Week 6 - Antiemetics Flashcards
Emesis is defined as the action or process of _______ OR the reflex act of _____ the contents of the _____ through the ______.
vomiting, ejecting, stomach, mouth
What are some of the common causes of Emesis?
- Ingestion of toxins:
Poisonous plants
Spoiled cat/dog food
Various human medication
Pieces of string or yarn (cats)
Certain human foods - Certain medications, cancer chemotherapy and radiation
- Intense pain
- Emotional stress (such as fear)
- A reaction to certain smells or odors
- Early stages of pregnancy (not enough data in animals)
What are locally acting emetics?
Locally acting emetic cause gastric irritation
What are central acting emetics?
No BBB so drugs can enter and act faster here
What are the triggers and centers of emesis?
Nausea and vomiting may be manifestations of many conditions and may occur due
to stimulation of emesis vomiting center (VC) that responds to inputs from:
What parts of the brain are involved in emesis?
Vomiting enter is located in the medulla oblongata.
Receptors listed under each
What connects with vomiting center?
What are the main NTs and their receptors involved in the pathophysiology of N&V?
Receptors in green
When is therapeutic emesis used?
In prevention of clinical signs in dogs and cats who have had oral exposure to toxins,
medications, plant hazards, people food (apple seeds, apricot seeds, alcohol, coffee, chocolate).
What are some examples of therapeutic emetics used on dogs?
Apomorphine
Hydrogen peroxide
What are some examples of therapeutic emetics used on cats?
Xylazine
Medetomidine/dexmedetomidine
Midazolam/Hydromorphone combination
Receptors in CTZ
Dogs
* Increase ____ receptors compared to cats — stimulation
of emesis is more ______
* Increased ___ receptors — _____ is a more potent emetic agent in dogs
D2, successful, H1, histamine
Receptors in CTZ
Cats
Decreased ___ receptors … _______ ______ as anti-emetic drugs are less successful in cats
* Increased sensitivity to ___ -receptors… greater emesis production by certain ___-________
D2, Dopamine, antagonists, α2, α2, stimulants
What does this mean?
Dogs and cats respond differently to emetic and anti-emetic drugs
What is Apomorphine’s MOA?
a non-selective Dopamine Agonist (activates D2 and D1
What is a brand name of Apo?
Apokyn^R
Because dogs have more ______ receptors, they are more likely
to _____ when given apomorphine
dopamine, vomit
What are the therapeutic uses of Apomorphine?
Can be given orally (slow action)
Rapid onset when injected
The ability to reverse
Dose: 0.02 -0.04 mg/kg , IV or IM
Because dogs have more ______ receptors, they are more likely
to _____ when given apomorphine
dopamine, vomit
Because cats have less ___ receptors, they are less likely to vomit when given apomorphine.
D2
Apomorphine act directly on the ____
CTZ
Contrary to its name, apomorphine does not bind
to ______ receptors. However, it has some ____-like effects. ______ have repressive effects on the CNS, such as?
opioid, opioid, Opioids
* Cause sedation
* Cardiac and respiratory depression
* Suppression of the emetic (vomiting) center
Apomorphine causes?
Emesis and it can also suppress emesis.
Apomorphine’s effect depends on ? Provide examples.
which center in the brain is reached faster.
* If it reached the CTZ first, we get emesis
IV injection of apomorphine will reach the CTZ in the blood and emesis will start immediately
Crossing BBB takes longer for the drug: by the time it has its suppressing effect…. Its good!
Apomorphine
* If its opioid properties reach the Emesis Center first, it will shut it down and prevent emesis
What is important about administering Apomorphine?
The route of administration is important.
When administering apomorphine, __ or ______ (___) is best to win the race to the CTZ.
IV, transmucosal, Clevor
Transmucosal administration and Apo:
Highly dissolvable tablet into conjunctiva and eye ball
Easy absorption into mucosal
Can be irritation to sclera
Now you have to fish out the tablet back
Can you reverse Apomorphine? If so, explain how.
Too much sedation?
Can reverse with an opioid antagonist such as Naloxone
So, this is reversal of CNS effects - Not reversal of emesis
Too much emesis?
Can reverse with a dopaminergic antagonist such as Acepromazine (ACE)
Emesis in cats
Cats like ___-____ drugs such as ?
α2 -agonist
xylazine & medetomidine/dexmedetomidine
Alpha-agonist drugs are
* Highly ______, directly stimulate receptors in the brain and __
* Stimulate ___ -receptors in ____ and ____ center
* Dose: ?
* Vomiting within ____
lipophilic, GI, α2, CTZ, emetic
0.4-0.5 mg/kg, IV or IM
minutes
Which emetics are most successful in cats? Explain why.
α2- antagonists: Yohimbine (xylazine)
Atipamezole (medetomidine)
* Best option for cats
* Commonly used
* Not reliable in dogs
* Use lower doses than are used for sedation
What do you have to be mindful of when adminstering antiemetics?
vomiting is a protective mechanisms, only use anti-emetics when
vomiting become a deterrent to patient’s health and recovery
Mask signs of disease / improvement
Toxin ingestion: may allow it to remain in GI tract
What is the MOA of Ondansetron and Graniestron?
