I want to say something about the hallucinogens. We are seeing LSD nowadays. It’s in lower concentrations than when we were teenagers and so people aren’t flying out the window thinking they can fly like Art Linkletter’s daughter did which is one of the things that turned people off to LSD. But acid is back in a lower concentration and kids are using it at parties and it is producing problems acutely. Tolerance showing it has a serotonergic effect. It can also produce an adrenergic state. PCP, while developed as an anesthetic, has a very interesting dose response and this is one line I would circle just so it stays in your head. At low dose, it acts like alcohol or the benzodiazepines with ataxia. At the middle dose you get illusions and a propensity to violent outbursts with paranoia. At a high dose, 70 mg or greater, you see coma so it’s a particularly bad therapeutic window assuming you think intoxication is therapeutic. So even there it’s bad.
Management. I still find the urine is the key issue and there are several ways to do this. 10% of mental health patients are abusing anticholinergics, particularly Cogentin and just review why because that’s a likely thing to show up on the test.
The final thing is anabolic steroids. One out of 10 high school kids is using them. Mark McGwire didn’t help because androstenedione, while not excluded from baseball, does increase testosterone levels and the withdrawal is the problem. The stimulus to mania is a problem. Rageful behavioral and aggression on withdrawal.
The main problem in overdose is brainstem respiratory CO2 sensitivity falls and the patient stops breathing. The purity of heroin on the streets is strong enough now that we’re seeing this even with inhaled and smoked heroin sometimes. Now, tolerance occurs rapidly particularly to the nausea and that kind of discomfort and it becomes purely pleasurable at that point but only one in ten people who try heroin tend to become addicted to it. So we have to be realistic about this and reasonable, not that heroin could ever be thought of as a legalized substance, but not everybody who walks in who says, you know, “I used heroin at a party” is a heroin addict and we have to do some work to tease out “Do we have a criteria of dysfunction being met?”
Cheap nexium online Canada pharmacy.
What’s the withdrawal amount? Well, the locus caeruleus is suppressed by chronic heroin use and when that suppression is released we have up-regulation of noradrenerigic receptors and suddenly the adrenergic arousal goes wild. There isn’t up-regulation of the opioid receptors themselves but there is up-regulation in terms of dopamine activity and the two sides are the ventral tegmental area – VTM – and nucleus accumbens which we talked about before but both of these are involved. Heroin is not a one site reinforcer. It seems to involve this system.
Viagra professional without prescription.
I’m not going to talk about the long term treatment, for instance methadone. Harm reduction is an important goal nowadays because it reduces HIV transmission. So needle exchange works. Even in areas with lots of severe heroin addicts, we see reduction in HIV transmission thanks to needle exchange regardless of what the government’s policy is. Generic viagra 100 mg online at cheap pharmacy mall. Rapid detox can be done in less than five days with a combination of either these two – clonidine or naltrexone – plus or minus buprenorphine which I think actually improves the experience and retention for the patients and the L Group published on this. I think it’s definitely better combined.
Anesthesia detox. You actually can get a full blown heroin addict onto full dose naltrexone totally blockaded at the mu-receptor – they can’t become high now – in five hours using anesthesia. The problem is you don’t know if the therapeutic change has happened so that the patient doesn’t go out and then try and overcome naltrexone and dose themselves so badly that they overshoot and go into coma which has happened now a few times.
LAM – levo acetyl methadone. LAM is now FDA approved. It’s just a long acting type of methadone. So you can dose 100 mg Monday, 100 mg Wednesday, 150 mg on Friday and the patient is covered in the intervening days. They have more freedom. They can return to a more normal life. The patients like it. They retain better on it. Not available in all states. Call for details.
Buprenorphine. I hope it’s going to come out this year from the FDA. I keep saying that. The slowdown has been that the FDA is being pushed to allow dispensing in physicians’ offices. Buprenorphine is another long acting opioid like LAM, like methadone, safer and we may get to use it in office practice.
Generic pills
The dopamine agonists – bromocriptine, amantadine, mazindol – this is conclusively disproved now. Amantadine hasn’t done as well as bromocriptine and bromocriptine has had side effects and has had some negative trials now too. So the answer on do we have a treatment for cocaine? No. All we have is longitudinal treatment and then relapse prevention. Isolating from the cues. Reintroducing the cues as the patient succeeds to give them a chance to bolster their techniques of thinking about the consequences, reminding themselves of the spouse’s wishes to stay clean and various counseling techniques. Stress. Coping with stress, learning to pamper one’s self in ways other than the most immediate gratification. These are things our patients really don’t know how to do.
You probably are seeing all the advertisements for tramadol, Ultram. A new pain agent, nonsteroidal but it’s not one of the NSAIDs. It’s a nonopiate analgesic but there is some concern that it can trigger relapse so we have to be careful with it. I haven’t seen a big market in Ultram abuse but there is actually a study assessing that rationally. So far, so good. One of the physiologic effects of the opiates that is helpful to remember for the boards but also for looking at patients in emergency situations, remember that aside from the analgesia and the rush and the euphoria of opioids they also produce smooth muscle inhibition and that’s down at the bottom of page 284. You might just want to put a check mark or a star there. That helps you think of several other things without having to memorize all of them.
