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47 Cards in this Set

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Pathophysiology of H. pylori

Possesses a high ______ activity. This enzyme converts urea to _______. The _______ buffers the H+ and forms _______ hydroxide, creating an alkaline cloud around the bacterium, protecting it from the acidic environment of the stomach or duodenum.
Pathophysiology of H. pylori

Possesses a high urease activity. This enzyme converts urea to ammonia. The ammonia buffers the H+ and forms ammonium hydroxide, creating an alkaline cloud around the bacterium, protecting it from the acidic environment of the stomach or duodenum.
H. pylori releases several pathogenic proteins that induce cell injury. For ex., the ____ protein, produced by cytotoxic-associated gene A (____), is a highly immunogenic protein that is associated with more severe clinical syndromes, such as gastric cancer and gastric mucosa-associated lymphoid tissue ________.
H. pylori releases several pathogenic proteins that induce cell injury. For ex., the CagA protein, produced by cytotoxic-associated gene A (cagA), is a highly immunogenic protein that is associated with more severe clinical syndromes, such as gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma.
-Acid is secreted from gastric parietal cells by a proton pump (K+/H+ ATPase).
-The three endogenous secretagogues for acid are _________, ___ and _______.
-Acid is secreted from gastric parietal cells by a proton pump (K+/H+ ATPase).
-The three endogenous secretagogues for acid are histamine, ACh and gastrin.
-Prostaglandins E2 and I2 inhibit acid, stimulate _____ and ___________ secretion, and dilate mucosal blood vessels
-Prostaglandins E2 and I2 inhibit acid, stimulate mucus and bicarbonate secretion, and dilate mucosal blood vessels
HCl + NaHCO3 → NaCl + H2O + ___ (Burp!)
CO2
Magnesium hydroxide (Milk of ________)
Mg (OH)2 + 2HCl → MgCl2 + 2H2O
Produces magnesium salts, which, because they are poorly absorbed, cause the ________ commonly associated with this compd
Magnesium hydroxide (Milk of Magnesia)
Mg (OH)2 + 2HCl → MgCl2 + 2H2O
Produces magnesium salts, which, because they are poorly absorbed, cause the diarrhea commonly associated with this compd
Milk of magnesia

Does not produce systemic _________ because Mg2+ is poorly absorbed from the gut.
Milk of magnesia

Does not produce systemic alkalosis because Mg2+ is poorly absorbed from the gut.
Because some sodium bicarbonate is absorbed in the intestine, large doses or frequent administration of this antacid can cause _________.
Because some sodium bicarbonate is absorbed in the intestine, large doses or frequent administration of this antacid can cause alkalosis.
Aluminum hydroxide gel (Amphojel)
Al (OH)3 + 3HCl → AlCl3 + 3 H2O
Aluminum chloride reacts with hydrochloric acid to form aluminum chloride, which is insoluble & causes ____________.
Aluminum hydroxide gel (Amphojel)
Al (OH)3 + 3HCl → AlCl3 + 3 H2O
Aluminum chloride reacts with hydrochloric acid to form aluminum chloride, which is insoluble & causes constipation.
Aluminum hydroxide raises the pH of the gastric juice to about 4, & also absorbs ______. Its action is gradual & its effect continues for several hrs.
Aluminum hydroxide raises the pH of the gastric juice to about 4, & also absorbs pepsin. Its action is gradual & its effect continues for several hrs.
Colloidal aluminum hydroxide combines with phosphates in the GI tract, & the increased excretion of phosphate in the feces that occurs results in decreased excretion of phosphate via the kidney. This effect has been used in treating patients with _______ _____ _______
Colloidal aluminum hydroxide combines with phosphates in the GI tract, & the increased excretion of phosphate in the feces that occurs results in decreased excretion of phosphate via the kidney. This effect has been used in treating patients with chronic renal failure
Sodium bicarbonate


The carbon dioxide stimulates _______ secretion & can result in a 2ndary rise in acid secretion
Sodium bicarbonate


