Gi - Pharm Ii

Front 1

What are the different anatomical parts of the stomach and their respective functions?

Back 1

Body - most secretions
Antrum - crushing
Pylorus - passage into duodenum

Front 2

What is a pharmacological TARGET?

Back 2

metabolic/biochemical point at which an agent exerts a clinical effect

Front 3

What are the 3 agonists that control Gastric Acid secretion?
- released from?

What is the final common pathway to acid secretion?

Back 3

- Histamine - from ECL cells
- Acetylcholine - from autonomic enteric nervous system
- Gastrin - from antral G cells

Final Point: H+/K+ ATPase (Proton Pump)

Front 4

What are the stimuli that lead to acid secretion?

Back 4

1. Food in antrum --> Gastrin releases --> stimulates parietal cells (release acid) AND ECL cells (release His)

2. Enteric Nervous System --> Muscarinic Receptors --> ACh releaseed --> stims parietal cells (acid released)

3. Somatostatin --> stimulates ECL cells (his released)

Front 5

What are the H2-receptor antagonists?
- mode of admin?

Back 5

Cimetidine (tagamet) - IV, PO
Ranitidine (zantac) - IV, PO
Famotidine (pepcid) - IV, PO
Nizatidine (axid) - IV, PO

***many available OTC

Front 6

H2-Receptor Antagonists
- MOA?
- results?

Back 6

MOA:
- bind to and inhibit the H2 receptors on the basolateral membrane of the parietal cell --> lowers acid production
- (there are still other mechs of acid production but this signif lowers it)

***90% reduction in basal and food-stimulated secretion of gastric acid after single dose

Front 7

H2-receptor antagonists
- pharmacokinetics

Back 7

- rapidly absorbed
- little liver metab
- renally excreted (dose reduction in kidney dysfunction)
-**Cimetidine = CYP450

Front 8

What are the clinical applications of H2-receptor antagonists?

Back 8

- promote healing of duodenal and gastric ulcers
- prevent ulcer recurrence
- suppress nocturnal acid secretion (***most important determinant of duodenal ulcer healing rate)

Front 9

What is the main drawback to H2-receptor antagonists?

Back 9

TOXICITY - rate of adverse reactions is 3% (HIGH!)

AEs:
- confusional states (mostly elderly on cimetidine)
- gynecomastia (reversible - cimet causes elevation in PRL)
- headache (ranit, famot)

Front 10

What can/cannot H2-receptor antags be combined with?

Back 10

- combining with antacids has no value
- combining with PPIs reduces effectiveness of PPIs

Front 11

Refractory Disease with H2-receptor inhibitors
- frequency?
- usually when....?
- tx?

Back 11

- 20% fail to heal ulcers after 4 wks
- often when have Z-E
- tx: use higher dose, use longer tx, or switch to PPI

Front 12

PPIs
- names?

Back 12

- omeprazole (prilosec)
- lansoprazole (prevacid)
- rabeprazole (aciphex)
- pantoprazole (protonix)
- esomeprazole (nexium)

Front 13

PPIs
- MOA?
- when should they be administered?

Back 13

= PRODRUGS --> acidic environment activates them
... best admin'd before meal so food stimulates acid production by parietal cells
(thus, H2-r antags may reduce efficacy)
- IRREVERSIBLE inhibition of gastric-parietal cell proton pump
... NO ACID SECRETION

Front 14

PPIs
- pharmacokinetics?

Back 14

- rapidly absorbed
- high protein bound
- extensive liver metab
- excreted by kidneys
****NOT for pts with kidney OR liver failure
- CYP3A4, CYP2C19

Front 15

PPIs
- results?

Back 15

**Single daily dose can inhibit 100% acid secretion!

Front 16

PPIs
- clinical applications?

Back 16

- short-term (4-8 wks) tx of gastric or duod ulcers
- better than H2-r inhibs and misoprostol for tx of NSAID ulcers
- treatment of GERD
- ***DOC for ZE, MEN, systemic mastocytosis
- Part of combo tx for H.Pylori - induced ulcer

Front 17

What is the DOC for ZE?

Back 17

PPI!!!

Front 18

What is the tx for an H-Pylori-induced ulcer?

Back 18

PPI + Clarithromycin + Ampicillin for 10 days

Front 19

What is Zollinger Ellison Syndrome?

Back 19

= Gastrinoma
- unmitigated production of gastric acid ---> ulcer

Front 20

What are the adverse reactions/drug interactions of PPIs?

Back 20

- CYP 450 interactions

- generally well-tolerated
- Lack of negative feedback from acid, so GASTRIN is elevated --> potential CARCINOID tumor due to stim of ECL cells (not demonstrated in humans, only rodents)
- rarely, nausea, abd pain , constipation, diarrhea

Front 21

Octeotride
- what is?
- MOA?

