GI Pharmacology 2 - Slides 1-15 Flashcards
List the indications for anti-emetic drugs
Severe nausea and vomiting
Motion sickness
Post-operative nausea and vomiting
Nausea and vomiting associated with chemotherapy
What causes vomiting reflex?
Mediated through the vomiting center in the medulla
Vagus nerve, spinal motor nerves to the abdominal muscles
What happens when the vomiting reflex is activated?
Reverse peristalsis of the upper GI tract
Glottis closes, breath is held, esophageal and gastric sphincters relax
Abdominal muscles contract to eject gastric contents
What are anti-muscarinic agents used for? What options do we have?
Motion sickness
Scopolamine
Side effects of scopolamine?
Dry mouth
Blurred vision
Urinary retention
What anti-histamines are used as anti-emetics?
Dimenhydrinate (Dramamine)
Promethazine
They cause sedation, anti-muscarinic side effects
What are ondansetron, dolasetron, granisetron?
5-HT3 receptor antagonists
Both CNS and peripheral
Indications for ondansetron, dolasetron, granisetron?
Effective in CINV (cisplatin)
Adverse effects of ondansetron, dolasetron, granisetron?
Headache, diarrhea, constipation
What are the phenothiazines?
Prochlorperazine
Chlorpromazine
Fluphenazine
Haloperidol
What is the MOA of the phenothiazines?
D2 receptor antagonists in the CTZ
Adverse effects of the phenothiazines?
Dizziness Fatigue Seizures Sedation Increase prolactin Neuroleptic malignant syndrome
What are the cannabinoids?
Dronabinol
THC, oral formulation
Can be used for CINV when other agents have failed
MOA of Dronabinol?
Works via central action on the vomiting center
Adverse effects of Dronabinol?
Confusion Euphoria Dizziness Mood changes Orthostatic hypotension Increased appetite
What is Aprepitant?
Substance P antagonists
It is an antagonist at NK1 substance P receptor
What is Aprepitant used for?
Vomiting due to cisplatin in all acute (24 hr) patients and many delayed phase (36-72 hour) patients
How does Aprepitant compare to the 5ht antagonists?
5ht antagonists work best against acute phase, Sub P best against delayed phase
How is Aprepitant administered?
Given with chemo and on following 2 days
What is Metoclopramide?
PROKINETIC DRUG
D2 antagonist, D2 receptors suppressed
Decreased CTZ sensitivity, antiemetic
Works by blocking the presynaptic D2 receptors and increasing ACH release
This increases gastric emptying/upper GI motility/Lower esophageal sphincter tone
Indications for Metoclopramide?
Gastroparesis
GERD
Adverse effects of Metoclopramide?
Dizziness, fatigue, seizures, sedation
Increases prolactin, can cause neuroleptic malignant syndrome
What is Cisapride?
Prokinetic
5HT4 agonist
5HT3 antagonist
Indications for Cisapride?
GERD
Gastroparesis not controlled by other treatments
Adverse effects of Cisapride?
Cardiac arrhythmias, prolonged QT interval due to CYP3A4 interaction with other drugs (increases cisapride)
Headache, N/V, abdominal pain
What is erithromycin?
Prokinetic drug
Motilin type actions in upper GI tract, LES
Indications for erithromycin?
Diabetic gastroparesis
Toxicities with erithromycin?
Cramps
Impairs motility
Dumping of stomach contents into small bowel (used for bezoars due to Procardia XL)
Which agent is used for bezoars due to procardia XL?
Erithromycin
What is Lubiprostone?
PGE1 analog used for IBS
It activates Cl channels to increase fluid secretion into the GI tract
Indications for Lubiprostone?
Treatment of chronic idiopathic constipation and IBS-constipation
LUB = lube = lubes GI tract = less constipation
What is Alosetron?
5HT3 antagonist, decreases gastric motility
Indications for Alosetron?
Diarrhea predominant IBS in women
Cautions with Alosetron?
It was introduced and withdrawn in 2000 due to acute ischemic colitis
Reintroduced in 2002 with a black box warning and lower dose/specific education and monitoring conditions
Use is very limited, a prescribing program is required, at lower doses
Adverse effects of Alosetron?
Constipation, sometimes severe requiring constipation
Hypertension
Arrhythmias
Sleep disorders
