Seyed Mostafa Mirakbari MD Acute opioid overdose Seyed Mostafa Mirakbari MD Assistant Professor of clinical toxicology & Chair, QUMS

Opioid overdose syndrome sensitivity 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

Sedation

Binding profile (affinity, nM) µ-OR NE 5-HT Morphine 0.3 IA IA Buprenorphine 4 IA IA Oxycodone 9 IA IA Hydrocodone 10 IA IA d-Propoxyphene 30 IA IA Codeine 200 IA 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

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.

The end

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