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Mera kal pharmacological and toxicological screening ka papar he or usme anti emetics aa rha he toh mujhe iske ek simple exam form answer bna ke do or sb cheez ka acche se define Krna mene photo bheje he vaise hi bas simple English me jada tough language me mat likhna bas accha exam form me ho
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Pharmacological Screening of Antiemetic Drugs
Cisplatin-Induced Emesis Model in Pigeons
Definition of Emesis
Emesis means vomiting. It is the forceful expulsion of stomach contents through the mouth due to contraction of the stomach, intestine, diaphragm, and abdominal muscles.
Antiemetic drugs are drugs that prevent or reduce nausea and vomiting.
Types of Emesis
-
Acute emesis
Vomiting occurs within a few minutes to 24 hours after giving an emetic agent such as cisplatin. -
Delayed emesis
Vomiting occurs after 24 hours and may continue for 2-3 days. -
Breakthrough emesis
Vomiting that occurs even after preventive treatment with an antiemetic drug.
Classification of Antiemetic Drugs
| Class | Examples |
|---|---|
| 5-HT3 receptor antagonists | Ondansetron, Granisetron, Palonosetron, Tropisetron |
| Dopamine D2 receptor antagonists | Metoclopramide, Prochlorperazine, Chlorpromazine, Domperidone |
| H1 receptor antagonists | Promethazine, Diphenhydramine, Cyclizine, Hydroxyzine |
| Muscarinic receptor antagonist | Hyoscine or Scopolamine |
| NK1 receptor antagonists | Aprepitant, Fosaprepitant |
| Corticosteroid | Dexamethasone |
Cisplatin-Induced Emesis Model in Pigeons
Aim
To evaluate the antiemetic activity of a test drug or plant extract by using cisplatin-induced vomiting in pigeons.
Principle
Cisplatin is an anticancer drug which produces vomiting. It causes the release of serotonin (5-HT) and other vomiting-producing chemicals from the gut.
These chemicals stimulate:
- Vagal afferent nerves
- Chemoreceptor trigger zone (CTZ)
- Vomiting centre in the brain
This produces vomiting in pigeons.
An effective antiemetic drug reduces the number of vomiting episodes and increases the time taken for first vomiting.
Flow chart:
Cisplatin
↓
Release of serotonin and other mediators in gut
↓
Stimulation of vagal afferents and vomiting centre
↓
Vomiting / emesis in pigeon
↓
Antiemetic drug blocks 5-HT3, D2, H1, M1, or NK1 receptors
↓
Decrease in vomiting
↓
Release of serotonin and other mediators in gut
↓
Stimulation of vagal afferents and vomiting centre
↓
Vomiting / emesis in pigeon
↓
Antiemetic drug blocks 5-HT3, D2, H1, M1, or NK1 receptors
↓
Decrease in vomiting
Cisplatin can produce both early and delayed vomiting responses in pigeons, so this model is useful for antiemetic screening. A published pigeon study also supports its use for testing antiemetic activity against cisplatin-induced vomiting pigeon emesis study.
Requirements
Animals
- Healthy pigeons
- Body weight: approximately 250-350 g
- Animals should be acclimatized for 5-7 days before the experiment.
- Ethical approval and proper animal-care rules must be followed.
Drugs
- Cisplatin: emetic agent
- Ondansetron: standard antiemetic drug
- Test drug / plant extract
- Normal saline (0.9% NaCl): vehicle or control
Instruments
- Syringes
- Oral gavage tube, if required
- Weighing balance
- Observation chamber or cage
- Stopwatch
- Record sheet
Experimental Groups
Animals are divided into six groups. Each group contains an equal number of pigeons.
| Group | Treatment |
|---|---|
| Group I: Normal control | Normal saline only |
| Group II: Cisplatin control | Cisplatin only |
| Group III: Standard group | Ondansetron + cisplatin |
| Group IV: Test low dose | Test drug low dose + cisplatin |
| Group V: Test medium dose | Test drug medium dose + cisplatin |
| Group VI: Test high dose | Test drug high dose + cisplatin |
Example doses from the practical record:
- Ondansetron: 1 mg/kg, oral
- Cisplatin: 6 mg/kg, intravenous
- Test drug: 50, 100 and 200 mg/kg or as prescribed in the practical manual.
In the exam, write the dose used in your college practical manual. Dose and route can vary in different laboratory protocols.
Procedure
-
Select healthy pigeons and acclimatize them for 5-7 days.
-
Divide pigeons randomly into six groups.
-
Give normal saline to the control group.
-
Give ondansetron to the standard group.
-
Give low, medium, and high doses of the test drug to Groups IV, V, and VI respectively.
-
Give the standard drug or test drug 30 minutes before cisplatin administration.
-
Induce vomiting by giving cisplatin to all groups except the normal control group.
-
Keep each pigeon separately in an observation chamber.
-
Observe the pigeons continuously for about 6 hours after cisplatin administration.
-
Record the following:
- Number of vomiting episodes
- Latency period, that is, time taken for first vomiting
- Any clinical or behavioural changes
- Record observations at regular intervals, for example every 30 minutes.
Evaluation Parameters
1. Number of emetic episodes
Count the total number of vomiting episodes in each pigeon.
A lower number of vomiting episodes shows better antiemetic activity.
2. Latency to first emesis
It is the time between cisplatin administration and the first vomiting episode.
A longer latency period shows better antiemetic activity.
3. Percentage inhibition of emesis
[
\text{Percentage inhibition of emesis} =
\frac{\text{Mean emesis in control group} - \text{Mean emesis in treated group}}
{\text{Mean emesis in control group}}
\times 100
]
4. Clinical observations
Observe:
- Activity or movement
- Feeding behaviour
- Weakness
- Sedation
- Any abnormal behaviour
Result
- The cisplatin control group shows maximum vomiting episodes.
- The ondansetron-treated group shows a marked reduction in vomiting.
- If the test drug decreases vomiting episodes and increases the latency period, it has antiemetic activity.
- A higher percentage inhibition of emesis indicates a stronger antiemetic effect.
Conclusion
The cisplatin-induced emesis model in pigeons is used to screen antiemetic drugs. Cisplatin causes vomiting mainly by release of serotonin and stimulation of vagal nerves and the vomiting centre. Ondansetron, a 5-HT3 receptor antagonist, reduces cisplatin-induced vomiting. A test drug is considered antiemetic if it reduces the number of vomiting episodes and delays the onset of vomiting.
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