Pharm II: GI 2

Antiemetics (7)

- 5-HT3 Receptor Antagonists

- Neurokinin 1 Receptor Antagonists

- Corticosteroids

- Dopamine Antagonists/Antipsychiotics

- Antihistamines/Muscarinic Antagonsts

- Benzodiazepines

- Cannabinoids

5-HT3 Receptor Antagonists

- Ondansetron (Zofran)

- Dolasetron

- Granisetron

- Palonosetron

5-HT3 Receptor Antagonists MOA

- selective 5-HT3 receptor antagonists

- work on the chemoreceptor trigger zone (CTZ), vestibular system (VC), enteric vagal and spinal afferent nerves

5-HT3 Receptor Antagonists ID (4)

- acute/delayed chemotherapy induced N/V (CINV)

- post op N/V (PONV) + post radiation

- acute gastroenteritis

- hyperemesis gravidarum

5-HT3 Receptor Antagonists onset

~30min

5-HT3 Receptor Antagonists ADR (6)

- HA

- dizziness

- constipation

- QT prolongation

- Hepatic insufficiency

- Serotonin Syndrome

Neurokinin 1 Receptor Antagonists

- Aprepitant

- Rolapitant

- Netupitant

Neurokinin 1 Receptor Antagonists MOA

- central blockade of neurokinin 1 receptors

- receptors in CTZ/VC

- inhibit binding of substance-P

Neurokinin 1 Receptor Antagonists ID (2)

- Delayed CINV

- PONV

Neurokinin 1 Receptor Antagonists half life

longer; 12-180hr

Does Neurokinin 1 Receptor Antagonists cross the BBB?

Yes

Neurokinin 1 Receptor Antagonists ADR (4)

- fatigue

- dizziness

- diarrhea

- hiccups

What should you avoid Neurokinin 1 Receptor Antagonists with?

CYP3A4 drugs

Corticosteroids

Dexamethasone PO/IV

Corticosteroids MOA

- blockade of prostaglandins

- reduced serotonin release

Corticosteroids ID

Combine with 5-HT3 and NK1 antagonists for all CINV, PONV

Corticosteroids ADR (3)

- hyperglycemia

- dyspepsia

- insomnia

Antipsychotics (2)

- Olanzapine

- Phenothiazines

Olanzapine MOA

combine dopamine D2 and serotonin 5-HT3 receptor antagonist

Olanzapine ID (3)

- schizophrenia

- bipolar I/II

- CINV - refractory/MEC-HEC

Olanzapine ADR (7)

- sedation

- insomnia

- weight gain

- hyperglycemia

- motor impairment/falls

- DRESS

- NMS

Olanzapine Box Warning

Dementia - related psychosis (SI)

Phenothiazines

- Prochlorperazine maleate

- promethazine

- chlorpromazine

Prochlorperazine maleate MOA

dopamine antagonist in the chemoreceptor trigger zone (CTZ)

Prochlorperazine maleate onset/duration

40-50min; ~4hr

Prochlorperazine maleate ID (3)

- schizophrenia

- migraine N/V

- CINV

Prochlorperazine maleate ADR (4)

- EPS/TD

- hypotension

- sedation

- dizziness

Promethazine MOA

H1 receptor antagonist, less dopamine antagonist activity

Promethazine onset

- ~5min IV

- ~20min PO

Promethazine ID (3)

- breakthrough CINV

- PONV

- motion sickness

Promethazine ADR (4)

- sedation

- hypotension

- EPS

- respiratory depression

Promethazine Block Box Warning

Severe Tissue Injury (gangrene)

Promethazine C/I

pts < 2yo

Chlorpromazine black box warning

dementia related psychosis

Benzamides: Prokinetic GI motility

- Metoclopramide

- Trimethibenzamide

Benzamides MOA

- central blockade

- dopamine-D2 receptor antagonist

Benzamides ID (3)

- CINV

- gastroparesis

- GERD

Benzamides ADR (3)

- dystonia

- parkinsonism

- hepatic impairment/elevated PFT

Benzamides block box warning

Tardive dyskinesia

Benzamides: other

Lorazepam

Lorazepam MOA

GABA-A receptor agonist

Lorazepam ID

anticipatory anxiety related to CINV

Lorazepam ADR (5)

- sedation

- dizziness

- unsteady

- confusion

- amnesia

Lorazepam Block Box Wwarning

concomitant opioid use increases risk for abuse/misuse/dependence/withdrawal

Antihistamines + Muscarinic Antagonists

- diphenhydramine

- dimenhydrinate

- meclizine

- scopolamine

diphenhydramine MOA

antihistamine antagonists

diphenhydramine ID (3)

- allergies

- insomnia

- vertigo

diphenhydramine ADR (5)

- sedation/drowsiness

- constipation

- dizziness

- blurry vision

- dry mouth

dimenhydrinate MOA

antihistamine and muscarinic receptor blocker

dimenhydrinate ID (3)

