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Learn about diagnosing heroin overdose, symptoms of stimulant withdrawal, and tramadol pharmacology. Understand the criteria for early discharge of opioid overdose patients and the lack of naloxone block in humans.
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Acute opioid overdose SeyedMostafaMirakbari MD Assistant Professor of clinical toxicology & Chair, QUMS
Opioid overdose syndromesensitivity for diagnosing heroin overdose, 92%; specificity, 76% • Abnormal mental status • Decreased respiration • Miotic pupils • The response of naloxone does not improve the sensitivity of this diagnosis.
The algorithm for the diagnosis of the drug intoxication and withdrawal current research grant stock; speaker Constricted
Symptoms of stimulant Withdrawal Each person quitting stimulants will have slightly different symptoms. They vary based on a number of factors, like the person’s tolerance and metabolism, as well as their history of use. Withdrawal from stimulants is characterized by a dysphoric mood and the presence of two or more of the following symptoms: *Jittery reactions/ Chills *Hallucination/Paranoia *Anxiety *Weight loss or gaunt appearance * Dehydration * Insomnia or hypersomnia *Dulled senses * Drug cravings *Slowed speech *Unpleasant dreams *Loss of interest *Body aches *Slowed movement *Impaired memory * Slow heart rate *Increased appetite * Irritability *Depression *Fatigue
The algorithm for the diagnosis of the drug intoxication and withdrawal Dilated
Binding profile (affinity, nM) µ-ORNE 5-HT Morphine 0.3IA IA Buprenorphine 4IA IA Oxycodone 9IA IA Hydrocodone 10IA IA d-Propoxyphene 30IA IA Codeine 200IA IA Dextromethorphan 1,300 20 200 Tramadol 2,100 800 1,000 (+) enantiomer 1,300 2,500 500 (–) enantiomer 24,800 430 2,400 Imipramine 3,700 20 7 Source: Raffa et al., J Pharmacol Exp Ther 260:275-85, 1992 Raffa et al., J Pharmacol Exp Ther 267:331-40, 1993
Early discharge criteriae of patients with presumed opioid overdose • tramadol is a racemate with only weak opioid binding • the enantiomers have synergistic pharmacologies • M1 metabolite is opioid () • No other metabolites are active M1
Adverse events within 24 hours after the one-hour assessment • more tramadol than M1 enters the brain • the ratio increases with dose mice rats Source: Tao et al., J Clin Pharm Ther 27:99-106, 2002
Remember: • 60% of patients will suffer adverse events if they do not meet discharge criteria. • It does not guarantee methadone patients.
Lack of naloxone block: humans • Randomized, placebo-controlled, crossover study • Transcutaneous electrical stimulation of the sural nerve Analgesia assessment • Objective test (R-III Reflex) • Subjective test (Pain Visual Analog [PVA] scale) • Tramadol (100 mg, po) naloxone (0.8 mg, iv) Mean maximal inhibition of tramadol analgesia by naloxone was 26% (R-III) and 31% (PVA) Reduced >50% by yohimbine Source: Desmeules et al., Brit J Clin Pharmacol 41:7-12, 1996