Term
|
Definition
| Peptic ulcer Dz GERD Prokinetic agents Laxitives Antidiarrheals IBS IBD Antiemetics Pancreatic enzyme supplements |
|
|
Term
| What are the peptic acid Dzs? |
|
Definition
| Gastric & duodenal ulcers, GERD and even the hypersecretory condition known as Zollinger-Ellison syndrome |
|
|
Term
| What are the factors that play a role in gastric acid production? |
|
Definition
| Gastrin, Ach, H2 receptors (histamine), helicobacter pylori & decreased mucosal resistance (cause of lack of bicarbs and prostaglandins (PGE2) and stomatostatin (which has a protective feature)) |
|
|
Term
| How do you Tx peptic ulcers? |
|
Definition
| You can neutralize them with antacids (chemical antagonism); or you can reduce the gastric acid: H2 blockers, proton pump inhibitors (PPIs), anticholinergics (used to be main stay in the old days); cytoprotective (mucosal protective) agents like PGE2; and finally antibiotics against H. pylori |
|
|
Term
| What are some of the chemical antagonists? |
|
Definition
| Aluminum/ Magnesium hydroxide or calcium carbonate |
|
|
Term
| What are the A/Es of Aluminum hydroxide? |
|
Definition
| Forms a complex w/ hydrochloric acid -> constipation. Bioavailability of Tetracycline (TC), digoxin, antimuscarinics may be reduced |
|
|
Term
| What are the A/Es of Magnesium hydroxide? |
|
Definition
| Mg is poorly absorbed -> diarrhea. Bioavailability of Tetracycline (TC), digoxin, antimuscarinics may be reduced |
|
|
Term
| What are the A/Es of Calcium carbonate? |
|
Definition
| Nephrolithiasis & dense fecal matter formation |
|
|
Term
| What are the three main players in gastric acid secretion? |
|
Definition
| Histamine, Ach, Gastrin. NB that the common pathway is the activation of the H+/K+ ATPase pump |
|
|
Term
|
Definition
|
|
Term
| What shud pts with NSAID-induced ulcers be taking rather then H2R blockers? |
|
Definition
|
|
Term
| What is the prototype H2R blocker? |
|
Definition
| Cimetidine - oral; kidney; short T1/2; inhibits P450 (NB that this will slow down metabolism of warfarin, diazepam, phenytoin, quinidine, carbamazepine, theophylline & imipramine) |
|
|
Term
| What H2R blocker is more potent and doesnt share the same A/Es like antiandrogenic & prolactin-stimulating? |
|
Definition
| Ranitidine & it also doesnt inhibit P450 |
|
|
Term
| What is the most potent H2R blocker? |
|
Definition
|
|
Term
| Which H2R blocker has 100% bioavailability? |
|
Definition
| Nizatidine, has no first pass effect, kidney |
|
|
Term
| What are some of the A/Es of H2R blockers? |
|
Definition
Rare but most common are: headache, dizziness, diarrhea, muscular pain.
CNS: confusion, hallucinations in elderly or after IV
Endocrine: (cimetidine) acts as an antiandrogen; prolactin stimulant causing: gynecomastia, galactorrhea; and reduce sperm count (?) |
|
|
Term
|
Definition
|
|
Term
| What is the PPI prototype? |
|
Definition
| Omeprazole (next one is esomeprazole) |
|
|
Term
| What are PPIs used to Tx? |
|
Definition
Erosive esophagitis, active duodenal ulcers, Zollinger-Ellison syndrome (a gastrin producing tumor (?)).