Back 21

= long-acting synthetic somatostatin analogue

MOA
- binds to somatostatin receptors on ECL cells --> inhibits secretion of several peptides, as well as pancreatic and gastric secretion

Front 22

Octeotride
- indications?

Back 22

- most often used in ZE patients
- portal hypertensive bleeding

Front 23

Antacids
- types?
- side-effects for each type?
- contraindication?

Back 23

- Mg(OH)2-containing (diarrhea)
- Al(OH)2-containing (constipation)
- CaCO3 (can cause "acid rebound" - stim gastrin and acid release)

*Contraindicated in renal failure patients!

Front 24

Antacids
- MOA?
- indications?

Back 24

MOA: neutralize gastric acid

Indications:
- used widely for dyspeptic sx
- may hasten ulcer healing (mech unclear)

Front 25

Sucralfate
- what is?
- MOA?
- Indications?
- adverse effects?

Back 25

= metal salt of sulfated sucrose - contains Al(OH)2

MOA
- acid causes Al(OH)2 to dissociate from sulfate anions, which then bind to positively charged proteins from damaged tissue
--> adheres to ulcer and creates protective barrier

Indicated for ulcer tx

Little adverse effects - may bind to other oral meds

Front 26

What is the best tx for GERD?
- acute?
- maintenance?

Back 26

Acute:
- PPIs most effective (over H2s)
- Healing rate 80-90% in 4-8 wks
- Empirical trial for up to 12 wks is approp IF pt has no "alarm sx" - weight loss, dysphagia, advanced age, etc (which are NOT typical of just reflux)

Maintenance:
- **high relapse rate of GERD after acute tx
- Give PPIs

Front 27

What is appropriate tx for Peptic Ulcer Disease (PUD)?

Back 27

Uncomplicated:
- PPIs

Bleeding
- IV PPIs with endoscopy

NSAID-ulcers:
- PPIs
- cessation of NSAID or selective COX-2 inhibitor

Front 28

Stress-related ulcers
- when do these usually occur?
- how?
- tx?

Back 28

- occur in burn, head trauma victims
- involves acid AND mucosal ischemia

Tx:
- PPIs or H2s
- sucralfate may reduce risk of nosocomial pneumonia

Front 29

What is the treatment for ulcer-like sx in patients who do not have an overt ulcer?

Back 29

NOT been proven to be efficacious!

Front 30

What are the reasons for non-healing ulcers?

Back 30

- Non-compliance with meds
- H. Pylori inf
- NSAIDs
- Tobacco
- Inadequate duration of tx
- Hypersecretory state (ZE Syndrome)
- Non-peptic ulcer related disease (maligncancy)

Front 31

Gastric Motility
- what is the body's control over this?
- what is the principle immediate mediator of GI smooth muscle contraction?

Back 31

- Enteric Nervous System
- Central Nervous System (autonomic, somatic)
- Humoral pathways

*ACh - released from primary motor neurons of myenteric plexus (ENS) = primary mediator of GI sm muscle contractions

Front 32

What are the 2 major patterns of GI motility?
- time length of each?

Back 32

1. Migrating Motor Complex (MMC)
- fasting state
- "sweeps" bowel clean of its contents
- 2-4 hours

2. High Frequency Contractions
- fed state
- mixing and propulsion of bowel contents
- 12-15 per minute

Front 33

How do Cholinergic Agents work on GI motility?
- names?

Back 33

Carbechol and Bethanechol

MOA:
- target muscarinic receptors --> activate to increase intracellular Ca --> increase motility

Front 34

Dopamine-receptor antagonists
- Names?
- MOA?

Back 34

- Metaclopromide
- Domperidone (not US available)

MOA
- inhibit dopamine
--> STIMULATES intest motility

Front 35

Dopamine
- MOA?

Back 35

- INHIBITS intest motility via suppressing ACh release from ENS

Front 36

Metaclopromide
- what is/MOA?

Back 36

= dopamine antagonist
AND
= serotonin-receptor modulator
- antagonizes 5-HT3 --> increases motility
- stimulates 5-HT4 --> increases motility

Front 37

Metaclopromide
- pharmacokinetics

Back 37

- rapidly absorbed
- short t1/2 (2-4 hours) - quick effects!

- Enters CNS!!

Front 38

What are the serotonin receptors in the GI tract?
- locations?
- functions?

Back 38

Receptors present in ECL cells and ENS

5-HT3 - post-synaptic enteric neurons and afferent sensory fibers
- INHIBITORY motility

5-HT4
- EXCITATORY response on motility

Front 39

Metaclopromide
- clinical uses?

Back 39

- relief to patients with gastric motor failure (e.g., diabetic gastroparesis)
- decreases heartburn in GERD pts
- anti-emetic (e.g., use during chemo)

Front 40

Metaclopromide
- adverse effects?

