Ulcer and Inflammation + Laxatives Flashcards
Know more about the pharmacology of antacids, cytoprotective agents and all that jazz
what is a peptic ulcer
erosion of small patch of the lining of stomach (gastric ulcer) or duodenum (duodenal ulcer)
how do NSAIDS cause ulcers
less prostaglandins so less cytoprotection of gastric antrum
State Factors that attack the gastric and duodenal mucosae
- Acid and pepsin
- H.pylori
- Bile reflux and delayed gastric emptying – autonomic system dysfunction
- Absence of protective prostaglandins (NSAID side effect – inhibit production of PGI2)
- Microvascular vasoconstriction
- Failure of epithelial regeneration – anticancer drugs, cytotoxic drug
- Presence of stress and other risk factors - e.g. alcohol, smoking, aspirin
Worldwide diarrhoeal diseases
cholera or rotaviral infections
why take glucose with electrolytes and rice water
to optimise absorption of electrolytes into the blood from GIT
What is Dexamethszone? When used?
an Anti-emetic corticosteroid. Used in Post-Operative or Cancer associated vomiting.
name protective mechanisms of the stomach
Mucus layer - good mucosal blood flow - HC03 buffer - cytoprotective prostaglandins that inhibit acid release - epithelial regeneration
Histamine is often known as:
the ‘final common mediator’, although Ach and gastrin can both activate the paritetal cell directly.
State the three acid stimulators that cause release from acid from the parietal cell
Histamine, Gastrin and Acetylcholine
Stimulant laxative indication and action
Bisacodyl (synthetic drug, based on active principle of senna); acts in about 8hr, take the night before; stimulates enteric nerves to cause peristalsis. Suppository acts quicker. ‘Abuse’ –> cramps: not suitable for repeated use.
Glycerol suppositories; act as a rectal stimulant (mild irritant)
Crohns Disease and Ulcerative Colitis are both..
manifestations of IBD
what is a natural alternative to ORS?
Rice water with electrolytes - boil rice water and use the starchy water produced. add salt.
How does Misoprostol work?
it’s a PG analogue that mimics PGE2 which works by increasing Mucus and HCO3 secretion + Vasodilation
name the two classes of drugs for IBD
Anti-inflammatories (Corticosteroids, Aminosalicylates) Anti-cytokine agents (infliximab)
how does PGE2 work?
It inhibits the ATP-dependent proton pump within parietal cells
what’s the most common type of ulcer
Duodenal Ulcer
benefits of dietary fibre?
- gives bulk, enhances mechanical efficiency of intestine
- speeds up transit (reduces exposure to toxins ),
- Adsorbs water (keeps stools soft but bulky),
- Promotes regular bowel habit
Describe the Biosynthesis of Prostaglandins
H2 Antagonists (block histamine’s effect E.g Cimetidine) - PPI’s (irreversible inhibition E.g Omeprazole, Lansoprazole) Prostaglandin Analogues (Misoprostol)
Acid-Modifying drug examples
what does IBD stand for
Inflammatory Bowel Disease
What should we NOT do in patients with diarrhoea
Do not employ bulk-forming agents with anti-spasmodics as this could lead to intestinal obstruction
Domperidone is a
D2 receptor antagonist at the CTZ
what does bismuth sulfate do
improve mucosal defence
List the Key Treatments of IBS
reassurance
anxiolytics
anti-spasmodics
dietary improvement
General causes of diarrhoea
(a) too rapid transit through colon - hypermotility, or (b) failure of colonic water reabsorption; or both
For radiation and cancer sickness/emesis, give..
Ondansetron, dolasetron (5HT3 antags) very effective against severe nausea/vomiting esp. post anticancer chemotherapy (i.v. plus oral dexamethazone)
- Aprepitant (first of the NK1 antagonists)
- Nabilone (synthetic cannabinoid, given if patient is refractory to above drugs, or significant side effects)
- Dexamethasone – anti-emetic corticosteroid
- Domperidone – short term only (D2 antag, less sedating)
what drugs can inhibit the vomiting centre?
Hyoscine and Promethazine
What is PGF2-Alpha?
bronchiconstrictor
Define IBS
Abnormal bowel activity, alternating episodes of diarrhoea & constipation assoc. with colic and pain. Patients are often anxious.
Side effects of H2 Antagonists
Highly sedative
What is the best treatment for Diarrhoea in healthy people? What do we check for in at-risk groups?
The best treatment of mild diarrhoea in healthy people is to abstain from food and drink plenty of clear fluids • In infants, children and the elderly check that fluid intake is adequate • Check patient’s diet : increasing the amount of fibre may help in the longer term
Osmotic laxative indication and action
Osmotic laxatives attract water. E.g lactulose (non-absorbed disaccharide) acts in 24-48 hours. Suitable for chronic constipation.
Macrogols (intert polymers of ethylene gylcol)
Side effects; abdominal distension, pain, nausea
What is the presenting symptoms of peptic ulcer
inflammation and pain. Gastric irritation. Vomiting, loss of appetite and poor sleep
Bulk forming laxatives: Indication and action etc
E.g Ispagula husk, sterculia- theyre Indigestible materials, attracts water & swells in colon, increasing peristalsis and promoting soft stool.
Takes several days to work.
e,g of BFL: Methylcellulose, Bran, High Fibre diets - similar principle. Take plenty of water with all these. Can cause abdominal swelling
General treatment strategies to peptic ulcer
- Relieve pain e.g Antacids
- Allow healing, e.g antisecretory agents and mucosal strengtheners.