The carbon dioxide stimulates gastrin secretion & can result in a 2ndary rise in acid secretion
Calcium carbonate (Tums, Os-Cal)
CaCO3 + 2HCl → CaCl2 + H2O + CO2 (Burp!)
Excessive intake of calcium carbonate along with calcium foods can result in ____________.
Calcium carbonate (Tums, Os-Cal)
CaCO3 + 2HCl → CaCl2 + H2O + CO2 (Burp!)
Excessive intake of calcium carbonate along with calcium foods can result in hypercalcemia.
Both magnesium & aluminum are absorbed & excreted by the kidneys. Hence, patients with renal insufficiency should not take these agents ____ term.
Both magnesium & aluminum are absorbed & excreted by the kidneys. Hence, patients with renal insufficiency should not take these agents long term.
___ antacids may affect the absorption of other medications by binding the drug (reducing its absorption) or by increasing intragastric pH so that the drug’s dissolution or solubility (especially weakly basic or acidic drugs) is altered.
ALL antacids may affect the absorption of other medications by binding the drug (reducing its absorption) or by increasing intragastric pH so that the drug’s dissolution or solubility (especially weakly basic or acidic drugs) is altered.
Antacids should not be given within 2 hours of doses of _____________, ________________, ____________, and ____.
Antacids should not be given within 2 hours of doses of tetracyclines, fluoroquinolones, itraconazole, and iron.
Reversible, competitive histamine (H2) receptor antagonists
Dose-dependent effects
Reduce gastric acid - Inhibit basal, food stimulated and nocturnal secretions
Additional therapeutic value - Effective for ________ more than gastric ulcers. They have been shown to be effective in promoting the healing of duodenal & gastric ulcers as well as relieving esophageal _______ disease.
Reversible, competitive histamine (H2) receptor antagonists
Dose-dependent effects
Reduce gastric acid - Inhibit basal, food stimulated and nocturnal secretions
Additional therapeutic value - Effective for duodenal more than gastric ulcers. They have been shown to be effective in promoting the healing of duodenal & gastric ulcers as well as relieving esophageal reflux disease.
Cimetidine (TAGAMET)

Inhibits several cytochrome P-450 isozymes, phase - 1 oxidations, the half-lives of drugs metabolized by these pathways may be prolonged, e.g. w_______, ph_______, q________, several benzodiazepines, and procainamide.
Cimetidine (TAGAMET)

Inhibits several cytochrome P-450 isozymes, phase - 1 oxidations, the half-lives of drugs metabolized by these pathways may be prolonged, e.g. warfarin, phenytoin, quinidine, several benzodiazepines, and procainamide.
Cimetidine (cont.)

Binds to\blocks androgen receptor (modest affinity): may decrease libido, cause male impotency
Inhibits a CYP that hydoxylates estradiol
May increase prolactin, galactorrhea (continuous release/discharge of milk)(females), gynecomastia (males)
Can cause _________ in the elderly
Not recommended for use in _________
Cimetidine (cont.)

Binds to\blocks androgen receptor (modest affinity): may decrease libido, cause male impotency
Inhibits a CYP that hydoxylates estradiol
May increase prolactin, galactorrhea (continuous release/discharge of milk)(females), gynecomastia (males)
Can cause confusion in the elderly
Not recommended for use in pregnancy
Ranitidine (______) - Compared to Cimetidine, it is longer acting & is 5-10 fold more potent. Does not produce the anti__________ or prolactin-stimulating effects of Cimetidine. Slight inhibition of the ______.
Ranitidine (Zantac) - Compared to Cimetidine, it is longer acting & is 5-10 fold more potent. Does not produce the antiandrogenic or prolactin-stimulating effects of Cimetidine. Slight inhibition of the P-450s.
Famotidine (______) – Similar to Ranitidine in its pharmacologic action, most potent, __-__ times more potent than Cimetidine. Does not inhibit ______.
Famotidine (Pepcid) – Similar to Ranitidine in its pharmacologic action, most potent, 20-50 times more potent than Cimetidine. Does not inhibit P-450s.
Nizatidine (Axid) – Similar to Ranitidine in its pharmacologic action & potency. Does not inhibit ______. In contrast to Cimetidine, Ranitidine & Famodipine, which are metabolized by the liver, Nizatidine is eliminated principally by the _______. Because little 1st pass metabolism occurs with Nizatidine, its bioavailability is nearly ___%. No IV prep is available.
Nizatidine (Axid) – Similar to Ranitidine in its pharmacologic action & potency. Does not inhibit P-450s. In contrast to Cimetidine, Ranitidine & Famodipine, which are metabolized by the liver, Nizatidine is eliminated principally by the kidney. Because little 1st pass metabolism occurs with Nizatidine, its bioavailability is nearly 100%. No IV prep is available.
Hormonal effects of Cimetidine: _________, ____________ (males), ____________ (females)
Hormonal effects of Cimetidine: impotency, gynecomastia (males), galactorrhea (females)
DRUG INTERACTIONS

