Withdrawal / Including Alcohol Withdrawal

Alcohol Use and Withdrawal

Severity of alcohol use disorder (based on >12 signs, symptoms and lab findings associated with alcohol use disorder): Definition of severity 
  • Mild: 2-3 Sx
  • Moderate: 3-5 Sx
  • Severe : 6 or more Sx
Ref: Uptodate 

Case 39-2012: A 55-Year-Old Man with Alcoholism, Recurrent Seizures, and Agitation NEJM

Recognition and Management of Withdrawal Delirium (Delirium Tremens) NEJM 2014

Benzodiazepine Withdrawal
Opiates Abuse / Withdrawal
  • Pathophysiology of Opiate Analgesics / Overdose
    • Receptors: mu, delta, and kappa opioid receptors 
      • Nociceptor receptor location: anterior and ventrolateral thalamus, the amygdala, and the dorsal-root ganglia
      • Brainstem Opiate Receptors: Regulates respiratory response to hypercarbia and hypoxia in co-ordination with dopaminergic neurons
      • Receptors in Edinger-Westphal Nucleus of oculomotor Nerve: control pupilary constriction
      • GI tract: Decrease Gut motility
    • Activated by Endogeneous Peptide, and Exogeneous ligands like Morphine
    • Major clinical features is due to mu receptors
      • Both Dependence, and Analgesic effect
      • Mu receptor desensitization leads to tolerance 
        • BUT these receptor undergo endocytosis causing the resensitization when the mu receptors are expressed back in surface. 
        • Endogeneous Peptide: Absence of tolerance due to endocytosis and resensitization
        • Exogeneous Peptide: Persistent binding leads to desensitization
    • Tolerance to analgesic and respiratory depressive effect
      • Due to mu receptor sensitization (as above)
      • Conditioned Tolerance
      • Note: Respiratory tolerance develops at lower rate slower rate than the analgesic tolerance. This over time put the patient with long history of opiates use at a risk of respiratory failure due to narrow therapeutic window
    • Toxikokinetic of opiates overdose
      • Absorption pattern is often irratic after overdose
      • After absorption, most medications undergo first-order-kinetics i.e constant fraction of drug is converted by enzymatic process per unit of time. However, after overdose, due to saturated biologic process, first pass metabolism switches to zero-order-kinetics from first-order-kinetics.
        • Zero-order-kinetics: 2 Phenomenon adds to severe, delayed onset toxicity.
          • Small increase in the drug dose can lead to disproportionate increase in plasma concentration leading to intoxication
          • Constant amount (NOT fraction)  is metabolized per unit of time. 
  • Look out for 10 clinical features of opiate overdose (Figure 2 of Opiate OD NEJM 2012)
  • Signs of opiate abstinence are: yawning, lacrimation, piloerection, diaphoresis, myalgias, vomiting, and diarrhea 
  • 5 points to avoid pitfalls in management of opiate toxicity
    • 1. Naloxone does not shorten the duration of respiratory depression due to opiates due to its short half life. 
    • 2. Dose of nalaxone required to restore respiration, does not correlate with severity of opiate toxicity. This leads to error in dosing, and in admitting to lower level of care while patient needed higher level of care. 
    • 3. Peak plasma opiate concentration does not correlate with the greatest degree of respiratory depression
    • 4. Early acetaminophen toxicity may go unrecognized
    • 5. Pharmacological response in elderly and children are different than in healthy young adults leading to shortening of the observation period
  • Reference
  • Additional Reading
  • Avoid Opiates in 
    • Fibromyalgia
    • Lower Back Pain
      • Prescribing opiates for > 6weeks in first 6 weeks after acute low back pain, causes increased incidence of patient going into disability 
    • Monitor adherence with
      • Pill count 
      • Drug Test 
    • Should not be driving on initiation or dose titration of any sedatives 

Sedative Drugs:
Hypnotic Drugs:
Nicotine Addition: IN GIM Section