SUBSTANCE ABUSE & TOXICOLOGY BY TIKAL KANSARA BARODA MEDICAL COLLEGE (BMC)
PHYSIOLOGY OF SUBSTANCE ABUSE Main addiction pathway is “Dopaminergic Pathway”. Activation leads to “positive reinforcement” feeling and makes us want to repeat the action that triggers the feeling. If there is an environmental stimulus, this pathway makes behavior adaptive and goal directed.
Activated by all substances that have the tendency to produce dependence. The most common examples are: Gambling Being in LOVE…
ROLE OF INSULA CORTEX Anterior insula: Direct projections from thalamus and amygdala Project directly to amygdala Amygdala important for emotional anticipation and conditional response Functions Conscious desires, “craving” Damage to this area, example by stroke, addiction to cigrette smoking eliminated.
ALCOHOLISM Costs to US health system more than $ 100 billion per year. Most common abused drug Binge drinking has become more common and per capita drinking is declining Implicated in: Auto accidents Homicides Hospital admissions
MEDICAL COMPLICATIONS Fatty liver, Alcoholic hepatitis, Cirrhosis Gastric & Duodenal ulcers All complications of cirrhosis Peripheral Neuropathy Myopathies Wernicke-Korsakoff Syndrome
BEHAVIORAL MODIFICATIONS Psychotherapy and behavioral therapy useful Stages of behavioral therapy: Precomtemplation - unaware of the problem Contemplation – aware but ambivalent about the action Preparation – 1st decision to change Action – change begins. Trial & error Maintenance – new behaviors practiced. Focus on relapse prevention Relapse – efforts to change abandoned.
PHARMACOTHERAPY Disulfiram (Antabuse) Decreases alcohol consumption Interaction with alcohol produces Nausea, chest pain Hyperventilation, tachycardia, vomitting For short term use only Must be accompanied with psychotherapy.
MECHANISM OF ACTION OF DISULFIRAM Disulfiram inhibits Aldehyde dehydrogenase Alcohol dehydrogenase
OTHER DRUGS USED ACAMPROSATE Helps prevent relapse Reduce activity of glutamate receptors (chronic alcoholism increases its activity) Effect persists even after treatment has ended
TOPIRAMATE (ANTICONVULSANT) Helps support abstinence Abstinence 6x more likelyy if not on any other drug for the last one month
BENZODIAZEPINES (e.g. lorazepam) Helps prevent seizures Seizures occur during heavy drinking & also during detoxification FLUMAZENIL Benzodiazepine receptor antagonist Can help prevent relapse.
NALTREXONE Given to recovering alcoholics Reduces craving. Drinks don’t taste good. Helps them to stop the first drink On naltrexone, relapse = 50%, if not, relapse = 95%
TOBACCO INTOXICATION Forms of tobacco intake are:
TREATMENT OF TOXICITY Basic steps: Gastric lavage Supportive measures – patent airway, assisted respiration, oxygen, fluid infusion. For barbiturate toxicity Alkaline diuresis – jsod. Bicarb 1 mEq/kg IV with/without mannitol Hemodialysis & hemoperfusion. For BZD toxicity Flumazenil 0.2 mg/min till patient regains consciousness
OPIOIDS Most common drugs of abuse are Morphine, Heroin, Methadone, Fentanyls and Other Opioids. Activate opioid u, k & delta. Potent u receptor activators have the most abuse & dependence liability, via dopaminergic transmission.
ORGANOPHOSPHATE POISONING Orgaanophosphates are irreversibly acting anticholinesterases They are available as agricultural & household insecticides Initial signs are of local manifestations & then signs of systemic involvement appears
CLINICAL FEATURES The very well known pneumonic is SLUDGE i.e. Salivation Lacrimation Urination Defecation Gastric upset Other symptoms include: fall in BP, brady/tachycardia, arrythmias, vascular collapse Excitement, tremers, ataxia, convulsions, coma & death
TREATMENT Termination of further exposure to the poison – freash air, wash the skin & mucus membrane with soap & water, gastric lavage with NS or KMnO4 solution Maintain airway, positive pressure ventilation if it is falling Supportive measure – maintain BP, hydration, control of convulsions
SPECIFIC ANTIDOTES ATROPINE: Effective in counteracting muscarinic effects. 2 mg IV every 10 mins till symptoms subside or pupil dilation occurs OXIMES: Used only for OP poisoninig. Pralidoxime(2-PAM) is given 1-2 gm slowly IV, but within 24 hours.