Tramadol online - Tramadol is a non-opioid pain relief medication that is meant to help alleviate moderate to moderately severe pain. Tramadol is a synthetic analgesic, not an anti-inflammatory, which means that people who cannot take anti-inflammatories due to the side effects can often take Tramadol to help relieve their pain.
Smooth muscle inhibition. So the pinpoint pupils in patient’s eyes when they’re intoxicated with heroin, that’s because the smooth muscle that opens the iris for a full pupil is being relaxed. So that smooth muscle inhibition allows the pupil to close down that tight. It’s also responsible for some of the initial nausea and vomiting that people have sometimes when they try codeine for the first time. Heroin does it too, by the way. The same thing is true of withdrawal. If smooth muscle inhibition is part of the intoxication what do you think happens in withdrawal? You get smooth muscle hyperactivation so you get all nausea and diarrhea and the loss of appetite and the pupils get enlarged.
Ultram online - cheap canadian medications.
The mu-opioid receptor system is the primary analgesic receptor system. It’s anti nociception. Anti nociception means you don’t feel pain. You can feel pressure but you don’t feel pain when these sites are occupied. Heroin, morphine, methadone, the m’s go with mu. The delta receptors are also supportive for analgesia and the akephalines have the better binding for this. So we have these three major systems. The kappa system you know about. Talwin, pentazocine produces analgesia there but it is also associated with a risk for dysphoria and Talwin is contraindicated in a patient who has mu-opioid dependence – heroin, morphine or methadone. Contraindicated because it will trigger a dysphoric reaction.
Canadian pharmacy - a lot of cheap canadian medications.
That’s how the physiologic process is and people turned on him right away, “What’s wrong? What’s wrong?” He told his story. They said, “Look, you know. You can’t use tonight. You’ve been doing too well. You’ve got too much to lose.” He said, “I don’t know if I can help it.” So they said, “Well, how do you use?” He says, “Well I get some cash out of my bank with my ATM card.” So I said, “Do you have your card with you here?” He said, “Yeah.” I said, “Can I have it?” He said, “Yeah.” So I held it up and I said, “This is how you’re going to fall tonight? Do you mind if I cut it in half?” He looked down, calmed down immediately, he had the depressive affect that Melanie Klein talks about and we cut the card in quarters and he didn’t use that night.
So behavioral steps are critical with such a potent agent. You have to disrupt that binge cycle. It’s not daily use but it’s periodic heavy all encompassing use until the drug is all used up. We need a lot of modalities. Not just one. Individual drug counseling is potent but in a cocaine psychotherapy study it did better combined with group therapy than group therapy alone. So this multi-psych study has inclusively shown that group alone is not as effective as group plus individual. Bringing the family and spouse in, very important. Concurrently using the support groups. Big help. Cialis online 20 mg
We saw in the Night of Cocaine psychotherapy study individual plus group did best because it was a 12 step oriented counseling method and it promoted a lot of involvement in AA and NA and CA – the anonymous groups. Even though people tended to stop coming to that treatment earlier than cognitive therapy or supportive expressive therapy but because they were doing so many of their meetings, they had better outcomes with their urines and with their lives.
Education of the family. So the family understands somebody who stops using is not suddenly a nice person who’s pleasant to have around. They’re irritable. They’re frustrated. They’re upset. They’re dealing with affect for the first time since childhood maybe so they need the support of family members. I’ve written a prescription B-I-T-C-H and handed it to my patient to show the spouse. I said he needs a license to bitch. This is a bad time. Let him go through it to get better.
Urine testing and contingencies. Restricting the money, the access. Restricting social activity with people who might promote relapse. So don’t be surprised to see a bunch of these on a multiple choice test and feel quite comfortable calling for multiple concurrent treatment modalities. Canadian viagra online.
So we deal with behavioral techniques but do we have any pharmacologic techniques for cocaine? The answer, unfortunately not great no. A good open trial promises lousy, I would say, control trial conclusions. Desipramine may be the best studied one. Five positive control trials but we have quite a few unsuccessful trials too even though the laboratory shows that they can subdue or even reverse intracranial self stimulation with cocaine. So the laboratory studies of these agents don’t always pan out in the patients. Health articles at canadian pharmacy blog.
So two factors to know about in stereotypy is one, there is a kind of strange sensitization that occurs. If somebody stays with the same amount of cocaine and starts to develop stereotypy they’ll get more and more and more of it even if they don’t increase their cocaine and that’s sensitization. Viagra Super Active new medication.
Another factor is reverse tolerance and that is somebody who has become dependent on cocaine and begun to show stereotypy might try to use less cocaine but they will have increasing stereotypy. They want to stay healthy. For instance, they might not use for awhile and go back to cocaine at much smaller levels than they last left it and they’ll have much more active stereotypy. So there is a reverse tolerance related to the sensitization.
