Pharmacology Of Antiemetics Flashcards
What are the 3 stages of emesis
1) nausea
2) retching
- spasmodic respiratory movements that generates the pressure gradient for vomiting (increases intrabdominal pressure to exceed esophageal)
3) vomiting
- contraction of muscles in abdomen and chest wall to evacuate the stomach contents through the mouth
Where does vomiting occur
Occurs within the NTS and includes
- area postrema
- chemoreceptors trigger zone (CTZ)(detects the toxins and chemicals in blood)
The nucleus tractus solitary receives inputs from all of the above
What areas supply input to the NTS
1) Higher centers (cortex regions in times of pain/anxiety/stress/etc.)
2) stomach and intestines (if irritated or distended) via CN10
3) chemoreceptor trigger zone and area postrema(if toxins are present in blood)
4) vestibular system via CN8
What receptors are located in each aspect of the vomiting complex?
1) CTZ
- D2 receptors
- 5-HT3 receptors
- NK1 receptors
2) nucleus of tractus solitarius
- H1 receptor
- M1 receptor
- NK1 receptor
- 5-HT3 receptor
3) GI tract and heart
- Mechanoreceptors
- chemoreceptors
- 5-HT3main one
4) CNS
- so many its not worth listing
5) vestibular system
- H1 receptors
- M1 receptors
* *antagonists for M1 receptors are used for motion sickness or vertigo that causes nausea**
What neurotransmitters are implicated in vomiting?
1) ACh: from CNS and parasympathetics
- acts on M1 receptors Found in vestibular system and nucleus of tractus solitaries (NTS)
2) serotonin (5-HT3): CNS chromaffin cells of gut, enteric cells
- acts on 5-HT3 receptors located in GI tract, heart, CTZ and NTS
3) dopamine: CNS
- acts on D2 receptors found in CTZ
4) histamine: hypothalamus, mast cells, basophilic
- acts on H1 receptors in vestibular system and NTS
5) substance P: immune system
- acts on NK1 receptors found in CTZ and NTS
What is the overall MOA for anti-emetic agents?
Receptor antagonists acting at the vomiting center receptors
Risk factors for post-operative nausea and vomiting (PONV)
Age less than 50 yrs Female gender Non smoker History of past PONV History of motion sickness Dehydration Use of general anesthesia Use of volatile anesthetics Use of NO Use of opiods Long surgery duration
0-1 risk factors = 10/20% risk
2-3 risk factors = 30-40% risk
3-5 risk facotrs = 50-80% risk
Can you give benzos to pregnant patients?
Technically yes, but they are catagory D, so dont unless absolutely have to
High yield antiemetic to use in specific cases
Moderate-high risk patients:
- should use prophylactic antiemetics
- add proposal and hydration as well
- avoid Nitrous
Moderate-risk = 1-2 drugs from DIFFERENT classes
High-risk = 2-3 drugs from DIFFERENT classes
What is the gold standard drug to use for post-op N/V
Ondansetron
When to use rescue therapy for N/V?
If patient still experiences N/V after being on a prophylactic combination (usually ondansetron and dexamethasone)
In this case give a different drug class
- usually droperiodol or phenothiazine
What is the guideline combination used for acute chemo-induced N/V in a HIGH RISK patient?
A serotonin receptor Antagonist (5-HT3)
Dexamethasone
A NK-1 antagonist
What is the guideline combination used for acute chemo-induced N/V in a moderate RISK patient?
Palononsetron
Dexamethasone
What is the guideline combination used for acute chemo-induced N/V in a LOW RISK patient?
Only 1 of the following:
Dexamethasone
5-HT3 antagonist
Dopamine receptor antagonist
What is the guideline combination used for delayed chemo-induced N/V in a HIGH RISK patient?
Both:
dexamethasone
NK-1 antagonist