- Prevent relapse, e.g maintenance therapy
- Avoidance of risk factors Stop smoking
Anti-spasmodics used in IBS and how they work
peppermint oil capsules, mebeverine (both relax the smooth muscle & reduce pain)
How do the acid stimulators work?
Act on the parietal cell to activate ATP-dependent ‘proton pump’ which exchanges H+ for K+
Lubiprostone. Whats it for?
stimulates colonic fluid secretion, used to treat chronic idiopathic constipation in adults. Can be used in IBS
Generally speaking, whats given for motion, pegnancy, vertigo and post-op nausea, give..
- Motion sickness: hyoscine
- Pregnancy-associated sickness (only in severe cases): promethazine (sedating H1 antagonist, use with caution)
- Vertigo & other vestibular disorders: cinnarizine or cyclizine (H1 antags, less sedating than promethazine)
- Post-operative nausea and vomiting: effective drugs are 5HT3 & H1 antags, and dexamethazone, some phenothiazines
State the four types of Laxatives
- Bulk Forming Laxatives
- Osmotic Laxatives
- Stimulant Laxatives
- Lubrican Laxatives
Acid-Modifying drug examples
H2 Antagonists (block histamine’s effect E.g Cimetidine) - PPI’s (irreversible inhibition E.g Omeprazole, Lansoprazole)
Prostaglandin Analogues (Misoprostol)
What does a Thrombotic do?
Promotes platelet aggregation
Indication for PG Analogue
Prophylaxis in the frail elderly whose use of NSAIDS cannot be withdrawn
lubricant laxative indication and action
Useful in management of haemorroids and anal fissure. • Arachis (peanut/ground nut) oil - warmed enema of 130 ml used to soften impacted faeces, promote bowel movement.
Glycerol - as a suppository in infants
name an example of an Anti-cytokine agent for IBD. What else can it be used to treat?
infliximab, used elsewhere in Rheumatoid Arthritis
What is Colic?
Episodes of crying for more than three hours
Treatment of IBD
A - Corticosteroid (inhibit PLA2 activity and AA-PG cascade) e.g Prednisolone, Hydrocortisone, Budesonide (as adjunct to aminosalicylates)
B - Immunosuppressants (ciclosporin)
C - Monoclonal TNFα Antibodies (infliximab inhibits TNFα actions
D - Aminosalicylates - Maintain remission in ulcerative colitis
Main stimulant laxatives available otc and side effects
Bisacodyl or senna are the main OTC therapies currently with limiting side effects, e.g. abdominal cramping, diarrhoea, dehydration.
Traditional remedies for Diarrhoea
charcoal, kaolin (china clay) are helpful for mild infective diarrhoea (BUT - will also help absorb toxins if not a mild infection).
Vomiting can be triggered by activation of the CTZ - what does that stand for?
Chemoreceptor Triggering Zone
What is peppermint oil
a direct acting antispasmodic which relaxes the smooth muscle and reduces pain
What is loperamide
an antumotility drug
Key Differences between IBS and IBD
Irritable bowel syndrome (IBS) is a non-inflammatory condition, while inflammatory bowel disease (IBD) causes chronic swelling (or inflammation).
Both conditions can lead to abdominal pain, constipation, or urgent bowel movements, but IBD can also cause extreme fatigue or rectal bleeding.
The cAMP induced pathway in acid secretion is switched on by
Histamine.
what is acid rebound? why is it bad?
when bicarbonates neutralise the acid, more acid is produced to counteract. hence pain returns!
name 2 highly selective antagonists
Ranitidine and Cimetidine
How does cancer and other cytotoxic drugs cause ulcers
they interfere with regeneration of epithelial cells that line the gastric Antrum
Main treatment to peptic ulcers
1.Avoid risk factors, stress, smoking, alcohol, aspirin 2.Neutralise acid (antacids) or reduce its secretion Mg carbonate, Al(OH)3; NaHCO3 in indigestion remedies 3.Encourage healing with H2 antagonists, or 4.Eliminate H.pylori (after positive urease test) antibiotics 5 Improve mucosal defence
state the triple therapy to eradicate H.Pylori
Omeprazole Clarithromycin Metronidazole
Bicarbonate pros and cons in gastric ulcer treatment
Rapid relief as acid is neutralised chemically. Cons of Acid rebound, and cannot be used for weeks
H Pylori Eradicaiton Regime. How long is this therapy? what side effects?
Omeprazole 20mg BD (S/E - Nausea)
Amoxicillin 1g BD (S/E - Rash)
Clarithromycin 500mg BD (insomnia)
Metronidazole 400mmg TDS (darkening urine)
Last seven days
if we cant give a penicillin, what do we give?
Tetracycline 500mg QDS
risk factors of PUD?
Age (>65) - Previous peptic ulcer or GI bleed - Combining anti-inflammatories - Concurrent warfarin - Smoking - Alcohol
- Anti-cholinergic drug (M antagonist), e.g. hyoscine
- Sedating anti-histamines (H1 antagonists) e.g. promethazine, cinnarizine – useful against motion sickness etc.
- Phenothiazines (D2 antagonists), e.g. prochlorperazine
- More D2 antagonists, e.g. droperidol, domperidone ]
- 5HT3 antagonists, e.g. granisetron, ondansetron
- Neurokinin (NK)1 antagonists, e.g. aprepitant, fosaprepitant
- Dexamethazone, has anti-emetic effects useful against vomiting assoc. with chemotherapy (mechanism not clear)
