Antiemetic drugs

1. Muscarinic blockers Atropine , Hyoscine Antiemetic mechanism: They block M1 receptors in the vestibulocerebellar pathway, solitary tract nucleus, and CTZ. Uses as antiemetic : Prevention (and less effectively to treat) vomiting due to motion sickness Adverse effects; antimuscarinic side effects

2. H1-blockers Diphenhydramine, Cyclizine, Meclizine Antiemetic mechanism: They block H1 (also M1) receptors in the vestibulocerebellar pathway and CTZ. They have sedative action. Uses as antiemetic Vomiting due to motion sickness Vomiting of pregnancy Vertigo Adverse effects: Sedation (excitation may occur in children). Atropine-like actions Hypotension (block alpha1)

3. 5-HT3 blockers Ondansetron, Granisetron, dolasetron Antiemetic mechanism: Competitively block 5HT3 receptors in the GIT, solitary tract nucleus and CTZ. Uses as antiemetic: Vomiting due to cancer chemotherapy or radiotherapy. Postoperative nausea and vomiting. Not effective against motion sickness

Adverse effects: Generally are well tolerated Dizziness, headache, and constipation. Prolong QT interval, torsade de points is reported especially if co-administered with another drug that prolong the QT interval

4. Dopamine blockers Benzamides; (Metoclopramide, Domperidone) Phenothiazines (e.g.  Prochlorperazine, chlorpromazine) Antiemetic mechanism: Benzamide Metoclopramide causes central and peripheral dopamine D2 antagonism at low doses, and weak 5-HT3 blockade  Domperidone is a D2-blocker with selective peripheral activity in the upper gastrointestinal tract. Phenothiazines Antagonizing D2-dopamine receptors in the area postrema of the midbrain, also block M, H1

Uses: Vomiting due to drugs or febrile illness Vomiting due to cancer chemotherapy. Postoperative nausea and vomiting. Adverse effects: Benzamides;   Metoclopramide; (anxiety, restlessness, and depression, hyperprolactinemia, irreversible tardive dyskinesia and QT interval prolongation Domperidone; it does not cross the blood-brain barrier and therefore lacks the neurologic side effects of metoclopramide Phenothiazine Sedation, Hyperprolactinemia, Postural hypotension Extrapyramidal effects e.g. dystonia and dyskinesia.

5. Cannabinoids Dronabinol A purified synthetic delta-9-tetrahydrocannabinol Antiemetic mechanism: It is a cannabinoid receptor agonist. the drug likely activates specific cannabinoid receptors in the vomiting center, which results in decreased excitability of target neurons Naloxone blocks its action Uses as antiemetic: Vomiting due to cancer chemotherapy Patients refractory to other antiemetics.

Adverse effects: Sedation Paranoia Dysphoria Hypotension Drug abuse. NB; The modest antiemetic activity of this and their relatively unfavorable side effect profile, especially in older patients, has limited their clinical use.

6. Vitamin B6 Pyridoxine is a water-soluble vitamin Antiemetic mechanism: Is unknown Uses as antiemetic: Vomiting in pregnancy. Pyridoxine has a good safety profile with minimal side effects  Vomiting in children

7. Corticosteroids Dexamethasone the commonest steroid used Antiemetic mechanism; The exact mechanism is unclear. Uses as antiemetic: Effective and well-tolerated antiemetic for chemotherapy induced emesis Adverse effects: Hyperglycemia Immunosuppression Osteoporosis Salt and water retention

8. Benzodiazepines The most commonly used drugs in this class include Lorazepam, alprazolam As single agents, the benzodiazepines are relatively weak antiemetic agents. They are given primarily as adjunctive agents Antiemetic mechanism: Unknown

Uses as antiemetic: Stress-related vomiting Adjunctive agents to reduce akathisia associated with metoclopramide To controls symptoms in Ménière disease Adverse effects: Anterograde amnesia Physical dependence Paradoxical excitement

9. Neurokinin-1 receptor blockers Aprepitant Antiemetic mechanism Neurokinin 1 (NK1) receptor antagonist on nucleus of tractus solitaries and Visceral afferent nerves Neurokinin-1 receptors mediate most of central and peripheral effects of substance P. So it prevent both peripheral and central stimulation of the vomiting center

Uses as antiemetic: In combination with 5-HT3 blockers to treat vomiting due to cancer chemotherapy Adverse effects: Diarrhea and fatigue Inhibit CYP3A4 so increase the level of many drugs

Smooth Muscle Relaxants Antispasmodic Drugs

Classification Anticholinergic drugs: Atropine Hyoscine Direct smooth muscle relaxants: Papaverine Mebeverine Alverine, drotaverine. Combinations: Libra x ( clidinium + chlordiazepoxide ), Donnatal (hyoscine + phenobarbital).

Direct smooth muscle relaxants Papaverine:It is opium alkaloid but chemically different from morphine Mebeverine, Alverine, Drotaverine They are synthetic drugs Mechanism of action: The exact mechanism is unclear but may be due to inhibition of PDE enzyme increase cAMP . Smooth muscle relaxation. Uses : Spasms of the GIT, bile duct and genitourinary tract. Irritable bowel syndrome (IBS).

Side effects: Cardiac arrhythmia. Abnormal liver functions in the form of ↑ serum transaminases and alkaline phosphatase. Headache and dizziness C/I : Paralytic ileus. Constipation for more than one week