L2 Antiemetics.pdf

Academic logo Antiemetics This lecture was presented by: Dr.Alaa Alanteet Dr. Mohammed Almutairi • • • • • • EDITING FILE Main text Male slide Female slide Important Dr, notes Extra info Objectives Classify the main different classes of antiemetic drugs according to their mechanism of action....

Academic logo Antiemetics This lecture was presented by: Dr.Alaa Alanteet Dr. Mohammed Almutairi • • • • • • EDITING FILE Main text Male slide Female slide Important Dr, notes Extra info Objectives Classify the main different classes of antiemetic drugs according to their mechanism of action. Know the characteristic pharmacokinetics & dynamics of different classes of antiemetic drugs. Identify the selective drugs that can be used according to the cause of vomiting. Learn the adjuvant antiemetics. Describe the major side effects for the different classes of antiemetics. Dr. Fouda Videos 13:24- 17:00 min 27:37 min 43:24 min For more quizzes & mnemonics check our channel :) ! Vomiting It is the forceful expulsion of gastric movements through the mouth. Can vomiting be considered a disease? It is a manifestation of many conditions and diseases. Severe Vomiting may result in (Consequences of vomiting): ● Dehydration ● Acid-base imbalance (Loss of H+ → Metabolic Alkalosis) ● Electrolyte depletion ● Aspiration, pneumonia Classification of Antiemetic Drugs: 1. 5-HT3 antagonists 2. D2 receptor antagonists 3. NK1 antagonists 4. H1-receptor antagonists 5. Muscarinic receptor antagonists 6. Cannabinoids (the only agonist drug, not commonly use because of its side effects) 7. Glucocorticoids ( treat the inflammation which would suppress substances that causes vomiting and potentiate the effect of antiemetic drugs) Ach(Muscarinic receptors) Opioid (Opioid receptors) Dopamine (D2) Chemical Transmitters & Receptors Involved in Vomiting: Substance P (Neurokinin receptors, NK1) Serotonin (5 -HT3) Intrinsic: Substance P, Acetylcholine, Histamine Histamine (Histaminergic receptors H1) How is Vomiting Induced? vomiting center (medulla) responds to inputs from: Area Information ● Chemoreceptor trigger zone (CTZ) stimulation Disturbance of the vestibular system Higher cortical centers stimulation (CNS) The periphery stimulation (pharynx, GIT) via sensory nerves ● CTZ is an area of the medulla that communicates with the vomiting center to initiate vomiting. It is physiologically outside BBB (responds to signals from blood) - Receptors ● ● ● ● ● ● Anticipatory emesis - D2 receptors, 5-HT3 receptors Opioid receptors Substance P receptors H1 (Histamine) M1 (acetylcholine) - ● ● ● ● ● Acetylcholine Histamine. 5-HT3, Substance P Mechano receptors Triggered by ● ● ● ● ● Emetogenic (causing emesis) drugs: opioids, general anesthetics, digitalis, L-dopa). Chemicals & toxins (blood, CSF). Radiation Chemotherapy Uremia ● Motion Sickness ● ● ● Emotional factors Nauseating smells or sights thoughts ● ● ● ● ● GIT irritation Myocardial infarction Renal or biliary stones Gastroenteritis Chemo and radiotherapy Chemotherapy cause irritation of Enterochromaffin cellls of GIT —> Cells injury —> release histamine and 5HT3 —> activate vagal nerve —> activate vomiting center 5-HT3 Antagonists Drugs M.O.A P.K Granisetron Ondansetron ● Act by blocking 5-HT3 receptor: 1. centrally (in vomiting center, CTZ) 2. peripherally (5-HT3 receptors on GI vagal afferents). ● It is the most potent antiemetic drug blocks 5-HT3 in 3 areas: 1. vomiting center 2. peripheral (GI) 3. central (CTZ) ● ● Orally or parenterally. Have a long duration of action,first pass effect. ● First choice for prevention of moderate to severe emesis(except motion sickness vomiting: Ondansetron → Oncology Uses ADRs Chemotherapy-induced nausea and vomiting (CINV) especially cisplatin Post-radiation NV & Post-operative NV (nausea and vomiting) Their effects are augmented by combination with corticosteroids and NK1 antagonists (Aprepitant). “ if the patient is still not responding, we combine other medications” ● ● ● Minimal as they are well tolerated in general ● Headache, ● Dizziness ● Constipation. ● Minor ECG abnormalities: (QT prolongation) Glucocorticoids Potentiate the effect of antiemetic drugs Dexamethasone Drug methylprednisolone Uses ● ● Used in chemotherapy-induced vomiting. combined with 5-HT3 antagonists or NK1 receptor antagonists. ADRs ● ● ● ● ● ● ● Hypertension Hyperglycemia Cataract Osteoporosis Increased intraocular pressure Increased susceptibility to infection Increased appetite & obesity ↑ 3 Bs : 1- Blood pressure 2- Blood glucose 3- Body weight D2 Receptor Antagonists 1- Prokinetics Domperidone Drug Metoclopramide Blocks D2 Dopamine receptors in the CTZ→ Both drugs have antiemetic effects as CTZ is outside the blood brain barrier M.O.A P.K They are prokinetic agents: Increases upper GI motility and gastric emptying —> ↓Stimulation of vomiting center Increase GI motility is achieved by stimulating: 1- parasympathetic system , 2- 5-HT4 receptor agonist ● Given orally ● Does not cross BBB ● Given orally or IV ● Crosses BBB Uses ● Prokinetic action ( 5-HT4 agonist activity): - Gastroesophageal reflux disease (GERD) - Gastroparesis (stomach paralysis) (impaired gastric emptying after surgery, or as a complication of diabetes) ● Antiemetic action (due to blocking D2 receptor in CTZ): - Effective against vomiting due to cytotoxic drugs, gastroenteritis, surgery, toxins,uremia, radiation. ADRs Only for Metoclopramide: “as it crosses the BBB ( ADRs Similar to antipsychotics)” ● Dyskinesia (extrapyramidal side effects). ● Galactorrhea (↓ dopamine → ↑ prolactin), menstrual disorders, impotence. ● Postural hypotension (α- blocking action). ● Sedation, drowsiness. Can domperidone produce these side effects? - Metoclopramide crosses BBB but domperidone can not cross in a significant amount. - both have antiemetic effects as CTZ has incomplete blood brain barrier located outside BBB, we prefer to use drugs than don’t cross BBB to avoid CNS side effects ). 