02 3 / 2014
Oxycodone aka oxy is one of those drugs that are not that common in the UK but more so in the USA mainly due to availability and preference. Now I don’t have any peer reviewed sources but street wise methadone or even straight heroin are considered as being better alternatives to oxy primarily due to price; heroin is miles cheaper than oxy but oxy gives a more ‘euphoric’ high and comes in a convenient pill. One dude I know described it to me as such: taking heroin is like napping in clouds whilst oxy is like wearing a onesie made of clouds then being continuously hugged by it…
Unlike codeine which is a naturally derived opiate, oxy is a semisynthetic opioid extracted from thebaine; another form of naturally occurring opiates derived from opium poppies. Not sure if I mentioned this earlier or not but opium poppies are more like cocktails containing many different opiates. The poppies themselves are known as P. somniferum; the only species of Papaver used to produce opium. The cocktail contains morphine, codeine, noscapine, papaverine, and thebaine; the most abundant being morphine at about 12-17%. All of the above other than thebaine are used clinically as analgesics to reduce pain without a loss of consciousness. Thebaine on the other hand doesn’t have analgesic effects but is used to produce semisynthetic opioid morphine analogues such as oxycodone, dihydromorphenone, and hydrocodone. Now, you may ask why even use thebaine if you’ve got several other opiates that actually work…well dear reader, if utilised correctly, thebaine can be used to synthesise analogues that are far more potent than morphine. Oxy is an example of such a thing which was made in 1919 in Germany due to pharmaceutical companies trying to improve pre-existing medicines.
The synthesis is as follows:
Extracted from patent: EP2121699 B1
After being taken, oxy is metabolized by the cytochrome P450 enzymes CYP2D6 and CYP3A4 where it’s metabolised into quite a few metabolites:
(Lalovic et al., 2005)
Now, unlike morphine, which acts upon μ-opioid receptors the active metabolites of oxy then go on and act on κ-opioid receptors, present in the hypothalamus, periaqueductal gray, spinal cord and in pain neurons. When activated, it induces feelings of sedation specifically dissociative anesthetist effects. Thereafter, the metabolites are mainly excreted via the renal system and also by sweat.
Oxy is a straight up class A scheduled drug without a prescription and holds a bounty of Up to 7 years in prison, an unlimited fine or both for possession and Up to life in prison, an unlimited fine or both for dealing.
Legal bits again taken from https://www.gov.uk/penalties-drug-possession-dealing
Patent found from: http://www.google.com/patents/EP2121699B1?cl=en
Figure 1 from Lalovic B, Kharasch E, Hoffer C, Risler L, Liu Chen LY, Shen DD. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther. 2006 May;79(5):461-79. PubMed PMID: 16678548.
23 2 / 2014
Since I wanted to discuss the different types of opiates, I thought I’d talk about codeine first. Codeine is a naturally occurring opiate extracted from the opium poppy but since this is a pretty long, tedious and highly inefficient process (each opium poppy has around 3% codeine), codeine is mass produced either semi-synthetically or synthetically. The latter of which has the potential to become more common as it eliminates the poppy altogether. The new method was detailed by Magnus et al in 2009. Check it:
So, once ingested; readily by the GI tract I might add, codeine enters the body and heads on over to the liver where CYP2D6; a cytochrome P450 enzyme, converts codeine to good ol morphine via demethylation which then goes on to act upon the μ-opioid receptor - which is found in abundance in the peri aquiductal gray; a location which is predominantly used by endorphins to induce analgesia. On a side note, endorphins are about 18 to 33 times more potent than morphine (Loh et al, 1976)
BUT! Only about 5-15% of codeine goes through this route. The rest of it is subjected to other enzymes like CYP3A4 and UGT2B7 (both in the liver) which transform it into the inactive products norcodeine and a conjugate respectively:
Once all is said and done, morphine then undergoes glucuronidation and undergoes renal clearance.
Codeine’s a bit of a tricky one as the legality of it in the UK depends on it being combined with another drug like paracetamol or ibuprofen as long as its max amount doesn’t exceed 12.8 mg or 15mg in liquid form - both of which apply for over the counter only. Any higher requires a prescription but even that must be combined with another drug AND must be below 100mg… By itself it’s considered a class B drug for which the penalty is up to 5 years in prison, an unlimited fine or both for possession and up to 14 years in prison, an unlimited fine or both if you feel like producing and supplying it.