Block 5-HT3 receptor in VC and CTZ
What are the routes of administration commonly used for Ondansetron and Graniestron?
Orally or i.p
In what situations would you use Ondansetron or Graniestron?
Chemotherapy induced nausea and vomiting (cisplatin)
Post-radiation and post-operative nausea and vomiting
Effects are increased by combination with corticosteroids and NK1 antagonists
What are the adverse effects of Ondansetron and Granisetron?
(well tolerated)
Mild headache
Dizziness
Itching
Constipation/diarrhea
Minor ECG abnormalities
Ondanstron and Graniestron are ?
Serotonin 5-HT3 Antagonists
What are the two types of Dopamine D2 Antagonists?
Prokinetic drugs
Neuroleptics (antipsychotics)
Give two examples of Dopamine - prokinetic drugs
Metoclopramide (ReglanR)
Domperidone
Give two examples of Dopamine - neuroleptics (antipsychotics)
Chlorpromazine
Droperidol
What is the MOA of Dopamine D2 Antagonists?
Block D2 receptors and serotonin receptors in CTZ
What are Dopamine D2 Antagonists typically used for?
Most commonly used for NV of non-specific causes
Drug response, post-operative
What are the adverse effects of Dopamine D2 Antagonists?
Dyskinesia
Sedation
Postural hypotension
Extrapyramidal symptoms: tremor, rigidity
List two examples of Substance P Antagonists?
- Aprepitant (PO)
- Cerenia (PO; SC; IV), 2 hr before travel (pain management)
What is the MOA of Substance P Antagonists?
Competitively binds to the neurokinin1 (NK1) receptor
in VC and other areas
What are Substance P Antagonists used for?
To treat motion sickness
In prevention of acute and delayed chemotherapy-induced NV
Post-operative NV (less often)
Usually combined with 5-HT3 antagonists and corticosteroids
What are the adverse effects of Substance P Antagonists?
Dyskinesia
Sedation
Dizziness
Hiccups
Hypotension
Name two examples of Antihistamines: H1 Antagonists
Diphenhydramine (Benadryl R )
Dimenhydrinate (Gravol R
What is the MOA of Antihistamines: H1 Antagonists
Block histamine at H1 receptor (dogs have lot of H1 receptors)
Block Ach at muscarinic M1 receptor
What are Antihistamines: H1 Antagonists typically used for?
Effective for motion sickness (some benefit for dogs, poor response in cats)
morning sickness in pregnancy
What are the adverse effects of Antihistamines: H1 Antagonists?
Prominent sedation, hypotension, confusion
Anticholinergic effects (dry mouth, dilated pupils, urinary retention, constipation)
List two examples of Anticholinergics: Muscarinic Receptor Antagonists
Hyoscine Butylbromide (Hysomide R )
Dicyclomine
What is the MOA of Anticholinergics: Muscarinic Receptor Antagonists
Block Ach at the muscarinic M1 receptor
What is the route of administration typically used for Anticholinergics: Muscarinic Receptor Antagonists?
Orally, injections, patches
What is the route of administration typically used for Anticholinergics: Muscarinic Receptor Antagonists?
Orally, injections, patches
What are Anticholinergics: Muscarinic Receptor Antagonists typically used for?
In motion sickness (transdermal patches behind the ear)
Morning sickness (dicyclomide)
Not in chemotherapy-induced NV
What are the adverse effects of Anticholinergics: Muscarinic Receptor Antagonists
Tachycardia
Blurred vision
Dry mouth
Constipation
Urinary retention (atropine-like actions)
List some examples of Benzodiazepines?
Lorazepam (PO, IV)
Diazepam (PO, IV, PR)
Midazolam (PO, IV, PR, Intranasal, SL)
What is the MOA of BDZ’s?
Enhance effects of GABA by binding to receptors in the brain
What are BDZ’s used for?
Psychotropic medication
Calming effect on the brain (GABAA –mediated)
Anticipatory nausea and vomiting (chemotherapy – induced )
What are the adverse effects of BDZ’s?
Sedation
Dry mouth
Dizziness
Paradoxical agitatio
List some examples of corticosteroids?
Dexamethasone
Methylprednisolone
What is the MOA of Corticosteroids?
Not well understood (anti-inflammatory effects)
What are Corticosteroids used for?
In chemotherapy-induced vomiting
Combined with 5-HT3 antagonists or NK1 receptor antagonists
What are the adverse effects of corticosteroids?
Hyperglycemia
Hypertension
Osteoporosis
Insomnia
increased intraocular pressure,
Increased susceptibility to infection
increased appetite & obesity
List some examples of Cannabinoids
Nabilone
Dronabinol
What is the MOA of Cannabinoids?
not understood, act at CB1 receptors in VC
What are cannabinoids used for?
Not commonly
Anticancer drug-induced vomiting
What are the adverse effects of cannabinoids?
Euphoria
Dysphoria
Sedation
Agitation
Hallucination
Withdrawal syndrome:
Restless
Insomnia
Irritability
Autonomic effects:
Tachycardia
Palpitation