Back 40

- somnolence
- nervousness
- dystonia
- Parkinsonism; tardive dyskonesia in elderly
- galactorrhea and menstrual disorders (PRL increase)

Front 41

Tegeserod Maleate
- what is?
- MOA?
- clinical use?

Back 41

- 5HT4 partial agonist --> increases motility

- used in constipation-predominant IBS (usually women)

Front 42

Erythromycin
- what is?
- GI effect?/MOA?
- use?
- problem?

Back 42

= macrolide antibiotic

MOA:
- Motilin agonist --> stimulates motility in stomach

- used in diabetic gastroparesis and intestinal psuedo-obstruction

- problem: tachyphylaxis

Front 43

What are/where are MOTILIN Receptors?

Back 43

- on smooth muscle cells
- when stimulated, induce/amplify MMC

Front 44

Laxatives
- MOA?
- important one?

Back 44

MOA
- increase mucosal secretion
- stimulate colonic propulsive activity

*Bisocodyl

Front 45

Opiates
- MOA?

Back 45

- antidiarrheals
- increase phasic segmenting activity
- cause presynaptic and postynaptic inhibition

Front 46

Irritable Bowel Syndrome (IBS)
- definition
- diagnosis

Back 46

= abnormal bowel patterns without an identifiable anatomic, structural, motor, or infectious etiology
.... must rule out all of these and be left with just sx

DIAGNOSIS: Rome Criteria
- absence of anatomic, motor, neuro pathology
- at least 3 months of continuous abd pain - relieved by defecation or associated with change in stool freq/consistency
- 2+ of the following (at least 20% of the time):
--- altered stool freq
--- altered stool form
--- tenesmus
--- mucous in stool
--- bloating/distension

Front 47

IBS - tx??

Back 47

Constipation-Predom Disease
- bulking agents
- prokinetics
- serotonin receptor modulators (tegaserod maleate for women)

Diarrhea-Predom Disease
- antispasmodicts/anticholinergics
- antidepressants

Front 48

Pancreas
- what is the main anatomical unit of secretion?

Back 48

Acinus - made up of acinar cells
- secrete digestive enzymes into gastric lumen
- secrete HCO3

Front 49

What is the physiology behind Pancreatic gastric secretion?

Back 49

1. Thought/smell/sight of food --> VAGUS NERVE --> releases ACh --> stims pancreatic acinar cells --> secretes enzymes and HCO3

2. Food --> fat/prot --> stims acid secretion in gut --> stims S Cells in duod wall --> secrete Secretin --> stims Acinar Cells to release enzs and HCO3

3. Food --> fat/prot/acid --> stim I Cells in distal stomach --> release CCK --> stims Acinar Cells to release enzs and HCO3

Front 50

Pancreatic Insufficiency
- causes?
- main sx? why?

Back 50

Causes: atrophy, scarring, calcification (ex: chronic inflammation due to CF)

- main sx: steatorrhea

- no digestive enzs released --> unable to break down fats in food --> FAs irritate gut lumen --> gut secretes water, etc. -------> steatorrhea

Front 51

At what pH are pancreatic enzymes deactivated?

Back 51

pH < 4

Front 52

What are the 2 most common causes of pancreatitis in US?

Back 52

1. alcoholism
2. gall stones

Front 53

Pancreatic Insufficiency
- tx??
- dosing?
- drug interactions?
- adverse effects?

Back 53

Give enzymes:
- Pancreatin
- Pancrelipase

Dosing:
- give with MEALS!
- titrate dose to therapeutic effect

**Cimetidine and other drugs that increase gastric pH (suppress acid) enhance effectiveness

AE:
- uric acid renal stones (due to the enzs' high purine content)
- lactose-containing, so poorly tolerated by lactards

Front 54

Inflammatory Bowel Disease
- major diseases?
- etiology?
- pathogenesis?

Back 54

- Major: Crohn's and UC
- Etiology: unknown (autoimmune?)
- Path (postulate):
-- series of events initiated by a putative antigen in a susceptible individual
-- host response is immune activation mediated by cytokines, O radicals, metabolites of arachidonic acid (leukotriene B4)

Front 55

IBD - what are the goals of the pharmaceutical tx?

Back 55

- symptom relief
- induction of remission
- prevention of relapsse
- healing of fistulae
- avoidance of emergency situations
(**No one agent addresses all of these needs)

Front 56

5-aminosalicylates
- Indication?
- MOA?

Back 56

Indication: DOC for mild-to-moderate IBD

MOA:
- target mult sites in arachidonic acid pathway - critical in pathogenesis of inflammation
---> inhibit leukotrienes!!! (most important)
- possible free radical scavenger

Front 57

What is FIRST LINE therapy for mild or moderate IBD?

What is FIRST LINE therapy for severe IBD?

Back 57

5-aminosalicylates (mild-moderate)

Glucocorticoids (severe)

Front 58

5-ASA
- mode of admin?

Back 58

cannot be taken orally in a sufficient dosage to produce a useful effect in colon without excessive toxicity

Front 59

Sulfasalazine
- what is?
- indication?

Back 59

= 5-ASA + sulfapyridine linked by azo biond
...... azo link broken by bacterial flora in distal ileum and colon --> releases 5-ASA

Indication: mild or moderaltely active UC
***Must be used for UC in distal ileum and colon - NOT small bowel disease (bc no bacteria here)
- more useful in maintaining remission in UC than achieving it

Front 60

Sulfasalazine
- AE?

Back 60

*Most toxicities attributed to sulfa moeity (sulfapyradine)
- malaise
- nausea
- abd discomfort
- impaired folic acid absorption (must co-administer folic acid!)
- reversible decrease in sperm count
- rare - stevens johnson syndrome
- rare - bone marrow suppression

Front 61

Mesalamine
- what is?
- mode of admin?

Back 61

- coated 5-ASA
- admin:
--- oral - allows slow release as travels down bowel
--- topical - delivered as enema for tx of active distal colitis

Front 62

Mesalamine
- forms/names?
- where effective?

Back 62

Asacol - coated form
... releases in terminal ileum and colon

Pentasa - semipermeable membrane
... releases in jejunum through colon = SMALL BOWEL UC!!!

Front 63

Olsalazine
- what is?
- where effectve?

Back 63

- two 5-ASAs linked by diazo bond
- bond broken by bacteria in COLON

Front 64

What is the only drug useful for small bowel UC?

Back 64

Pentasa (releases jejunum through colon)

Front 65

Probiotics
- used for what?
- MOA?

Back 65

- used for UC (more than Crohn's)
- introduces normal flora into GIT
- maintains remission
- decreases incidence of pouchitis (inflamm of surgically constructed pouch following bowel resection)

Front 66

Glucocorticoids
- what is their indication in GI disease?
- results?

Back 66

- First line tx for SEVERE IBD
- Causes remission in 90% cases

Front 67

What is SEVERE IBD?

Back 67

accompanied by abd pain, fever, leukocytosis, rectal bleeding, weight loss, need for hospitalization

Front 68

What are topical glucocorticoids used for?

Back 68

- effective for patients with distal colitis
- given as enema
- systemic effects might be seen if used over long pd of time

Front 69

What is Budesonide?
- indication?

Back 69

= anti-inflamm oral glucocorticoid
- maintenance use in Crohn's disease
- prolongs time to relapse

Front 70

Cytotoxic Agents
- what are?
- indication?
- main drugs?

Back 70

= anti-metabolites
- second-line tx for severe (or steroid-resistent/dependent) IBD patients

- azathioprine (prodrug)
- 6-mercaptopurine,
- metabolite = 6-thioguanine

Front 71

Cytotoxic Agents used for IBD
- adverse effects?

Back 71

- bone marrow suppression
- pancreatitis
- drug-induced malignancy (small risk)

Front 72

Cyclosporine
- what is?
- indication?
- MOA?

Back 72

= immunosuppressant
- indicated for SEVERE UC not responding to seroids

MOA
- calcineurin inhibitor (calcineurin recruits lymphocytes and causes inflammation)
- suppresses proinflamm transcription factors

Front 73

Cyclosporine
- adverse effects?

Back 73

**Short-term only!!
Use limited by toxcity:
- hypertension
- nephrotoxicity

Front 74

Infliximab
- what is/MOA?
- indication?
- results?
- AEs?
- problem???

Back 74

- monoclonal Ab that binds to TNF (TNF is a critical cytokine in pathogenesis of inflamm- increased in mucosa of Crohn's patients)

- indicated for Crohn's Disease

- 1 infusion induces remission lasting 2-6 wks
- significant reduction in fistulae

AE: infrequent

EXPENSIVE!! 1 infusion = $2000

Front 75

Bile
- made of?
- what determines stone-forming potential?

Back 75

- made of 3 lipids: cholesterol, bile salts, phospholipids

**Relative concentrations of lipids in bile determine stone-forming potential (high cholesterol --> higher precipitation and stones)

Front 76

Bile Salts
- where/how made?
- what are?

Back 76

- made in liver from cholesterol

- Primary Salts: cholic acid, chenodeoxycholic acid
- Secondary Salts: lithocholic acid, deoxycholic acid (result from action of intestinal bacteria on primary salts)

Front 77

Bile Salt Therapy
- drugs?
- uses?
- AEs?

Back 77

Chenodiol - oral therapy to dissolve gallstones
- AE = diarrhea

Ursodiol - epimer of chenodiol - for gallstone dissolution and primary biliary cirrhosis
- few toxicities