Mostly __________, related to P-450 inhibition, eg. phenytoin, warfarin
Decrease absorption of drugs requiring GI acidity, eg ____________
Antacids decrease absorption of __ receptor antagonists.
DRUG INTERACTIONS

Mostly Cimetidine, related to P-450 inhibition, eg. phenytoin, warfarin
Decrease absorption of drugs requiring GI acidity, eg ketoconazole
Antacids decrease absorption of H2 receptor antagonists.
Proton Pump Inhibitors (PPIs)

PPIs most effective reducers HCL secretion, They can essentially inhibit 100% of gastric acid secretion with a single daily dose.
Prodrugs become “+ charged” in ______ medium and irreversibly inhibit H+/_+ ATPase
Uses : Zollinger-Ellison syndrome, gastric/duodenal ulcers, ____. Also used in comb. with antibiotics to eradicate _________
Proton Pump Inhibitors (PPIs)

PPIs most effective reducers HCL secretion, They can essentially inhibit 100% of gastric acid secretion with a single daily dose.
Prodrugs become “+ charged” in acidic medium and irreversibly inhibit H+/K+ ATPase
Uses : Zollinger-Ellison syndrome, gastric/duodenal ulcers, GERD. Also used in comb. with antibiotics to eradicate H. pylori
Omeprazole inhibits ______, drug interactions (eg, warfarin, phenytoin)
Omeprazole inhibits P-450s, drug interactions (eg, warfarin, phenytoin)
Know all these PPIs

_____prazole (prevacid), ____prazole (Aciphex), _____prazole (Nexium), _____prazole (Protonix); minimal P-450 microsomal enzyme inhibition
Know all these PPIs

Lansoprazole (prevacid), rabeprazole (Aciphex), esomeprazole (Nexium), pantoprazole (Protonix); minimal P-450 microsomal enzyme inhibition
H2 Blocker vs PPIs

____ superior with H. pylori infection, hemorrhagic ulcers/bleeding (maintain clot better), and when pt using NSAIDs
H2 blockers lower incidence adverse effects, _cost__, _____ in pregnancy (exception cimetidine), less hypergastrinemia and potential for gastric _________ tumors
H2 Blocker vs PPIs

PPIs superior with H. pylori infection, hemorrhagic ulcers/bleeding (maintain clot better), and when pt using NSAIDs
H2 blockers lower incidence adverse effects, cheaper, safer in pregnancy (exception cimetidine), less hypergastrinemia and potential for gastric carcinoid tumors
Drugs that protect the MUCOSA

Sucralfate (CARAFATE), - A sulfated disaccharide developed for use in treating peptic ulcer disease.
Interacts with HCL to form viscous “- charged substance that binds “+” charged exposed ulcer proteins; QID (empty stomach). Major MA is polymerization & selective binding to ________ ulcer tissue, where it acts as a barrier to acid, pepsin & bile.
Drugs that protect the MUCOSA

Sucralfate (CARAFATE), - A sulfated disaccharide developed for use in treating peptic ulcer disease.
Interacts with HCL to form viscous “- charged substance that binds “+” charged exposed ulcer proteins; QID (empty stomach). Major MA is polymerization & selective binding to necrotic ulcer tissue, where it acts as a barrier to acid, pepsin & bile.
Sucralfate

May also directly absorb ____ salts & may stimulate endogenous prostaglandin synthesis.
GI disturbances: n-v/ ____________
Pts with renal failure/dialysis should have serum Al levels monitored
May bind to other medications impairing their absorption. Eg. tetracycline
Do not admin simultaneously with antacids/H2 blockers/ PPIs. Sucralfate requires an ____ pH to be activated.
Sucralfate

May also directly absorb bile salts & may stimulate endogenous prostaglandin synthesis.
GI disturbances: n-v/ constipation
Pts with renal failure/dialysis should have serum Al levels monitored
May bind to other medications impairing their absorption. Eg. tetracycline
Do not admin simultaneously with antacids/H2 blockers/ PPIs. Sucralfate requires an acid pH to be activated.
___________ (CYTOTEC)

PGE1 analogue that : inc mucus/NO/HCO3, inc cell proliferation, decreases acid secretion, preserves microcirculation, stabilizes lysosomes
Prevention and treatment NSAIDs gastropathy/ulcerations, QID with food
ADRs: diarrhea (30% of people taking drug), gas, cramps; stim sm muscle of GI and uterus, contraindicated in pregnancy
Misoprostol (CYTOTEC)

