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

2. 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.

3. The algorithm for the diagnosis of the drug intoxication and withdrawal
current
research grant
stock; speaker
Constricted

4. 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

5. The algorithm for the diagnosis of the drug intoxication and withdrawal
Dilated

6. Sedation

7. Binding profile (affinity, nM)
µ-OR NE 5-HT
Morphine IA IA
Buprenorphine IA IA
Oxycodone IA IA
Hydrocodone IA IA
d-Propoxyphene IA IA
Codeine IA IA
Dextromethorphan 1,
Tramadol 2, ,000
(+) enantiomer 1,300 2,
(–) enantiomer , ,400
Imipramine 3,
Source: Raffa et al., J Pharmacol Exp Ther 260:275-85, 1992
Raffa et al., J Pharmacol Exp Ther 267:331-40, 1993

9. 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

10. 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

11. Remember:
60% of patients will suffer adverse events if they do not meet discharge criteria.
It does not guarantee methadone patients.

12. The end

13. 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