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Emetic and anti-emetic drugs

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The Necessity

Humans are fundamentally animals, and in true Darwinian fashion, survival is key. The process of emesis, or vomiting, can often be regarded as a defensive mechanism adopted by humans and other animals. One example of this is using emesis to reverse the potentially deadly mistake of eating a poisonous substance. If the bodies natural defences failed to recognise the danger of the foreign toxin in the blood stream, it may be essential to induce emesis. Hence, a need for emetic drugs arose, drugs which would stimulate the body's natural defences and promote vomiting. However, not all vomiting is a defensive reflex, such as motion sickness, or the nausea associated with pregnancy, both of which cause no biological threat to the existence of the human. The extreme emesis suffered by chemotherapy patients is another strong cause for drugs to allow control over the vomiting process, and so the necessity for anti-emetic drugs also arose.

The Emetic Response

The act of emesis is in fact a fairly complex one, requiring the co-ordination of the somatic respiratory and abdominal muscles, and the muscles of the gastrointestinal tract. Two sections of the medulla function to regulate the event of emesis, the chemoreceptor trigger zone (CTZ) and the vomiting centre. The CTZ is located in the area postrema, on the floor of the fourth ventricle of the brain, and is sensitive to chemical stimuli present in the plasma. Many drugs can be used to counteract substances working on the CTZ, reaching the area of the brain via the blood stream. The blood-brain barrier around the CTZ is permeable, allowing drugs to act directly on it. The vomiting centre is, however, used to co-ordinate the actual event of emesis, regulating the movement of smooth and striated muscle. The CTZ transmits signals to the vomiting centre when a stimuli acts upon the CTZ, causing the activation of the emetic reflex.

Emetic Drugs

As previously stated, sometimes emesis is a desirable process, such as in the event of swallowing a toxic substance. It is also, perhaps [a bit irishly], necessary to promote vomiting in the test for anti-emetic drugs. The main emetic drug that is used is Ipecacuanha, which contains two substance, emetine and cephaeline, which irritate the gastrointestinal tract to cause the patient to vomit. However, migranes and indigestion are common side effects

Motion Sickness

Emesis can be induced without any influence from foreign substances within the body. Motion sickness is a prime example of this, and has no biological significance on the existence of humans. In the process of motion sickness, the labyrinth in the vestibular apparatus of the ear is moved in a certain way. This relays a signal to the floor of the fourth ventricle, but the mechanism of movement of the signal to the CTZ is yet unknown. It has been hypothesised that the cerebellum may possibly act as a second relay centre, but as the CTZ only responds to chemicals in the plasma, the synaptic pulses from the relay centres could not act directly upon it. However, although the mechanism of motion sickness is not yet fully known, many drugs for motion sickness have been designed, antagonising the H1 and muscarinic receptors.

H1-receptor antagonists

Histamine H1 receptor antagonists can prevent emesis by competing with histamine on the H1-receptor sites. The precise mechanism of action is yet unknown, but it has been thought that the administered antihistamine competitively blocks the H1-receptors of the vestibular apparatus, reducing sensitivity, and can act directly on the gut, which, in turn, relieves the vomiting associated with motion sickness. Furthermore, first-generation H1-receptor antagonist may also block the chemoreceptor trigger zone, and act on the nucleus of the solitary tract (brainstem) by crossing the blood-brain barrier, preventing vomiting in the patient. However, this treatment is mainly effective if administered before the onset of emesis, though may manage to help control emesis once it has began. As can be seem from the chemical structure opposite, the general structure of H1-receptor antagonists can be portrayed simply. Many first-generation antihistamines cause drowsiness as a very common side effect, due to the anticholinergic properties of the drug. However, this anticholinergic property can also act as an anti-emetic, making the first-generation antihistamine drugs more effective.

Muscarinic-receptor antagonists

Muscarinic receptor antagonists. Good for prevention of motion sickness.

  • scopolamine (Transderm-Scop)

Para4: (working on stomach)

  • muscarinic - receptor antagonist
  • Side effects, ways it works, problems, structures, point out where it acts, and how the structure makes it act in that way. Explain how the drug interferes with the normal emesis process.

Muscarinic-receptor antagonists (Chapter 7)

  • Hyoscine - active against nausea and vomiting caused by the stimuli of the labyrinth (ear), and against substances which act on the stomach directly, but not against things which act on the CTZ. (same as H1)
  • Hyoscine is best agent for prevention of motion sickness, but less useful once sickness occurs.
  • Effect peaks after 1-2 hours after ingestion, can also be given transdermally (via the skin like a nicotine patch), and is usually put behind the ear.
  • Unwanted side effects: drowsiness, dry mouth. (other side effects can include blurring vision and retention of urine, but don't normally occur at the doses given for anti-emetic effects)

Reference List:

  • Hawthorn, Jan. Understanding and Management of Nausea and Vomiting, Blackwell Science, 1st Edition, 1995
  • Rang and Dale
  • Bartholow, Roberts. Ipecacuanha, A Practical Treatise on Materia Medica and Therapeutics, Appleton and Company, 1908

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