4-26 Drugs of Abuse CIS Flashcards
What is the most abused drug in the world? What is it like in the US?
Ethanol
- Most commonly abused drug in the world
- In the U.S., about 75% of the adult population uses alcohol regularly
- But only 8% of the U.S. general population has an alcohol-use disorder
- Dependence and abuse
- 17 million in US
- 30% of all individuals admitted to US hospitals have coexisting alcohol problems
What are the pharmacokinetics of EtOH?
Pharmacokinetics
- Amphipathic properties guide absorption and distribution
- First-pass metabolism
- Zero order kinetics
- Blood-brain barrier
Explain the relationship between BAC levels and clinical effrects in non-tolerant individuals?
What happens with tolerance to alcohol?
- Tolerance: a decrease in responsiveness to a drug following repeated exposure
- Dose-response curve shifts to the right
- Common with alcohol and opioids
What happens with sensitization with alcohol?
- Sensitization (reverse tolerance): an increase in responsiveness to a drug following repeated exposure
- Dose-response curve shifts to the left
- Common with cocaine
What is appropriate treatment of acute EtOH intoxication?
- Respiratory support
- Gastric lavage, naloxone if any suspicion of additional drugs
- