Gastrointestinal Pharmacology I: Management Of Active Pud

Front 1

Antacid
a)mechanism of action

Back 1

Antacid
a)mechanism of action: neutralize secreted gastric acid thereby reduce gastric aciditiy (increase gastric PH)

Front 2

Antacid
b)clinical indications

Back 2

Antacid
b)clinical indications: used as an ADJUNCT to other approaches for relief of PU pain and to promote healing of PUs

Front 3

Antacid
c)adverse effects

Back 3

Antacid
c)adverse effects:
1. GI: diarrhea (magnesium salts), constipation (aluminum, calcium salts).
2. HYPOphosphatemia: associated with aluminum-containing antacids
3. HYPERmagnesemia, HYPERaluminemia: in patients with renal failure taking large doses chronically
4. acid rebound: associated with calcium containing antacids

Front 4

Antacid
d)cautions and considerations

Back 4

Antacid
d)cautions and considerations:
1. pregnancy: concern only with chronic high doses
2. breast-feeding: no documented problems in neonates
3. pediatrics: NOT recommended < age 6 years, unless proper diagnosis made

Front 5

Antacid
e)drug interactions

Back 5

Antacid
e)drug interactions
1. adsorb drugs to surface, thereby decreasing bioavailability: tetracycline; ciprofloxacin, norfloxacin
2. increased gastric PH, thereby altering drug absorption: a) decreased absorption, decreased THERAPEUTIC effect: digoxin, phenytoin, isoniazid, ketoconazole; and b)increased absorption, increased ADVERSE effects: salicylates, levodopa.

NOTE: In general, do not take antacids within 1-2 hours of other oral drugs

Front 6

Antacid
f)acid neutralizing capacity of antacid products

Back 6

Antacid
f)antacid neutralizing capacity of antacid products: Delcid (highest), Tums (lowest)

Front 7

Antacid
g)dosage and administration

Back 7

Antacid
g)dosage and administration:
*usual duration of therapy: 4-8 weeks; continue therapy for at least 4-6 weeks after all symptoms have disappeared.
*LIQUID forms preferable to tablets- more potent, more effective
*tablets should be chewed well and followed with a glass of water

Front 8

Histamine H2-Receptor Antagonists (H2As)
a)available agents

Back 8

Histamine H2-Receptor Antagonists (H2As)
a)available agents:
1. cimetidine (Tagamet)
2. ranitidine (Zantac)
3. famotidine (Pepcid)
4. nizatidine (Axid)
*C.R.F.N.

Front 9

Histamine H2-Receptor Antagonists (H2As)
b)mechanism of action

Back 9

Histamine H2-Receptor Antagonists (H2As)
b)mechanism of action: block gastric acid secretion by inhibiting the action of histamine at the histamine H2-receptor sites on the PARIETAL CELL; also inhibit acid secretion stimulated by GASTRIN and ACETYLCHOLINE

Front 10

Histamine H2-Receptor Antagonists (H2As)
c)pharmacokinetics

Back 10

Histamine H2-Receptor Antagonists (H2As)
c)pharmacokinetics:
1. metabolism: HEPATIC; RANITIDINE (extensive first-pass metabolism of oral dose)
2. elimination: primarily RENAL
3. distribution: distributed into BREAST MILK; crosses the PLACENTA

Front 11

Histamine H2-Receptor Antagonists (H2As)
d)clinical indications (FDA-approved)

Back 11

Histamine H2-Receptor Antagonists (H2As)
d)clinical indications (FDA-approved):
1. treatment and prevention of DU: C.R.F.N.
2. treatment of active benign GU: C.R.F.N.
3. ZOLLINGER-ELLISON SYNDROME: cimetidine, ranitidine, famotidine

Front 12

Histamine H2-Receptor Antagonists (H2As)
e)adverse effects

Back 12

Histamine H2-Receptor Antagonists (H2As)
e)adverse effects (udually mild and infrequent):
1. GI: n/v/d, constipation
2. CNS: headache, dizziness, drowsiness, mental confusion, and seizures (with CIMETIDINE)
3. allergic: skin rash
4. endocrine (with CIMETIDINE): gynecomastia, impotence, galactorrhea
5. hematologic: thrombocytopenia

Front 13

Histamine H2-Receptor Antagonists (H2As)
f)cautions and considerations

Back 13

Histamine H2-Receptor Antagonists (H2As)
f)cautions and considerations:
1. pregnancy: ALL H2A's CROSS THE PLACENTA
2. breastfeeding: ALL H2A's EXCRETED INTO BREAST MILK
3. pediatrics: consider risk-benefit in children <16 y/o age due to limited clinical experience
4. geriatrics: no problems documented to date

Front 14

Histamine H2-Receptor Antagonists (H2As)
g)drug interactions

Back 14

Histamine H2-Receptor Antagonists (H2As)
g)drug interactions: CIMETIDINE inhibits the CYTOCHROME P450 MIXED-FUNCTION OXIDASE ENZYME in the liver, thereby decreasing hepatic metabolism, delaying elimination, and increasing serum concentrations of drugs metabolized by this system. Drugs most frequently implacted are theophylline, phenytoin and warfarin.

Front 15

Histamine H2-Receptor Antagonists (H2As)
h)dosage and administration

Back 15

Histamine H2-Receptor Antagonists (H2As)
h)dosage and administration:
1. Cimetidine: oral, IM, IV
2. Ranitidine: oral, IM, IV
3. Famotidine: oral, IV
4. Nizatidine: oral

Front 16

Histamine H2-Receptor Antagonists (H2As)
i)general administration guidlenines

Back 16

Histamine H2-Receptor Antagonists (H2As)
i)general administration guidelines:
1. usual duration of therapy for active DU: 4-8 weeks; for benign GU: 6-8 weeks; symptoms may subside within 1-2 weeks of starting therapy, but this does not mean the ulcer has healed
2. a single bedtime dose is very effective
3. when treating gastric acid hypersecretory conditions such as ZES, adjust dosage as needed and continue as long as clinically indicated.
4. with moderate to severe renal function impairment or severe liver disease: dosage reduction (or less frequent administration) recommended.

Front 17

Sucralfate (Carafate)
a)mechanism of action

Back 17

Sucralfate (Carafate)
a)mechanism of action: binds to the ulcer site (local action) forming a coating which protects the ulcer site from acid. Adsorbs bile salts and pepsin thereby inhibiting their local destructive action on the mucosa.

Front 18

Sucralfate (Carafate)
b)pharmacokinetics

Back 18

Sucralfate (Carafate)
b)pharmacokinetics:
1. absorption: minimal
2. elimination: primarily FECAL

Front 19

Sucralfate (Carafate)
c)clinical indication

Back 19

Sucralfate (Carafate)
c)clinical indication: short-term treatment of active DU; maintenance therapy for DU

Front 20

Sucralfate (Carafate)
d)adverse effects

Back 20

Sucralfate (Carafate)
d)adverse effects:
1. few systemic adverse effects
2. GI: constipation; dry mouth; metallic taste; nausea; stomach cramps/pain
3. allergic: skin rash; hives; pruritis
4. hypophosphatemia
5. increased serum aluminum levels with compromised renal function

Front 21

Sucralfate (Carafate)
e)cautions and considerations

Back 21

Sucralfate (Carafate)
e)cautions and considerations: RENAL FAILURE- with long-term use, aluminum absorption may cause aluminum toxicity

Front 22

Sucralfate (Carafate)
f)drug interactions

Back 22

Sucralfate (Carafate)
f)drug interactions:
1. antacids: may interefere with binding of sucralfate to mucosa
2. digoxin; phenytoin; theophylline; quinidine; warfarin; oral tetracyclines; ciprofloxacin, norfloxacin: decreased absorption of these drugs- separate administration times of 2 hrs.
3. vitamin A, D, E, K: decreased absorption; vitamin requirements may be increased
4. levothyroxine: decreased absorption- separate administration times by 8 hours or d/c sucralfate

