Download Hx - Palliative Care

A mechanistic approach to Nausea
Vomiting and Constipation in the ED
Emergency/Palliative Medicine Workshop for
UBC Emergency Medicine Residents
Susanne Moadebi PharmD BCPS
July 27th, 2016
HOPE Centre
Outline

List common mechanisms which cause nausea and vomiting

Classify antiemetic agents based on major neurotransmitters and
receptor targets

Review antiemetic use and new agents for treatment of
constipation in the emergency department

Outline treatment principles for Malignant Bowel Obstruction

Cases
2
RECEPTOR ANTAGONISM
D2
Metoclopramide
H1
AchM
5HT2
+++
Domperidone
++++
Haloperidol
++++
+
Methotrimeprazine
++++
+++
++
CPZ
++++
++
+
Olanzapine
++
+
+
Prochlorperazine
++
+
Dimenhydrinate
+
++++
5HT3
5HT4
+
++
NK1
+++
+++
++
++
++++
Granisetron
++++
+
CB1 + 2
+
Ondansetron
Scopolamine
Notes
+
++++
Nabilone
(++)*
*Agonist
Sativex
(++)*
*Agonist
Aprepitant
+++
Case 1
17
y/o female
Presents
to ED with Mother
due to crampy dull generalized
abdominal pain 6/10 for 2
weeks
Having
difficulty keeping
water down, 3 episodes of
emesis in 24 hours
Last
BM 12 hours ago was
loose no blood
Travel
to France with school 3
weeks ago
Hx Bipolar depression/ADHD/ no eating disorder no
drug allergies no gluten allergies, reviewed sexual
history
Meds
Lithium carbonate LA 600mg/day
Methylphenidate LA 54 mg/day increased from
36mg/day 2 weeks ago during midterm exams
PE BP 124/80 HR 95 T37C oral Pain 6/10 Mild
tenderness, no peritoneal signs, no guarding no
rebound no acute appendicitis
Labs Lipase WNL Hcg negative Lithium WNL
CBC (WBC normal) urinalysis normal
ERP
contacted Pharmacist to review her
home medications
What
add?
anti-emetic would you think to
Case 1 continued

methylphenidate acts as a dopamine and norepinephrine
reuptake inhibitor resulting in a prolongation of dopamine
(D1/D2) receptor effects. It is believed that methylphenidate
activates the brain stem arousal system and cortex.

The most common side effects associated with
methylphenidate include headache, nausea, vomiting,
anorexia, dizziness, and insomnia.
Case 1 Resolution
Optimizing Therapy
The Dopamine Dilemma
Treating
side effects of a
stimulant with an antipsychotic,
may mask symptoms
temporarily while worsening
the underlying chemical
imbalance over the long term
Lithium
or MPH can provide
visceral stimulation mediated
nausea involves using the D2
and 5HT3 antagonist which are
effective with IV rehydration
Intervention
Metoclopramide 10 mg iv dose then
switch to po at home. Iv fluid rehydration
Temporary stop lithium. Concern about
level trending up and renally accumilation
Pharmacist contacted Psychiatrist to
review her home medications – return to
previous dose methylphenidate 36 mg
daily
Monitoring and Evaluation
What
options could we consider for
further management of her nausea?
What
happens if her nausea worsens
and is accompanied by intermittent
vomiting and retching?
+
Cannabis and cannabinoids
Plant derived cannabinoids


THC – has psychotropic effect
that produces “high”
CBD cannabidiol & CBN
Cannabinol have anti-seizure
anti-nauseant anti-anxiety
Tolerance may occur with
chronic use. Hyperemesis may
be observed with larger doses
or chronic use
Synthetic cannabinoids

Nabilone Cesamet®
Endocannabinoids

anandamide

-2-arachidonolglycerol 2_AG

The body produces stimulate
cannabinoid receptors naturally.

There are at least two different
types of cannabinoid receptors
in the body: CB1 receptors in the
brain and nervous system, and
CB2 receptors in the immune
system.
Case 2
Hx HR+ HER2-mBC mets to lung/spine no known drug
allergies. Followed by GP for palliative services
Meds
64
y/o female
Presents
to ED with declining
oral intake due to intractable
nausea.
Complains
of hard stools,
incomplete evacuation,
bloating, abdo pain. No BM x 10
days
She
has tried PEG 3350 17g x
2 doses, glycerine
suppositories, magnesium
citrate, docusate sodium and
psyllium powder
Exemestane 25mg po daily
Morphine Long-acting capsules 120mg po BID
recently increased 2 weeks ago
PE BP 178/89 HR 108 T37.6C oral Pain 8/10
Labs CHEM7/CBC (WBC normal) urinalysis normal,
lipase, liver panel normal
Abdominal XR – no obstruction but faecal loading
shown on x-ray
ERP
contacted Pharmacist to review her
home medications
What
would you treatment would you
consider?
Case 2 Resolution
Opioid induced constipation – how would you treat?

