Meperidine toxicity

Immunocompetent patients 800 mg q4h (Stimesa day) for7days Severely immunosuppressed or ophthalmic zoster 10 mg/kg IV over 1 hour q8h keep patient vyell-hydrated lethargy, confusion, tremor. May cause meperidine toxicity. 

Semiquantitative and qualitative immunoassays can measure high concentrations of meperidine in the urine. Meperidine toxicity is reported with serum levels of 10-30 tg ml however, drug levels do not guide treatment. Normeperidine toxicity occurs with serum levels from 450 to SOOngml. ... 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

Symptoms of overdose with meperidine are qualitatively different from those of morphine in that seizures rather than sedation are common. Respiratory depression and miosis are present. While naloxone reverses overdose-associated toxicity, its use in patients who have received large, frequent doses of meperidine may precipitate seizures. 

Neither selegiline nor rasagiline should be taken by patients receiving meperidine. They should be used with care in patients receiving tricyclic antidepressants or serotonin reuptake inhibitors because of the theoretical risk of acute toxic interactions of the serotonin syndrome type (see Chapter 16), but this is rarely encountered in practice. The adverse effects of levodopa may be increased by these drugs. 

Rasagiline Inhibits MAO-B selectively, higher doses also inhibit MAO-A Increases dopamine stores in neurons may have neuroprotective effects Parkinson s disease adjunctive to levodopa smooths levodopa response Oral Toxicity interactions may cause serotonin syndrome with meperidine, and theoretically also with selective serotonin reuptake inhibitors, tricyclic antidepressants... 

Phenelzine Blockade of MAO-A and MAO-B (phenelzine, nonselective) MAO-B irreversible selective MAO-B inhibition (low dose selegiline) Transdermal absorption of selegiline achieves levels that inhibit MAO-A Major depression unresponsive to other drugs Very slow elimination Toxicity Hypotension, insomnia Interactions Hypertensive crisis with tyramine, other indirect sympathomimetics serotonin syndrome with serotonergic agents, meperidine... 

Meperidine (Schedule II) is a synthetic analgesic with opiate activity. It has 10-20% of the potency of morphine with all of the addictive side effects. It has a rapid onset of action and duration which makes its useful for relieving the pain associated with labor or as a preanesthetic before surgery. Its biotransformation produces normeperidine which has been associated with seizures. It was a botched clandestine attempt to synthesize a meperidine modification which produced the toxic drug that induced parkinson-type destruction of DA neurons in its users. 

Meyer, D. and Halfin, V. Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors a case report and critical review, J. Clin. Psychopharmacol. 1981, 1, 319-321. 

It should be noted, however, that the TI is a relative term. Acetaminophen, a nonprescription analgesic, has a TI of approximately 27 (i.e., the ratio of the median toxic dose to the median effective dose equals 27). Prescription agents tend to have lower TIs. For instance, the narcotic analgesic meperidine (Demerol)... 

Methadone, in general, exerts a pharmacological action similar to that of morphine. Its action on smooth muscle resembles that of meperidine. analgesic potency, but /-methodone is twice as effective. When used in comparable analgesic doses, methadone is as toxic as morphine and exerts the same effects on the pulse rate and respiration as does morphine. Methadone exerts no sedative effect and, hence, is of no value as a preanesthetic agent. 

In the early 1980s, a form of designer meperidine, known as MPPP, was being illegally manufactured. MPPP was also referred to as synthetic heroin. In some cases, the chemical technique was not precise, and a toxic chemical byproduct, MPTP, was produced. MPTP is a known industrial toxin that can destroy nerve cells in certain portions of the brain... 

Two drugs widely used to control diarrhea are diphenoxylate [di PHEN ox a late and loperamide [loe PER a mide]. Both are analogues of meperidine (see p. 138) and have opioid-like actions on the gut, activating presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis. Side effects include drowsiness, abdominal cramps and dizziness. Since these drugs can cause toxic megacolon, they should not be used in young children or patients with severe colitis. 

Environmental Toxins. Several substances have been shown to produce a Parkinson s-like syndrome. l-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), a by-product of various meperidine derivatives, has received considerable attention since the report by Langston et al. (L4). This neurotoxin has been studied in animal models and found to selectively destroy the dopaminergic substantia nigra. Further studies showed the MPTP was converted by MAOb to the toxic 1-methyl-4-phenylpyridinium cation (MPP+). Following reduction by P450 reductase, the MPP free radical is formed, which reduces oxygen to 02 (A4). 

Simopoulos TT, Smith HS, Peeters-Asdourian C, Stevens DS. Use of meperidine inpatient-controlled analgesia and the development of a normeperidine toxic reaction. Arch Surg 2002 137(l) 84-8. 

G Infusion-related toxicities secondary to amphotericin are common and may be prevented with premedication with diphenhydramine and acetaminophen. Meperidine is effective in halting rigors and muscle spasms. Thus, it is typically given in response to rigors, and not as premedication. Sodium loading with normal saline may prevent some of the renal toxicities, particularly prere-nal azotemia, associated with amphotericin and is administered prior to amphotericin. 

When greater than therapeutic amounts are administered, CNS and respiratory depression, which may progress to cessation of respirations, may be seen. Pulmonary edema has been reported following therapeutic and toxic exposures to opiates. Peripheral vasodilation can cause hypotension and possibly circulatory collapse. In addition to the usual opiate toxicities, the course may be complicated by development of seizures. With daily doses of >3g meperidine, convulsions may be seen due to metabolism of meperidine to normeperidine. Myoclonus will usually precede convulsions. Mydriasis may be present secondary to anoxia. Meperidine may also produce tachycardia through a vagolytic action, which increases ventricular response. 

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