Lect 10

• DRUGS Acting on the Central Nervous System (CNS) Lecture 16: Antiemetic Drugs Anait S Levenson, M.D., Ph.D
• Substance P Antagonists, such as Aprepitant, compete with the neurokinin1 (NK1) receptor in the VC and other areas.
• Anticholinergics block Ach at the muscarinic M1 receptor.
• Dopamine D2 Antagonists are used for the treatment of nausea and vomiting, with two types: prokinetic drugs and neuroleptics (antipsychotics).
• Corticosteroids are used in chemotherapy-induced vomiting.
• Benzodiazepines (BDZs) enhance the effects of GABA by binding to receptors in the brain.
• Antihistamines block histamine at the H1 receptor and Ach at the muscarinic M1 receptor.
• Dopamine D2 Antagonists block D2 receptors and serotonin receptors in the CTZ.
• Apomorphine can cause sedation, cardiac and respiratory depression, and suppression of the emetic (vomiting) center.
• The dose of Apomorphine is 0.02 - 0.04 mg/kg, IV or IM.
• Apomorphine, contrary to its name, does not bind to opioid receptors.
• Apomorphine, because cats have fewer D2 receptors, are less likely to vomit when given apomorphine.
• Apomorphine, because dogs have more dopamine receptors, are more likely to vomit when given apomorphine.
• Apomorphine, also known as Apokyn R, can be given orally for a slow action, but it has a rapid onset when injected.
• Apomorphine acts directly on the CTZ.
• Apomorphine causes emesis.
• Apomorphine is a non-selective Dopamine Agonist that activates D2 and D1 receptors, but it also has some opioid-like effects that can have repressive effects on the Central Nervous System (CNS).
• Apomorphine can suppress emesis.
• Dogs and cats respond differently to emetic and anti-emetic drugs.
• Apomorphine has the ability to reverse its effects.
• Nausea and vomiting may be manifestations of many conditions and may occur due to stimulation of the emesis vomiting center that responds to inputs from the Chemoreceptor Trigger Zone (CTZ), the Vestibular System, the Higher Cortical Centers (CNS), and the Periphery (Pharynx, GI) via sensory nerves.
• Emetics can be centrally acting or locally acting.
• Apomorphine, Hydrogen peroxide, Xylazine, Medetomidine/dexmedetomidine, Midazolam/Hydromorphone combination are used as therapeutic emesis agents.
• An emetic agent is used to induce vomiting in poisoning.
• Therapeutic emesis is used in the prevention of clinical signs in dogs and cats who have had oral exposure to toxins, medications, plant hazards, people food.
• Emesis is the action or process of vomiting and the reflex act of ejecting the contents of the stomach through the mouth.
• The Vomiting Center (VC) and the Centrally Triggers Zone (CTZ) do not have a Blood-Brain Barrier (BBB).
• Different receptors in the Centrally Triggers Zone (CTZ) are present in dogs and cats, with dogs having increased D2 receptors compared to cats, and increased H1 receptors.
• Common causes of emesis include ingestion of toxins, certain medications, cancer chemotherapy and radiation, intense pain, emotional stress, a reaction to certain smells or odors, and early stages of pregnancy.
• Cats have decreased D2 receptors, increased sensitivity to α2-receptors, and greater emesis production by certain α2-stimulants.
• Main NTs and their Receptors in the Pathophysiology of Nausea and Vomiting.
• Antiemetic drugs stop or decrease nausea and vomiting, but should only be used when vomiting becomes a deterrent to patient’s health and recovery.
• The choice of antiemetic drugs depends on the etiology of emesis.
• Apomorphine is highly dissolvable into the conjunctiva and eyeball, facilitating easy absorption into mucosal.
• Apomorphine, if its opioid properties reach the Emesis Center first, will shut it down and prevent emesis.
• Apomorphine can be reversed with a dopaminergic antagonist such as Acepromazine (ACE), which is not a reversal of emesis.
• 5-HT3 receptor antagonists block the receptor in the VC and CTZ, and can be administered orally or i.p.
• Apomorphine can cause irritation to the sclera, making it necessary to fish out the tablet back.
• Apomorphine can be administered via IV or transmucosal (Clevor R) to win the race to the CTZ.
• Apomorphine can be reversed with an opioid antagonist such as Naloxone, which is not a reversal of emesis.