GIT Lec 4 Pt 4 - Anti D1/D2 Agents

Question 1

What are the classifications of dopamine antagonists?

Answer 1

A. Non-specific D1 and D2 receptor antagonists:
I. Phenothiazines (thiethylperazine, prochlorperazine, chlorpromazine and perphenazine
II. Butyrophenones (haloperidol and droperidol)
B. Specific D2 antagonists (metoclopramide and domperidone)

Question 2

What are the indications of phenothiazines?

Answer 2

They are indicated in the following:
1. Post-operative nausea and vomiting
2. Cytotoxic-drug induced vomiting
3. Radiation therapy induced vomiting
4. Ménière’s disease

Question 3

What are the side effects of phenothiazines?

Answer 3

Intra-pyramidal side effects: hypotension and restlessness
Extra-pyramidal side effects (rarer): dystonias and dyskinesias

Question 4

What are the indications of Butyrophenones?

Answer 4

Butyrophenones like haloperidol and droperidol are moderately effective emetics.
Droperidol is mostly indicated as a sedative prior to endoscopy and surgery, usually combined with an opiate or benzodiazepine.

Question 5

What are the things that we can not use metoclopramide for?

Answer 5

Labyrinthine diseases and motion sickness.

Question 6

What is the MOA of plasil?

Answer 6

1. It works by blocking the action of D2 receptors in the CTZ thereby preventing the stimulation of the vomiting center.
2. In the GIT, metoclopramide does the following:
   A. Increases the tone (pressure) of the LES (lower esophageal sphincter) which prevents gastro-esophageal reflux.
   B. Increases the stomach’s peristaltic movement
   C. Decreases the tone (pressure) of the pyloric sphincter (gastric hurrying action)
   D. Increases the intestinal peristaltic movement and increases emptying of the upper gut thereby having prokinetic and gastrokinetic effects.

Question 7

What are the pharmacokinetics of metoclopramide?

Answer 7

1. It is rapidly absorbed orally, however it can also be administered intravenously or intramuscularly in patients with severe emesis.
2. It is partially metabolized in the liver and excreted by the kidney (in urine)
3. It is administered in a dose of 10mg in adults and three times day (either orally or via IV or IM injection) and in a dose of 0.25-0.5mg in children, also three times a day.

Question 8

What are the therapeutic uses of metoclopramide?

Answer 8

1. Prokinetic agent.
2. Gastrokinetic agent: it is more often indicated in patients with gastroparesis in whom it can cause low to moderate improvement in gastric emptying.
3. To control nausea and vomiting caused by GIT disorders, cytotoxic drugs (at high doses against cisplatin), post-operation, migraine, radiotherapy and it also facilitates gastric intubation
4. It doesn’t work for labyrinthine disorders and motion sickness
5. Hiccups (metoclopramide, baclofen or chlorpromazine)
6. GERD

Question 9

What are the adverse effects of plasil?

Answer 9

1. Sedation, diarrhea and restlessness; observed in 20% of patients.
2. Although it has no anti-psychotic effects in humans; it does penetrate the CNS and it can cause extra-pyramidal effects like dystonia in 1% of patients which could increase up to 3% of patients at higher doses used in cancer therapy. Some of the extra-pyramidal effects include:
   I. Dystonia and dyskinesias
   II. Torticollis
   III. Facial spasms
   IV. Trismus (locking jaws)
   V. Oculogyrus crises; almost twice as common in women compared to men, also very common in children who are taking other anti-dopaminergic drugs concomitantly. That’s why the dosage should be reduced in children.
3. Long term use of metoclopramide could lead to tardive dyskinesia in elderly
4. Blocking of D2 receptors in the anterior pituitary could lead to increased prolactin production which increases lactation in females and could lead to gynocomastasia in males.

Question 10

What is the MOA of domperidone?

Answer 10

Domperidone inhibits the D2 receptors in the CTZ which inhibits the vomiting center but also stimulates the production of prolactin from the anterior pituitary which leads to gyncomastasia and galactorrhea

Question 11

What are the indications of domperidone?

Answer 11

1. It is used in the treatment of nausea and vomiting induced by GIT disorders, levodopa in patients with Parkinsonism and cytotoxic drugs (higher doses)
2. It is used in managing and controlling bloating in patients with non-ulcer dyspepsias
3. It increases the tone of the lower esophagus (LES) and peristaltic movement.

Question 12

What are the preparations available for domperidone?

Answer 12

1. 10mg tablets
2. 1mg/ml suspensions

Question 13

What are the side effects of Domperizone?

Answer 13

1. Cardiac arrest and arrhythmias can occur when the medication is taken intravenously at higher-than-normal dosages.
2. Headaches, dry mouth and diarrhea are frequently encountered when taken orally.