PGE1 analogue that : inc mucus/NO/HCO3, inc cell proliferation, decreases acid secretion, preserves microcirculation, stabilizes lysosomes
Prevention and treatment NSAIDs gastropathy/ulcerations, QID with food
ADRs: diarrhea (30% of people taking drug), gas, cramps; stim sm muscle of GI and uterus, contraindicated in pregnancy
Bismuth subsalicylate (PEPTO-BISMOL)

Indicated for dyspepsia & acute ________
Colloidal preparation of Bi (heavy metal, not absorbed) and salicylate (absorbed)
Bi binds mucous glycoproteins, coats/protects GI from pepsin/bile acids; increase mucus/HCO3/PG synthesis; inhibits intestinal secretions
Have some antimicrobial activity against H. pylori
May stain ______, stools black due to bacterial interaction to form bisulfide
Overuse/dosage: Bi toxicity (encephalopathy-ataxia, headaches, confusion, seizures)), salicylate toxicity
Bismuth subsalicylate (PEPTO-BISMOL)

Indicated for dyspepsia & acute diarrhea
Colloidal preparation of Bi (heavy metal, not absorbed) and salicylate (absorbed)
Bi binds mucous glycoproteins, coats/protects GI from pepsin/bile acids; increase mucus/HCO3/PG synthesis; inhibits intestinal secretions
Have some antimicrobial activity against H. pylori
May stain tongue, stools black due to bacterial interaction to form bisulfide
Overuse/dosage: Bi toxicity (encephalopathy-ataxia, headaches, confusion, seizures)), salicylate toxicity
Antimicrobial Treatment

Triple therapy/2weeks: ____________ QID/_____________ 500 mg BID/____________ or amoxicillin 500 mg BID for 10-14 days
Replace metronidazole with clarithromycin 500 mg BID, less development of resistance
___ added to therapy; combo: lansoprazole + amoxicillin + clarithromycin (PREVPAC)
PPI also incs intragastric pH which incs action of antibiotics, esp amoxicillin
Antimicrobial Treatment

Triple therapy/2weeks: Pepto-bismol QID/metronidazole 500 mg BID/tetracycline or amoxicillin 500 mg BID for 10-14 days
Replace metronidazole with clarithromycin 500 mg BID, less development of resistance
PPI added to therapy; combo: lansoprazole + amoxicillin + clarithromycin (PREVPAC)
PPI also incs intragastric pH which incs action of antibiotics, esp amoxicillin
Gastroesophageal reflux disease or GERD occurs when the _____ __________ _________ (___) does not close properly & stomach contents reflux back up into the esophagus.
Gastroesophageal reflux disease or GERD occurs when the lower esophageal sphincter (LES) does not close properly & stomach contents reflux back up into the esophagus.
Metoclopramide (REGLAN) – blocks enteric GI presynaptic _____ receptors to inc Ach cholinergic), inc upper GI tone/motility; also an anti______ and anti______ drug [blocks DA2 receptors in the chemoreceptor trigger zone of the medulla (area _________) resulting in potent anti______ and anti______ action]
Metoclopramide (REGLAN) – blocks enteric GI presynaptic DA-D2 receptors to inc Ach cholinergic), inc upper GI tone/motility; also an antiemitic and antinausea drug [blocks DA2 receptors in the chemoreceptor trigger zone of the medulla (area prostrema) resulting in potent antinausea and antiemetic action]
ARDs of Metoclopramide
ADRs: inc GI - diarrhea, central DA antagonism: sedation,extrapyramidal effects, seizures, inc prolactin/galactorrhea/menstrual irregularities
_______chol – ACh derivative with muscarinic (M3) actions; inc LES pressure / GI motility. Seldom used now due to multiple cholinergic effects & the advent of less toxic agents
Bethanechol – ACh derivative with muscarinic (M3) actions; inc LES pressure / GI motility. Seldom used now due to multiple cholinergic effects & the advent of less toxic agents
Use of Acid Suppressors in GERD

H2 blocker (OTC & prescription) to hasten healing and when excessive heartburn is present; 2-4 divided doses better than once/day
Proton pump inhibitors are _________ drugs, esp for more serious conditions with esophageal erosion
Antacids, sucralfate also provide some relief in milder conditions
Use of Acid Suppressors in GERD

H2 blocker (OTC & prescription) to hasten healing and when excessive heartburn is present; 2-4 divided doses better than once/day
Proton pump inhibitors are preferred drugs, esp for more serious conditions with esophageal erosion
Antacids, sucralfate also provide some relief in milder conditions
Antimotility Agents

