Antiemetics Flashcards
What is emesis?
the action or process of vomiting as a reflex to eject contents of the stomach through the mouth
What are 6 common causes of emesis?
- ingestion of toxins - plants, spoiled food, human medication, string/yarn, certain human food
- medications - chemotherapy, radiation
- intense pain
- emotional stress - fear, anxiety
- reaction to certain smells or odors
- early stages of pregnancy (not really in animals)
In what 2 ways do most emetics work?
- locally acting on GI system
- centrally acting on the chemoreceptor trigger zone (CTZ) and vomiting center in the CNS
What are the 3 major parts of the brain responsible for emesis? What stimuli do they respond to?
- CTZ - uremic toxins, hepatotoxins, endotoxins
- vestibular aparatus - motion
- cerebral cortex - anxiety, stress
What stimuli does the GI tract respond to when inducing emesis?
- toxins
- cell necrosis
- inflammation
- distension
- chemotherapy
- radiation
Emesis triggers and centers:
What 4 stimuli tend to stimulate the vomiting center in the brain, causing nausea and vomiting?
- CTZ stimulation
- disturbance of vestibular system
- higher cortical centers stimulation
- periphery (pharynx, GI) via sensory nerves
4 parts of the brain responsible for emesis and their receptors:
What are the 7 main neurotransmitters in the emetic center?
- histamine (H1)
- serotonin (5-HT3)
- substance P (NK1)
- GABA (a + b)
- endorphins (µ, κ, CB1)
- dopamine (D2)
- acetylcholine (M1)
When is therapeutic emesis induced?
in prevention of clinical signs in dogs and cats who have had oral exposure to toxins, medications, plant hazards, and people food
What 2 emetics are commonly used in dogs?
- apomorphine
- hydrogen peroxide
What 3 emetics are commonly used in cats?
- xylazine
- medetomidine/dexmedetomidine
- midazolam/hydromorphone combo
Why do dogs and cats respond differently to emetics?
dogs and cats have different receptors in their CTZ
DOGS: increased D2 and H1 receptors
CATS: decreased D2 receptors and increased sensitivity to α2 receptors
(dopamine and histamine = dog)
(α-2 stimulants = cats)
What is the mechanism of action of Apomorphine (Apokyn)? How does it work as an emetic in dogs and cats?
non-selective dopamine agonist (D1 and D2)
DOGS: works really well due to high numbers of D2 receptors
CATS: have less D2 receptors - less likely to vomit
Why are drugs readily able to act on the CTZ?
no BBB
Where in the brain does Apomorphine act?
CTZ
Contrary to its name, Apomorphine does not bind opioid receptors. Why does it have this name?
has some opioid-like repressive effects on the CNS
- sedation
- cardiac and respiratory depression
- suppression of emetic vomiting center (causes and represses???)
Why is Apomorphine able to stimulate and repress emesis?
depends on which center in the brain is reached faster
- CTZ first = emesis (IV injection)
- emesis center first = prevents emesis (once it crosses BBB, the animal is able to stop vomiting)
What is the best way to administer Apomorphine to stimulate emesis?
IV or transmucosal
What version of Apomorphine is used transmucosally?
Clevor, a highly dissolvable tablet applied to conjunctiva and eyeball, making it easily absorbable
- can irritate sclera
- tablet must be fished out
In what 2 situations is Apomorphine reversed? How is this done?
too much sedation
- opioid antagonist = Naloxone, which reverses CNS effects, NOT EMESIS
too much emesis
- dopaminergic antagonist = Acetopromazine (ACE)
What classification of drugs works best for emesis in cats? Where in the brain does it affect?
α2-agonists, like Xylazine and Medetomidine/Dexmedetomidine
CTZ and emetic center - highly lipophilic, directly stimulates receptors in brain and GI —> vomiting in minutes
What 2 drugs are used to reverse emesis in cats?
(α2 antagonists)
1. Yohimbine (when using Xylazine)
2. Atipamezole (when using Medetomidine)
- not reliable in dogs
- can be used in lower doses for sedation
What is the purpose of antiemetics? Why should they be used carefully?
stop or decrease nausea and vomiting
vomiting is a protective mechanism —> only use when vomiting is deterrent to patient’s health and recovery
- can mask signs of disease/improvement and allow toxins to remain in GI
What are the 7 most common antiemetic drug classes?
- serotonin (5-HT3) receptor antagonists
- dopamine (D2) receptor antagonists
- substance P (NK1) receptor antagonists
- histamine (H1) receptor antagonists
- acetylcholine (muscarinic) receptor antagonists
- cannabinoids
- glucocorticoids
What determines the choice of antiemetic drugs?
etiology
What are the most common 2 serotonin antagonists used and antiemetics? What is their mechanism of action?
- Ondansetron (Zofran)
- Granisetron
block 5-HT3 receptors in VC and CTZ
What are 2 common situations where serotonin antagonists are used as antiemetics? What is it used in combination with?
- chemotherapy-induced nausea and vomiting (Cisplatin)
- post-radiation and post-operative nausea and vomiting
increases effect when used with corticosteroids and NK1 antagonists
Serotonin antagonists are pretty well-tolerated antiemetics. What are 5 possible adverse effects?
