Inflammation Terlecky1 Flashcards
What enzyme is responsible for histamine formation?
histidine decarboxylase
What cofactor does the enzyme histidine decarboxylase require?
pyridoxal phosphate (activated vitamin B6)
Histamine promotes WHAT?
*Vasodilation, smooth muscle contraction, increased vascular permeability, gastric secretion.
also, platelet aggregation, complement activation, mucous secretion, chemotactic attractant for inflame cells
How does histamine exist in the blood?
complexed with heparin and proteoglycans in metachromatic secretory granules in basophils. slow turn over.
What enzymes degrade histamine?
histamine n-methyltransferase (withMOA) converts to MIAA
or directly to imidazole acetic acid by diamine oxidase (histaminase)
The release of histamine is energy dependent… what mediates this?
ATP and Ca+2!
What does cromolyn sodium do?
blocks the influx of divalent ions (and so, histamine release). prophylactic tx of asthma
What do compound 48/80 and polymixin B do?
Ionophores! soooo influx of ca andrelease of histamine
Where do we find H1 receptors?
Smooth muscle of gut and bronchi, endothelium, brain.
How do H1 receptors elicit their effects?
second messengers IP3, DAG, Ca2+, NFB
where do we find h2 receptors?
Gastric mucosa (parietal cells), cardiac muscle cells, mast cells, brain.
H2 post receptor mechanism?
cAMP production
What are the cardiovascular effects of histamine?
Increased HR (via H2) decreased blood pressure (due to vasodilator effects H1)
How does histamine cause itching?
H1 receptor mediated stimulation of sensory nerve endings
What is an example of a physiological antagonist to histamine?
epinephrine! important for cases of systemic anaphylaxis
How do inverse agonists work?
Block histamine receptors!
What is the difference between first generation antihistamines and second gen anti histamines?
Sedative effects!!! 2nd gen do not have access to CNS
What are examples of first generation antihistamines(h1 blocker)?
diphenhydramine and chlorpheniramine
(dimenhydrinate, hydroxyzine, meclizine, promethazine)
used to reduce symptoms of allergy, allergic rhinitis, uticaria
2nd gen example/
loratadine, fexofenadine, desloratadine, cetirizine, levocabastine, acrivastine
What is gastrin?
polypeptide hormone, secreted from mucosa of gastric antrum in response to eating or alkanization of the stomach. Causes gastric secretion of pepsin, HCl, promotes growth of GI mucosa
WHat is pepsin?
Proteinase of gastric juice- elaborated and secreted by chief cells
what is zollinger Ellison syndrome?
gastrin secreting tumor!
How do we treat ulcerative and inflammatory GI diseases?
Neutralize the acid! reduce gastric acid secretion! enhance mucosal defenses through cytoprotective/antimicrobial intervention
How do antacids also confer mucosal protection?
Stimulate mucosal prostaglandin production
Cytoprotective by binding irritating compounds
examples of antacids
sodium bicarb, magnesium hydroxide, aluminum hydroxide, calcium carbonate, magnesium trisilicate
what are three agonists that control gastric acid secretion?
histamine, acetylcholine, gastrin
Antihistamines do what?
They are h2 antagonists, promote the healing of gastric and duodenal ulcers.
examples of antihsitamines
cimetidine, famotidine, ranitidine, nazatidine
how does omeprazole work?
Proton pump inhibitor! irreversibly inhibits the gastric parietal cell proton pump. Activated in acidic environment
what is octreotide?
somatostatin analog that inhibits gastric secretion
How do barrier drugs work
forms protective coating on ulcer crater
ex- sucralfate, bismuth subsalicylate
What is the drug of choice for ulcers from NSAIDS?
Misoprostol!
how does metoclopramide effect gastric motility?
cholinomimetic activity! dopamine antagon!
stimulates motility of the upper GI tract without increasing gastric, biliary, pancreatic secretions.
increases resting tone of lower esophageal sphincter: accelerates gastricemptying.alsoantiemitic.
Metoclopramide side effect?
tardive dyskinesia
How do we treat heliobacter pylori infection?
Two antibiotics (amoxicillin and clarithromycin) and a proton pump inhibitor
Three basic steps involved in the process of vomiting?
- Sensors-excitation of one of the many receptors for the diff types of vomiting
- Vomiting center receives stim from chemoreceptor trigger zone (CTZ) on floor of 4th ventricle (dop agonists here)
- effector side of response: inc pulse, salivation, dilation. contraction of the pylorusand relaxation of gastric smooth muscle, etc. REFLEX SLOWING of the heart! drop bp,
Locally acting emetic?
Ipecac- irritant action on stomach wall and on CTZ
what is a centrally acting agent?
Apomorphine! works primarily on CTZ as dopamine agonist
where do most anti emetics work?
serotonin 5ht antagonists or neurokinin receptor antagonists at ctz
5 ht antag
ondansetron
granisetron
neurokinin antag
aprepitant
what are the different classes of laxatives
- irritants/stimulants
- bulking agents- osmotic and fiber
- softeners
Two categories ofanti diarrheal agents?
motility and water absorption
How do stool softeners work
Lubricate! promote laxation by coating and lubricating fecal matter (ex: mineral oil) prevent normal absorptionofwater
What does glycerin do?
administered as a rectal suppository. both lubricating and produces local irritation to initiate defecation reflex.
Examples of anti-diarrheal motility agents?
Opiates! promote sustained contraction of intestine and interrupt normal organized sequence of peristaltic contractions. exposure time of feces in colon increases and greater dessication occurs
ex: loperamide + diphenoxylate/atropine
Examples of absorbent anti-diarrheal agents?
Bismuth subsalicylate.. kaolin
absorb water and toxins and provide protective coating to inflamed intestine
