Antiemetics/IBD Tx

Question 1

5HT3 antagonists

Answer 1

-setrons

Dolasetron, Granisetron, Ondansetron, Palonosetron

Question 2

-setrons MOA and use

Answer 2

5HT3 antagonists
block peripheral 5HT3 receptors on intestinal vagal afferents
CNS actions at both CTZ and vomiting center

Use: primary agents for prevention and tx of chemo-induced n/v
Restricted to vomiting involving significant vagal stimulation (no good for motion sickness, inner ear)
off label for diarrhea predominant IBS

Question 3

setrons adverse effects

Answer 3

mostly well tolerated
common SE are transient: mild headache, dizziness, constipation
Prolong QT interval- monitor

Question 4

D2 agonists names:

Answer 4

Droperidol, metoclopramide

Phenothiazines: prochlorperazine, prometazine

Question 5

D2 agonist MOA and use:

Answer 5

MOA: blockade of D2 and muscarinic receptors in CTZ; could counter reverse peristalsis
results in sedation via antihistaminergic properties

Use: vomiting d/t uremia, radiatino sickness, chemotherapy, infection, hyperemesis gravidarum, labor

Question 6

D2 agonist Side effects:

Answer 6

somnolence, nervousness, agitation, anxiety
IRREVERSIBLE: dystonia, parkinsonism, tardive dyskinesia
Increased prolactin release: importence, menstrual disorders, galactorrhea

Question 7

Antimuscarinic (scopalamine) MOA and use

Answer 7

MOA: blocks muscarinic and dopaminergic receptors in the cerebellum; rapid and full distribution in CNS
Use: Motion sickness

Question 8

Antimuscarinic Side effects:

Answer 8

scopalamine

Side effects: dry mouth, dry eyes, blurred vision, constipation, increased GERD, urinary retention, feelings of restlessness, cognitive problems-memory, and confusion, somnolence

Question 9

Antihistamine (1st gen) names:

Answer 9

Dimenhydrinate, diphenhydramine, meclizine

Question 10

Antihistamine MOA and use:

Answer 10

MOA: blockade of H1 and muscarinic receptors in cerebellum (older antihistamines are better emetics- may be d/t muscarinic involvement)

Use: motion sickness, hyperemesis gravidarum (use with caution)

Question 11

Antihistamine side effects:

Answer 11

somnolence, anticholinergic side effects (dry mouth, confusion, urinary retention, etc.)

Question 12

NK1 antagonist name(s)

Answer 12

aprepitant (oral form)

fosaprepitant (IV form)

Question 13

NK1 antagonist MOA and use

Answer 13

Blockade of neurokinin (tachykinin) receptor 1 (intrinsic agonist is substance P) in CNS and the GI tract

Use: prevention of both acute and delayed phases of chemotherapy- induced n/v
Typically given with a 5HT3 antagonist and dexamethasone

Question 14

NK1 side effects:

Answer 14

generally well tolerated
fatigue, dizziness, diarrhea
drug-drug interactions (metabolized by CYP 3A4)

Question 15

Cannabinoids names:

Answer 15

dronabinol, nabilone, medical mariijuana

Question 16

Cannabinoid MOA and use

Answer 16

MOA: activation of central cannabinoid receptors (intrinsic agonist is anandamide) in CNS

Use: cancer chemotherapy induced n/v
combo chemotherapy with phenothiazines

Question 17

Cannabinoid Side effects

Answer 17

euphoria, dysphoria, sedation, hallucinations, dry mouth, and increased appetite

rare: tachycardia, conjunctival injection, orthostatic hypotension

Question 18

corticosteroid used for n/v?

Answer 18

dexamethasone

Question 19

Corticosteroid MOA and use:

Answer 19

MOA for n/v is unclear

Use: combo use for chemo n/v, post-op n/v, increased ICP, opioid induced n/v

Question 20

IBD Anti-inflammatories:

Answer 20

Aminosalicylates:

balsalazide, mesalamine, sulfasalazine

Question 21

Aminosalicylate MOA and use:

Answer 21

MOA: all are variants of mesalamine (5-aminosalicylic acid) that is poorly absorbed from GI tract; block prostaglandin synthesis by inhibiting COX–>reduced inflammation

Balsalazide and sulfasalazine are limited until bacteria in colon break them down–> topical rather than systemic

Question 22

Aminosalicylate Side effects:

Answer 22

mostly well tolerated
Sulfasalazine has higher SE rate–dose related nausea, GI upset, headaches, arthralgias, bone marrow suppression and malaise; also hypersensitivity rxn similar to that with sulfa antibx

Question 23

Immunosuppressive IBD agents

Answer 23

corticosteroids and antimetabolites

Question 24

Corticosteroids for IBD:

Answer 24

budesonid, prednisone, prednisolone

Budesonide has local rather than systemic effect

Question 25

Antimetabolite for IBD

Answer 25

azathioprine–>6-mercaptopurine, methotrexate

Question 26

Anti-TNFalpha antibodies for IBD

Answer 26

Adalimumab, certolizumab, infliximab

Question 27

Anti-TNFalpha antibody MOA

Answer 27

dysregulation of Th1 response occurs in IBD of which TNFalpha is a key cytokine.

Infliximab and adalmumab bind the soluble and receptor-bound TNFalpha to prevent binding of the cytokine to its receptors
Certolizumab is recominant antibody that has an Fab conjugated to polyethylene glycol

Question 28

Side effects of anti-TNFalpha antibodies:

Answer 28

infection (including reactivation of latent TB)
acute infusion rxn
delayed infusion rxn
severe hepatic rxn
lymphoma risk is increased

Question 29

Anti-alpha4 subunit of integrin: MOA and use

Answer 29

Natalizumab
MOA: inhibit diapedesis
Use: MS, IBD (but is restricted use)

Question 30

Anti-alpha4 subunit Side efects

Answer 30

Stop immunosuppression and anti-TNF tx for 2 mo prior to starting this medication
acute infusion rxn
Reactivation of human polyomavirus–can result in progressive multifocal leukoencephalopathy (PML)–reason for restricted use