Gastrointestinal Flashcards
What drugs are used for Nausea causing stimulants: Drugs, Ketoacidosis, Uremia
Phenothiazines
Metaclopramide
Work in the CTZ (dopamine, opiate receptors)
What drugs are used for nausea causing stimulants: Obstruction, Gastroparesis, Visceral Pain
Metaclopramide
Analgesics
Work on the afferent impulses from the periphery (dopamine, opiate receptors)
What drugs are used for nausea causing stimulants: Motion sickness, vestibular inflammation
Antihistamines
Anticholinergics
Work in the vestibular apparatus (acetylcholine, norepinephrine receptors)
What drugs are used for nausea causing stimulants: Higher brain stem (Emotions, Sights, Smells, Tastes)
Benzodiazepines
Dronabinol
Corticosteroids
Work in the cortical structures
CTZ location and mechanism
Located in the area postrema on the fourth ventricle floor of the Medulla
Exposed to both blood and CSF - toxins in the blood can stimulate a response in the CTZ
GI tract nausea stimulants MOA
Visceral afferent nerves - splanchnic nerves - from the pharynx and GI tract transmit impulses along the vagus nerve to the vomiting center
CNS nausea stimulants MOA
Motion sickness is a CNS mediated response by the vestibular system.
Acetylcholine and histamine receptors in the vestibular center need to be blocked to block the effects of nausea
Limbic system nausea stimulants MOA
Increased ICP can stimulate nausea. Higher brain functions - emotions, mood, feelings, memory - can trigger a nausea response
What are the physiologic symptoms of nausea?
Flushing, pallor, tachycardia, hyper salivation, gstric stasis and decreased pyloric tone, mucosal blood flow, and duodenal contractions iwth reflux into the stomach
What is retching?
The second phase of emesis.
The involuntary synchronized labored movement of the abdominal and thoracic muscles before vomiting.
What is vomiting?
The coordinated contractions of the abdominal and thoracic muscles to expel the gastric contents
Phenothiazines (Prochlorperazine / Compazine; Promethazine / Phenergan) MOA:
Dopamine receptor blockade in the CTZ.
Anticholinergic activity in the vomiting and vestibular centers
Phenothiazines (Prochlorperazine / Compazine; Promethazine / Phenergan) Indications:
Monotherapy or combo for mild to moderate nausea and vomiting. IV, PO, Rectal, IM
Migraine, GI d/o, CINV, Sedative properties
Phenothiazines (Prochlorperazine / Compazine; Promethazine / Phenergan) CXN:
BEERS criteria
CNS depression
High doses = extrapyramidal symptoms (by blocking central dopaminergic receptors) - Tx with Benadryl
Decrease Sz threshold
Contraindicated: Parkinson’s Dz, Sz d/o
Antihistamines-Anticholinergics (Hydroxazine/Vistaril, Atarax; Meclizine/ Bonine, Antivert; Dimenhydrinate / Dramamine; Scopolamine / Transderm Scop) MOA:
Antihistamine MOA: Block H1 receptors in vestibular system and brainstem preventing signaling to vomiting center
Anticholinergic MOA: Block muscarinic receptors in the vestibular system and the vomiting center inhibiting PNS and reduce communication between vestibular and vomiting center
Antihistamines-Anticholinergics (Hydroxazine/Vistaril, Atarax; Meclizine/ Bonine, Antivert; Dimenhydrinate / Dramamine; Scopolamine / Transderm Scop) Uses:
Useful for post op nausea, mild nausea, motion sickness
Nausea in Pregnancy
Take 30-60 min before the event
Antihistamines-Anticholinergics (Hydroxazine/Vistaril, Atarax; Meclizine/ Bonine, Antivert; Dimenhydrinate / Dramamine; Scopolamine / Transderm Scop) Contraindications:
Nursing Mothers
Asthma
Glaucoma
GI or Urinary obstruction
BEERS Criteria
Antihistamines-Anticholinergics (Hydroxazine/Vistaril, Atarax; Meclizine/ Bonine, Antivert; Dimenhydrinate / Dramamine; Scopolamine / Transderm Scop) Adverse Events:
Sedation, Drowsiness, Confusion
Blurred vision, dry mouth, urinary retention, tachycardia
Benzodiazepines (Lorazepam/Ativan) MOA:
Unclear, most likely acts centrally to inhibit the vomiting center. Act on the CNS to reduce anxiety and have sedative effect
Benzodiazepines (Lorazepam/Ativan) Uses:
Anticipatory nausea as a pre-treatment to prevent CINV
Antiemetic + anxiolysis + amnesia
Benzodiazepines (Lorazepam/Ativan) CXN:
