Decontamination agents and Antiemetics Flashcards
Sensory receptor zone
–Especially in the stomach and small intestine, the pharynx, and the inner ear; visual, olfactory, and painful stimuli that can also elicit vomiting
Chemoreceptive trigger zone (CTZ)
- -Located in area postrema, on floor of 4th ventricle.
- -OUTSIDE THE BBB.
- -Primary region for detection of blood-borne emetics
Vomiting center
- -Connected to chemoreceptive trigger zone
- -Located in medulla
- -Responsible for initiation and coordination of complex motor patterns needed for vomiting.
“Higher centers”
Responsible for memory, fear, dread, and anticipation
3 major stimuli that activate the vomiting center
- -Mechanical and/or painful stimuli (esp. in inner ear, local GI irritation, pharynx)
- -Blood borne emetics
- -Higher centers
How does local GI irritation trigger the vomiting center
Irritation–> vagal and sympathetic afferents from the stomach and small intestine that can be modulated by actin of 5HT3 receptors–> solitary tract nucleus and chemoreceptive trigger zone–> vomiting center
How does the gag reflex trigger the vomiting center?
Glossopharyngeal and trigeminal afferents–> solitary tract nucleus–> vomiting center
What are the chemoreceptive trigger zone receptors?
- -Serotonin
- -Histmine
- -Muscarinics
- -Opioids
- -Dopamine
Serotonin receptor locations
- -GI tract* (primary)
- -Chemoreceptive trigger zone
- -Inside BBB
Dopamine receptor locations
- -GI tract
- -CTZ*
- -BBB
Muscarinic receptor locations
- -GI tract
- -CTZ
- -BBB*
Histamine receptor locations
Inside BBB
NK1 receptor locations
Inside BBB
Cannabinoid receptor location
Inside BBB
Opioid receptor locations
- -GI tract
- -CTX*
- -BBB
Activated charcoal
- -Absorbs many drugs and poisons because of large SA
- -Must be given 10:1 by weight
- -Doesn’t bind Iron, lithium, potassium
- -Binds EtOH and cyanide poorly
- -Not useful in cases of corrosive mineral acids or alkalis
- -Upper GI
Polyethylene glycol-electrolyte solution
- -May help hasten removal of toxins and reduce absorption
- -Whole bowel irrigation can enhance decontamination after ingesting iron, enteric coated medicines, illicit drugs, foreign bodies
- -Used for endoscopic procedures
- -Cathartics
- -Lower GI
IPECAC
- -Emetic agent
- -Induces vomiting
- -Controversial use
- -Don’t use for poison remedy OTC
- -Local irritant effect
- -Acts on CTZ
- -Emesis may not occur if stomach emptied
- -15-30 min to effect
Antiemetics
- -Gen. more effective at preventing vomiting than stopping emesis once it has started
- -Often used in combo because they act synergistically
Serotonin (5HT3) Anagonists
- -Dolasetron
- -Granisetron
- -Ondansetron
- -Palonosetron
Serotonin (5HT3) antagonist MOA
- -Blockade peripheral 5HT3 receptors on primary afferents
- -Also in CTZ and vomiting center
Therapeutic uses for serotonin antagonists
- -Drug of choice for chemotherapy induced nausea and vomiting
- -More effective preventing acute phase (24 hrs after start) if given 30 min before antineoplastic
- -Not as good for delayed phase
- -Post-op and post-radiation nausea and vomiting
Are serotonin antagonists effective for motion sickness?
No
Side effects of serotonin antagonists
- -Well tolerated with good safety profiles
- -Most side effects transient
- -Constipation, dizziness, mild headache
- -Small QT elongation, but not clinically relevant
What is the most effective drug for most effective agent for motion sickness treatment
Scopolamine when given as a transdermal patch
Anticholinergic name
Scopolamine
What are the only truly effective agents for the prevention of cancer chemotherapy induced emesis?
Serotonin (5HT3 antagonists)
MOA of scopolamine
- -Muscarinic and dopaminergic receptor antagonist in cerebellum –> widely distributed in CNS
- -Transdermal patch–> decreases side effects compared to oral or parenteral admin
Neurokinin receptor 1 (NK1) Antagonist
Aprepitant (oral)/ Fosaprepitant (IV)
Aprepitant/ fosaprepitant MOA
Substance P receptor antagonists. Central “higher order center” NK receptors
Therapeutic uses for aprepitant/fosaprepitant?
Chemo induced N and V in combo with 5HT3 antagonist and dexamethasone
Side effects for aprepitant/fosaprepitant?
- -Generally well tolerated
- -Fatigue, dizziness, diarrhea
- -Metabolized by CYP3A4 (esp. some chemo agents! Can make other side effects worse, need to pay attention to bone marrow suppression)
Antihistamine drug names
- -Dimenhydrinate
- -Diphenhydramine
- -Meclizine
Antihistamine (H1) MOA
- -Sedation
- -H1 may not be primary mechanism, may be anti-muscarinic
Antihistamine side effects
- -Anticholinergic (confusion, dry mouth etc,)
- -Drug interactions w/ some antibiotics
- -Don’t use during pregnancy
Dopamine receptor antagonist names
- -Droperidol
- -Metoclopramide
- -Prochlorperazine
- -Promethazine
- -Thiethylperazine
Dopamine receptor antagonists
- -Receptors in CTZ zone
- -May have muscarinic antagonism?
- -“Reseting” GI motility
- -Sedation
Cannabinoid names
Dronabinol
Nabilone
Side effects of cannabinoids
- -Euphoria
- -Sedation
- -Hallucinations
- -Dry mouth
- -Increased appetite (good for cancer patients)
What are cannabinoids often given with?
Phenothiazines
Corticosteroid MOA in vomiting
Unknown
Corticosteroids
Dexamethasone, methylprednisolone
What are corticosteroids used with?
5HT3 antagonists and aprepitants