Loh HH, Tseng LF, Wei E, Li CH. beta-endorphin is a potent analgesic agent. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2895-8. PubMed PMID: 8780; PubMed Central PMCID: PMC430793.
Legal bits taken from https://www.gov.uk/penalties-drug-possession-dealing
Magnus’s method of synthesis taken from https://www.chem.wisc.edu/areas/reich/syntheses/codeine-magnus.htm
16 2 / 2014
As stated in previous posts, there are many types of opioids classified into types:
- Natural opiates derived from the opium poppy e.g. codeine
- Semi-synthetic opioids – derived by modifying natural opiates e.g. oxycodone
- Fully synthetic opioids – analogues of opium e.g. methadone
- Endogenous opioids – opioids produced in the body e.g. endorphins
Whilst working to all complete the same end result; analgesia, they differ in their biochemistry – structure, mechanisms of action, pharmacodynamics pharmacokinetics etc. Since there are a few drugs to discuss I decided to summarise them in to a neat table:
You may notice that I didn’t include endogenous opioids mainly because they’re not drugs of abuse…However, I will include them next week as a way of comparing the drugs of abuse to endogenous molecules.
16 2 / 2014
So, my research buddy very generously allowed me to take opioids as my main research topic from the 3 main categories of drug types of abuse (opioids, CNS depressants and stimulants). I’ll be dividing my blogging into parts during this research and aim to cover (hopefully in this order):
- Mechanism of action
- Analytical techniques to test for the drug
- Legality/statistics and reasons for abuse
And on with the show!
05 2 / 2014
Well that’s the whole what question sorted out (what drugs are abused) but what about the why? Why are these drugs abused? Well my fellow reader, the answer is pretty straightforward really as you shall now see
Opioids – Mainly abused by heroin addicts or addicts trying to recover from addiction whilst trying to minimise withdrawal symptoms. Abuse of opioids such as methadone occurs because the effects of methadone are pretty weak sauce when compared to a full on heroin dose. Also, opioids are a class of analgesics (pain killers) which have a tendency of creating a feeling of immense euphoria or a ‘high’ in the users leading to its constant abuse. I’ll be going into detail about the mechanisms of reward and addiction at a later date. In somewhat related news, a study conducted in the Netherlands by van den Brink etal found that patients exhibited a marginally better response to heroin withdrawal when methadone was combined with a controlled and supervised does of heroin when compared with methadone alone. He states that supervised co-prescription of heroin is feasible, more effective than and probably as safe as methadone alone in reducing the many physical, mental, and social problems of treatment resistant heroin addicts.
CNS Depressants – These drugs are primarily prescribed to people who suffer from conditions such as anxiety, panic attacks, insomnia etc. They are abused simply because they make people not care as much by sedating themselves and making them feel like every little thing is gonna be alright thus allowing them to mask their problems.
Stimulants – Amphetamines are a classic example of prescription abused drugs such as Adderall; not so much in the UK when compared to the USA. The reason why they are abused is that the users say that it gives them an edge both mentally and physically; a performance and cognitive enhancer. It’s mainly prescribed for sufferers of attention deficit hyperactivity disorder (ADHD) but is commonly abused by otherwise ‘normal’ people. To put things into perspective, have you seen the movie limitless starring Bradley Cooper? Yeah, that film was described as being a 2 hour long Adderall advert…
Others – ones that don’t fit into the other categories such as DMX (Dextromethorphan) which acts as a hallucinogen. It’s abused because it’s pretty simple to pick up from any pharmacy (again, more common the USA), and provides the user with an easy means of trippin balls. Oh, and Viagra also fits into this category but I’ll let your imagination decide why that’s abused :|
Van den Brink W, Hendriks VM, Blanken P, Koeter MW, van Zwieten BJ, van Ree
JM. Medical prescription of heroin to treatment resistant heroin addicts: two randomised controlled trials. BMJ. 2003 Aug 9; 327(7410):310. Erratum in: BMJ. 2003 Sep 27; 3217(7417):724. PubMed PMID: 12907482; PubMed Central PMCID: PMC169643.