CNS depression, polypharmacy
Contraindicated: Hepatic or renal failure
Serotonin 5-Hydroxytryptamine (5-HT3) Receptor Antagonists (Ondansetron / Zofran; Granisetron / Kytril, Sanusco; Palono-Setron / Aloxi; Dolsetron / Anzemet) MOA:
Block the 5HT3 in CTZ and vagal nerve terminals. Antagonizing type 3 serotonin receptors centrally in the CTZ and peripherally in the intestinal wall, stomach
Serotonin 5-Hydroxytryptamine (5-HT3) Receptor Antagonists (Ondansetron / Zofran; Granisetron / Kytril, Sanusco; Palono-Setron / Aloxi; Dolsetron / Anzemet) Uses:
Post Op N/V,
CINV,
Radiation-Induced N/V
Serotonin 5-Hydroxytryptamine (5-HT3) Receptor Antagonists (Ondansetron / Zofran; Granisetron / Kytril, Sanusco; Palono-Setron / Aloxi; Dolsetron / Anzemet) Adverse Effects:
Mild-Moderate HA
Diarrhea or constipation
Epigastric pain
Increased hepatic enzyme levels
Prolonged PR and QT interval, widened QRS
CXN: studies reveal limited teratogen risk in the 1st trimester
Can cross into breastmilk
Metoclopramide / Reglan MOA:
in addition to blocking D2 receptors, enhances gastric motility by stimulating the release of acetylcholine in the GI tract increasing the duration and extent of esophageal contractions, the LES resting tone, gastric congtractions, and peristalsis of the duodenum and jejunum.
Metoclopramide / Reglan Uses:
Prevention and treatment of CINV
Post Op N/V
GI motility d/o
Diabetic gastric-stasis
GERD
Metoclopramide / Reglan Adverse Effects:
EPS - facial spasms, rhythmic protrusions of the tongue, involuntary mvmts of the limbs, motor restlessness, agitation, dystonia
Diarrhea
HTN if used with MAOI’s
Corticosteroids (Dexamethasone/Decadron; Methylprednisalone / Solu-Medrol) MOA:
Unknown, reduce inflammation in the vomiting center and inhibit prostaglandin synthesis. May cause anti-inflammatory effect on the brainstem and GI tract
Corticosteroids (Dexamethasone/Decadron; Methylprednisalone / Solu-Medrol) Uses:
CINV
N/V 2/2 ICP
Use in conjunction with other agents
Corticosteroids (Dexamethasone/Decadron; Methylprednisalone / Solu-Medrol) Adverse Events:
Mood swings
Depression
Anxiety
Aggression
Frank psychosis and personality changes
HA, Restlessness, insomnia
Increase in BG
Muscle wasting, adrenocortical insufficiency, osteoporosis
Cannabinoids (Tetrahydrocannabinol / THC; Dronabinol / Marinol; Nabilone / Cesamet) MOA:
Cannabinoid receptor and opiate receptors in the CNS and cerebral cortex, most likely the CTZ
NK1 receptor antagonists
Block the action of substance P, a neuropeptide involved in the emetic reflex
Cannabinoids (Tetrahydrocannabinol / THC; Dronabinol / Marinol; Nabilone / Cesamet) Uses:
Chemotherapy induced N/V, unresponsive to conventional therapy, stimulate appetite for weight loss
Cannabinoids (Tetrahydrocannabinol / THC; Dronabinol / Marinol; Nabilone / Cesamet) Adverse Events:
Sedation, ataxia, dysphoria
Hallucinations, anxiety, fear, memory loss, time disorientation
Orthostatic hypotension, blurred vision, tachycardia
Cannibinoid Hyperemesis Syndrome Characteristics
1) several years of preceding cannabis use, predating the onset of illness;
2) a cyclical pattern of hyperemesis every few weeks to months, at which time the patient is still using cannabis and;
3) resolution of the symptoms after cessation of cannabis use, confirmed by a negative urine drug screen.
KEY aspect of a patient’s presenting history is that their symptoms are relieved by hot baths or showers. This activity introduces the pathophysiology, clinical manifestation, and management of cannabis hyperemesis.
Cannibinoid Hyperemesis Syndrome Treatment
Benzodiazepines (short term)
Tricyclic Antidepressants (Long term)
Antiepileptics (levetiracetam)
Antipsychotics (Haloperidol)
First-Line Antiemetic Therapy
An antiemetic is selected based on patient-specific factors. Initially, a phenothiazine is used for mild to moderate nausea and vomiting. Promethazine and prochlorperazine are usually sufficient.
Second-Line Antiemetic Therapy
An antihistamine or anticholinergic preparation can be used. These are usually not as effective as phenothiazines but may be useful in mild nausea.
