Presentation on theme: "Prof. Hanan Hagar Pharmacology Department College of Medicine"— Presentation transcript:
1 Prof. Hanan Hagar Pharmacology Department College of Medicine AntiemeticsProf. Hanan HagarPharmacology DepartmentCollege of Medicine
2 Learning objectivesClassify 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.
3 Causes of VomitingNausea and vomiting may be manifestations of many conditions and may occur due to stimulation of vomiting center that respond to inputs from:Chemoreceptor trigger zone (CTZ) stimulationDisturbance of vestibular systemHigher cortical centers stimulation (CNS)The periphery (Pharynx, GIT) via sensory nerves
4 CTZ is physiologically outside BBB. 1. Chemoreceptor trigger zone stimulationCTZ is an area of medulla that communicate with vomiting center to initiate vomiting.CTZ is physiologically outside BBB.CTZ Contains opioid receptors, D2 receptors & 5 HT3 receptors, Substance Pstimulated by:Drugs (opioids, general anesthetics),Chemicals and toxins in blood, CSF.Radiation.
5 2. The periphery via sensory nerves GIT irritation, myocardial infarction, renal orbiliay stones.3. Disturbance of vestibular systemby motion sickness4. Higher cortical centers stimulation:emotional factors, nauseating smells or sights.
11 5-HT3 antagonists Drugs as Ondansetron, Granisetron Orally or parenterallyPotent antiemetic effectsBlock 5-HT3 receptor in vomiting center, CTZ and 5HT3 receptors on intestinal vagal afferents.
12 Uses of 5-HT3 antagonists First choice for prevention of:Chemotherapy-induced nausea and vomiting (CINV) especially cisplatin.Post-radiation NV& Post-operative NVTheir effects is increased by combination with corticosteroids and NK1 antagonists.Side effectsWell toleratedmild headache, dizziness and constipationminor ECG abnormalities (QT prolongation)
13 D2 receptor antagonists block D2 dopamine receptors in the CTZTwo types exist:Prokinetics drugsNeuroleptics (antipsychotics)Uses of D2 receptor antagonistsare among the most commonly used drug for nausea and vomiting of non-specific causes.Effective against vomiting due to drugs,gastroenteritis, post-operative, toxins, uremia, radiation.
14 D2 receptor antagonists 1) Prokinetics drugs Drugs as metoclopramide, domperidoneBoth are prokinetic agents due to their 5 HT4 agonistic activity.used in GERD (gastroesophageal reflux disease), gastroparesis.Used as antiemetics (blocking D2 receptors)Metoclopramide crosses BBB but domperidone cannot (both have antiemetic effects as CTZ is outside BBB).
15 Side effects (only for metoclopramide): Dyskinesia (extra-pyramidal side effects),Galactorrhea, menstrual disorders, impotence.Sedation, postural hypotension.
17 Neurokinin1 (NK1) receptor antagonists AprepitantIs a substance P antagonists that acts by blocking neurokinin 1 receptors.OrallyUsed in prevention of acute and delayed chemotherapy-induced nausea and vomiting and for prevention of postoperative nausea and vomiting.Usually combined with 5-HT3 antagonists and corticosteroids.
18 H1-receptor antagonists Effective for motion sickness, morning sickness in pregnancyDrugs asDiphenhydramineMeclizine - CyclizinePromethazine: severe morning sickness of pregnancy (if only essential).Side effects:prominent sedation, hypotension, anticholinergic effects (dry mouth, dilated pupils, urinary retention, constipation.
19 Muscarinic receptor antagonists Hyoscine (scopolamine)Orally, injection, patchesUsed as transdermal patches in motion sickness (applied behind the external ear).Not in chemotherapy-induced vomitingSide effects: tachycardia, blurred vision, dry mouth, constipation, urinary retention (atropine-like actions).
20 Cannabinoids Nabilone, dronabinol mechanism of action not understood. act at central cannabinoid receptors.Used in vomiting due to cytotoxic anticancer drugs (adjuvant therapy).Not commonly used.Side effects: euphoria, dysphoria, sedation,hallucination.
21 Glucocorticoids Dexamethasone - methylprednisolone Used in chemotherapy-induced vomitingcombined with 5-HT3 antagonists or NK1 receptor antagonists.
22 Glucocorticoids Side effects: Hyperglycemia Hypertension Cataract OsteoporosisIncreased intraocular pressureIncreased susceptibility to infectionIncreased appetite & obesity
23 SummaryThe choice of antiemetic depends on the etiologyMotion sicknessMuscarinic antagonistsAntihistaminicsVomiting with pregnancy (morning sickness)avoid all drugs in the first trimesterPyridoxine (B6)Promethazine ( late pregnancy).
24 Drug- induced vomiting (CTZ) Dopamine antagonistsPost operative nausea & vomiting5-HT3 antagonistsNK1 antagonistsVomiting due to cytotoxic drugs.D2- antagonistsGlucocorticoidsCannabinoids