Kindling you know from other lectures of the course is the ability to yield a seizure focus with progressive generalization of the seizure with what was originally a subthreshold incident whether it was electrical or chemical. Cocaine will produce kindling. That is, it will lead to seizures even at doses that don’t increase. Where is cocaine doing its damage? Actually cocaine acts at multiple sites and they don’t all explain reinforcement or addiction. The anesthesia peripheral effect does not explain addiction. The improvement in attention and wakefulness is happening in the reticular activating system. That is a norepinephrine effect but it’s not primarily responsible for addiction because as you know we’ve got other substances that produce enhanced attention that are not to any great extent addicting, for instance, Ritalin. Canadian viagra erectile dysfunction treatment.
So where else could they lie? Well, we know that cocaine can provoke alarm, anxiety and autonomic arousal throughout the body. That’s an adrenergic effect too and it’s through the locus caeruleus, the alarm center in the midbrain but that is not the region responsible for reinforcement. We have mentioned that the reinforcement center, the pleasure center is the nucleus accumbens and that is a dopaminergic mediated process, not purely, but I want to uncomplicate this so that we are immediately familiar with it when we see it on tests or in our work with patients and can explain it and some basic mechanisms. So nucleus accumbens, reinforcement pleasure center, dopaminergic process. Stereotypy and motor hyperactivity, that’s not part of the pleasure center. That’s happening in the nigra striatal region and it’s a limbic process. Also dopamine, not related to reinforcement. Cialis Jelly at canadian online pharmacy.
We’re now moving to the bottom of page 283 into the treatment and the treatment of such a powerful, deadly and widely available substance has to be vigorous. It’s not a strict conversational process so we use behavioral techniques. Here’s one that I had to use in one of my group members in the men’s cocaine group. He was in recovery, hadn’t used for a month. He had been threatened with losing his job. He came into the group. He was fidgeting. Fidgeting in a group is a sign that somebody either is using or is aching to use.
We’re going to move now into specific substances of abuse. Cocaine has a long history of use. The cocaine problem absolutely preceded George W. Bush’s youthful indiscretions. Actually, it even preceded Henry Hyde’s youthful indiscretions and I almost wish, it’s as old at least as Benjamin Franklin but he was public and he didn’t really stop his indiscretions just for political life and I respect a man like that. Some people would say that our president hasn’t really stopped his youthful indiscretions for his political life either. Cheap nexium without prescription.
But it does show that this is a ubiquitous problem. All classes are affected. Cocaine has really gone through the gamut from people at the highest level of society to the bottom and it tells you that one’s morals, one’s upbringing, one’s wealth, education is no defense against the physiological processes of these substances. So when I talk about cocaine I want us to understand what these physiological processes are.
The neuropharmacology of cocaine has been important for understanding addiction but also for understanding how the brain works and that’s partly why there’s such a big investment in this. Reinforcement is so powerful with cocaine in animal laboratory experiments that rats, given freedom to press a lever to get a full squirt of cocaine into the brain or the bloodstream will press it continuously until they stop eating, stop mating, stop drinking and begin dying in 14 days mostly of cardiopulmonary disease. They also develop rapid infection and 90% will be dead in 30 days and that is the most deadly of the common drugs of illicit use. So that’s an important factor to have in mind. Viagra professional canadian medications.
Administration of drugs that are rewarding isn’t limited to the drugs themselves. How do we know where this happens? Well, we know by putting electrodes into the brain at different places and giving the animal free rein to move around the cage and hit the lever once in awhile and get a little microampere jolt, not to do damage but to see is there a synapse that likes this stimulation.
What we find is there is a nucleus accumbens capsule that is the most potent site of the brain. That is, it takes the least amount of current for self administration to be rewarded so the rats or mice or whatever animal we choose will press that lever again and again to get that little tiny bit of current. So we have a site. We know that lesions of this site will block the acquisition of that self administration behavior. So this is convincing evidence.
What else is involved here? Well, endorphins are not primarily involved. Opiates have actually some bearing on it and we’ll talk about that later but they’re not primarily involved and the anesthesia is not the reason that the animal does this. That’s a peripheral effect.
What about other substances? Well, heroin will yield that kind of rapid self administration too. To get a squirt of heroin, animals like rats will press again and again hundreds of thousands of times in a day believe it or not and if they’re given free rein every time they press they get a squirt, about a third will be dead in a month. So you can now compare cocaine’s lethality to heroin’s lethality which is opposite to what we thought in the ‘80s, by the way. We thought heroin was the real killer and cocaine, you know, yeah it’s fun. Some people get carried away with it. Now we know different.
So we have this problem but there are some other physiologic processes with stimulants of cocaine as well. One is stereotypy. What is stereotypy? It will show up on the boards and it is a process of compulsive repetitive purposeless behavior. In a cat, it might be grooming to the point that the cat actually wears off its fur and digs into its skin and is bleeding from it. In human beings stereotypy with cocaine is pacing around the coffee table in the den where he uses his cocaine and wearing out a track in the shag carpet. Generic pharmacy blog.
Recent Comments