Supportive and Palliative Care Flashcards
List the drug class useful for anticipatory nausea/ vomiting
Benzodiazepine
List the classes that are useful for BOTH acute and delayed nausea/ vomiting (3+1)
NK-1 antagonist
Corticosteroid
Olanzapine
Dopamine Antagonist (less useful)
State which drug class only useful for acute n/v but not delayed
5HT3 Antagonist
State the definition of:
a) Acute
b) Delayed
c) Breakthrough
d) Anticipatory
e) Refractory N/V
Acute:
- Usually starts within 1-2 hours after administration
- Peak intensity within 5-6 hours, resolution at 12-24 hours
Delayed:
- Peak onset 48-72 hours after chemotherapy, diminishing after 1- 3 days
- Occurs in 50-90% (highly emetogenic regimens), 35%-80% (moderately emetogenic therapy) of patients
Breakthrough:
- N/V occurring despite preventive therapy
Anticipatory:
- Conditioned response (e.g due to fear of chemo)
- Associated with uncontrolled emesis prior chemotherapy
Refractory:
- N/V occurring during subsequent cycles of chemotherapy when antiemetic prophylaxis or rescue therapy has failed in previous cycles
- May involve use of multiple antiemetics, even those with lesser evidence
List the risk factors for CINV (7) (Hint: think of what cause puking)
1) Younger age (<50 years old)
2) Female gender
3) History of low prior chronic alcohol intake (<1 glass of alcohol/day)
* Alcohol use is protective factor
4) History of previous chemotherapy induced emesis
5) History of motion sickness
6) History of emesis during past pregnancy
7) Anxiety
List the ADRs of NK-1 antagonist (4)
fatigue, weakness, nausea, hiccups, headache, constipation
List the ADRs of 5HT3 antagonist (3)
Headache and constipation, QTc prolongation, Hiccup
List the classes reserved for refractory n/v
- Butyrophenones (haloperidol)
- Phenothiazines (prochlorperazine, chlorpromazine, promethazine)
List non-pharmacological management of CINV (6)
o Take small, frequent meals. Avoid heavy meals.
o Avoid greasy, spicy, very sweet or salty food and food with strong flavors or smells.
o Sip small amounts of fluid often instead of trying to drink a full glass at one time.
o Avoid caffeinated beverages.
o Avoid lying flat for 2 hours after eating.
o Suck candies such as lemon drops
List the general steps in managing breakthrough N/V (4) (Hint think of reasons why this may occur and consequence of this occuring)
o General principle is to give an additional agent from a different drug class -> see what N/V pathway hasn’t been blocked
o Choice of agent should be based on assessment of the current prevention strategies used
o Consider use of several agents utilizing different mechanism of actions if necessary
o If PO route not feasible due to ongoing vomiting, consider IV route
o Hydration and fluid repletion for losses (consider oral rehydration salts)
o Reassess next cycle’s antiemetics to ensure anti-emetic regimen is appropriate
List the steps in the management of Anticipatory CINV (4)
1) Prevention is key -> Use optimal anti-emetic therapy during every cycle of treatment
2) Behavioral therapy
* Relaxation/systematic desensitization
* Hypnosis/guided imagery
* Music therapy
3) Acupuncture/ acupressure
4) Consider use of benzodiazepines before treatment
Risk Factors for CID (~10)
o 1) Age greater than 65 years
o 2) Female
o 3) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of at least 2
- How fit the patient is; 0 means very fit, more than 2 is not so fit. Fit = ability to do daily activities
o 4) Bowel inflammation or malabsorption
o 5) Bowel malignancy
o 6) Biliary obstruction
o Other predictive factors may include first cycle of chemotherapy, cycle duration greater than 3 weeks, concomitant neutropenia, other symptoms such as mucositis, vomiting, anorexia, or anaemia.
