Owen 1-8-08 Pharmacology Of Antacids, Etc

Front 1

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.

Back 1

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.

Front 2

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 ________.

Back 2

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.

Front 3

-Acid is secreted from gastric parietal cells by a proton pump (K+/H+ ATPase).
-The three endogenous secretagogues for acid are _________, ___ and _______.

Back 3

-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.

Front 4

-Prostaglandins E2 and I2 inhibit acid, stimulate _____ and ___________ secretion, and dilate mucosal blood vessels

Back 4

-Prostaglandins E2 and I2 inhibit acid, stimulate mucus and bicarbonate secretion, and dilate mucosal blood vessels

Front 5

HCl + NaHCO3 → NaCl + H2O + ___ (Burp!)

Back 5

CO2

Front 6

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

Back 6

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

Front 7

Milk of magnesia

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

Back 7

Milk of magnesia

Does not produce systemic alkalosis because Mg2+ is poorly absorbed from the gut.

Front 8

Because some sodium bicarbonate is absorbed in the intestine, large doses or frequent administration of this antacid can cause _________.

Back 8

Because some sodium bicarbonate is absorbed in the intestine, large doses or frequent administration of this antacid can cause alkalosis.

Front 9

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 ____________.

Back 9

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.

Front 10

Aluminum hydroxide raises the pH of the gastric juice to about 4, & also absorbs ______. Its action is gradual & its effect continues for several hrs.

Back 10

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.

Front 11

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 _______ _____ _______

Back 11

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

Front 12

Sodium bicarbonate


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

Back 12

Sodium bicarbonate


The carbon dioxide stimulates gastrin secretion & can result in a 2ndary rise in acid secretion

Front 13

Calcium carbonate (Tums, Os-Cal)
CaCO3 + 2HCl → CaCl2 + H2O + CO2 (Burp!)
Excessive intake of calcium carbonate along with calcium foods can result in ____________.

Back 13

Calcium carbonate (Tums, Os-Cal)
CaCO3 + 2HCl → CaCl2 + H2O + CO2 (Burp!)
Excessive intake of calcium carbonate along with calcium foods can result in hypercalcemia.

Front 14

Both magnesium & aluminum are absorbed & excreted by the kidneys. Hence, patients with renal insufficiency should not take these agents ____ term.

Back 14

Both magnesium & aluminum are absorbed & excreted by the kidneys. Hence, patients with renal insufficiency should not take these agents long term.

Front 15

___ 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.

Back 15

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.

Front 16

Antacids should not be given within 2 hours of doses of _____________, ________________, ____________, and ____.

Back 16

Antacids should not be given within 2 hours of doses of tetracyclines, fluoroquinolones, itraconazole, and iron.

Front 17

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.

Back 17

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.

Front 18

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.

Back 18

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.

Front 19

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 _________

Back 19

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

Front 20

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 ______.

Back 20

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.

Front 21

Famotidine (______) – Similar to Ranitidine in its pharmacologic action, most potent, __-__ times more potent than Cimetidine. Does not inhibit ______.

Back 21

Famotidine (Pepcid) – Similar to Ranitidine in its pharmacologic action, most potent, 20-50 times more potent than Cimetidine. Does not inhibit P-450s.

Front 22

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.

Back 22

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.

Front 23

Hormonal effects of Cimetidine: _________, ____________ (males), ____________ (females)

Back 23

Hormonal effects of Cimetidine: impotency, gynecomastia (males), galactorrhea (females)

Front 24

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.

Back 24

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.

Front 25

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 _________

Back 25

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

Front 26

Omeprazole inhibits ______, drug interactions (eg, warfarin, phenytoin)

Back 26

Omeprazole inhibits P-450s, drug interactions (eg, warfarin, phenytoin)

Front 27

Know all these PPIs

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

Back 27

Know all these PPIs

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

Front 28

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

Back 28

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

Front 29

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.

Back 29

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.

Front 30

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.

Back 30

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.

Front 31

___________ (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

Back 31

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

Front 32

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

Back 32

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

Front 33

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

Back 33

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

Front 34

Gastroesophageal reflux disease or GERD occurs when the _____ __________ _________ (___) does not close properly & stomach contents reflux back up into the esophagus.

Back 34

Gastroesophageal reflux disease or GERD occurs when the lower esophageal sphincter (LES) does not close properly & stomach contents reflux back up into the esophagus.

Front 35

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]

Back 35

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]

Front 36

ARDs of Metoclopramide

Back 36

ADRs: inc GI - diarrhea, central DA antagonism: sedation,extrapyramidal effects, seizures, inc prolactin/galactorrhea/menstrual irregularities

Front 37

_______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

Back 37

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

Front 38

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

Back 38

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

Front 39

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

Back 39

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

Front 40

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.

Back 40

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.

Front 41

NSAIDs, such as aspirin and indomethacin, are effective in controling diarrhea. This antidiarrheal action is probably due to inhibition of _____________ synthesis.

Back 41

NSAIDs, such as aspirin and indomethacin, are effective in controling diarrhea. This antidiarrheal action is probably due to inhibition of prostaglandin synthesis.

Front 42

______ 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.

Back 42

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.

Front 43

_________ (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.

Back 43

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.

Front 44

Examples of osmotic agents (laxitives)

Back 44

Saline cathartics such as magnesium hydroxide
Nondigestible sugars such as sorbitol

Front 45

Exs of bulking agents

Back 45

Hydrophillic colloids (from indigestible parts of fruits and vegetables
Bran

Front 46

Exs of stool softeners

Back 46

Mineral oil
Docusate sodium (Colace)

Front 47

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

Back 47

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