Gi--Upper Gi Pharmacology

Front 1

How to PPI's get to the parietal cells?

Back 1

They are absorbed into the intestines and move directly to the site of action

Front 2

True/False: PPI's block both active and inactive pumps.

Back 2

FALSE

Front 3

When should PPI's be administered? Why is this important? How long do they take to have an effect and how long does their effect last?

Back 3

An hour before food is consumed--this is because the pumps are turned on by eating..maximal effect is attained by taking 1 hr before
Effect lasts up to 24 hours because new pumps must be made and it may take up to 3 days to take effect because it only affects active pumps

Front 4

What interaction is a concern with PPI's? Therefore?

Back 4

Omeprazole inhibits the metabolism of clopidigrel to its active form and the increase in gastric pH might reduce the absorption of clopidigrel
If you have a patient with a high risk for GI bleed--these are high risk patients for whom you would use something OTHER THAN OMEPRAZOLE LIKE ESOMEPRAZOLE OR PANTOPRAZOLE
For other patients--maybe use an H2 receptor antagonist or antacid instead of the PPI

Front 5

What are some examples of H2 antagonists?

Back 5

Cimetidine, ranitidine, famotidine, nizatidine
Tagament, Zantac, Pepcid, and Axid

Front 6

How are H2 antagonists excreted?

Back 6

Renal excreted so you have to adjust for renal patients

Front 7

What interactions are of concern with cimetidine? Which drug has fewer relative interactions?

Back 7

Warfarin and amniodarone
Will increase the amounts of both
Ranitidine has fewer reactions and Nizatidine only inhibits CYP3A4 weakly
Famotidine is the BEST with the LEAST interactions

Front 8

Which H2 antagonist is known to be the safest with respect to drug interactions?

Back 8

Famotidine--it has no effect on the CYP450

Front 9

What is misoprostol's(cytotec) mechanism of action? What is it therefore used for?

Back 9

Prostaglandin analogue--bind to receptor on parietal cells to stimulate Gi pathway and decrease cAMP which decreases gastric acid secretion
Prevent gastric injury by stimulation of mucin and bicarb secretion and INCREASED MUCOSAL BLOOD FLOW

Front 10

What are the two mechanisms for NSAID toxicity?

Back 10

The are absorbed across the gastric mucosa due to not being ionized at the pH found in the stomach
COX-1 is expressed in most tissues including the GI mucosa and NSAID's cause reversible COX-1 inhibition and this decreases PG activity leading to GI mucosal damage

Front 11

How do 5-HT3 receptor antagonists work?

Back 11

Blocks the serotonin 5HT3 receptors that are found centrally in the chemoreceptor trigger zone and peripherally at vagal nerve terminals in the intestines
They are used to treat chemo and post-op related vomiting

Front 12

What is metoclopramide?

Back 12

Dopamine receptor antagonist that also blocks serotonin receptors in the chemoreceptor trigger zone of the CNS
It is useful with nausea and vomiting associated with decreased gastric motility
Increases lower esophageal sphincter tone, aids gastric emptying

Front 13

True/False: Fewer side effects are noted with meclizine.

Back 13

TRUE--this antihistamine does not cross the blood brain barrier and so its ASE's are less

Front 14

Where are aminosalicylates first absorbed?

Back 14

In the small intestine and than it is carried in the bile to the colon where it is metabolized by bacteria into the active form

Front 15

What prevents the sulfasalazine from being absorbed in the stomach?

Back 15

The azo linkage

Front 16

What are the two groups of aminosalicylates?

Back 16

Prodrugs and coated drugs

Front 17

What are some ASE's of aminosalicylates?

Back 17

Antacids, H2RA's, and PPI's

Front 18

How should corticosteroids be administered for GI diseases?

Back 18

Taper to lowest effective dose--longer taper than other therapies

Front 19

When should hydrocortisone based products be used in the GI system?

Back 19

Distal disease/colorectal problems

Front 20

What is a good drug to use for ileal disease?

Back 20

Budesonide

Front 21

Why should 6-TG levels be checked?

Back 21

For thiopurine metabolism--high levels of 6TG will cause bone marrow suppression

Front 22

What are some major drug interactions for thiopurines?

Back 22

allopurinol(inhibits xanthine oxidase)

Front 23

What are some ASE's associated with Natalizumab?

Back 23

risk of progressive multifocal leukoencephalopathy and rarely fatal demyelinating disease of the CNS

Front 24

What are some problematic ASE's of methotrexate?

Back 24

Leukopenia, renal failure, SJS, pharyngitis, HTN

Front 25

What are some drug interactions of methotrexate?

Back 25

Bactrim or drugs interfering with folate metabolism
Nephrotoxic drugs(NSAID's)
Myelosuppressives

Front 26

What is special about the structure of oral vancomycin?

Back 26

It is not absorbed systemically and can therefore selectively battle against C. diff

Front 27

What is the first line therapy for non-severe C. diff? Severe?