State the criteria for Uncomplicated CID
- Grade 1 (Increase of < 4 stools per day above baseline) or 2 (Increase of 4-6 stools per day above baseline + Limiting activities of daily living)
- No complicating signs or symptoms
State the criteria for complicated CID
- Grade 3 or 4
- Grade 1 or 2 with at least one of the following:
o Cramping
o >Grade 2 nausea or vomiting
o Decreased performance status
o Fever
o Sepsis
o Neutropenia
o Frank bleeding
o Dehydration
Goals of therapy for CID? (5)
o CTCAE Grade 0 or 1
o Decrease morbidity and mortality from CID
o Improve quality of life and activities of daily living.
o Improve recovery of intestinal mucosa.
o Decrease hospitalization
What are the non-pharmacological ways to manage CID? (7) (Hint: think of what chemo does to the gut, what causes diarrhea)
o Probiotics with Lactobacillus are suggested to prevent chemotherapy- or radiation induced diarrhea.
o Avoid caffeine, alcohol, fruit juice, foods that contain lactose, foods that are spicy or high in fat or fiber, or dietary supplements with high osmolarity.
* Up to 10% of patients experience 5-FU–induced lactose intolerance because lactase activity can be lost temporarily.
o Lactose-containing foods should be avoided for at least a week after CID has resolved.
o Eat small, frequent meals.
o BRAT diet (bananas, rice, applesauce, toast)
o More than 3 L of clear fluids containing salt and sugar
o Electrolyte-containing fluids are ideal.
State the general management of uncomplicated CID (including what to do if diarrhea persists for longer than 24hr and after 48 hour)
1) Withhold chemotherapy for grade 2. -> only applicable for PO not so much for IV
* a) Resume when symptoms resolve
* b) Consider dosage reduction of drug
* Note: requires consideration of risk vs benefit as well -> stopping may have the risk of cancer progression as well
2) Diet modifications
* Oral hydration with 8–10 large glasses of clear liquids
* Loperamide 4 mg by mouth, then 2 mg by mouth every 4 hours or after every episode of diarrhea. Continue until 12 hours free of diarrhea, then stop.
* If diarrhea is improving after 12–24 hours, continue with diet modifications and begin to add solid food.
* If diarrhea persists after 12–24 hours:
o a) Schedule loperamide 2 mg every 2 hours.
o b) Start oral antibiotics.
o c) For diarrhea that progresses to severe or complicated, treat as such.
o d) For diarrhea that persists as uncomplicated 12-24 hours after scheduled loperamide (36-48 hours after diarrhea onset), begin octreotide or other second-line agent.
State the management of complicated CID (5) include doses of drugs used
1) Withhold chemotherapy. Resume when all symptoms resolve.
2) Restart at decreased dosage.
3) Administer octreotide 100–150 mcg subcutaneously three times a day or IV with dose escalation up to 500 mcg three times a day.
4) Start IV fluid hydration.
5) Start IV antibiotics (e.g., ciprofloxacin × 7 days). -> concerns about infection
* Note that antibiotics may cause diarrhea too
MOA of Octreotide
Causes decreased hormone secretion, which increases transit time within intestine, decreases secretion of fluid, and increases absorption of fluid and electrolytes
ADRs of Octreotide (8) (think of its MOA)
Bradycardia, arrhythmias, constipation, abdominal pain, enlarged thyroid (hypothyroidism), nausea and vomiting, headache, dizziness
State what liver enzyme deactivates SN-38 and which phenotype increases risk of toxicity
UGT1A1
Those homozygous for UGT1A1 *28
Describe the pathophysiology of irinotecan induced diarrhea
Early onset: Inhibits acetylcholine esterase leading to cholinergic response
Late onset: Mediated by increased formation of SN-38 an active, toxic metabolite -> deactivated by UGT1A1 to SN-38G by liver but once it enters gut, it can undergo deconjugation by beta-glucoronidase by gut bacteria. SN-38 damages gut mucosa during excretion.
Leads to ablation of crypts, villus blunting, and atrophy of the epithelium in the small and large intestine
