Pharmacology Chapter 52- Antiemetic and Antinausea Drugs

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Vomiting Center and Chemoreceptor Trigger Zone

-Neurotransmitter signals are sent to the vomiting center from the chemoreceptor trigger zone (CTZ),
-These signals alert those areas of the brain to the existence of nauseating substances (noxious stimuli) that need to be expelled from the body.
- Once the CTZ and vomiting center are stimulated, they initiate the events that trigger the vomiting reflex.

Neurotransmitters involved:
Acetylcholine (ACh)
Histamine (H1)
Prostaglandins
Serotonin (5-HT3)

Mechanism of Action and Indications:
Anticholinergic Drugs

ACh blockers
-Bind to and block acetylcholine (ACh) receptors in the inner ear labyrinth ( vestibular nuclei <-- book says this)
-Block transmission of nauseating stimuli to CTZ
-Also block transmission of nauseating stimuli from the reticular formation to the VC
- Also tends to dry GI secretions and reduce smooth muscle spasms

Drug: Scopolamine ( transderm-Scop)

INDICATIONS: Motion sickness, secretion reduction before surgery, nausea and vomiting


INDI

Mechanism of Action and Indications:
Antihistamines

H1 receptor blockers ( NOTE: not to be confused with the H2 blockers used for gastric acid control)

-Inhibit ACh by binding to H1 receptorsts)
- Act in a manner similar to anticholinergic drugs ( also have anti spasm and anti secretory effec
-Prevent cholinergic stimulation in vestibular and reticular areas, thus preventing nausea and vomiting
-Also used for motion sickness, nonproductive cough, allergy symptoms, sedation

Drugs:
dimenhydrinate (Dramamine)
diphenhydramine (Benadryl)
meclizine (Antivert)

INDICATIONS: Motion sickness, nonproductive cough, sedation, rhinitis, allergy symptoms, nausea and vomiting

Mechanism of Action and Indications:
Antidopaminergic drugs

-Block dopamine receptors on the CTZ
-Also used for psychotic disorders, intractable hiccups

Drugs:
prochlorperazine (Compazine)
promethazine (Phenergan)
droperidol (Inapsine): Use is controversial because of associated cardiac dysrhythmia

INDICATIONS:
Psychotic disorders (mania, schizophrenia, anxiety), intractable hiccups, nausea and vomiting

Mechanism of Action and Indications:
Prokinetic drugs

-Block dopamine in the CTZ
-Cause CTZ to be desensitized to impulses it receives from the GI tract
-Also stimulate peristalsis in GI tract, enhancing emptying of stomach contents
-Also used for GERD, delayed gastric emptying

Drug:
metoclopramide (Reglan)
Long-term use may cause irreversible tardive dyskinesia

INDICATIONS:
Delayed gastric emptying, gastroesophageal reflux, nausea and vomiting

Mechanism of Action and Indications:
Serotonin blockers

-Block serotonin receptors in the GI tract, CTZ, and VC
-Used for nausea and vomiting in patients receiving chemotherapy and for postoperative nausea and vomiting
-The receptor subtype involved in the mediation of nausea and vomiting is the 5-hydroxytryptamine 3 (5-HT3) receptor.

Drugs:
dolasetron (Anzemet)
granisetron (Kytril)
ondansetron (Zofran)
palonosetron (Aloxi)

INDICATIONS:
Nausea and vomiting associated with cancer chemotherapy, postoperative nausea and vomiting

Mechanism of Action and Indications:
Tetrahydrocannabinoids

THC<-- weed
-Major psychoactive substance in marijuana
-Inhibitory effects on reticular formation, thalamus, cerebral cortex
-Alter mood and body's perception of its surroundings
- dronabinol (Marinol)<.. nonintoxicating form
-Used for nausea and vomiting associated with chemotherapy, and anorexia associated with weight loss in AIDS patients

INDICATIONS:
Nausea and vomiting associated with cancer chemotherapy, anorexia associated with weight loss in patients with AIDS and cancer. Glaucoma

Adverse Effects of Antiemetic drugs

Anticholinergics
- CNS: Dizziness, drowsiness, disorientation
- Cardiovascular: Tachycardia
- ENT and eyes:Blurred vision, dilated pupils, dry mouth
- GU: Difficult urination, constipation
-Skin: Rash, erythema

Antihistamines
-Central nervous: Dizziness, drowsiness, confusion
-Ears, eyes, nose, throat: Blurred vision, dilated pupils, dry mouth
-Genitourinary:Urinary retention

Antidopaminergics
-Cardiovascular: Orthostatic hypotension, electrocardiographic changes, tachycardia
-Central nervous: Extrapyramidal symptoms, pseudoparkinsonism, akathisia, dystonia, tardive dyskinesia, headache
-Ears, eyes, nose, throat: Blurred vision, dry eyes
-Genitourinary: Urinary retention
-Gastrointestinal: Dry mouth, nausea and vomiting, anorexia, constipation

Prokinetics:

-Cardiovascular: Hypotension, supraventricular tachycardia
-Central nervous: Sedation, fatigue, restlessness, headache, dystonia
-Gastrointestinal: Dry mouth, nausea and vomiting, diarrhea

Prokinetics:

-Cardiovascular: Hypotension, supraventricular tachycardia
-Central nervous: Sedation, fatigue, restlessness, headache, dystonia
-Gastrointestinal: Dry mouth, nausea and vomiting, diarrhea


Serotonin Blockers

-Central nervous: Headache
-Gastrointestinal: Diarrhea, transient increase in AST and ALT levels
-Other: Rash, bronchospasm


Tetrahydrocannabinoids:

-Central nervous: Drowsiness, dizziness, anxiety, confusion, euphoria
-Ears, eyes, nose, throat: Visual disturbances
-Gastrointestinal: Dry mouth

Herbal Products: Ginger

-Used for nausea and vomiting including that caused by chemotherapy, morning sickness, and motion sickness
-Adverse effects:
Anorexia, NAUSEA AND VOMITING , skin reactions

-Drug interactions
May increase absorption of oral medications
Increase bleeding risk with anticoagulants

- Contraindications:
Contraindicated in cases of known product allergy; may worsen cholelithiasis (gallstones); anecdotal evidence of abortifacient properties—some clinicians recommend not using during pregnancy

Nursing Implications

-Assess complete nausea and vomiting history, including precipitating factors
-Assess current medications
-Many of these drugs cause severe drowsiness; warn patients about driving or performing any hazardous tasks
-Taking antiemetics with alcohol may cause severe CNS depression
-Teach patients to change position slowly to avoid hypotensive effects
-For chemotherapy, antiemetics are often given 30 to 60 minutes before chemotherapy begins

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