______ derivatives that presynaptically inhibit cholinergic activity/dec motility
Diphen_______ (LOMOTIL), derv of __________ (DEMEROL), GI effect greater than CNS effects; Schedule V
_________ (MOTOFEN), active metabolite of diphenoxylate; Schedule IV controlled drug
Diphanoxylate is formulated with antimuscarinic alkaloids (eg. Atropine) to reduce the likelihood of abuse .
__________ (IMODIUM), deriv. of meperidine, GI effects, doesn’t cross BBB, lacks CNS effects, OTC drug
Constipation is main side effect
Not use in Ulcerative Colitis or Toxic Megacolon
Antimotility Agents

Opioid derivatives that presynaptically inhibit cholinergic activity/dec motility
Diphenoxylate (LOMOTIL), derv of meperidine (DEMEROL), GI effect greater than CNS effects; Schedule V
Difenoxin (MOTOFEN), active metabolite of diphenoxylate; Schedule IV controlled drug
Diphanoxylate is formulated with antimuscarinic alkaloids (eg. Atropine) to reduce the likelihood of abuse .
Loperamide (IMODIUM), deriv. of meperidine, GI effects, doesn’t cross BBB, lacks CNS effects, OTC drug
Constipation is main side effect
Not use in Ulcerative Colitis or Toxic Megacolon
Adsorbent agents such as: K_____, P_____, Methycellulose, Magnesium aluminum silicate are widely used to control diarrhea.
Presumably these agents act by adsorbing intestinal toxins or microorganisms and/or by coating or protecting the intestinal mucosa. They are less effective than antimotility agents.
In addition to causing constipation, they can interfere with the __________ of other drugs.
Adsorbent agents such as: Kaolin, Pectin, Methycellulose, Magnesium aluminum silicate are widely used to control diarrhea.
Presumably these agents act by adsorbing intestinal toxins or microorganisms and/or by coating or protecting the intestinal mucosa. They are less effective than antimotility agents.
In addition to causing constipation, they can interfere with the absorption of other drugs.
NSAIDs, such as aspirin and indomethacin, are effective in controling diarrhea. This antidiarrheal action is probably due to inhibition of _____________ synthesis.
NSAIDs, such as aspirin and indomethacin, are effective in controling diarrhea. This antidiarrheal action is probably due to inhibition of prostaglandin synthesis.
______ oil – is broken down in the small intestine to ricinoleic acid which is irritating to the gut & promptly inc. peristalisis
_____ (Senokot) – contains emodin, which stimulates colonic activity
_________ (Dulcolax) is a potent stimulant of the colon.
Caster oil – is broken down in the small intestine to ricinoleic acid which is irritating to the gut & promptly inc. peristalisis
Senna (Senokot) – contains emodin, which stimulates colonic activity
Bisacodyl (Dulcolax) is a potent stimulant of the colon.
_________ (ZELNORM), 5HT4 partial agonist effective in the treatment of the constipation-predominant form of IBS. It is too early to be certain about the long term benefit of this drug.
Tegaserod (ZELNORM), 5HT4 partial agonist effective in the treatment of the constipation-predominant form of IBS. It is too early to be certain about the long term benefit of this drug.
Examples of osmotic agents (laxitives)
Saline cathartics such as magnesium hydroxide
Nondigestible sugars such as sorbitol
Exs of bulking agents
Hydrophillic colloids (from indigestible parts of fruits and vegetables
Bran
Exs of stool softeners
Mineral oil
Docusate sodium (Colace)
IBS is a functional disorder that mainly affects the bowel causing cramping, bloating, gas, diarrhea & constipation,
Other names for IBS are s______ colon, mucous colon, spastic colitis and n______ stomach.
IBS is caused by disturbed interaction of the intestines, brain and ANS that alters bowel motility (motor function) or sensory function.
Symptomatic treatment: inc dietary fiber, antidiarrheals, laxatives, antispasmotics, avoid drinks/foods known to activate condition
New drugs that affect serotonin receptor activity
IBS is a functional disorder that mainly affects the bowel causing cramping, bloating, gas, diarrhea & constipation,
Other names for IBS are spastic colon, mucous colon, spastic colitis and nervous stomach.
IBS is caused by disturbed interaction of the intestines, brain and ANS that alters bowel motility (motor function) or sensory function.
Symptomatic treatment: inc dietary fiber, antidiarrheals, laxatives, antispasmotics, avoid drinks/foods known to activate condition
New drugs that affect serotonin receptor activity