Pharm Lecture 5 Anti-emetics

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Pharm Lecture 5 Anti-emetics
2013-06-20 10:21:41
BC CRNA ANES PHARM Lecture Anti emetics

Summer 2013
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  1. What things INHIBIT the CTZ?
    • Dopamine Antagonist
    • Serotonin Antaonist
    • Histamine Antagonist
    • Acetylcholine (Muscarinic) Antagonist
    • Benzodiazapines
    • Propofol?
  2. What things stimulate the CTZ?
    • Vestibular
    • Opioids (dose dependent)
  3. What does the CTZ stimulate?
    the vomiting center :)
  4. What things stimulate the vomiting center  (via the vagus nerve)?
    • GI distension
    • Pharynx
    • Higher Centers
    • Mediastinum
  5. Can opioids stimulate and inhibit N/V?
    Yes. They stimulate the CTZ (dose dependent) but can also inhibit the vomiting center.
  6. 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
  7. What are risk factors for PONV? (common ones)
    • Age
    • Pedi > adult
    • Pediatrics - Postop emesis increase with age to a peak in preadolescence
    • ? Increasing age in adulthood may decrease emesis
    • Gender
    • 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
  8. What are some other risk factors for PONV?
    • Anxiety
    • 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
    • Orchiopexy
    • Middle ear surgery
    • The longer  the surgery the greater the risk
    • Anesthetic agents
    • Nitrous oxide
    • Opioids
  9. What are some post-op factors that influence PONV?
    • pain
    • movement (getting up and ambulating pt.)
    • hypovolemia
    • hypoglycemia
    • hypoxia
    • the use of opioids
    • Premature PO.
  10. Serotonin, 5 hydroxytryptamine (5-HT) is an Endogenous vasoactive substance involved with... (What 3 things)?
    • Vasoconstriction
    • Emesis
    • Pain transmission
  11. Serotonin (5-HT) if found in large amounts in CNS, GI tract, & platelets.
    It is important neurotransmitter in CNS, where is it located?
    • Retina
    • Limbic system
    • Hypothalamus
    • Cerebellum
    • Spinal cord
  12. How is serotonin formed? What inactivates it?
    • Formed by decarboxylation of tryptophan
    • (from dietary sources)

    MAO inactivates serotonin into 5-HIAA
  13. How many receptors types + subtyes are there for serotonin?
    At least 7 receptor types + subtypes
  14. What are the 5-HT 3 receptors?
    • Excitatory ligand-gated nonselective cation channels
    • (Like Na+ or Ca+ channel)
  15. 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
  16. What are some serotonin agonist?
    • sumatriptan for migraines.
    • Phen/Phen used for weight loss but withdrawn from market
  17. 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)
  18. What are the side effects of the 5HT3 antagonists?
    • Headache
    • Prolonged QT interval *(significant SE--most frequently seen with Dolasetron)
  19. 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
  20. Name a Dopamine antagonist
    Benzamides (Metoclopramide)

    Donperidone and cisapride also other types but we don't use them
  21. What is the dopamine antagonist Metaclopramide structurally similar to?
    procainamide but no local anesthetic activity
  22. 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)
  23. What is the dose of the Dopamine antagonist Metaclopramide?
    10-20 mg IV over 3-5 minutes
  24. 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))
  25. 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.
  26. Which drug has the possibility of an increase in arrhythmias if combined w/ ondansetron?
  27. Because of potential for EPS, don’t combine metaclopromide with what drugs?
    butyrophenones  or phenothiazines
  28. 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
  29. What are the two types of Neuroleptics?
    • Butyrophenones(Droperidol)
    • Phenothiazines (Chlorpromazine)-Thorazine, compazine or phenergan
  30. 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”
    • Neuroleptanalgesia
    • ---Combined with fentanyl (Innovar)
    • ---Trance-like cataleptic immobility, pt is dissociated & indifferent to environment
  31. If EPS were to occur from Droperidol, how would you treat it?
  32. What is the ant-emetic dose of Droperidol?
  33. 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
  34. What is the typical anti-emetic dose of Corticosteroids
    4-10mg IV
  35. 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
  36. What are some non-pharmacologic treatments for N/V?
    • Acupressure
    • Sea bands