Intervention – use a peripherally acting mu-opioid receptor
antagonist- 62 kg give Methylnaltrexone 8mg sc

T1/2 8 hours and T peak 30 minutes with no withdrawal of
analagesia

Time to first laxation is 4 hours & will see appetite improve

Monitoring Watch for dizziness, abdo pain cramping start
regular PEG and sennosides

PEG is more effective than lactulose for prevention
Drug name
Indication
Class/Mech.
of Action
Onset of
Action
Methylnaltrexone
(Relistor)
Adjunct in
refractory
opioid
induced
constipation
for palliative
care patients
Mu opioid
receptor
antagonist
30-60m
Naloxegol
(Movantik)
Opioid
induced
constipation
Mu opioid
receptor
antagonist
Lubiprostone
(Amitiza)
Opioid
induced
constipation
Prucalopride
(Resotran)
Linaclotide
(Constella)
Drug Dosing/Dosage
Form
Metabolism/Cle
arance
Adverse Effects
Administered subQ q48
hours PRN
Weight and Renal Fxn:
8mg / 12mg /‘0.15mg/kg
CrCl <30mL/min:
↓ dose by 50%
Dosage Form:
Subcutaneous injection
Substrate of
CYP2D6 (minor);
Urine (54% as
unchanged drug)
T1/2 = 8h
Abdominal pain,
diarrhea, flatulence,
nausea, dizziness.
Risk of GI
perforation in
patients with cancer,
GI malignancy, GI
ulcer, Ogilvie’s
syndrome
Time to
peak: <2h
25mg PO daily
CrCl <60ml/min - start at
12.5mg daily and may
increase to 25mg daily if
well tolerated
Dosage Form: Tablets
(12.5mg, 25mg)
Substrate of
CYP3A4
Urine (16% as
unchanged
drug); Primarily
hepatic
T1/2 = 6-11h
Headache, nausea,
diarrhea, vomiting,
hyperhidrosis
Type 2
Chloride
Channel
Activator
Time to
peak: ~1h
24mcg PO BID
Dosage Form: Capsule
(8mcg, 24mcg)
Rapid and
extensive within
stomach and
jejunum by
carbonyl
reductase
T1/2 = 0.9-1.4h
Headache, nausea,
diarrhea, edema,
dizziness,
abdominal pain,
dyspnea
Refractory
opioid
induced
constipation
in females
5HT4 Recepto
r Agonist
2-3h
2mg PO daily
CrCl <30mL/min =
1mg PO daily
Dosage Form: Tablet
(1mg, 2mg)
Substrate of Pglycoprotein
Minor route of
elimination
T1/2 = ~24h
Nausea, diarrhea,
abdominal pain,
headache
Refractory
opioid
induced
constipation
Guanylyl
cyclase C
agonist
Not
available
Metabolized
within GI tract to
active metabolite
T1/2 =
Diarrhea, headache,
abdominal pain,
flatulence, URTI
145mcg PO daily
Dosage Form: Capsule
(145mg, 290mg)
Case 3
Hx Stage IV gastric CA dx 1 year ago; anxiety and
depression. Multiple cycles of chemo (last one month
ago) with progressive carcinomatosis. Has tried TPN
several times but failed J-tubes in the past.
Meds oxycodone 10 mg TID
56
y/o male
Presents
to ED with recurrent
nausea seen here yesterday –
recalcitrant nausea NYD.
No
emesis, no diarrhea, loose
stools last few days; covering
eyes states makes it better for
his nausea
He
has tried ondansetron and
metoclopramide; admit for
symptom management
clonazepam 0.5mg TID
paroxetine 60 mg once daily
PE BP 178/89 HR 108 T37.6C oral Pain 8/10 Mild
Labs CHEM7/CBC (WBC normal) urinalysis normal,
lipase, liver panel normal
Abdominal CT –found malignant intestinal obstruction
due to carcinomatosis
ERP
contacted Pharmacist to review his
home medications
What
would you treatment would you
consider?
Dx Malignant Bowel Obstruction

Metoclopramide

Haloperidol (5–15 mg/day)

Methotrimeprazine (50–150 mg/day)

Hyoscine butylbromide (Buscopan®)
(60-120mg/day)

Octreotide (200 - 900 mcg/day)

Steriods
Case 3 Resolution

Decadron 8mg SQ BID, metoclopramide10mg SQ q6h,
octreotide 100mcg SQ q8h

Corticosteroids also are used to reduce inflammatory edema
and decrease water and salt secretion in bowel. They are
relatively inexpensive and well tolerated. First line involves
steroids, antiemetics,

anti-cholinergics, analgesics and parental rehydration. If it
fails, somatostatin analogues supersede steroid and anticholinergics.
Take home points
1)
2)
3)
4)
VOMIT acronym
Better to use metoclopramide consider
D2 antagonism which may offset
decreased persistalsis caused by the
opioids
For palliative/frail patients with
constipation add an osmotic laxative (e.g
PEG 3350) Don’t use docusate
insufficient evidence to support its use.
Use octreotide for malignant bowel
obstruction
Questions?