Pharmacology 2

Question 1

What consitutes a dx of constipation?

Answer 1

< 3 Bowel movements per week

Question 2

Describe the Rome III criteria of constipation.

Answer 2

> 25% of the time you have:

• straining
• lumpy/hard stool
• incomplete evacuation
• sensation of anorectal blockage
• manual maneuvers needed

Plus less than 3 BMs a week.

Question 3

Study used to diagnose constipation?

Answer 3

Sitz marker study: measures number of markers passed in a 24hr period

Anorectal manometry (balloon expulsion test):

Defecography: evaluates anorectal function via barium insertion into the rectum

Question 4

How many grams of fiber recommended per day?

Answer 4

~25 grams per day

Question 5

Most commonly used laxatives for colonoscopy prep?

Answer 5

Osmotic laxatives (MgOh, Mgcitrates, Polyethelene glycol, lactulose

Question 6

What is the indication for Linaclotide (Lizness)

Answer 6

• Chronic idiopathic constipation.
• IBS- constipation as well.

Increases Cl and HCO3 secretions through CFTR ion channel via cGMP increase

Question 7

Adverse effects of Linaclotide (Lizness)

Answer 7

Diarrhea, abdominal pain, flatulence

Question 8

Contraindications of Linaclotide (Lizness)?

Answer 8

Mechanical GI obstructions
Peds <6 y/o
Pregnancy category C

Question 9

What drug is used to counteract Opioid-induced constipation?

Answer 9

Methylnaltrexone (Relistor)

Selective PERIPHERAL opioid receptor antagonist

Question 10

Adverse effects of Methylnaltrexone (Relistor)?

Answer 10

Abdominal pain 
Flatulence
Nausea
Dizziness
Hyperhidrosis
Bowel Perforation (rare)

Question 11

Contraindications of Methylnaltrexone (Relistor)?

Answer 11

mechanical GI obstruction

pregnancy B

Question 12

Definition of diarrhea?

Answer 12

increase in daily stool weight above 200 grams, liquidity

must be diff. from “loose Bowel Movement”

Question 13

Most useful in clinical practice for eval/treatment of patients with diarrhea?

Answer 13

History and stool characteristics

Question 14

Drug indicated for diarrhea secondary to hypercholesterolemia?

Answer 14

Bile acid sequestrants (colesevalam powder)

also off label for bile acid diarrhea due to distal ileum resection and C. difficile diarrhea.

Question 15

Adverse effects of bile acid sequestrants?

Answer 15

Nausea, vomiting, abdomen pain, heartburn, bloating.

Acidosis 2nd to hyperchloremia, gallstones, pancreatitis, peptic ulcers, malabsorption, Vit. K deff assoc. coagulopathy.

Question 16

Where is the central vomiting center in the brain?

What projects to it?

Answer 16

Medulla

• Lateral Reticular Formation
• Chemoreceptor Trigger Zone (CTZ) (bottom of 4th ventricle)
• GI —> Vagus Nerve
• Cortex (anticipatory)
• Vestibular apparatus (motion sickness)

Question 17

Describe the vomiting center outputs and the receptors acted on by the medulla?

Answer 17

Outputs are CN 5/7/9/10/12

Act on: Muscarinic cholinergics (AChm), Histamine type 2 (H2), Serotonin type 2 (5HT2)

Question 18

Describe a drug mainly used as motion sickness prophylaxis?

Contraindications?

Answer 18

Scoploamine (patch form) - antimuscarinic action

M1 receptor antagonist - blocks vestibular inputs to central vomiting center

CNS depression, dry mouth, Restlessness/irritability.

DONT TAKE if have Glaucoma or enlarged prostate.

Question 19

What is the main antihistamine used for nausea?

Answer 19

promethazine (dopamine receptor antagonist)

prevent nausea associated with anesthesia or surgery, or prophylax motion sickness.

Question 20

Black box warning for promethazine?

Answer 20

Gangrene due to excessive CNS depression ?

Respiratory failure.

Question 21

What is the most commonly used general purpose anti-nausea/anti-emetic?

Answer 21

Dopamine receptor antagonists (eg. phenothiazine)

Also used for migraine associated nausea.

Question 22

Example of phenothiazine, and receptors/ properties?

Answer 22

Prochlorperazine

block D2 at CTZ, but also have M1 and H1 so it has sedative properties

Question 23

Common uses of prochlorperazine>

Answer 23

Phenothiazine (D2 antagonists)

prevent/control of nauseaand vomiting

prophylax motion sickness

migraine nausea

chemotherapy-induced emesis

Question 24

Adverse effects of prochloroperazine?

Answer 24

TARDIVE DYSKINESIA (involuntary movements)

BLACKBOX - dementia-related psychosis

Question 25

Describe what dopamine receptor antagonist can be used for nausea 2nd to pregnancy?

Answer 25

Metoclopramide

also gastroparesis, chemo vomiting, hiccups

Question 26

Adverse effects of metoclopramide?

Answer 26

Extrapyramidal effects like pheyothiazines (prochloroperazine)

(Tardive dyskinesia)- black box warning@!!!

PREGNANCY (B)

Question 27

What can be a particular use of Domperidone (motilin), why?

Answer 27

Manage nausea/emesis related to levodopa treatment of parkinson disease.

Good because it doesnt corss BBB

Question 28

How to 5HT3 antagonists work for emesis?

Answer 28

Block 5HT3 in CTZ (central trigger zone)

Question 29

What is the most prominent indication of 5HT3 antagonists?

Answer 29

(Odansetron is #1) – preg - C
Chemo and radiation induced emesis (1st line)

Pregnancy related emesis (second line due to Pregnancy B classification)

Question 30

First line for pregnancy induced emesis?

Answer 30

Metoclopramide (D2 antagonist?

Question 31

How do neurokinin receptor antagonists work?

Answer 31

(Aprepitant/Fosaprepitant)
Inhibit substance P - neuropeptide used in CTZ

Good for long-term and acute emesis.

Question 32

Indications for neurokinin receptor antagonists? (aprepitant/fosaprepitant)

Answer 32

Chemo emesis

Question 33

Adverse of neurokinin receptor antagonists?

Answer 33

dose-dependent CyP450 inhibition (CYP3A4)

decreased chemo drug clearance in some

Question 34

Mech of prokinetic agents in the prevention of emesis?

Answer 34

Enhance coordinated GI motility.

Cholinergic agents
Motilin-like agents
Serotonin (5HT4) agonists

Question 35

What is commonly used to treat colonic pseudo-obstruciton and paralytic ileus?

Answer 35

Neostigmine, Physostigmine

Cholinergic prokinetic agents