Front 23

Sucralfate (Carafate)
g)dosage and administration

Back 23

Sucralfate (Carafate)
g)dosage and administration:
1. adult/adolescent: 1 g QID (active ulcer); 1 g BID (maintenance)
2. pediatric dose not established

Front 24

Sucralfate (Carafate)
h)general administration guidelines

Back 24

Sucralfate (Carafate)
h)general administration guidelines:
1. usual duration of therapy: 4-8 weeks
2. take with water on an empty stomach (1h before meals and at bedtime)
3. antacids can be adminstered 1/2 hr before/after sucralfate
4. suspension for pts unable to take tablets

Front 25

Misoprostol (Cytotec)
a)mechanism of action

Back 25

Misoprostol (Cytotec)
a)mechanism of action:
1. mucosal defense effect- increases gastric mucus production and mucosal bicarbonate secretion
2. antisecretory effect- inhibits gastric acid secretion

Front 26

Misoprostol (Cytotec)
b)pharmacokinetics

Back 26

Misoprostol (Cytotec)
b)pharmacokinetics: elimination- primarily RENAL

Front 27

Misoprostol (Cytotec)
c)clinical indication

Back 27

Misoprostol (Cytotec)
c)clincal indication: prevention of NSAID and aspirin-induced GU in patients at high risk of developing GU or complications thereof.

Front 28

Misoprostol (Cytotec)
d)adverse effects

Back 28

Misoprostol (Cytotec)
d)adverse effects:
1. GI: diarrhea and mild abdominal/stomach cramping (dose-related;self-limiting, usually resolves after 8 days); constipation; flatulation; nausea; vomiting
2. CNS: headache

Front 29

Misoprostol (Cytotec)
e)cautions and considerations

Back 29

Misoprostol (Cytotec)
e)cautions and considerations:
1. contraindicated during PREGNANCY; risk of miscarraige via uterine stimulation
2. breast-feeding: NOT recommended due to possibility of significant diarrhea in nursing infant

Front 30

Misoprostol (Cytotec)
f)drug interactions

Back 30

Misoprostol (Cytotec)
f)drug interactions: magnesium-containing antacids- may aggravate misoprostol-induced diarrhea

Front 31

Misoprostol (Cytotec)
g)dosage and administration

Back 31

Misoprostol (Cytotec)
g)dosage and administration:
1. adults: 200mcg (0.2mg) QID or 400mcg (0.4mg) BID
2. pediatric and adolescent dose not established

Front 32

Misoprostol (Cytotec)
h)general administration guidelines

Back 32

Misoprostol (Cytotec)
h)general administration guidelines:
1. take WITH or AFTER meals and at bedtime
2. intitiate misoprostol therapy when NSAID therapy started
3. renal impairment: dosage reduction NOT usually required

Front 33

Omeprazole (Prilosec)
a)mechanism of action

Back 33

Omeprazole (Prilosec)
a)mechanism of action: IRREVERSIBLY inhibits the H+/K+ ATPase enzyme system (the acid/proton pump of the gastric mucosa) of the parietal cells, thereby profoundly inhibiting gastric acid secretion

Front 34

Omeprazole (Prilosec)
b)pharmacokinetics

Back 34

Omeprazole (Prilosec)
b)pharmacokinetics:
1. metabolism: hepatic (first pass metabolism)
2. elimination: primarily RENAL

Front 35

Omeprazole (Prilosec)
c)clinical indications (FDA-approved)

Back 35

Omeprazole (Prilosec)
c)clinical indications (FDA-approved):
1. short-term treatment of active DU and GU
2. treatment of gastric acid hypersecretory conditions such as ZES
3. erosive esophagitis
4. GERD poorly responsive to other treatment

Front 36

Omeprazole (Prilosec)
d)adverse effects

Back 36

Omeprazole (Prilosec)
d)adverse effects:
1. GI: n/v/d, abdominal pain, constipation
2. CNS: headache, dizziness, unusual drowsiness or tiredness
3. allergic: skin rash; pruritis
4. hematologic: anemia, leukocytosis, neutropenia, thrombocytopenia
5. hypoglycemia: in diabetic patients

