GIT - Antiemetics and Prokinetics

Pharmacological Management of Nausea and Vomiting

Overview of Nausea and Vomiting

• The session introduces the pharmacological management of nausea, vomiting, and gastrointestinal motility disorders, highlighting their prevalence in clinical practice.

• Emphasizes that these symptoms are linked to complex neurophysiological processes involving various systems and neurotransmitters rather than being mere symptoms.

Understanding Anti-emetics and Prokinetics

• By the end of the session, participants should be able to classify anti-emetics and prokinetics, explain their mechanisms, recognize adverse effects, and apply this knowledge clinically.

• The vomiting center in the medulla integrates signals from multiple sources; effective anti-emetic therapy must target these inputs rather than just suppressing vomiting.

Mechanisms Behind Nausea

• Anticipatory nausea can occur due to psychological stimuli like sight or smell; benzodiazepines may help by reducing anxiety rather than blocking receptors directly.

• Motion sickness is explained through vestibular pathways where antihistamines are more effective compared to dopamine or serotonin blockers.

Drug Selection Based on Stimulus Source

• Peripheral irritation activates vagal afferents leading to serotonin release; this underpins the use of 5HT3 antagonists for chemotherapy-induced nausea.

• The chemoreceptor trigger zone (CTZ), outside the blood-brain barrier, senses toxins and drugs; most modern anti-emetics act here targeting various neurotransmitter receptors.

Classification of Anti-emetics

• Anti-emetics are classified based on receptor antagonism: H1 blockers for motion sickness, M3 blockers for vestibular signaling, D2 blockers at CTZ, 5HT3 blockers for vagal-mediated vomiting, NK1 blockers for substance P inhibition.

• Combination therapy is often necessary as no single drug blocks all pathways effectively; understanding underlying pathways is crucial for rational pharmacology.

Treatment Considerations in Specific Scenarios

• During active vomiting, oral medications are ineffective; IV or rectal routes are preferred. Treating the underlying cause is essential alongside symptomatic relief.

• In pregnancy-related nausea, conservative treatment is prioritized with doxylamine and vitamin B6 recommended due to safety data.

Multimodal Approaches in Severe Cases

• Post-operative and chemotherapy-induced nausea require combination therapies including 5HT3 antagonists, NK1 antagonists, cannabinoids, corticosteroids along with sedatives for anticipatory components.

Prokinetic Agents in Gastrointestinal Motility

Role of Prokinetic Drugs

• Prokinetic agents enhance gastrointestinal motility through serotonin-mediated signaling via 5HT4 stimulation which increases acetylcholine release.

Mechanisms of Action

• Serotonin release from enterochromaffin cells stimulates intrinsic primary afferent neurons via 5HT1P receptors promoting reflex peristalsis.

• Stimulation of presynaptic terminals enhances acetylcholine release which promotes reflex activity critical for gut motility.

Safety Considerations with Prokinetics

• Among prokinetic drugs, 5HT4 receptor stimulants are vital but have had safety concerns (e.g., cisapride withdrawal due to cardiac toxicity), emphasizing a balance between efficacy and safety.

Blocking D2 Receptors and Gastric Motility

Mechanisms of Action

• Blocking D2 receptors leads to the removal of inhibition, which in turn increases gastric motility.

• Drugs such as domperidone and metoclopramide are commonly used to enhance gastric emptying due to their action on D2 receptors.

• Colonomics directly stimulate contraction but may result in systemic side effects that limit their use.

• Model agonists like arithromycin are noted for stimulating migrating motor complexes, contributing to improved gastrointestinal function.