05 2 / 2014
So I spoke with my mate down in Boots about the drugs most commonly abused by folks in the UK and he gave me the following list:
(The first name is the drug name, the second name is the trade name and the drug class is given in brackets)
- Methadone - Dolophine (Synthetic opioid)
- Buprenorphine - Subutex (Semi synthetic opioid)
- Codeine - (Opiate)
- Codeine phosphate - Galcodine (Opiate)
- Diazepam - Valium (Benzodiazepine)
- Temazepam - Restoril (Benzodiazepine)
Common prescription drugs abused in the USA:
- Codeine - (Opiate)
- Oxycodone - OxyContin (Semi synthetic opioid)
- Methadone - Dolophine (Synthetic opioid)
- Alprazolam – Xanax (Benzodiazepine)
- Amobarbital - Amytal (Barbiturate)
- Adderall – mixed amphetamines (Stimulant)
- Dextromethorphan DXM – Various cough syrups e.g. Robitussin or NyQuil. Antitussive (cough suppressant) in normal doses but excess leads to dissociative hallucinogenic effects.
Note: Opiates are based on natural narcotic opioid alkaloids derived from the opium poppy e.g. Morphine, Codeine, Thebaine, papaverine etc. whilst Opioids are analogues (structurally similar molecules) of morphine and are either synthetic or semi synthetic e.g. Hydrocodone Oxycodone, Diacetylmorphine (heroin - semi synthetic).
Generally, people refer to both opioids and opiates as opioids - used as a blanket term because they all act on the opioid receptors; more on receptors later on!
As stated in my blog post last week, most or if not all of the drugs most commonly abused fall under one of the 4 categories: Opioids, Central Nervous System (CNS) Depressants, Stimulants or Others. This is pretty much the same for both the UK and the USA but studies have found that CNS depressants (benzodiazepines/barbiturates) and stimulants (Amphetamines) are far more common in the USA; specifically within colleges and other educational institutions (McCabe etal, 2004).
McCabe, S. E., Knight, J. R., Teter, C. J. and Wechsler, H. (2005), Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey. Addiction, 100: 96–106. doi: 10.1111/j.1360-0443.2005.00944.x
31 1 / 2014
The most commonly abused drugs fall into the following categories:
- Opioids – Morphine and morphine derivatives
- Central Nervous System Depressants - Benzodiazepines
- Stimulants - Amphetamines
- Others e.g. cough syrup (Dextromethorphan)
The categories above have been done according to the frequency of abuse; opioids being the most common and cough syrup being the least. The examples of the drugs given next to each are singular examples only and do not form a complete list!
As you may have already guessed, each one of these drugs function using very distinct mechanisms of action to produce the ‘desired’ effects. I’ll be going into each one of these properly during the course of this semester; such as biochemistry, synthesis, mechanisms of action, what they were supposed to be used for and how they are abused.
I shall also be covering legality; status of the drugs and the punishment for abusing them. I’ll also be listing the differences between the drugs abused in the UK and other parts of the world; mainly the USA along with some reasons why.
So yaaaaah, this is going to be one action packed semester filled with a ridiculous amount of information. Look forward to future updates!
27 1 / 2014
sup guys, after much deliberation (new assignment brap brap) I have decided to switch the direction of this blog to being about the abuse of prescription drugs! Big change from mass graves yes I know but whatevs. Heres to a new year!
16 12 / 2013
sorry all for the lack of blog this week. I am currently focusing on the wiki. Keep in touch!
08 12 / 2013
So, after digging a bit deeper (see what I did there) into the results of the excavations, it turns out that some of the bodies found from the graves dated to different time periods…
Period 14 – 1120 – 1200, 512 People
Period 15 – 1200 – 1250, 1390 People
Period 16 – 1250 – 1400, 2835 People
Period 17 – 1400 – 1539, 650 People
We see that the highest body count was from period 16; 1250 – 1400, the time our volcano erupted.
Below I present to you the results from the height measurements from the periods:
Let’s examine this juicy piece of data. First if we see the differences in heights between the individuals (mean) buried in graves ABC as opposed to D, we see that the individuals in D are consistently shorter for every time period for both males and females. This supports my theory before about how the poorer people would be given ‘communal graves’; mass graves within mass grave sites for the poorer folk.
Just in case you’ve forgotten the grave types, I have linked the pics for the grave types - http://i.imgur.com/4I8nta3.jpg
Generally, the less nutrition a person has, the less they will grow. Being poorer; especially during famine times, meant that you’d go hungry often and therefore, lack of food = shorter in height.
Unfortunately, I need to cut this week’s blog post short due to exam revision (booooo!), but next time, I’ll be posting up tables for age and pathological measurements so there’s that to look forward to!
Until next time mah duckies!