Anti-Emesis ✅.pdf

Vomiting Zones It can respond directly to chemical stimuli in the blood or cerebrospinal fluid. What CTZ ? Vomiting center What does it coordinate? Motor mechanism of vomiting Impulses are received from sensory centers (CTZ, cerebral cortex and visceral afferents from the pharynx and GIT) Saliva...

Vomiting Zones It can respond directly to chemical stimuli in the blood or cerebrospinal fluid. What CTZ ? Vomiting center What does it coordinate? Motor mechanism of vomiting Impulses are received from sensory centers (CTZ, cerebral cortex and visceral afferents from the pharynx and GIT) Salivation center Mechanism of vomiting Respiratory center The afferent impulse are integrated by VC resulting in efferent impulses to: Pharyngeal muscle GI and abdominal muscles resulting in vomiting GIT infection Neurological disorders Trigger Factors Metabolic disease Psychological disease Chemotherapeutic agents Easier to prevent what than what? % of patients experience nausea and vomiting in anticipation of chemotherapy? 10 - 40 % Young patient ………… are more susceptible than older patients and ………… Anticipation of chemotherapy Women , Men Chemotherapy-induced ……… and ………. (CINV) not only affect quality of life but can also lead to rejection of potentially curative chemotherapy. Uncontrolled vomiting can produce ……….., profound metabolic Imbalances, and ……… depletion. Nausea , Vomiting Dehydration Nutrition Emetic potential of anticancer agents effective against low or moderately emetogenic chemotherapeutic agents Effective against what? Phenothiazines (for example, fluorouracil and doxorubicin). Prochlorperazine sedation, liver dysfunction and dystonias SE: What does it inhibit? Substituted benzamides (Metoclopramide) Dopamine receptors in CTZ prokinetic drug for the treatment of GERD How previously was used? Anti-dopaminergics: extrapyramidal symptoms, limit long-term high-dose use. SE: Eg: Types of neck dystonia Droperidol & haloperidol How does it act? blocking dopamine receptors. moderately effective antiemetics. Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines Butyrophenones Extrapyramidal reactions Hypersensitivity reactions Liver dysfunction Adverse reactions? Bone marrow aplasia Excessive sedation Ondansetron, granisetron, palonosetron, alosetron, and dolasetron. These agents selectively block 5-HT3 receptors in the periphery (visceral vagal afferent fibers) and in the brain (CTZ). What does these agents do? This class of agents is important in treating emesis linked with chemotherapy, largely because of their longer duration of action and superior efficacy. Anti-Emesis Important for what? These drugs can be administered as a single dose prior to chemotherapy (intravenously or orally) and are efficacious against all grades of emetogenic therapy. Ondansetron and granisetron prevent emesis in 50% to 60% of cisplatin –treated patients. 5-HT3 Receptors Blockers These agents are also useful in the management of postoperative nausea and vomiting. 5 -HT3 antagonists are extensively metabolized by the liver; however, only ondansetron requires dosage adjustments in hepatic insufficiency. Pharmacokinetics: Elimination is through the urine. Constipation, headache and asthenia Electrocardiographic changes, such as a prolonged QTc interval, can occur with dolasetron and high doses of ondansetron . S/E: For this reason, dolasetron is no longer approved for CINV prophylaxis. They are appropriate for the treatment of simple N/V especially motion sickness. Treat what? Scopolamine Antiemetic drugs Dimenhydrinate Meclizine Drugs: Diphenhydramine Hydroxyzine Antihistamine-anticholinergic drugs: Doxylamine Notes: lorazepam Drugs: alprazolam The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties. Benzodiazepines: These same properties make benzodiazepines useful in treating anticipatory vomiting. Concomitant use of alcohol should be avoided due to additive CNS depressant effects Benzodiazepines possess anterograde amnesic properties, Amnesiac property: The amount of amnesia is systematically related to dose effects and half-life differences among the benzodiazepines. Dexamethasone Drugs: Corticosteroids: disrupting both short-term and long-term memory function. methylprednisolone They are effective against mildly to moderately emetogenic chemotherapy. Their antiemetic mechanism involve blockade of prostaglandins. neurokinin receptor in the brain and blocks the actions of the natural substance. Aprepitant targets the: Substance P/neurokinin-1 receptor blocker : Aprepitant is indicated only for: How administered? undergoes extensive metabolism, S/E? Phosphate carbohydrate solutions: Efficacy of antiemetic drugs primarily by CYP3A4, it may affect the metabolism of other drugs that are metabolized by this enzyme, nabilone Act on what? Uses? orally with dexamethasone and a 5-HT3 antagonist for sever chemotherapy-induced nausea Dronabinol Drugs: Cannabinoids: highly or moderately emetogenic chemotherapy regimens Vomiting center in brain When other agents failed in therapy anxiety, motor incoordination, memory loss, fear, confusion, hallucination, euphoria, sedation and paranoia Uses? For mild symptoms May cause what? hyperglycemia (soft drinks) such as: warfarin oral contraceptives.