- N/V

- acute vertigo

- motion sickness

dimenhydrinate ADR (2)

- sedation

- anticholinergic effects (dry mouth, constipation, blurry vision)

meclizine MOA

histamine-H1 and muscarinic-M1 receptor antagonists

meclizine ID (2)

- vertigo (BPPV)

- motion sickness (N/V)

meclizine ADR (2)

- sedation

- anticholinergic effects (HA, dizzy, dry mouth, blurry vision)

scopolamine MOA

muscarinic receptor antagonist

scopolamine ID (3)

- motion sickness

- vertigo

- PONV

scopolamine ADR (4)

- sedation

- dry mouth

- blurry vision

- withdrawal

scopolamine C/I (3)

- pregnancy (seizures)

- BH (psychosis)

Cannabinoids

Dronabinol

Dronabinol MOA

synthetic THC; cannabinoid receptor agonist

Dronabinol ID (2)

- CINV

- appetite stimulant (AIDS)

Dronabinol ADR (6)

- euphoria/paranoia

- sedation

- dizzy

- BP/HR changes

- seizures

- Schedule III: increase risk for misuse and dependence

IBS Pain/cramping tx

Antispasmodics

Antispasmodics

- dicyclomine

- hyoscayamine

- peppermint oil

dicyclomine MOA

muscarinic antagonists at parasympathetic sited of smooth muscle, secretory glands, and CNS

dicyclomine ADR

Anticholinergic effects (dry mouth, constipation, dizziness, confusion, sedation)

dicyclomine C/I (2)

- GI obstruction/bleeding

- severe ulcerative colitis

Hyoscyamine MOA

muscarinic antagonist at site in smooth muscles (+ histamine and serotonin antagonists)

Hyoscyamine ADE (5)

- anticholinergics (sedation, dry mouth, constipation, blurry vision, confusion)

- GI blockage

- decreased urine output

- changes in mood/behavior

- overheating

Peppermint Oil MOA

calcium channel blocker relaxes smooth muscles, anti-inflammatory

Peppermint Oil ADR/SE (2)

- heartburn/reflux

- avoid 2hr w/ antiacids

IBS Pain tx

Amitriptyline

Amitriptyline MOA

- tricyclic antidepressant (TCA)

- inhibition of serotonin and norepinephrine reuptake

Amitriptyline ADR (6)

- sedation

- weight gain

- N/V

- constipation

- HA

- behavior changes

IBS Diarrhea 1st line

- loperamide

- Ondansetron

IBS Diarrhea 2nd line

- Alosetron

- Eluxadoline

- Rifaximin

Alosetron MOA

potent 5-HT3 receptor antagonist

Alosetron ID (2)

- 2nd line severe IBS-D in women

- >6mo of failed prior tx + ruled out other abnormalities

Alosetron ADR (2)

- constipation

- ischemic colitis

Eluxadoline MOA

opioid receptor agonist/antagonist

Eluxadoline ID

severe IBS-D (male/female approved)

Eluxadoline ADE (2)

- acute pancreatitis

- misuse/dependence

Rifaximin MOA

nonabsorbable abx that prevents bacterial RNA syntheses + anti-inflammatory

Rifaximin ID (3)

- 2nd line IBS-D

- Traveler's diarrhea

- hepatic encephalopathy

Rifaximin ADR (4)

- nausea

- HA

- potential C.diff

- hepatic insufficiency

IBS: constipation 1st line (3)

- soluble fiber

- osmotic laxatives

- probiotics

IBS: constipation 2nd line (4)

- Lubiprostone

- Linaclotide

- Plecanatide

- Prucalopide

IBS: constipation 3rd line

Tenapanor

Tenapanor MOA

- sodium/hydrogen exchanger 3 inhibitor

- increases water into the intestines and reduces pain

Tenapanor ID (2)

- IBS-C Bloating

- CKD

Tenapanor ADR

Diarrhea

Tenapanor downside

So expensive

Maintenance Medications for Crohn Disease (5)

- 5-Aminosalicylic Acid

- Immune Modulator

- Anti-Tumor Necrosis Factor

- Anti-Integrin

- Anti-IL-12/23

Mild-Mod US tx

Maintenance 5-ASA

Moderate UC induction tx

Budesonide MMX

Mod-Severe UC induction tx

Prednisone

Mod-Severe UC if no response to induction tx (6)

- thiopurines

- anti-TNF

- IL-12/23i

- a4B7 integrin inhibitor

- JAK inhibitor

- S1P receptor modulator

Mod-Severe UC if no response to tx

Elective colectomy

Acute severe ulcerative colitis (ASUC) induction tx

IV corticosteroids

ASUC: if response to induction tx after 3-5 days; what to add (5)

- anti-TNF

- IL-12/23i

- a4B7 integrin inhibitor

- JAK inhibitor

- S1P receptor modulator