Study Notes on Nausea, Vomiting, and Antiemetic Drugs

Loperamide
- Member of the opioid family.
- Primarily works on the gut, which is why it is not categorized under controlled substances.
- Does not cross the blood-brain barrier, leading to lower risks of CNS effects unless taken in excess.
- When combined with other medications, CNS effects may occur.

Duration of Lecture: Approximately 45 minutes with an interactive activity.
Personal Anecdote: Raised awareness of nausea/vomiting through a personal experience involving a child.

Discuss the pathophysiology of nausea and vomiting.
Identify various antiemetic and anti-nausea drugs along with their classifications.
Discuss mechanisms of these drugs, indications for their use, and any special considerations.

Nausea and Vomiting Mechanisms:
- Originates from more than just the stomach.
- Involves signals from various body pathways to the brain signaling the need to expel contents.
- Vomit Center: Located in the brain stem (medulla oblongata) responsible for vomiting acts.
- Chemoreceptor Trigger Zone (CTZ): Processes signals of nausea and vomiting and transmits them to the vomit center.

Chemoreceptor Trigger Zone: Triggered by drugs, cytotoxic agents, hormones, and changes in blood chemicals.
Vestibular System: Triggers from motion sickness signals from the inner ear to the CTZ.
Cerebral Cortex: Triggers nausea due to pain, emotional responses, or sensory stimuli (like smell).
Gastrointestinal System: Sends signals via the vagus nerve to the CTZ, contributing to nausea and vomiting.

Neurotransmitters Linked to the Pathways:
- Acetylcholine (ACh)
- Histamine
- Dopamine
- Neurokinins
- Serotonin
- Excess levels activate receptors leading to signals sent to the vomiting center.

Types:
- Chemotherapy Induced Nausea and Vomiting (CINV)
- Postoperative Nausea and Vomiting (PONV)
- Nausea and vomiting due to infections (bacterial, viral) and food poisoning.
Aggressive Treatment Criteria:
- CINV and PONV are treated aggressively due to higher associated complications.
- Reasons to treat aggressively for CINV include risk of malnourishment, dehydration, and the significant side effects impacting quality of life.
Postoperative Considerations:
- Effective management is essential to promote recovery, allow for nutrition intake, and mitigate risks of complications (e.g., dehiscent incisions), aspiration, and prolonged hospitalization.
- NPO status pre-op increases dehydration risk; nausea can further complicate recovery.

Risks:
- Dehydration
- Electrolyte imbalance
- Impact on pediatric patients due to their higher body water percentage, leading to further risk for complications.
- Metabolic Alkalosis risk due to loss of acid (vomiting) as opposed to metabolic acidosis from diarrhea.

Goals: Alleviate nausea and vomiting by disrupting the pathways and blocking various neurotransmitters, improving patient comfort and outcomes.
Classifications:
- Anticholinergic and Antihistamines for vestibular pathway.
- Serotonin blockers and prokinetics for GI pathway.
- THC and corticosteroids for cerebral cortex pathway.
- Antidopaminergic and prokinetics for CTZ pathway.

Some patients may require multiple antiemetics targeting different pathways to be effective.
Combination Therapy: Optimizing nausea management by using multiple agents targeting various receptors simultaneously for a greater overall effect.

Mechanisms: Block ACh action on muscarinic receptors in the vestibular system; dry up gastric secretions, reduce smooth muscle spasms.
Scopolamine: Commonly used in patch form; kin to nausea during motion and dry secretions pre-surgery. Considerations (e.g., contraindications like urinary retention) are crucial.

H1 Antihistamines: Block histamine at H1 receptors in the vestibular system; sedative effects may occur due to CNS penetration.
First Generation vs. Second Generation: First generation causes sedation; second generation primarily for allergies with minimal CNS effects (e.g., Meclizine, Diphenhydramine).

Block dopamine receptors at CTZ to alleviate nausea/vomiting; also used for psychiatric disorders due to dopamine's role.
Common drugs in this category include Promethazine, which is used carefully due to the risk of necrosis with IV administration.
EPS Risk: Extrapyramidal Symptoms (EPS) are a critical complication stemming from rapid administration of these drugs.

Target 5-HT3 receptors at GI tract and CTZ; examples include Ondansetron (Zofran). Effective for CINV but carries risks such as QT interval prolongation affecting heart rhythm.

Mechanism: Increase GI motility and helpful in gastroparesis and GERD; major drug is Reglan, also a dopamine antagonist.

Modulate perception, useful in cancer-related nausea, particularly for patients with decreased appetite or anorexia; including Marinol.

Imitrol (Phosphorated Carbohydrate Solution): Calms stomach muscles, neutralizes acid; utilized safely for morning sickness alternatives with off-label considerations.

Monitor sedation effects; warn against using with alcohol or other sedatives.
Encourage premedication before high-risk situations (chemotherapy/surgery).
Employ non-pharmacological interventions as first steps where feasible (e.g., diet manipulation for nausea).
Train on recognizing and managing EPS symptoms from antidopaminergic drugs.