But also used for GERD and NSAID-induced ulcers over H2R blockers |
|
|
Term
| How are PPIs administered? |
|
Definition
| They are prodrugs with a enteric coat that only disolves in the alkaline medium of the duodenum and the prodrug is transported to the parietal cell canaliculus (?) where it is activated and forms an irreversible bond to the cysteine residue of the H+/K+-ATPase (takes 18hrs for it to be resynthesized) |
|
|
Term
| What are some of the A/Es of PPIs? |
|
Definition
| Increased gastric carcinoid tumors in animals; Omeprazole inhibits metabolism of warfarin, phenytoin, diazepam, and cyclosporine; prolonged uses of either PPI or H2R blocker -> less acid and thus less Vit. B12 absorbed; source of Ca2+ needs to be changed from Calcium carbonate to Calcium citrate; diarrhea, Clostridium difficile colitis; rarely pancreatitis, hepatotoxicity & interstitial-nephritis |
|
|
Term
| What are the two Cytoprotective (mucosal protective) agents? |
|
Definition
| Sucralfate (complex of aluminum hydroxide & sulfated sucrose) & Bismuth subsalicylate |
|
|
Term
| How does Sucralfate work? |
|
Definition
| It needs an acid pH to start up thus dont give w/ H2R blockers or antacids. It complexes further w/ proteins to form a gel layer on top of the epithelial cells, protecting against HCL and mucus degradation by pepsin and acid. Futhermore it stimulates release of prostaglandin, mucus and bicarb release. Its a long-term Tx and prevents recurrence. |
|
|
Term
| Does Bismuth subsalicylate have antimicrobial axn? |
|
Definition
| Yes along w/ inhibiting pepsin, increasing mucus & interacting w/ glycoproteins in necrotic tissue to form a coat to proect the ulcer crater |
|
|
Term
| What is the analog of PGE1 and what does it do? |
|
Definition
| Misoprostol, is used to Tx NSAID-induced gastric ulcers. PGE2, produced by gastric mucosa, inhibits HCL secretion but stimulates secretion of mucus & bicarbonate. NB that PGs are not that gud for acute Tx as H2R blockers and PPIs are. |
|
|
Term
| What is one new A/E of PGs? |
|
Definition
| Dose-related diarrhea and nausea |
|
|
Term
| What are the two anticholinergics? |
|
Definition
| Pirenzepine & Dicyclomine |
|
|
Term
| How does Pirenzepine work? |
|
Definition
|
|
Term
| How does Dicyclomine work? |
|
Definition
| It binds to mAchR on parietal cells to block Ach release. NB that its not as effective as H2RB or PPI. Used however in IBS |
|
|
Term
| What A/Es do both anticholinergics share? |
|
Definition
| Apart from the understood effects, others include arrhytmias & constipation at higher doses |
|
|
Term
| What is the Tx regimen for H. pylori? |
|
Definition
|
|
Term
| What are the two prokinetic Rxs? |
|
Definition
| Metoclopramide & Cisapride |
|
|
Term
| Which prokinetic Rx do you know that has three different activites at three different Receptors? |
|
Definition
Metoclopramide acts on the following receptors:
D2 - antagonist, acts on CTZ(?) in CNS as a anti-emetic
5-HT3 - at higher doses is an antagonist -> anti-emetic
5-HT4 - agonist -> muscarinic activity
NB that the 3 uses for Metoclopramide are in: diabetic gastroparesis, anti-emetic & GERD |
|
|
Term
|
Definition
It releases Ach into the myenteric plexus -> increases mm tone in esophageal sphinter. Used in GERD, Gastroparesis and constipation.
A/Es include: long QT interval -> arrhythmias w/ erythromycin or ketoconazole; diarrhea |
|
|
Term
| How can the laxatives be classified? |
|
Definition
Stimulants/ irritants, bulking or softeners.
NB that a long term use can result in electrolye inbalance |
|
|
Term
| What are 3 stimulants/ irritants you know? |
|
Definition
Senna - widely used, oral, 8hrs, used in combo w/ a softener (Docusate) to Tx opiod-induced constipation
Bisacodyl - as a suppository or enteric-coated (thus dont take w/ antacids as the alkaline will dissolve it earlier - the stomach -> irritation & pain), potent as it acts directly on the nerve fiber
Castor oil - broken down in SI to ricinoleic acid (very irritating), provides uterine contrations like misoprostol |
|
|
Term
| Who shudnt use bulk laxitives and what are they? |
|
Definition
| Bed-bound pts due to potential for obstruction; methylcellulose, psyllium seeds & bran |
|
|
Term
| What are some of the Saline & osmotic laxatives? |
|
Definition
| Mg citrate/ sulfate/ phosphate/ hydroxide, lactulose, PEG (polyethylene glycol) |
|
|
Term
| Emollient laxatives/ surfactants (?)/ Stool softners are? |
|
Definition
| Docusate sodium/ calcium/ potassium |
|
|
Term
| Mineral oils & glycerin suppositories are? |
|
Definition
| Lubricants and aid in passage of stool |
|
|
Term
| What Receptors do anti-emetics work on? |
|
Definition
| D2, 5-HT3, Ach, Neurokinin-1/ substance P in CNS, H1 (?) |
|
|
Term
|
Definition
| Dimenhydrinate, meclizine, cyclizine |
|
|
Term
| What antiemetic Rs does Phenothiazine work on? |
|
Definition
D2, low to moderate chemo Rxs (Fluorouracil & doxorubicin).
