Methyl In Drugs

[Silencer]

Why is it that many drugs, including some of the most potent, contain the methyl group?

[Drug addict]

In order for a drug to exert an effect, it has to cross at least one cellular barrier, regardless of the route of administration. Hydrocarbon chains are not pharmacologically active, so we can play around with them to a certain extent. Altering the length of a hydrocarbon chain, or adding a new one (eg by esterification) alters the lipid solubility of the drug, therefore changing its absorption. There are several examples where this has been done, but the only one I can remember at the moment is the esterification of betamethasone to betamethasone-17-valerate to increase absorption across the skin.

[Silencer]

ah. thanks.

[Drug addict]

No problem. There are another few things I should also have mentioned:

1) Drugs interact with biological systems, so you don't want too many reactive groups present as they could cause damage (though there are exceptions to this such as cytotoxics)

 

2) I can't think of any examples where a drug is administered as the pure drug. Whatever form it is given as contains excipients, whether they be bulking agents, preservatives, lubricants etc. Again you don't want too many reactive groups present as they may react with the excipients present (or oxygen) and alter the properties of the drug and so affect its absorption or efficacy. Though excipients are normally considered inert, this is not the case. The classical example I've been taught several times is that of phenytoin. Originally it was formulated with calcium sulphate as the capsule filler. Phenytoin forms an insoluble complex with calcium sulphate which affects its bioavailability. Some bright spark decided to change the capsule filler to lactose, without conducting any trials. Phenytoin does not form an insoluble complex with lactose and therefore the bioavailability was higher compared to the formulation with calcium sulphate. The result - people died from phenytoin toxicity.

 

 

I've just realised that what I said about phenytoin isn't that relevant, but its interesting anyway.

[Silencer]

That's ok, I like reading interesting things.

 

I'm going to point my friend to this board. He is very interested in pharmacology.

[Drug addict]

'Pharmacology' by Rang, Dale and Ritter (Churchill Livingstone) is an excellent pharmacology text book which has helped me enormously throughout my degree. 'Clinical Pharmacy and Therapeutics' by Walker & Edwards (Churchill Livingstone) is very good if you need to know about clinical pharmacology.

[YT2095]

ever read or seen "the PHARMACEUTCAL pocket book"?

 

I have one here from 1953 (sixteenth edition)

 

it was 1`st published in 1906 (man I`de love a copy of that!).

 

anyway, it`s a great little book, packed with data (some`s prolly been banned or updated since, Tincture of cannabis of Arsenic from a chemists??? Naah

 

it`s a fantastic read though! (if you like raw data and I do), esp the antidote section, it even has a veterinary posological table!

[jdurg]

Another reason the drug's structure is 'altered' is to affect its absorption in certain parts of the body. For example, if you wanted a drug to be absorbed in the brain instead of the muscles, you'd want it to be less polar since there is a higher fat content in the brain area than in the muscle area. So a non-polar drug will be more likely to absorb into the brain than it would into other, 'less fatty' organs.

[YT2095]

the sufix of the drug is also a clue as to how to administer it, Sulphates, Gluconates, Hydrochlorides etc...

 

some to ingest, some for direct (injection), some are topical treatments or inhaled etc...

 

the same medicine, just a different method of introduction

[Drug addict]

ever read or seen "the PHARMACEUTCAL pocket book"?

 

I have one here from 1953 (sixteenth edition)

 

it was 1`st published in 1906 (man I`de love a copy of that!).

 

anyway' date=' it`s a great little book, packed with data (some`s prolly been banned or updated since, Tincture of cannabis of Arsenic from a chemists??? Naah

 

it`s a fantastic read though! (if you like raw data and I do), esp the antidote section, it even has a veterinary posological table! [/quote']

 

Damn goverment and Royal Pharmaceutical Society won't let us have fun anymore

 

Another reason the drug's structure is 'altered' is to affect its absorption in certain parts of the body. For example, if you wanted a drug to be absorbed in the brain instead of the muscles, you'd want it to be less polar since there is a higher fat content in the brain area than in the muscle area. So a non-polar drug will be more likely to absorb into the brain than it would into other, 'less fatty' organs.

 

Strictly speaking, that's true, however life is not that simple! There are efflux mechanisms in the brain which mean that even if the drug crosses the blood-brain barrier, it can still be actively removed before reaching its target. The most important efflux mechanism is P-glycoprotein, which just happens to have an affinity for lipophilic compounds.

 

http://www.pharmj.com/pdf/articles/pj_20041002_newdrugtechnologies03.pdf gives a brief overview of drug delivery to the CNS.

