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What things INHIBIT the CTZ?
- Dopamine Antagonist
- Serotonin Antaonist
- Histamine Antagonist
- Acetylcholine (Muscarinic) Antagonist
What things stimulate the CTZ?
- Opioids (dose dependent)
What does the CTZ stimulate?
the vomiting center :)
What things stimulate the vomiting center (via the vagus nerve)?
- GI distension
- Higher Centers
Can opioids stimulate and inhibit N/V?
Yes. They stimulate the CTZ (dose dependent) but can also inhibit the vomiting center.
PONV is complex. Explain the physiology
- Vomiting center gets input from chemoreceptor trigger zone in medulla but gets input from other areas including the pharynx, the GI tract, mediastinum, visual center, also the vestibular
- portion of the 8th cranial nerve. (Because of that even ambulation or motion [people who have hx of motion sickness] just riding in
- stretcher can trigger).
- So for prophylaxis and tx of opioid induced nausea, want to hit a # of different receptors, so you see different receptors that will all effect Chemoreceptor trigger zone
What are risk factors for PONV? (common ones)
- Pedi > adult
- Pediatrics - Postop emesis increase with age to a peak in preadolescence
- ? Increasing age in adulthood may decrease emesis
- Females > males (2-3 times) & severity of vomiting also greater
- Varies according to menstrual cycle with 4 fold increase during menses
- Body weight
- ? Obesity (BMI > 30) associated with ↑ PONV
- (Difficult airway, increase in gastric volume increase in accumultion of fat soluble anesthetics. Incidence of gall bladder disease and reflux)
- Smoking status
- PONV more common is nonsmokers
- Motion sickness or Hx N/V
- Increases risk
What are some other risk factors for PONV?
- May increase gastric volume 2° stress hormones
- May be due to air swallowing → gastric distention → activation of mechanoreceptors
- Presence or absence of food
- Both cause increased PONV
- Gastroparesis (autonomic dysfunction)
- Increased risk
- Type & duration of surgery
- More common in abdominal vs non-abdominal surgery
- Marked increase in females undergoing laparascopic surgery
- Strabismus repair
- T & A
- Middle ear surgery
- The longer the surgery the greater the risk
- Anesthetic agents
- Nitrous oxide
What are some post-op factors that influence PONV?
- movement (getting up and ambulating pt.)
- the use of opioids
- Premature PO.
Serotonin, 5 hydroxytryptamine (5-HT) is an Endogenous vasoactive substance involved with... (What 3 things)?
- Pain transmission
Serotonin (5-HT) if found in large amounts in CNS, GI tract, & platelets.
It is important neurotransmitter in CNS, where is it located?
- Limbic system
- Spinal cord
How is serotonin formed? What inactivates it?
- Formed by decarboxylation of tryptophan
- (from dietary sources)
MAO inactivates serotonin into 5-HIAA
How many receptors types + subtyes are there for serotonin?
At least 7 receptor types + subtypes
What are the 5-HT 3 receptors?
- Excitatory ligand-gated nonselective cation channels
- (Like Na+ or Ca+ channel)
Can serotonin trigger the vomitting reflex?
YES~It can mediate vomiting & are found in GI tract & CTZ in brain
Hemmings: Serotonin activation of the CTZ and vagal afferents can both trigger the vomiting reflex
Antagonists cause anti-emetic effects
What are some serotonin agonist?
- sumatriptan for migraines.
- Phen/Phen used for weight loss but withdrawn from market
How do 5HT3 antagonists work?
- Selectively block serotonin 5-HT 3 receptors with little to no effect on dopamine receptors
- No effect on gastric motility or lower esophageal sphincter tone (unlike metaclopromide)
What are the side effects of the 5HT3 antagonists?
- Prolonged QT interval *(significant SE--most frequently seen with Dolasetron)
Name a few specific antagonists of the 5HT3 receptors and the corresponding dose.
- Ondansetron (Zofran) = 4-8mg (but as low as 1mg can be effective)
- Dolasetron (Anzemet) = 12.5mg
- Granisetron (Kytril) = 1mg
Name a Dopamine antagonist
Donperidone and cisapride also other types but we don't use them
What is the dopamine antagonist Metaclopramide structurally similar to?
procainamide but no local anesthetic activity
How does the Dopamine antagonist Metaclopramide work?
- Gastrointestinal prokinetic
- Increases lower esophageal sphincter tone
- Stimulates upper GI tract motility
- No effect on gastric acidity
- Mechanism of action: selective cholinergic stimulation
- ↑ smooth muscle tension in lower esophageal sphincter & gastric fundus
- ↑ gastric & small intestine motility
- Relaxation of pylorus & duodenum during gastric contraction
- Blocks dopamine receptors in CNS so may produce extrapyramidal side effects (Dopamine
- stimulates the CTZ)
What is the dose of the Dopamine antagonist Metaclopramide?
10-20 mg IV over 3-5 minutes
What are the side effects of Dopamine Antagonist Metaclopramide?
- Abdominal cramping
- Hypotension, tachycardia, bradycardia
- Extrapyramidal reactions
- --Akathisia (feeling of unease & restlessness in lower extremities-give midaz w/it if pt is awake)
- --Opisthotonus (type of spasm in which the head and heels arch backward in extreme hyperextension and the body forms a reverse bow)
- --Trismus (motor disturbance of the trigeminal nerve, especially spasm of the masticatory muscles, with difficulty in opening the mouth (lockjaw))
What are the contraindications to Dopamine Antagonist Metaclopramide?
- GI obstruction
- Malignant neurolept syndrome
- Also can cause increase ICP in head injury patients.
- Can be contraindicated in breast cancer
- can increase prolactin levels that may contribute to breast cancer.
Which drug has the possibility of an increase in arrhythmias if combined w/ ondansetron?
Because of potential for EPS, don’t combine metaclopromide with what drugs?
butyrophenones or phenothiazines
What are the Neuroleptics and how do they act as an anti-emetic?
Antipsychotic drugs, chemically diverse
Mechanism of action thought due to dopamine receptor blockade
What are the two types of Neuroleptics?
- Phenothiazines (Chlorpromazine)-Thorazine, compazine or phenergan
Tell me more about the Butyrophenones (Droperidol)
- Also decreases anxiety (haldol is a relative but with a longer duration of action & not used perioperatively)
- Prolonged QT interval due to impaired ventricular repolarization leading to Torsades de Pointe
- “Black box warning”
- ---Combined with fentanyl (Innovar)
- ---Trance-like cataleptic immobility, pt is dissociated & indifferent to environment
If EPS were to occur from Droperidol, how would you treat it?
What is the ant-emetic dose of Droperidol?
Corticosteroids can also act as an anti-emetic but only if they're given when?
- Only effective if give at the beginning of surgery
- --Decreases surgery induced inflammation
- --Increases endorphins resulting in mood elevation & appetite stimulation
What is the typical anti-emetic dose of Corticosteroids
What kind of patch can we use as an anti-emetic?
Scopolamine patch: also utilized particularly if pt has hx of motion sickness. Something that should be put on pre-op, takes a while to take effect. Pt need instruction about it.
Scopolamine is nice idea but need to think about it. Pupil dilation, tired? Not good for everyone
What are some non-pharmacologic treatments for N/V?