Drugs of Abuse - Withdrawal Symptoms & Treatment

Opioids

WITHDRAWAL:

• Begins 8-10 hours after last use, and can last for 7-10 days

• Symptoms - caused by overexcitation of locus cerulus

  • Starts with autonomic symptoms: lacrimation, rhinorrhea, yawning and sweating

    • Then restless sleep followed by weakness, chills, “cold turkey”, nausea and vomiting, muscle aches and “kicking the habit”

  • Secondary Phase (26-30 weeks): hypotension, bradycardia, hypothermia, mydriasis, and decreased responsiveness of the respiratory center to CO₂

Treatment of Opioid dependence

• Acute: Clonidine (to manage block excess catecholamines for treatment of withdrawal symptoms) and antagonists (i.e. Naloxone) in repeated doses

• Detoxification - Short course to reduce withdrawal

  • Involves ultrarapid detox, buprenorphine, or methadone (both have very long half lives)

• Replacement - maintenance therapies (for more than 180 days) utilizing methadone, buprenorphine, buprenorphine + naloxone, or naltrexone

Sedative-Hypnotics

• Short-term: Psychological > Physical dependence

• Patterns of abuse possible

• Tolerance

• WITHDRAWAL SYMPTOMS: Irritability, insomnia, phono and photophobia, depression, muscle cramps, and can include seizures (too much excitatory)

Treatment of Sedative withdrawal

• Stabilize patient, use long-acting benzodiazepine, withdraw gradually (15-25% decrease daily) until complete detoxification

Amphetamine, Methamphetamine, Methylphenidate

• Withdrawal can last for weeks

• Symptoms: Ravenous appetite, exhaustion, and mental depression

Treatment for Amphetamine withdrawal and overdose

• Antipsychotic or antidepressant for residual emotional disorders before detoxification

  • Antidepressants can help with relapse

• For overdose: use haloperidol

Cocaine

• Symptoms: Dysphoria, depression, sleepiness, fatigue, cocaine craving and bradycardia

Treatment for cocaine withdrawal and overdose

• For overdose: diazepam, calcium channel blockers

• Desipramine (TCA) can block NE uptake, and reduce desire

• Fluoxetine to treat depression

Nicotine

• Very addictive, leading cause of preventable death in the US

• Central effects:

  • stimulation of electroencephalographic activity

  • euphoriant activity (increases firing of VTA dopaminergic neurons)

  • reinforcing properties

• Peripheral Effects

  • release of catecholamines from peripheral adrenergic nerves

• Acute effects: stimulant and depressant

• WITHDRAWAL SYNDOME: Irritability, impatience, hostility, anxiety, dysphoric or depressed mood, difficulty concentrating, restlessness, decreased heart rate, increased appetite and weight gain

Treatment of nicotine withdrawal

• Replacement: nicotine gum, patch, inhalers (not good success rate)

• Reduce withdrawal: Clonidine to reduce anxiety and cravings

• Reduce craving: Nortriptyline and bupropion (main two)

  • Varenicline - partial agonist to nicotinic receptors in VTA

  • Rimonabant - CB1 inverse agonist, off label for smoking cessation

• To treat depression: Fluoxetine

Treatment for Hallucinogens

• For panic reactions - manage with sedation (benzodiazepines or barbituates)

• Talk down reckless acts causing harm

• For PCP - nasogastric suction may speed up eliminination

• Protection against seizures: diazepam

• For scopalamine - use physostigmine

Treatment for Inhalants withdrawal

• Education and supportive care

• Hospitalization if serious conditions and suicidial thhoughts

• Treat comorbidities (i.e. major depression, socality, conduct disorders)

  • Increased risk for future drug problems!

Inhalants

• Acute: CNS effects (euphoria, hallucinations, lethargy, seizures, coma, central respiratory depression), CV effects (ventricular arrhythmias, sudden death), pulmonary hypoxia, pulmonary edema, upper airway cold injury with edema, frostbite, methemoglobinemia, CO poisoning

• Chronic: Leukoencephalopathy (dementia, ataxia, anosmia, eye movement disorders), myeloneuropathy (distal paresthesias, posterior spinal tract abnormalities, sensorimotor peripheral neuropathy, hepatotoxicity, hypokalemia, hematuria, albuminuria and pyuria