2- Neuroleptics (Antipsychotics) Drug Chlorpromazine (CPZ) Uses ● ● Postoperative vomiting Chemotherapy-induced emesis ADRs ● ● ● Extrapyramidal symptoms Sedation Postural hypotension (alpha blocking effect) Droperidol Neurokinin-1 Receptor Antagonist Aprepitant Drug M.O.A P.K Uses Acts centrally as substance P(Stimulate NK1 ) antagonist by blocking neurokinin 1 receptors in vagal afferent fibers in Solitary Tract Nucleus (STN) and area postrema. (The CTZ is located within the area postrema, which is on the floor of the fourth ventricle and is outside of the blood–brain barrier)(441) ● Given orally usually combined with 5-HT3 antagonists and corticosteroids in prevention of chemotherapy-induced nausea and vomiting and post-operative NV. (add-on therapy if the patient is not responding to 5-HT3 antagonist) H1 Receptor Antagonists M1 , H1 receptors located in Vestibular system Drug Uses ADRs Diphenhydramine Promethazine Meclizine Cyclizine ● ● ● Motion sickness Morning sickness in pregnancy Promethazine: severe morning sickness of pregnancy (if only essential). ● ● ● Prominent sedation (1st generation antihistamines → cross BBB) Hypotension “α-blocking effect” Anticholinergic effects or atropine like actions: Dry mouth, dilated pupils, urinary retention, constipation Muscarinic Receptor Antagonists Hyoscine (Scopolamine) Drug M.O.A P.K Reduces impulses from vestibular apparatus by blocking muscarinic receptors Orally, injection, patches ● Uses ● ADRs ● ● Used as transdermal patches in motion sickness (should be taken before motion exposure as a prophylactic therapy) (applied to the postauricular area “behind the external ear”). Not in chemotherapy-induced vomiting Sedation Atropine like actions (Blurred vision, tachycardia, dry mouth, constipation, and urinary retention). Summary From slide Important The choice of antiemetic depends on the etiology Motion sickness ● ● Muscarinic antagonists Antihistamines Vomiting with pregnancy (morning sickness) ● ● ● Avoid all drugs in the first trimester Pyridoxine (B6) (unknown mechanism) Promethazine (late pregnancy). Drug- induced vomiting (CTZ), uremia, gastritis ● Dopamine antagonists (Metoclopramide, Domperidone) Post-operative nausea & vomiting ● Dopamine antagonists Vomiting due to cytotoxic drugs. ● ● ● ● 5-HT3 antagonists (Ondansetron) NK1 antagonists (Aprepitant) D2- antagonists Glucocorticoids MCQ 1 .Galactorrhea is considered a side effect of which of the following drugs? A. Promethazine B.Hyoscine C.Meclizine D.Metoclopramide 2.which of the following would be useful for promoting gastric emptying in a patient with a gastrostomy tube? A.Diphenhydramine B.Metoclopramide C.Ondansetron D.Aprepitant 3.Applied to the skin in a transdermal patch (transdermal therapeutic delivery system), this drug is used to prevent or reduce the occurrence of nausea and vomiting that are associated with motion sickness. A.Scopolamine B.Ondansetron C.Diphenhydramine D.Chlorpromazine 4.Which receptor is found in the vestibular system? A. 5-HT3 B. D2 C. H1 D. M3 5.A pregnant woman has early morning sickness what is the drug of choice for her condition? A-Dexamethasone B-Aprepitant C-Diphenhydramine D-Metoclopramide 6.Glucocorticoids have proved useful in the treatment of which of the following medical conditions? A.Chemotherapyinduced vomiting B.Essential hypertension C.Hyperprolactinemia D.Parkinson’s disease 1:D ,2:B ,3:A ,4:C ,5:C ,6:A SAQ 01 02 03 List the ADRs of the 5-HT3 antagonists? Headache, dizziness, constipation, Minor ECG abnormalities A 58 years old patient on chemotherapy came to the hospital due to having nausea and vomiting. The doctor gave him ondansetron and Aprepitant . what is the MOA & ADRs for Ondansetron? MOA: blocking 5-HT3 receptor: 1. centrally (in vomiting center, CTZ) 2. peripherally (5-HT3 receptors on GI vagal afferents). ADRs: Headache,constipation,Minor ECG abnormalities write two drugs from two different classes can be used in motion sickness? H1- receptor antagonists: Meclizine Muscarinic receptor antagonists: Hyoscine(scopolamine) Team Leaders Muhnnad Al-Otaibi Reema Almotairi Sarah Alajaji Team members Maryam Alghannam Alanoud Abdullah Aroub Almahmoud Nourah alarifi Layan Sulaiman Renad Alotaibi Aishah Boureggah Wafa Alakeel Areej Alquarini Wasan Alanazi Lama Alotaibi Ayedh Alqantash Jana alshiban Nazmi A Alqutub Layan Alruwaili Yousef badgesh Sara Alharbi Mohammed Alqutub Fatimah Alghamdi Fahad Aldhafian Special thanks to Norah Almania for the amazing logo