wilhelm n/v

which drugs may cause acute n/v

- chemo

- opioids

- digoxin (remember this also caused diarrhea!)

- abx

- anticholinergics (symp)

potential etiologies of acute n/v

- anything GI related (gastroenteritis, obstruction, surgery...etc)

- vestibular disorders

- metabolic (diabetic ketoacidosis, uremia)

- drugs (chemo, opioids, digoxin, abx, anticholinergics)

etiologies of chronic n/v

- obstruction (PUD, ulcer, carcinoma)

- motility disorders

- pregnancy

- neuro

stimuli: drugs, uremia, ketoacidosis [toxins that cross BBB]

mech/receptors:

CTZ: DA, 5HT3, NK1

(same as GI visceral afferents)

stimuli: obstruction, gastroparesis, visceral pain

mech/receptors:

GI visceral afferents: DA, 5HT3, NK1

(same as CTZ)

stimuli: motion sickness, vestibular inflammation [inner ear]

mech/receptors:

vestibular apparatus: muscarinic, NE, H1

stimuli: emotion, sight, smell, taste

mech/receptors:

cortical structures

-> use benzos. no direct receptor

summarize which receptors are targets for which n/v stimuli

drugs, ketoacidosis, uremia (BBB)-> DA, 5HT3, NK1

obstruction, gastroparesis, visceral pain-> DA, 5HT3, NK1

motion sickness, vestib, ear-> muscarinic, NE, H1

emotions, sight, smell-> cortical (use benzos)

fluid and electrolyte disturbances such as metabolic ______osis, _____natremia, and _______kalemia are common complications of vomiting

alkalosis

hyponatremia

hypokalemia

why would we want to use non-pharm methods for the tx of n/v in the following

pregnancy:

post operative:

motion sickness:

pregnancy: avoid teratogenic effects

post operative: avoid additive sedation

motion sickness: avoid sedation since moving

non-pharm diet for n/v tx

- frequent, small meals

- avoid spicy and fatty foods

- high protein snacks

- bland food, especially early morning

- starting prenatals at conception

other than diet, what other non-pharm tx are there for n/v

1. acupressure: P6 point in wrist (sea bands)

2. hypnosis/ psychotherapy

which phenothiazines are available for n/v?

moa?

prochlorperazine (Compazine)

promethazine (Phenergan)

chlorpromazine (Thorazine)

moa:

-blocks DA receptors in CTZ [so will work on drug-induced, toxins, BBB etc)

- some anticholinergic activity

what type of n/v do phenothiazines help with

blocks DA receptors so anything that affects CTZ [so will work on drug-induced, toxins, BBB etc)

phenothiazines ADEs

- sedation

- orthostatic hypotension (chlorpromazine)

- extra pyrimidal symptoms (prochlor)

- tissue necrosis and gangrene (if promethazine subQ or intra-arterially)

what can happen if promethazine is given subQ

tissue necrosis and gangrenes

what can be given to minimize EPS

diphenhydramine or benztropine (Cogentin)

what are EPS

extra pyrmidal symptoms

1. dystonia: muscle contractions

2. tardive dyskinesia: involuntary movements; cogwheel motions (might become irreversible!!)

3. akathisia: motor restlessness/ anxiety

t/f: EPS may be a side effect of phenothiazines but are always reversible

false. tardive dyskinesia (involuntary muscle movements) seen in EPS may be irreversible

which causes of n/v respond well to antihistamines/anticholinergics

issues in inner ear/ motion sickness

remember receptors: muscarinic, NE, H1

examples of antihists/anticholinergics for n/v

moa?

diphenhydramine

meclizine

scopolamine

dimenhydrinate

hydroxyzine

MOA: CNS anticholinergic activity in VC and vestibular system

-> so for motion sickness or labyrinth induced symptoms

ADEs for antihists/ anticholinergics

drowsiness, confusion, blurred vision, dry mouth, urinary retention, tachycardia

precautions/CI for antihistamines/anticholinergics

narrow angle glaucoma

urinary retention

prostatic hypertrophy

asthma

examples of butyrophenones?

moa?