A/Es: hypotension & restlessness, which make then dose limiting; extrapyramidal Sx & sedation |
|
|
Term
| 5-HT3 blockade both in CNS (chemoreceptor trigger zone - CTZ) & periphery (visceral vagal afferent fibers) are via? |
|
Definition
| Ondansetron & granisetron; long duration, given orally or IV for chemo A/Es, dolasetron prolongs QT |
|
|
Term
| What antiemetic do u know that has substituted benzamides? |
|
Definition
Metoclopramide, at high doses is effective against Cisplatin (highly emetogenic).
Has antidopaminergic side effects: sedation, diarrhea & extrapyramidal Sxs, limits it high dose use |
|
|
Term
| Which other D2R blocker do u know but is used only in refractory cases? |
|
Definition
| Butyrophenones: Droperidol (prolong QT interval) & Haloperidol |
|
|
Term
| Which antiemetics are useful in anticipatory vomiting? |
|
Definition
| Benzodiazepines: lorazepam & alprazolam, NB that potency is low, the MOA is likely due to their sedative, anxiolytic & amnesic properties |
|
|
Term
| We know that the Phenothiazines are of moderate potency as an antiemetic but what others are also of the same potency? |
|
Definition
| Corticosteriods (dexamethasone & methylprednisolone) and the marijuana derivatives (dronabinol & nabilone) |
|
|
Term
| Which only antiemetic do u know that works on blocking prostaglandins? |
|
Definition
| The corticosteroids, they are usually used in combo; A/Es include: insomnia, hyperglycemia (DM) |
|
|
Term
| Which antiemetic do u know that blocks neurokinin-1/ substance P in the CNS and also is extensively broken down by CYP3A4? |
|
Definition
| Aprepitant; usually given orally w/ dexamethasone & palonosetron; A/Es: constipation & fatigue |
|
|
Term
| What other Rx do u know that is broken down by CYP3A4? |
|
Definition
|
|
Term
| Which two Rxs do u know that cause emesis? |
|
Definition
| Apomorphine & Syrup ipecac; act on CTZ or via gastric mucosa irritation; used for accidental poisonings |
|
|
Term
| List some Rxs that cause emesis as a side-effect? |
|
Definition
| Morphine, quinine, amiodarone, digoxin, emetin, ergot, erythromycin, chloroquine, fluoroquinolones, metronidazole, captopril, diltiazem |
|
|
Term
| Name the four antidiarrheals? |
|
Definition
| Diphenaxylate, loperamide, octreotide, bismuth subsalicylate (pepto bismol) |
|
|
Term
| Which antidiarrheal Rx has opioid-like axn? |
|
Definition
| Diphenaxylate & loperamide, act presynaptically to prevent Ach release in the ENS to decrease peristalsis. Diphenaxylate needs to be given w/ atropine to discourage abuse. Standard doses don’t give analgesic effects. A/Es: abdominal cramps, drowsiness, dizziness. Contradicted (?) in toxic megacolon in kids and in pts w/ severe colitis |
|
|
Term
| Which antidiarrheal is a somatostatin derivative? |
|
Definition
| Octreotide, used for diarrheas associated w/ carcinoid tumors & VIP tumors |
|
|
Term
| What Rxs are used in IBD (UC & CD)? |
|
Definition
| Sulfasalazine derivatives like sulfapyridine (?) w/ their anti-inflammatory effects; 5-ASA which inhibits PGs & LTs; Infliximab which is a monoclonal Ab against TNF (can also be used in RA). Others include MTX, 6-MP, steroids (glucocorticoids – prednisone, prednisolone) |
|
|
Term
| What Rxs would u give for IBS-C? |
|
Definition
| First fibers, then try PEG, sorbitol or lactulose to help avoid “Cathartic colon” (?) |
|
|
Term
| What Rxs would u give for IBS-D? |
|
Definition
| Opioid analogues like loperamide, diphenoxylate or codein |
|
|
Term
| Pts with cramps & diarrhea can be Tx w/? |
|
Definition
| Antispasmodics which are anticholinergics: hyoscyamine, dicyclomine |
|
|
Term
| Why would u not give a kid w/ a viral infection a asprin? |
|
Definition
| Idoysyncratic effects -> Reye’s syndrome – fatty liver, hypoglycaemia and coma (hepatic-encephalopathy), use acetaminophen |
|
|
Term
| What are the Pancreatic proteases? |
|
Definition
| Trypsin, chymotrypsin, elastase, carboxypeptidase, secreted as proenzymes (unlike alpha-amylase which is secreted in the active form) |
|
|
