HX2.2 GI Symptoms in Advanced Disease

Question 1

What are the three main challenges in managing GI symptoms in advanced disease?

Answer 1

Nausea & Vomiting.
Constipation.
Bowel Obstruction.

Question 2

What is nausea?

Answer 2

“A subjective unobservable phenomenon of an unpleasant sensation experienced in the back of the throat and the epigastrium that may or may not result in vomiting.”

Question 3

What is vomiting?

Answer 3

The forceful expulsion of the contents of the stomach, duodenum or jejunum through the oral cavity

Question 4

Describe the vomiting sequence

Answer 4

1. Nausea and increased salivation.
2. Peristalsis is reversed stomach relaxation.
3. Glottis closes off trachea to prevent aspiration.*
4. Breath is held mid inspiration.
5. Abdominal muscles contract, lower esophageal sphincter and esophagus relax, expelling vomit.

Question 5

What is the logical approach for treating nausea + vomiting?

Answer 5

1. Signs & Symptoms.
2. Causes
3. Neurophysiology
4. Drug Receptors
5. Drugs

Question 6

What information should be elicited during the Hx for N+V?

Answer 6

1. Nausea? Retching? Vomiting?
2. When: did it start? Time(s) of day?
3. Constant/not?
4. What: does vomit look like? Amount? Blood?
5. How: did it start?
6. How has it been treated so far? - Exacerbating/Relieving factors?

Question 7

What are the possible categories of N+V causes

Answer 7

Psychological
Raised ICP
Vestibular 
Vagus Nerve
Liver Damage
GI Damages

Question 8

Which receptors mediate psychological causes of N+V?

Answer 8

Benzoreceptors

Question 9

Which receptors mediate raised ICP causes of N+V?

Answer 9

Histamine H1 receptor (H1)

Question 10

Which receptors mediate vestibular causes of N+V?

Answer 10

H1 + ACHM (muscarinic cholinergic receptors)

Question 11

Which receptors mediate vagal causes of N+V?

Answer 11

ACHM

Question 12

Which receptors mediate Toxin (blood) causes of N+V?

Answer 12

• D2 (Dopamine 2)
• 5HT2 (5-Hydroxytryptamine receptors/serotonin receptors)
• 5HT3
• 5HT4

Question 13

Which receptors mediate liver damage causes of N+V?

Answer 13

5HT4

Question 14

Which receptors mediate GI damage causes of N+V?

Answer 14

D2
5HT3
5HT4

Question 15

Against which receptors is Domperidone effective?

Answer 15

D2++

Question 16

Against which receptors is Metaclopramide effective?

Answer 16

D2++
5HT3+
5HT4++

Question 17

Against which receptors is Haloperidol effective?

Answer 17

D2+++

Question 18

Against which receptors is Cyclizine effective?

Answer 18

H1++

ACHM++

Question 19

Against which receptors is Ondansetron effective?

Answer 19

5HT3+++

Question 20

Against which receptors is Hycozine effective?

Answer 20

ACHM+++

Question 21

Against which receptors is Prochlorperazine effective?

Answer 21

D2++

H1+

Question 22

Against which receptors is Chlorpromazine effective?

Answer 22

D2++
H1++
ACHM+

Question 23

Against which receptors is Levomepromazine effective?

Answer 23

D2++
H1+++
ACHM++
5HT2+++

Question 24

Which drug/s are usually employed against psychological causes of N+V?

Answer 24

Benzodiazepines

Non-pharma treatments

Question 25

Which drug/s are usually employed against raised ICP causes of N+V?

Answer 25

Cyclizine (H1) | Steroids

Question 26

Which drug/s are usually employed against vestibular causes of N+V?

Answer 26

Hyoscine (Achm) | Cyclizine (Achm,H1)

Question 27

Which drug/s are usually employed against Vagal causes of N+V?

Answer 27

Hyoscine(Achm)

Question 28

Which drug/s are usually employed against Liver causes of N+V?

Answer 28

Metoclopramide(5HT4) | Steroids

Question 29

Which drug/s are usually employed against GI causes of N+V?