droperidol, haloperidol

MOA: block DA receptors in CNS

[so will work on CTZ: drug-induced, toxins, BBB etc]

t/f: butyrophenones such as haloperidol experience less EPS than phenothiazines such as prochlorperazine

true

what black box warning is seen with droperidol

QT prolongation

-> must have ECG before use

metoclopramide

brand:

moa:

Reglan (benzamide analog)

-blocks DA receptors in CTZ

- cholinergic activity in GI

- anti-serotonin at high doses

- prokinetic in UPPER GI (not used for constipation. used for gastroparesis)

metoclopramide ADEs

EPS, sedation!!, diarrhea, edema, HTN, hyperprolactinemia (increases milk production), impotence

metoclopramide CIs

intestinal obstruction or high risk for colonic rupture (bc not only for n/v but its also a prokinetic)

domperidone

benzamide analog/ dopamine antagonist like metoclopramide BUT

-does not cross BBB= less CNS ADRs

- not available in US

- may prolong QT interval

which n/v meds prolong QT interval

- domperidone

- droperidol

- serotonin antagonists (ondansetron)

which type of n/v are cannabinoids most often used for

chemo induced (CINV)

-moa unknown

what can prolonged use of cannabinoids for n/v lead to

cyclic vomiting syndrome

-heat may alleviate symptoms

corticosteroids for n/v

examples:

moa:

dexamethasone (Decadron)

methylprednisolone (Medrol)

moa: unknown

- inhibits PG synthesis in cortex

- decreased CNS serotonin turnover

- modulation of higher cortical pathways influencing VC

corticosteroids for n/v ADEs

short term: mood change, anxiety, insomnia, increased appetite, fluid retention, hyperglycemia, GI upset

long term: osteoporosis, cataracts, skin thinning, bruising, immunosuppression

benzodiazepines for n/v

examples:

moa:

used for?

lorazepam (Ativan), alprazolam (Xanax)

moa: unknown. suppression from higher brain to emetic center. lowers anxiety, amnesia, sedation

use: emotional triggers of N/V

benzos ADEs

sedation

prolonged amnesia

hypotension

perceptual disturbances

urinary incontinence

respiratory depression (no alcohol!!!)

serotonin antagonists for n/v

examples:

moa:

use:

"setrons"= ondansetron, granisetron, dolasetron, palonosetron

moa= block 5ht3 receptors in CTZ anddd vagal visceral fibers in GI

no anti motion sickness efficacy!!

use: CINV, PONV (chemo, post op)

5ht3 antagonists ADEs

"setrons"

mild headache, diarrhea, constipation, transient elevations in LFTs, asymptomatic ECG changes

t/f: serotonin antagonists such as ondansetron can be used for chemo, post op, and motion sickness

false.

motion sickness is muscarinic, NE, H1. no serotonin receptors

t/f: ondansetron requires ECG monitoring for pts at risk for QT changes

true

neurokinin receptor antagonists (NK1 antagonists)

examples:

moa:

uses:

aprepitant, fosaprepitant, netupitant/palonosetron, rolapitant

moa: blocks NK1 in CNS and GI

use: prevents CINV and PONV (aprepitant only)

aprepitant

moa?

use?

blocks NK1 receptors in brain

use: antiemetic for chemo (tripack) and post op (3hrs before) induced nausea and vomiting

aprepitant ADEs

- diarrhea OR constipation

- headache, dizziness

- hiccups

- transient elevation in LFTs and BUN

aprepitant DDIs

induces 2C9= warfarin, phenytoin, birth control

inhibits 3A4 (substrate)= steroids, benzos, chemo

- caution with 3a4 inhibitors and inducers

n/v in pregnancy most often occurs in the _______ trimester

first

hyperemesis gravidarum

severe nausea and vomiting in pregnancy that can cause severe dehydration in the mother and fetus (1-3%)

non pharm therapy for pregnant n/v

- modify diet

- acupressure/ acupuncture

- ginger

pharm tx for n/v in pregnancy

1. pyridoxine (B6)