- mild headache
- dizziness
- itching
- constipation/diarrhea
- minor ECG abnormalities
What are the 2 types of dopamine (D2) antagonists used as antiemetics?
- prokinetic drugs - Metoclopramide (Reglan), Domperidone
- neuroleptics (antipsychotics) - Chlorpromazine, Droperidol
What is the mechanism of action of Metoclopramide and Domperidone? In what 3 situations are they commonly used?
block D2 receptors and serotonin receptors in CTZ
- non-specific nausea and vomiting
- drug responses
- post-operative
What are 4 possible adverse effects of Metoclopramide and Domperidone?
(D2 antagonists)
1. dyskinesia (involuntary movements)
2. sedation
3. postural hypotension
4. extrapyramidal symptoms: tremor, rigidity
What are 2 common substance P antagonists used as antiemetics? What is their mechanism of action?
- Cerenia* (PO, SC, IV)
- Aprepitant (PO)
competitively binds to the neurokinin1 (NK1) receptor in VC and other areas
In what situation is Cerenia most commonly used?
- given 2 hours before travel for motion sickness
- pain management
What are 3 common situations where substance P antagonists are used? What is it commonly combined with?
- treat motion sickness
- prevention of acute and delayed chemotherapy-induced nausea and vomiting
- post-operative nausea and vomiting
combined with serotonin antagonists and corticosteroids
What are 5 common adverse effects of substance P antagonists?
- dyskinesia
- sedation
- dizziness
- hiccups
- hypotension
What are 2 common antihistamines used as antiemetics? What is their mechanism of action?
- Diphenhydramine (Benadryl)
- Dimenhydrinate (Gravol)
block histamine at H1 receptor (dogs) and block ACh at muscarinic M1 receptors (cats)
What are 2 common uses for antihistamines as antiemetics?
- motion sickness (dogs, poor response in cats)
- morning sickness (not common in animals)
What are 2 possible adverse effects of antihistamines as antiemetics?
- prominent sedation, hypotension, and confusion
- anticholinergic effects: dry mouth, dilated pupils, urinary retention, constipation
What are 2 common anticholinergics used as antiemetics? What is their mechanism of action?
- Hyoscine Butylbromide (Hysomide)
- Dicyclomine
(PO, injections, patches)
block Ach at the muscarinic M1 receptor
What are the 2 common situations that anticholinergics are used as antiemetics? When is it specifically NOT used?
- motion sickness (patches behind ears)
- morning sickness (Dicyclomide)
- chemotherapy-induced nausea and vomiting
What are 5 possible adverse effects of anticholinergics as antiemetics?
- tachycardia
- blurred vision
- dry mouth
- constipation
- urinary retention
What 3 benzodiazepines are commonly used as antiemetics? What is their mechanism of action?
- Lorazepam (PO, IV)
- Diazepam (PO, IV, PR)
- Midazolam (PO, IV, PR, IN, SL)
enhances the effects of GABA by binding to receptors in the brain
What are 3 situations where benzodiazepines are used as antiemetics?
- psychotropic medication
- calming effect (GABAa)
- anticipatory nausea and vomiting (chemotherapy)
What are 4 possible adverse effects of benzodiazepines as antiemetics?
- sedation
- dry mouth
- dizziness
- paradoxical agitation
What 2 corticosteroids are used as antiemetics? What is their mechanism of action?
- Dexamethasone
- Methylprednisolone
not well-understood - anti-inflammatory effects
When are corticosteroids commonly used as antiemetics? What is it commonly used in combination with?
chemotherapy-induced vomiting
serotonin antagonists or NK1 antagonists
What are 7 possible adverse effects of corticosteroids as antiemetics?
- hyperglycemia
- hypertension
- osteoperosis
- insomnia
- increased intraocular pressure
- increased susceptibility to infection
- increased appetite and obesity
What are 2 cannabinoids used as antiemetics? What is their mechanism of action?
- Nabilone
- Dronabinol
not well-understood - act on CB1 receptors in VC
Cannabinoids are not commonly used as antiemetics. When can it be used? What are some possible adverse effects?
anticancer drug-induced vomiting
- euphoria/dysphoria
- sedation
- agitation
- hallucination
- withdrawal syndrome: restless, insomnia, irritibility
- autonomic effects: tachycardia, palpitation
Antiemetic drugs and their actions in the brain:
What pneumonic is used for causes of emesis?
V = Vestibular - motion sickness, benign paroxysmal positional vertigo, Meniere’s disease, tumor, inner ear infection/inflammation
O = Obstruction - constipation, ileus, intestinal pseudo-onbstruction, partial/full bowel obstruction, ascites, adhesion
M = Motility disorder - gastroparesis, neurological, IBS, medications, hypo/hyperthyroidism, GERD, gastroenteritis, scleoderma
I - Infection, Inflammation, Increased ICP - bacteria/virus, strock, concussion, brain tumor, radiation/chemotherapy, gastroenteritis, pancreatitis, cholecystitis
T = toxins - metabolic disorders, medications, organ failure, poisoning, substance abuse