Front 37

Omeprazole (Prilosec)
e)cautions and considerations

Back 37

Omeprazole (Prilosec)
e)cautions and considerations:
1. breast-feeding: may be excreted in breast milk
2. pediatrics/geriatrics-lack of info
3. chronic hepatic disease: may require dosage reduction due to decreased elimination

Front 38

Omeprazole (Prilosec)
f)drug interactions

Back 38

Omeprazole (Prilosec)
f)drug interactions:
1. ampicillin; iron salts;ketoconazole: decreased absorption of these medications due to increased gastric PH
2. phenytoin, diazepam, warfarin: omeprazole INHIBITS CYTOCHROME P450 ENZYMES in liver; therefore, concurrent use may caused decreased hepatic metabolism, delayed elimination and increased blood concentrations of these drugs
3. bone marrow depressants

Front 39

Omeprazole (Prilosec)
g)dosage and administration

Back 39

Omeprazole (Prilosec)
g)dosage and administration
*for DU, GU, and ZES
*oral therapy
*pediatric dose not established

Front 40

Omeprazole (Prilosec)
h)general administration guidelines

Back 40

Omeprazole (Prilosec)
h)general administration guidelines:
1. take BEFORE a meal, preferably in the morning
2. can be taken with antacids for relief of pain
3. swallow capsule WHOLE
4. geriatric patients: daily dose should not exceed 20mg
5. renal impairment of hepatic dysfunction: dosage adjustment not required.

Front 41

Lanzoprazole (Prevacid)
a)mechanism of action

Back 41

Lanzoprazole (Prevacid)
a)mechanism of action: irreversibly inhibits the H+/K+ ATPase enzyme system (the acid/proton pump) of the PARIETAL CELL, thereby profoundly inhibiting gastric acid secretion

Front 42

Lanzoprazole (Prevacid)
b)pharmacokinetics

Back 42

Lanzoprazole (Prevacid)
b)pharmacokinetics:
1. metabolism: hepatic
2. elimination: BILIARY and RENAL

Front 43

Lanzoprazole (Prevacid)
c)clinical indications (FDA-approved)

Back 43

Lanzoprazole (Prevacid)
c)clinical indications (FDA-approved):
1. short-term treatment of active DU
2. short-term treatment of erosive esophagitis
3. gastric acid hypersecretory conditions such as ZES

Front 44

Lanzoprazole (Prevacid)
d)adverse effects

Back 44

Lanzoprazole (Prevacid)
d)adverse effects:
1. GI: n/d, abdominal pain
2. CNS: headache, dizziness
3. allergic: skin rash, pruritis

Front 45

Lanzoprazole (Prevacid)
e)drug interactions

Back 45

Lanzoprazole (Prevacid)
e)drug interactions:
1. ketoconazole, ampicillin, iron salts, digoxin: decreased absorption of these drugs due to increased gastric PH
2. theophylline: decreased metabolism, delayed elimination and increased serum theophylline levels since LANSOPRAZOLE INHIBTS CYTOCHROME P45O ENZYMES

Front 46

Lanzoprazole (Prevacid)
f)dosage and administration

Back 46

Lanzoprazole (Prevacid)
f)dosage and administration:
1. adult dose:
*for DU (4 wks)
*for ZES

Front 47

Lanzoprazole (Prevacid)
g)general administration guidelines

Back 47

Lanzoprazole (Prevacid)
g)general administration guidelines:
1. take BEFORE eating
2. swallow capsule WHOLE
3. severe hepatic disease- dosage reduction

Front 48

PHARMACOTHERAPY TO ERADICATE HELICOBACTER PYLORI INFECTION

Back 48

A. FDA-approved regimens:
1. Clarithromycin and Omeprazole
2. Clarithromycin and Tritec (ranitidine bismuth citrate)