2. H1 receptor antagonist= doxylamine, dimenhydrinate, meclizine, (B) diphenhydramine, hydroxyzine (C)

which of the following is the best tx approach for n/v in pregnancy

a. aprepitant

b. ondansetron

c. metoclopramide

d. Vit B6 + meclizine

d. Vit B6 + meclizine (h1 receptor antagonist)

note: for more severe NVP you can also use ondansetron, metoclopramide, prochlorperazine, corticosteroids (after 1st trimester)

if pregnant pt is not responding to B6/doxylamine, what other options are available?

ondansetron= best tolerated

metoclopramide= 2nd choice

prochlorperazine

corticosteroids (after 1st trimester)

Diclegis

brand of doxylamine/pyridoxine combo for pregnancy induced n/v

Bonjesta

doxylamine/pyridoxine indicated for nausea/vomiting in pregnancy

what is motion sickness caused by

stress in labyrinth (inner ear)

= motion, infection, neoplasm, idiopathic

receptors: muscarinic, histamine

non pharm tx for motion sickness

- minimize exposure to movement

- restrict visual activity

- distractions

- avoid alcohol, food overindulgence

- acupressure

- ginger

pharm approach for motion sickness

1. antihistamines

= diphenhydramine, dimenhydrinate, meclizine

2. anticholinergics

= scopolamine patch (for long term-> cruise_

MEDICATE PRIOR TO STIMULI!!

a pt comes in complaining of motion sickness. what would you recommend and what counseling would you give

antihistamine (diphenhydramine, dimenhydrinate, meclizine) or anticholinergic (longer time-> scopolamine patch)

- MEDICATE BEFORE YOU EXPERIENCE IT!!

what patient specific factors increase risk for post op n/v

female

motion sickness/ PONV hx

nonsmoking

use of post-op or intra-op opioids

obesity

what surgery-related factors increase risk for n/v

type= abdominal, gyne, ears nose throat

gas anesthetics= isoflurane, enflurane, NO

general anesthesia

long surgeries (>100min)

prevention for post op n/v

1. reduce risk factors

- opioid-sparing pain control

- regional, non volatile anesthesia

2. PONV prophylaxis (if 2+ risk factors OR history of PONV)

non-pharm tx for PONV

-acupressure, acustimulation

- ginger (if allowed to eat before/after surgery)

- aromatherapy (not rlllyyy proven. just take controlled breaths)

when is a pt eligible for PONV prophylaxis

1. if has 2+ risk factors:

-female

-motion sickness

-nonsmoking

-use of opioids during or after op

-obese

-ab/ears/nose/throat surgery

- volatile or non localized anesthesia

-long surgery

2. if has had PONV before

monotherapy prophylaxis options for PONV

- droperidol [qt prolongation]

- dexamethasone

- prochlorperazine [sedation risk]

- promethazine [gangrene]

- metoclopramide

- 5ht3 antagonist

(all valid options, no rank)

PONV dual therapy prophylaxis combos for higher risk pts

droperidol + 5ht3 antagonist

dexamethasone + 5ht3 antagonist

droperidol + dexamethasone

PONV triple therapy prophylaxis combo for highest risk pts

droperidol + dexamethasone + 5ht3 antagonist

what is the difference in treatment for a patient with PONV that has

1. received prophylaxis

2. has not received prophylaxis

received: choose an agent from different class

not received prophylaxis:

low dose 5ht3 antagonist

-granisetron, ondansetron, dolasetron

pt AB is going on a cruise and wants smtg for motion sickness. He has BPH, HTN, and an aspirin allergy. which is the best option

a. scopolamine patch

b. acupressure band

c. dimenhydrinate

d. aprepitant

b. acupressure band

a and c are correct mech but we dont want to give antihist/anticholinergic bc he has BPH. those will make his urination even worse. d is for NK receptor

which of the following are appropriate monitoring parameters for a pt receiving ondansetron + dexamethasone for post op n/v prophylaxis

a. hyperglycemia

b. EPS

c. ECG/EKG

d. sedation

a (diabetes and getting steroid) and c (ondansetron)

EPS-> thiazines

sedation-> antihist/anticholinergics/thiazines