Answer 29

Metoclopramide (D2) Ondansetron (5HT3,4) Steroids

Question 30

Which drug/s are usually employed against Toxic causes of N+V?

Answer 30

Haloperidol (D2) Ondansetron (5HT2) Metoclopramide (5HT3,4)

Question 31

Which neurological structures mediated the vomiting reflex?

Answer 31

The CNS Vestibular System (H1, M1) Cranial Nerves IX, X Feed into... The Vomiting Centre + The Chemoreceptor Trigger Zone Located in the Medulla Oblongata

Question 32

Which anti-emetics are considered to also be prokinetics?

Answer 32

Target = D2 antagonist Metoclopramide (maxalon) 10mg TDS PO. Crosses BBB = central effects. 5HT3 (at high doses), D2, Ach. Extrapyramidal side effects Domperidone (motilium) 10mg TDS PO. D2 Side effects rare. May exacerbate colicky abdominal pain. Erythromycin (not indicated as 1st line prokinetic) Motilin agonist = triggers wave of peristalsis. Useful in denervated Gut.

Question 33

What are the side effects of the anticholinergics?

Answer 33

E.g. Hycosine, atropine Dry mouth, constipation, blurred vision, urinary retention. Sedation, agitation, seizures (if crosses BBB)

Question 34

Side effects of the Phenothiazines & Butyrophenones:

Answer 34

Haloperidol Levomepromazine Prochlorperazine ``` Side Effects: Dystonia (esp. Stemetil). Anticholinergic effects. Postural hypotension. Sedation. ```

Question 35

What are the side effects of the antihistamines?

Answer 35

Cyclizine Promethazine Dimenhydrinate. Cyclizine may precipitate in syringe drivers. Urticaria & drug rash Anticholinergic side effects – dry mouth, urinary retention etc.

Question 36

What is the purpose of corticosteroids? MOA?

Answer 36

1.Reducing oedema 2.Reducing inflammation Reduces tissue damage Inhibition of release of mediators of emesis MOA: increase activity of 5HT3 antagonists after chemotherapy Reducing oedema & inflammation  Inhibition of release of mediators of emesis

Question 37

Give an example of a corticosteroid?

Answer 37

Dexamethasone

Question 38

What are the side effects of corticosteroid use?

Answer 38

``` Adrenal cortical atrophy. Anti-inflammatory/immunosuppressive effects. Avoid live vaccination to pts on steroids. Osteoporosis. Hypertension Hypokalemia Diabetes mellitus Peptic ulceration. Renal failure. Liver failure. Epilepsy. ```

Question 39

Give some examples of non-pharmacological methods of managing N+V?

Answer 39

Control of malodor from colostomy, fungating tumour or decubitus ulcer An environment away from the sight and smell of food Small frequent meals Avoid fatty, spicy, highly salty foods Behavioral approaches Distraction, relaxation Massage Acupuncture (Studies show effectiveness in chemo-induced nausea and anticipatory nausea)

Question 40

How should antiemetics be taken?

Answer 40

Give antiemetics regularly - not P.R.N.

Question 41

Which antiemetics should be used where intestinal obstruction is also present?

Answer 41

Prokinetics

Question 42

What are the steps if N+V present despite optimal prophylactic therapy?

Answer 42

``` 1.Rule out reversible causes.. Bowel obstruction, gastroparesis, gastritis medications brain mets, vestibular dysfunction electrolyte imbalance ``` 2.Control episodes of nausea Give a different agent from another drug class. Consider route of administration consider regular use rather than PRN 3.Plan adjusted prophylactic regimen for next cycle of treatment.

Question 43

What is constipation?

Answer 43

Constipation is characterized by difficult or painful defecation associated with infrequent bowel evacuations (+/- hard, small faeces, abdominal fullness and pain) 50-80% palliative care patients

Question 44

What are the possible complications of constipation?

