SSRI Stories note: There is a strong possibility that Michael Jackson died from serotonin syndrome due to a combination of the SSRI [selective serotonin reuptake inhibitor] Zoloft & the serotonergic medication Demerol.
http://entertainment.timesonline.co.uk/tol/arts_and_entertainment/music/article6585279.ece
From Times Online
June 26, 2009
Analysis: drug mix Michael Jackson took is key
Dr Martyn Lobley
The list of prescription drugs that Michael Jackson was reported as having taken as many as seven, according to one account includes drugs from three main chemical classes.
Those most frequently referred to are the anti-depressant sertraline, known as Zoloft in the US and Lustral in Britain, the Valium-like tranquilliser alprazolam (Xanax) and the morphine like painkiller pethidine (Demerol).
It is reported that Michael Jackson collapsed shortly after an injection of Demerol, presumably administered by a doctor or nurse. The timescale is not clear but the limited interval between the injection and his collapse suggests that the two may have been linked.
All tranquillisers and morphine-like painkillers are known to affect patients’ breathing patterns, especially if taken in excessive doses. Doctors know that the large single doses of opiates and sedatives given to patients in their final hours to relieve pain undoubtedly shorten the lives of some of them by depressing their respiratory efforts.
When two drugs are given together, especially if they are from different classes, the effects do not simply combine – they multiply. Doctors make use of this when treating high blood pressure where low doses of two drugs given simultaneously are often more effective than high doses of one or the other.
But the multiplication principle also holds true for unwanted effects. The death of the Australian actor Heath Ledger in 2008 was attributed to the combination of Xanax with another opiate painkiller, oxycodone.
The sedative effect of previous doses of Xanax combined with an injection of Demerol could have been responsible for the apparent shallowness of Michael Jackson’s breathing in the minutes that followed.
By the time the 911 call had been logged by the emergency services his breathing had stopped altogether. The sedation resulting from the drug combination may well have removed the desire for him to breathe for himself as surely as if the drugs had been administered deliberately by an anaesthetist.
When breathing stops and the heart is deprived of the oxygen required to function a cardiac arrest is inevitable. The term “cardiopulmonary arrest” is more accurate.
As soon as a patient collapses the priority is to re-establish some sort of circulation and to provide essential oxygen, usually by administering cardiopulmonary resuscitation CPR. If the cause of the collapse is known it is mandatory to deal with that too. A collapse as a result of a heart attack is often due to a pulse abnormality known as V-fib (ventricular fibrillation) and a couple of shocks from a defibrillator may well restore the heart’s normal rhythm.
If the reports are accurate, the short time between the injection and the collapse would mean that the doctor who injected the Demerol may have considered administering an opiate antagonist (or antidote) in an effort to reverse any respiratory depression.
The effects of the most commonly used antidote, naloxone, are short-acting but the time it buys the emergency response team, allowing them to ventilate a patient artificially, is invaluable.
But even in the best situations, attempts at CPR are not always successful. Michael Jackson was known to be physically frail, reportedly weighing as little as 7st and to be under great psychological stress in preparation for the shows scheduled for mid-July. Perhaps it is not surprising that the paramedics and emergency room staff were unable to revive him.
Dr Martyn Lobley is a general practitioner in South London
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http://en.wikipedia.org/wiki/Pethidine
Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Petidin Dolargan (in Poland );[1] Dolestine; Dolosal; Dolsin; Mefedina) is a fast-acting opioid analgesic drug. In the United States and Canada, it is more commonly known as meperidine or by its brand name Demerol.[2]
Pethidine is indicated for the treatment of moderate to severe pain, and is delivered as its hydrochloride salt in tablets, as a syrup, or by intramuscular or intravenous injection. For much of the 20th century, pethidine was the opioid of choice for many physicians; in 1983 60% of doctors prescribed it for acute pain and 22% for chronic severe pain.[3] Compared to morphine, pethidine was supposed to be safer and carry less risk of addiction, and to be superior in treating the pain associated with biliary spasm or renal colic due to its putative antispasmodic effects. In fact, pethidine is no more effective than morphine at treating biliary or renal pain, and its low potency, short duration of action, and unique toxicity (i.e., seizures, delirium, other neuropsychological effects) relative to other available opioid analgesics have seen it fall out of f
avor in recent years for all but a very few, very specific indications.[4] Several countries, including Australia, have put severe limits on its use or curtailed it outright.[5] Nevertheless, some physicians continue to use it as a first-line strong opioid.
Pharmacodynamics/Mechanism of Action
Main article: Opioid
Pethidine's efficacy as an analgesic was discovered almost accidentally; it was synthesized in 1939 as an antimuscarinic agent.[6] Pethidine also has structural similarities to atropine and other tropane alkaloids and may have some of their effects and side effects. [2] Pethidine exerts its analgesic effects by the same mechanism as morphine, by acting as an agonist at the -opioid receptor. In addition to its strong opioidergic and anticholinergic effects, it has local anesthetic activity related to its interactions with sodium ion channels. Pethidine's apparent in vitro efficacy as an " antispasmodic" is due to its local anesthetic effects. It does not, contrary to popular belief, have antispasmodic effects in vivo.[7] Pethidine also has stimulant effects mediated by its inhibition of the dopamine transporter (DAT) and norepinephrine transporter (NAT). Because of its DAT inhibitory action, pethidine will substitute for cocaine in animals trained to discriminate cocaine from saline.[8] Several analogues of pethidine have been synthesized that are potent inhibitors of the reuptake of the monoamine neurotransmitters dopamine and norepinephrine via DAT and NAT.[9] [10] It has also been associated with cases of serotonin syndrome, suggesting some interaction with serotonergic neurons, but the relationship has not been definitively demonstrated.[5] [6] [8][10] It is more lipid-soluble than morphine, resulting in a faster onset of action. Its duration of clinical effect is 120-150 minutes. Despite producing analgesia for 2-3 hours at most, pethidine is typically administered at 4-6 hour intervals, so that the patient spends at least an hour (and up to four hours) between doses without any analgesia, resulting in much unnecessary pain and suffering. In addition, pethidine has been shown to be less effective than morphine, diamorphine or hydromorphone at easing severe pain, or pain associated with movement or coughing.[6] [8] [10] Like other opioid drugs, pethidine has the potential to cause physical dependence or addiction. In fact, pethidine may be more addictive than other opioids because of its exceptionally rapid onset of action and associated "rush", and additional activity as a monoamine transporter inhibitor, which results in cocaine-like stimulant effects in addition to its typical opioid effects.[11] When compared with oxycodone, hydromorphone, and placebo, pethidine was consistently associated with more euphoria, difficulty concentrating, confusion, and impaired psychomotor and cognitive performance when administered to healthy volunteers.[12] The especially severe side effects unique to pethidine among opioids serotonin syndrome, seizures, delirium, dysphoria, tremor are primarily or entirely due to the action of its metabolite, norpethidine .[6] [10]