- 1 In‐depth discussion of antiemetics
- 1.1 Neurological mechanisms that trigger vomiting
- 1.2 Dopamine blockers: the antiemetics of choice for drug overdoses
- 1.3 Serotonin blockers: an overlooked complement
- 2 Antiemetic options
- 3 Vomiting and related matters
- 4 EPS: risks, symptoms and dealing with it
- 5 References
In‐depth discussion of antiemetics
Neurological mechanisms that trigger vomiting
The human body employs several distinct mechanisms to trigger vomiting in response to different stimuli. It follows that there is no universal antiemetic that would prevent vomiting irrespective of the cause; indeed, each particular antiemetic drug targets a specific vomiting mechanism. For instance, medicines used to prevent motion sickness will not work to stop nausea caused by general anaesthesia.
- Most over-the-counter (OTC) antiemetics are intended to alleviate travel sickness. Examples of such a drug is dimenhydrinate (Dramamine, Gravol). They work through the histaminic receptors and the cholinergic receptors; thus, they would not be suitable for the prevention of drug-induced vomiting, which is triggered by other neurotransmitters.
- Another class of antiemetics that would be slightly more efficient for drug-induced vomiting is that which is used for post-surgery and chemotherapy-induced emesis. This drug class acts by inhibiting the 5-HT receptors (serotonin blockers and drugs that work through the vagus nerve), primarily the 5-HT3 receptor. To some extent, these drugs can lower the instance of drug-induced vomiting, but they are not the antiemetic of choice for this purpose: dopamine, not serotonin, is the main neurotransmitter for triggering the brain's vomiting centre when a drug overdose occurs. However, it may be advisable to use a 5-HT3 antagonist as a complement to a dopamine blocker, see more below.
- The third class of antiemetics, most suitable for preventing vomiting due to a drug overdose, consists of dopamine blockers. They are discussed in detail below.
Dopamine blockers: the antiemetics of choice for drug overdoses
There are three well known dopamine blockers that would serve this purpose well:
- Prochlorperazine (Compazine, Stemzine, Buccastem, Stemetil, Phenotil)
- Metoclopramide (Reglan, Primperan)
- Domperidone (Motilium)
How they rank as dopamine blockers
If we sort these three widespread dopamine blockers by their potency, then it will look like this:
- 1. Prochlorperazine - this is the most potent dopamine blocker.
- 2. Metoclopramide
- 3. Domperidone - this is the least potent dopamine blocker
So, at first sight, Prochlorperazine might be considered as the premier choice. However, it being the strongest dopamine blocker and affecting the central nervous system (CNS) by crossing the blood-brain-barrier means that the likelihood of experiencing so called extra-pyramidal signs, EPS would be extremely high. EPS in itself is a distressing experience that may well cause you to abort your suicide attempt, or make it practically infeasible. Thus the risks outweigh the protection that you get.
In suicide literature, such as in the Peaceful Pill Handbook, Metoclopramide is often the drug of choice. It is also, as far as we know, the choice of Swiss euthanasia organisation Dignitas. Unlike Prochlorperazine, it possesses some gastro-prokinetic properties. The latter means that Metoclopramide would also speed up the rate of gastric emptying, which ultimately means that even if you do vomit, your stomach will be empty (so there is nothing to vomit), since its contents will have passed to the intestine by this time. This reduces the chances of dying by choking on the vomit, and the drug is absorbed quicker. However, Metoclopramide also affects the CNS, and may result in EPS, at least at higher doses. At higher doses, it has the advantage of being a 5-HT3 antagonist as well. In any case, there is good reason to believe that Metoclopramide is preferred to Prochlorperazine.
The last dopamine blocker is Domperidone, which is the mildest out of all three. It is not mentioned much in suicide literature. In some countries it is available without prescription. Its advantage is that it does not readily cross the blood-brain barrier, therefore there are no case reports of people experiencing EPS when using this drug. Like Metoclopramide, it is also a gastro-prokinetic. However, Domperidone is known to have some cardiotoxic effects such as QT interval prolongation and arrhythmias at higher doses. These effects are uncommon, but could be distressing to sensitive individuals. Domperidone is considered to be a potent enough antiemetic for drug overdose, and thus it may be an overlooked choice for drug cocktails, however, see the discussion below.
Metoclopramide or Domperidone?
