptors.
- Route of administration: oral and IV
- Indications: Treatment of peptic ulcer and GORD
- Adverse effect: Diarrhoea, dizziness, muscle pains, alopecia, transient rashes, confusion in the elderly and hypergastrinaemia,
- Cimetidine causes low sperm count due to its anti-androgen effects, gynaecomastia & impotence due to its modest affinity for androgen receptors.
•Contraindications: Cimetidine (hepatic enzyme inhibitor) not given to patients stabilized on warfarin, phenytoin and theophylline(given to asthmatic patients).(these three drugs have narrow therapeutic index)
How does vagus nerve cause the release of protons and chloride ,what drugs inhibits the muscarinic receptors,mechanism of action,route of administration,indications and adverse effects
Vagus nerve connects stomach to brain so when you sense food the vagus nerve activates themuscarinic receptors on the mast cells and activates the muscarinic receptors on the parietal cells using acetylcholine
Muscarinic receptor antagonists
•Examples: Atropine, pirenzepine, propantheline, dicyclomine (dicycloverine)
- Mechanism of Action: (The main effects of parasympathetic activity on the GIT are increased motility and increased secretory activity).
- Inhibition of parasympathetic activity, causing relaxation of GI smooth muscle may be of value in peptic ulcer since the condition may be accompanied by increased muscle spasm and reduces secretions of HCL
- Route of administration: oral or I.M.
- Indications: As adjuncts in the management of peptic ulcer(usually aren’t used but in some severe conditions they are used)
Adverse effects: Constipation due to reduced GI motility
How does misoprostol work ,mechanism of action,route of administration,contraindications,adverse effects
It’s an analogue (similar)of the PGE2
It activates prostaglandins receptors to cause the inhibition of the release of Hplus
Mucosal strengthener
Examples: Misoprostol (cytotec)
- Mechanism of action: Synthetic analogue of PG E1, imitating the action of endogenous PGE2 and PGI2, thereby maintaining the integrity of the gastroduodenal barrier.
- It therefore promotes healing by exerting a direct action on the ECL cell (and possibly parietal cell), inhibiting the basal secretion of gastric acid.
- It also increases mucosal blood flow and augments the secretion of mucus and bicarbonate
- Route of administration: oral
- Indications: Ulcer healing and prophylaxis with NSAID use(if you don’t have a choice to give non selective NSAID for use for a long time then you give misoprostol to prevent the person from getting ulcer)
- Contraindications: Hypotension, pregnant and breast-feeding women,causes abortion
- Adverse effects: Diarrhoea, nausea and abdominal pain
Ameritech is a combination of diclofenac and misoprostol to help the person
Can cause abortion
Name three antacids and they’re mechanism of action in PUD ,indications,adverse effects and how the adverse effects occur and contraindications
Antacids
Examples: Aluminium hydroxide, magnesium hydroxide ,sodium bicarbonate,tricilicate ,milk of magnesia
They consists of alkaline either aluminum,magnesium or sodium salts and are used to 1. raise the luminal pH of the stomach to stop pepsin from working and 2.when it’s raised they neutralize the acid and 1.(part of 1)reduce the damaging effect of pepsin which is pH dependent
Pepsin acts as a certain pH so it is not able to work for auto digestion to occur
3.These salts are heavy metals and can bind to pepsin to inactivate it
Indications- symptomatic relief of GORD and ulcers
Adverse effect-constipation and diarrhea ,belching,farting
Antacids with aluminum cause constipation and those with magnesium cause diarrhea
Nugel is a mixture of aluminum hydroxide and magnesium hydroxide to stop the diarrhea and prevent constipation
Sodium bicarbonate with HCL forms salt,water and carbon dioxide causing people to fart and belch
Not to be given to those with hypertension cuz of the salt
It shouldn’t be within two hours of giving antibiotics and anti Fungals cuz antacids have heavy metals which form complexes w the drugs and inactivates the drugs
What is the mechanism of action of sucralfate or carafate which is used to treat PUD,Indications,side effects,contraindications,
Can be used to prevent & treat PUD
•It is a complex of aluminium hydroxide and sulfated sucrose, which releases aluminium in the presence of acid.
•The residual complex carries a strong negative charge which binds to cationic groups in proteins to forms sticky polymer in acidic environment (pH <4) and adheres to the ulcer site, forming a barrier to cover the ulcers in the stomach lining
•This action restricts further caustic damage and stimulates mucosal prostaglandin and bicarbonate secretion from gastric mucosa.
Contraindications-May bind with other drugs and interfere with absorption of fluoroquinolone antibiotics, theophylline, tetracycline, digoxin and amitriptyline.
•Give approximately 2 hours before or after other drugs
•Take on an empty stomach before meals so that the food won’t cover the ulcer sites
Adverse effects: It may cause constipation, dry mouth, nausea, vomiting, headache
Mechanism of action of bismuth compounds,adverse effects,Indications,contraindications
Two bismuth compounds are available: bismuth subsalicylate and bismuth subcitrate potassium
•Bismuth coats ulcers and erosions, creating a protective layer against acid and pepsin.
•It may also stimulate prostaglandin, mucus, and bicarbonate secretion.
•Some activity against H. pylori
•Should not be used repeatedly or for more than 2 months at a time
•Can cause black stools and tongues, constipation
•Prolonged usage of some bismuth compounds may rarely lead to bismuth toxicity, resulting in ataxia,headache,confusion,seizures