[jdurg]

Well, that's true with everything. heh. If it were that simple, I wouldn't even have a job! (I work for a Clinical Research Organization where we process data on clinical trials of drugs prior to their submission to the FDA. If things were simple and went the way they were supposed to, there'd be no need for clinical trials and I'd be out of a job. )

[Drug addict]

In the US, do you have to show that a drug is better than those already on the market? I think they have to in Austraila, but in the UK it's not a requirement; MHRA/CSM only require you to show the drug's safety and efficacy, so you end up with lots of "me too" drugs which don't offer much of a step forward.

[Silencer]

No. In fact, the way US companies make money is by coming out with a new drup that does the same thing every few years.

 

Once a drug is approved for use there is a certain amount of time that the original developer "owns" it. After that it can be sold as a generic no-name brand that is still the same thing.

 

That is why a lot of insurance companies make you buy the generic version instead of name brand.

 

To combat this, the companies just make some sort of "improvement" on the drug and slap on a new name.

[Drug addict]

It's pretty much the same in the UK. There has been a lot of progress in getting doctors to write prescriptions generically, though this can cause several problems. Firstly there are drugs which should be prescribed by brand name, modified release diltiazem or m/r lithium for example. There can also be difficulties for the pharmacist in figuring out which product to dispense - generically written insulin prescriptions are a damn nightmare.

 

There is also a problem that may be somewhat unique to the UK, as most patients contribute through the tax system, where patients go to their doctor, get a generically written prescription and then ask for a certain brand as 'those tablets [the generic ones] don't work for me', not realising that the brand ones are often a lot more expensive than the generic ones. And then the doctor often won't change the prescription to the brand as it will affect their prescribing budget. Result - pharmacist has three options; try and convince the patient the brand and the generic are the same, dispense the brand and lose money, or refuse to dispense the brand and send the patient elsewhere, also losing money.

 

On a side note, it irritates the hell out of me when people complain about having to pay prescription charges (£6.40 at the moment) [ a word of explanation: NHS prescriptions are free for certain groups of people - those under 16, over 60, people with certain diseases such as diabetes or hypothyroidism, those on benefits. People who don't qualify for free prescriptions pay a fixed charge for each item, regardless of the amount prescribed or the actual cost].

 

Yes, some drugs are cheap, many are not and some are exceedingly expensive!

[jdurg]

For diabetics in the USA, it doesn't matter. You're going to pay a boatload of money for your prescriptions. Most insurance companies give you a limit on how much money they will cover, after that limit is met, you pay for it all out of your pocket. I've been a type I diabetic for about 22-23 years now, and every September that 'prescription fund' runs out and I have to pay hundreds of dollars each time I get a script refilled. It's annoying, it's obnoxious, and it's frustrating that I have to pay so much money for something I need to LIVE. Meanwhile, things like Darvocet, Vicodin, Oxycodone, etc. are dirt cheap. You don't absolutely need them to live, a full script only costs about 15 bucks. That's outrageous. Drug companies know that if someone needs something to live the next day, they'll be forced to pay anything. That's the situation I'm in, and there really are no 'generic' brand insulins over here. Eli-Lilly pretty much has a monopoly on the insulin market, and they are taking advantage of it. It's downright sickening how much money I'm forced to pay just because I'm an insulin-dependent diabetic.

[Drug addict]

That's why I prefer the UK healthcare system where any charges are nominal and access to healthcare is seen as a right and not a privelige. IMHO the American healthcare system is immoral and wrong. Don't get me wrong, I'm not claiming the NHS is perfect, nothing is, and I suspect that when I qualify as a pharmacist it would be easier to make money in the States than the UK, I just feel that the NHS offers a far more equitable system.

 

I think your ire would be better directed toward the US healthcare system than Eli-Lilly. I'm sure you appreciate the fact that the price of medication is related to how much it costs to manufacture. Insulin is expensive to manufacture because it is made biosynthetically, with all the problems that entails.

 

There are four manufacturers of insulin in the UK; Eli-Lilly, CP, Aventis Pharma and Novo Nordisk, although some insulins are only available from manufacturer e.g. only Aventis make Lantus (Insulin glargine). It would be interesting, though extremely problematic, to compare UK and US prices.