At least one study comparing the efficiency of Metoclopramide and Domperidone for chemotherapy-induced vomiting found Domperidone to be as efficient as Metoclopramide:
"In order to prevent vomiting induced by anti-cancer chemotherapy, the efficiency of Domperidone has been compared to Metoclopramide in a randomised trial. No difference has been observed between both emetic treatments."
So, as it stands, one would have to weigh the benefits of Metoclopramide (more potent dopamine blocker, some affinity for the 5-HT3 receptor) to the benefits of Domperidone (no EPS, sometimes available over the counter), and the disadvantages of the former (EPS) with disadvantages of the latter (some risk for cardiotoxicity, less recommendations in literature). There have been anecdotal reports on the internet on vomiting while on the domperidone procedure, which might speak for metoclopramide.
Serotonin blockers: an overlooked complement
Though, not much discussed in literature, the use of a serotonin blocker, notably a 5-HT3 antagonist alongside a dopamine blocker may be advisable to reduce failure in what constitutes such a serious act as drug overdose. Derek Humphry, on his blog, has advised the use of Ondansetron (Zofran) along with Metoclopramide, as has advisors on the US Death with Dignity act. The combination of Ondansetron and Domperidone seems as good. Please consider this addition seriously. Serotonin blockers do not induce EPS, and this combo would then act on both dopaminergic and serotonergic pathways in the body's vomiting response with mild side-effects.
General advice regarding antiemetics
Below we list several options for an antiemetic regimen. There is no right antiemetic; you may chose one based on availability of drugs or our analysis of risks.
No matter which option of the three mentioned below you decide to use, please apply a short and controlled test, just to confirm that you are not allergic to that specific antiemetic and to avoid any unexpected side effects in your actual suicide attempt. The test should include no more than a 10 mg dose to see if you are somehow badly affected by this antiemetic. If so, you might want to test an alternative. It could also be worth trying a higher dose to see if tendencies of EPS would occur. In this case, try the procedure well in advance and then stop to avoid building a tolerance.
General advice on eating and drug ingestion
The following advice comes from the US Death with Dignity act advisor George Eighmey:
- No ingestion of laxatives at least 24 hours prior to drug ingestion.
- No meal 4-5 hours prior to ingestion. This differs from advice from Dr Nitschke to eat a light snack some hour prior.
- Water and non-acidic juices are ok, while acidic, fatty, carbonated or caffeinated liquids should be avoided.
- Just before drug ingestion, eat 2-3 tablespoons of liquid honey or syrup and 2-3 tablespoons of Pepto-Bismol to mask the drug's bitter taste. This advice was given for a very caustic drug combo, but may be good advice in general. If consuming a powdered cocktail, the powder could be mixed in the sweetener.
- Take the whole amount of the drug cocktail within 1-2 minutes to avoid falling asleep before full dose has been ingested! This concerns quickly sedative cocktails such as barbiturates, but may be good advice in general.
The following advice comes from Dr Nitschke and other sources:
- If the drug comes as tablets, crush them to a powder and mix with something sweet such as applesauce or liqueur. If in capsule form, open the capsules. Keep the amount small, not more than a small glass.
- Consume some of your favourite alcohol after (not prior) to drug ingestion. This will potentiate the cocktail and mask the bitter taste. Do not drink heavily, which might dilute the drug or induce vomiting.
- Dignitas provides some chocolates after drug ingestion to mask the bitter taste.
- Tolerance to alcohol, benzodiazepines, analgesics, prolonged use of anti-psychotics, and gastrointestinal issues can complicate overdosing. It is advisable that medications that can be stopped (without affecting judgement), should be ceased a few weeks prior to the drug ingestion, as should alcohol and narcotics consumption.
The following lists procedures that start ahead. Do not exceed the suggested amount and do not cut down the suggested interval under any circumstances, since this may increase risk of EPS or failure.