Answer 44

``` Pain – colic or constant abdominal discomfort Nausea & vomiting Anal fissures Anal pruritis Haemorrhoids Faecal impaction and intestinal obstruction Spurious (overflow) diarrhoea Faecal incontinence Urinary retention or incontinence Delirium Cost - £43 million/year ```

Question 45

What are the 5 classes of pharmacological interventions for constipation?

Answer 45

1. Stimulants 2. Faecal Softeners 3. Osmotic Agents 4. Bulk Forming Agents 5. Rectal Agents

Question 46

Give some example of stimulant constipation meds?

Answer 46

Bisacodyl Danthron Senna

Question 47

Give some example of faecal softeners?

Answer 47

Docusate

Question 48

Give some example of osmotic agents?

Answer 48

Lactulose Magnesium Salts Polyethylene Glycol

Question 49

Give some example of bulk forming agents?

Answer 49

Methylcellulose | Ispaghula husk

Question 50

Give some example of rectal agents?

Answer 50

Bisacodyl Glycerol Microlax High phosphate enema

Question 51

What should always be prescribed with an opioid?

Answer 51

A laxative

Question 52

What options should be considered where a conventional laxative is not working?

Answer 52

Consider changing to a less constipating formulation | Opioid antagonists

Question 53

What are the principles of constipation management?

Answer 53

Regularly assess, be proactive Consider factors such as privacy, comfort Increase fluid and fibre as tolerated Encourage mobility if patient is able Start prophylactic laxatives when starting opioid drugs Use a combination of a stimulant and a softener/osmotic laxative Use oral laxatives in preference to rectal measures

Question 54

How is bowel obstruction classified?

Answer 54

May be intramural, intraluminal or extra luminal At each level, the obstruction can be functional (paralytic) or organic (mechanical), or both Partial or complete Transient (acute) or persistent (chronic)

Question 55

What are the clinical features of bowel obstruction?

Answer 55

GI symptoms depend on the site of obstruction Continuous abdominal pain is present in ~90% Intermittent colic ~ 75% May not have abdominal distension Vomiting develops early and in large amounts in gastric, duodenal and SB obstruction Bowel habit ranges from constipation to diarrhoea Bowel sounds vary from absent (functional obstructions) to hyperactive and audible (borborygmi) Tinkling bowel sounds NOT always present

Question 56

What radiological investigations can be used to dx bowel obstruction?

Answer 56

MUST BE CONSISTENT WITH GOALS OF CARE Plain abdominal film Supine and standing Contrast radiography Helps to evaluate dysmotility, partial obstruction and to define the site and extent of obstruction CT Useful in evaluating global extent of disease

Question 57

What are the goals of pharmacological management of bowel obstruction?

Answer 57

1.Anti-emetics Oral administration likely unreliable drug of choice is a prokinetic in functional bowel obstruction (not recommended in complete mechanical bowel obstruction) Cyclizine ± haloperidol or levomepromazine 2.Reducing GI secretions Anticholinergics – hyoscine butylbromide OR/AND Octreotide 3. Reducing bowel wall oedema Dexamethasone 8 mg SC before midday Evidence is equivocal – consider a 3 day trial 4. Reducing colic Strong opioid (likely required for background pain) Hyoscine butylbromide

Question 58

What should be considered before surgery in the bowel obstructed patient?

Answer 58

Is the patient likely to benefit? Surgery will only benefit selected patients with mechanical obstruction. Is it technically feasible? In advanced cancer… Operative mortality (death within 30 days of operation) of 9–40% Complication rates 9–90%

Question 59

What surgical procedures are available?

Answer 59

Self-expanding metallic stents (In recent years stents have been used increasingly in the management of obstructions in the gastric outlet, proximal small bowel and colon.) Nasogastric suction A NGT can be used temporarily to reduce a large volune of secretions before the start of pharmacological treatment and during the first few days of treatment.  Long term use of a NGT should only be considered if drug therapy ineffective and a gastrostomy cannot be performed.

Question 60

What are the take home points?

Answer 60

1. Using a targeted approach for nausea and vomiting, matching anti-emetic to likely cause 2. Always prescribe laxatives with opioids 3. Generally use a stimulant and softener laxative combination 4. Always consider whether investigations and treatments are appropriate to the individual patient 5. Continually reassess and re-evaluate, ask for help!