Lecture 22 - Antiemetics and Antitussives Flashcards
Pathways of activating the vomiting center (medulla) of the human body
1) Peripheral input from stomach neurons release serotonin (5HT) which acts directly on the medulla as well as goes to the higher centers (CNS)
2) CRTZ can act directly on the vomiting center through dopamine (DA), 5HT, and histamine (H). CRTZ can also act on the higher centers.
3) The Vestibular System releases mainly acetylcholine (Ach) as well as histamine to act on both the vomiting center and higher centers.
REMEMBER: Higher centers have some capability of overriding the vomiting center, however strong enough vomiting reflex is unable to be controlled.
Scopolamine
Anticholinergic Agent
- Primary action on vestibular system to prevent vertigo and motion sickness
- Side effects: anticholinergic effects such as dry mouth, constipation, urine retention, loss of visual accommodation. Also sedation.
- Transderm Scop preparation - placed behind the ear
Dimenhydrinate, Meclizine, Promethazine, Diphenhydramine, and Doxylamine (For Antiemetic purposes)
Antihistamines
- Primary action on vestibular system; Meclizine and Promethazine have weak CRTZ effects on the vomiting center.
- Used to treat and prevent motion sickness and vertigo. Meclizine and Promethazine may have more general antiemetic activity.
- Not most effective for nausea and vomiting caused by CRTZ activation
- Side effects: Anticholinergic effects (dry mouth, constipation, urine retention, loss of visual accommodation), sedation, possible teratogenic effects.
Prochlorperazine and Haloperidol
Dopamine (D2) Antagonists
- Act on chemoreceptor trigger zone and used as an antiemetic (postoperative nausea, cytotoxic drugs, radiation sickness, and toxins).
- Main side effects include parkinsonism as D2 blocking leads to psychomotor complications. (OTHER effects: anticholinergic effects, sedation, lethargy, psychomotor slowing)
- Teratogenic effects - AVOID IF PREGNANT!
Metoclopramide
Dopamine (D2) antagonist
- D2 antagonist in the CRTZ but also acts on enteric nerves to increase gastrointestinal tone and motility and increases the tone in the lower esophageal sphincter.
- Treats nausea and vomiting from cancer chemotherapy, post operation, or toxin or radiation induced
- Can also treat gastrointestinal problems (gastric stasis and GERD)
- **Common for preoperative medication to prevent possible aspiration of vomitus
- Side effects: sedation and extrapyramidal motor problems (parkinsonism and acute dystonia)
Ondansetron and Granisetron
5-HT3 (Serotonin) Antagonists
- Intravenous or orally taken drugs for preventing nausea and vomiting during cancer chemotherapy and post-op nausea and vomiting
– Work by depressing chemoreceptor trigger zone and inhibiting serotonin mediated afferent input from GI
- VERY EFFECTIVE IN 80% OF PATIENTS
-SEROTONIN ANTAGONISTS AT 5-HT3 RECEPTORS
-Side effects: Headache and constipation; drug interactions
Dronabinol
Cannabinoid
- Main active constituent of marijuana that can control nausea and vomiting during cancer chemotherapy in patients who don’t respond to other drugs
- **CNS SIDE EFFECTS: sedation, confusion, disorientation, loss of control, altered sensation, etc.
Dexamethasone and methylprednisolone
Corticosteroids
-Often used as adjunct antiemetics in cancer chemotherapy regiments
Aprepitant
Acts as an antagonist at a subtype of P/neurokinin receptor (NK1) for cancer chemotherapy induced nausea.
- Well tolerated and useful when traditional drugs don’t work but expensive
Benedictine
Pyridoxine (Vitamin B6) + deoxylamine.
- Alleviate nausea and vomiting during pregnancy.
- Replaced by Diclegis due to teratogenic effect.
Amphetamine
Some motion sickness benefits and counteract sedative effects of other drugs. Not used routinely because of CNS effects and abuse potential.
Benzodiazapines
Antianxiety drugs that can alleviate nausea and vomiting associated with anxiety, fear, and apprehension.
Antiemetic Drugs Summary
For the treatment or prevention of motion sickness and vertigo - antihistamines or anticholinergics
Post operative - Dopamine antagonists or 5-HT3 antagonists.
Radiation sickness - Dopamine antagonists or 5-HT3 antagonists.
Drug-induced vomiting - Dopamine antagonists, 5-HT3 antagonists or cannabinoids. Combinations more effective
Pregnancy - Avoid drugs if possible, diet modifications. If needed: antihistamine such as doxylamine or meclizine, otherwise dopamine antagonist.
Opioids (Codeine, hydrocodone, etc.)
Most effective antitussives
- Acts on the cough control center at a lower dose than if used as an analgesic.
- Side effects: Sedation, light headedness, confusion, nausea, dizziness, constipation.
- Very abusable; physically addicting
Dextromethorphan
Most commonly used antitussive drug (cough syrup)
- No opioid like analgesic or subjective effects. Has less abuse potential!
- As effective as codeine for mild-moderate cough, not severe.
- Blocks NMDA receptors in cough control center
- Mild side effects: sedation, dizziness, and confusion.