[jdurg]

Yeah, my ire isn't exactly towards Eli-Lilly. It's more towards the immoral fiend George W. Bush. I had actually forgotten about Aventis, but I use insulin glargine so I use products from them as well. Very few companies make insulin, because as you've stated, it's not cheap to make and they don't feel they can profit off of it. Canada has a nice system where EVERYBODY gets basically free health-care. The only problem is that you pay a LOT more taxes to get that benefit. I just feel that companies should charge more for drugs you don't need to survive and make their profits with them as opposed to charging more for the drugs people need to live. You don't need oxycodone to live. Sure it will help get rid of intense pain, but you can survive and see the next day without taking oxycodone. I can't survive and see the next day without insulin. That is the frustrating part. Why can't the companies just decide to not make a profit off of insulin when they can certaintly increase the price of things like pain killers and make their profits there? I don't know. It's just really, really frustrating.

[Silencer]

Major medical advances are made by the drug companies here in the states. Someone has to pay for them. It sucks, but that falls on us. If we were charged the same amount as other countries, there would be no money for new drug developement.

 

I don't think that a NHS is beneficial. For one, it is communist. For two, it introduces bureaucracy into the health care system which we just do not need.

 

Also, there are government programs that help provide medical care for those who can't afford it. If you can afford it, though, then you just have to deal with it. That's the way the cookie crumbles.

 

And jdurg, since you are so good in chemistry, synthesize your own insulin! (lol).

[jdurg]

And jdurg, since you are so good in chemistry, synthesize your own insulin! (lol).

 

 

lol. For the first few years of my life I did! Then my damned immune system said 'Enough of that!' and shut down my factory.

[Skye]

Methyl groups also participate directly in H-bonding to the target protein, though that's not likely a modification to a synthetic drug, it'll be part of the natural signal molecule.

 

Major medical advances are made by the drug companies here in the states. Someone has to pay for them. It sucks, but that falls on us. If we were charged the same amount as other countries, there would be no money for new drug developement.

People in other countries pay much less because the government subsidises drugs. Surely if the government subsidises drugs, more people can use them, so there's a greater amount of money going into the drug company coffers, and then more money can be spent on drug development?

[Silencer]

And where does the government get its money?

 

I would rather have to pay extra for my health than have to pay extra taxes for someone else's health.

[Crash]

who wouldnt?

I got a question, why is it that many drugs contain the NO or additions of this group like herione, cocaine, MDMA etc.

[Skye]

Do you mean NH groups?

 

Metabolites (compounds made by a metabolic pathway) containing nitrogen, and that are basic, are called alkaloids. They are commonly used as chemical defences in plants, and work by affecting the nervous system of animals, which makes them good drugs. Alkaloids are synthesised from amino acids, that's why they have the NH groups in them.

 

Edit: http://users.ox.ac.uk/~mwalter/web_04/resources/biosynthesis/alkaloids/alkaloids.shtml

[Drug addict]

Major medical advances are made by the drug companies here in the states. Someone has to pay for them. It sucks' date=' but that falls on us. If we were charged the same amount as other countries, there would be no money for new drug developement.

[/quote']

 

Drug companies do quite well from the NHS - the government recently agreed a deal to decrease the price they pay for brands by 7%, and pharmaceutical companies invest nearly £10 million per day on research (http://www.abpi.org.uk). The NHS drug budget for England next year is expected to be £11 billion. This is just for the cost of the drugs and does not include drugs used in hospitals.

 

 

I don't think that a NHS is beneficial. For one, it is communist. For two, it introduces bureaucracy into the health care system which we just do not need.

 

Yep, its so communist that it was never dismantled by the Conservatives when they were in power for 18 years in the 80's and 90's (though maybe they tried to starve it to death).

 

As for bureaucracy, I'm not sure. Yes there are a lot of managers in the NHS, but I'm sure there are plenty in America. From a patient perspective, surely it is less bureaucratic - you go and see a NHS doctor, who writes you a prescription which you take to a pharmacy to get dispensed for free (or a small charge). Seems pretty simple to me.

 

As for pharmacists getting paid? I don't know exactly how the American system works. Does the patient pay the cost and then claim it back from their insurance, or does the patient get the drugs and then the pharmacist claim it back from the insurance company? I'd appreciate clarification on this. Thanks.

 

The UK system is that at the end of the month the pharmacy sends all the prescriptions they've dispensed that month off to a government agency, who pay them three months down the line. Except its a bit more complex than that as what you get paid for a given month is an advance (based on previous figures), and the balance of payments from three months ago. And then there's a lovely book called the Drug Tarif which lists the price pharmacists get paid for drugs, except it's not that simple...

[Silencer]

I have no clue how pharmacist payment works.