|Source||Ahead regimen||Before ingestion|
|Wiki author best option||Take 15 mg Metoclopramide every 8 hours, i.e. 3 times per day, starting 48 hours in advance.||Take the last dose Metoclopramide 45-60 min prior to cocktail ingestion along with 8-16 mg Ondansetron.|
|Wiki author second best option||Take 15 mg Domperidone every 8 hours, i.e. 3 times per day, starting 48 hours in advance.||Take the last dose Domperidone 45-60 min prior to cocktail ingestion along with 8-16 mg Ondansetron.|
|Dr. Admiral's best option||Take 10 mg Metoclopramide every 8 hours, i.e. 3 times per day, starting at least 36 hours in advance.||Take the last dose of Metoclopramide 45 min before the drug ingestion.|
|Dr. Admiral's second best option||Take 10 mg Domperidone every 8 hours, i.e. 3 times per day, starting at least 36 hours in advance.||Take the last dose of Domperidone 45 min before the drug ingestion.|
|Dr. Nitschke's advice||Take 20 mg Metoclopramide every 8 hours, i.e. 3 times per day, starting 48 hours in advance.||Take the last dose of Metoclopramide 45-60 min before the drug ingestion.|
These regimens concern taking a single heavy antiemetic dose just before drug ingestion. This is used e.g. by Swiss euthanasia organisation Dignitas, and seems to work for them, although we have no accounts as to how often vomiting occurs.
|Wiki author best option||45 min prior to drug ingestion, take 40 mg Metoclopramide and 8-16 mg Ondansetron|
|Wiki author second best option||45 min prior to drug ingestion, take 40 mg Domperidone and 8-16 mg Ondansetron|
|Dr Nitschke's advice||40 min prior to drug ingestion, take 60 mg Metoclopramide|
|Dignitas' procedure as per their webpage||30 min prior to drug ingestion, take 20-30 mg liquid Metoclopramide|
|Death with Dignity George Eighmey's advice||60 min prior to drug ingestion, take 20-40 mg Metoclopramide and 8-16 mg Ondansetron|
Effect of sedatives on vomiting
In the drug cocktails described on this wiki which rely on sedatives (which any reasonable cocktail would), the sedatives should take effect in less than 10 minutes. Nevertheless, this means that we need the protection of an antiemetic (or antiemetics, depending on your preference) for a short period of time, until the sedatives depress the central nervous system, thus ultimately also depressing the vomiting centre in the brain, therefore preventing any chance for emesis to occur.
Vomiting is a very real risk, so drug overdosing without antiemetics is potentially problematic with regard to succesfully achieving a peaceful and successful end to one's life and should not be tried (unless failure or a painful death by choking a la Jimi Hendrix is sought). There are few accounts of vomiting from Dignitas and in reports on physician assisted suicide in the Netherlands, which suggests antiemetics are effective for most people. However, severe gastrointestinal issues due to disease render oral consumption of the drug unsuitable, unfortunately.
What to do if vomiting occurs, despite the antiemetic regimen?
See this quotation from The Peaceful Pill Handbook by Dr. Nitschke:
"If vomiting does occur, the individual should bring up (vomit up) as much of the drug from their stomach as they can and the attempt to end their life should be abandoned. Ipecac Syrup can be used to encourage vomiting. It may be advisable to have some on hand. Ipecac can be readily obtained from the local pharmacy."
Please take this advice seriously. Ipecac syrup is available by prescription only in some countries.
EPS: risks, symptoms and dealing with it
All of the antiemetic drugs efficient for our purposes carry a risk for extrapyramidal symptoms (EPS), although with Domperidone it's low. Because of the way these drugs work, they affect a part of the brain involved in the coordination of movement. EPS includes number of symptoms, including involuntary movements, tremors and rigidity, body restlessness, muscle contractions and changes in breathing and heart rate. If you wish, you can go to YouTube and see some videos that show what dystonia and dyskinesia (which are symptoms associated with EPS) look like; the disorders seen on the videos are typically not caused by the antiemetic drugs that we have discussed, but drug-induced EPS may take a similar form.
What to do if EPS happens to you:
Standard treatment for EPS is to take 50 mg of Diphenhydramine (Benadryl, Dimedrol).
You are at higher risk for EPS if one of the following applies to you:
- Previous episodes of EPS in life or other motoric disorders;
- The prolonged use of neuroleptic drugs before, such as Haloperidol;
- You are under 30 years old: people under that age tend to be more prone to EPS;
- You are a woman above the age of 50.
- (2.0 2.1) Comparative trial between two drugs in the treatment of vomiting induced by anti-cancer chemotherapy. Zylberait D, Krulik M, Audebert AA, Debray J. Sem Hop. 1981 Jan http://www.ncbi.nlm.nih.gov/pubmed/6258237
- Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook By Charles B. Nemeroff , Alan F. Schatzberg http://books.google.ch/books?id=4lK-1X-MOJEC, p 150