Back 27

Flagil
Oral vancomycin

Front 28

PPI ASE's

Back 28

Headache and B12 deficiency
Hip factures
C. diff because altering pH

Front 29

How can tolerance develop with H2 blockers?

Back 29

Effect of secondary hypergastrinemia to stimulate histamine release from ECL cells via alternative pathways

Front 30

True/False: PPI's are technically prodrugs

Back 30

TRUE--designed to get past gastric lumen and be absorbed in the SI

Front 31

True/False: PPI bioavailability is increased by food in the stomach

Back 31

FALSE--it is decreased by 50% so administer 1 hr before eating

Front 32

True/False: H2 receptor antagonists work like PPI's in that they are irreversible

Back 32

FALSE

Front 33

As a drug class, what drugs interactions are generally seen with H2 antagonists?

Back 33

Altering the pH of the stomach alters the absorption of drugs that require a low pH to become activated

Front 34

What are the three acid neutralizing agents?

Back 34

Sodium bicarb, calcium carbonate, and magnesium hydroxide

Front 35

Sodium bicarb

Back 35

Antacid that isn't used much because of its alkali and sodium load risk for heart/renal failure patients and its affect on systemic acid-base balance

Front 36

Calcium carbonate

Back 36

Antacid that may induce more acid rebound secretion and so requires more frequent administration--CO2 may cause gas

Front 37

Magnesium/Aluminum Hydroxide

Back 37

Antacid--use CAUTION with renal insufficiency patients
Poorly absorbed so extended action

Front 38

Antacids cause ________ absorption of weakly acidic drugs.

Back 38

Antacids cause decreased absorption of weakly acidic drugs and vice versa for weakly basic dugs

Front 39

What are antacids notorious for binding and preventing effectivity?

Back 39

TETRACYCLINES AND FLOUROQUINOLONES--give antacids separate from antibiotics

Front 40

Misoprostol ASE's and Interactions

Back 40

ASE's--diarrhea, abdominal pain
Interactions--should not be given with anything that causes uterine contraction DON'T GIVE TO PREGNANT WOMEN CAUSE IT CAUSES ABORTION

Front 41

What drug should never be given to pregnant women?

Back 41

Misoprostol

Front 42

Sucralfate MOA

Back 42

Reacts with HCl in the stomach to mach an acid buffer paste that adheres to active ulcers

Front 43

Sucralfate ASE's

Back 43

Constipation and aluminum absorption
Hypophosphatemia

Front 44

Sucralfate Interactions

Back 44

ALUMINUM--binds to other drugs so give separate
Also aluminum can cause severe renal impairment

Front 45

True/False: Selective COX-2 inhibitors eliminate ulcer risk

Back 45

FALSE--try to use selectives and non-selectives with increased Cox2 effect but they don't eliminate risk entirely

Front 46

What is standard 1st line therapy for H. pylori infection?

Back 46

A PPI AND Clarithromycin and amoxicillin OR metronidazole

Front 47

Onandsetron, Granisetron, Palonosetron, and Dolasetron are all what?

Back 47

5-HT3 receptor antagonists

Front 48

What are some ASE's for 5-HT3 receptor antagonists?

Back 48

Heacache, constripation, and QT PROLONGATION

Front 49

Who get metoclopramide?

Back 49

Patients with gastric emptying issues like diabetics

Front 50

Chronic use of metoclopramide has been associated with what?

Back 50

tardive dyskinesia

Front 51

Antidopaminergics: Phenotheazines

Back 51

Useful in patients with nausea and vomiting
Can induce sedation--limits their use
SEVERE TISSUE INJURY AND GANGRENE WITH IV ADMINISTRATION--give IM due to risk of tissue injury(subQ and intra-arterial have high risks)

Front 52

What are prochlorperazine and promethazine?

Back 52

Phenotheazines/Antidopaminergics/Anti-Nausea agents

Front 53

What are some common antihistamines?

Back 53

Cyclizine, hydroxyzine, diphenhydramine, and meclizine

Front 54

Antihistamine ASE's

Back 54

Urinary retention, drowsiness, dry eyes, LESS SIDE EFFECTS WITH MECLIZINE BECAUSE IT DOESN'T CROSS THE BBB

Front 55

Antihistamine MOA

Back 55

Act on vestibular afferents of the brain stem
H1 antagonists--good for motion sickness of inner ear
Work on NTS

Front 56

Scopolamine

Back 56

Prevention and treatment of motion sickness
Antagonizes ACh at anti-muscarinic receptors
As an antiemetic, scopolamine probably blocks neural pathways from the vestibular nuclei in the inner ear to the brain stem and from the reticular formation to the vomiting center

Front 57

Aprepitant and Fosaprepitant(EMENT)

Back 57

Substance P receptor antagonists(NK1 receptor antagonists)
Used to increase efficacy of standard anti-emetics with chemo
Interactions: Metabolized by CYP3A4 so may inhibit metabolism of other drugs; levels increased with clarithromycin or ritonavir

Front 58

Cannabinoids

Back 58

Dronabinol
Makes you kinda crazy
Anti-emetic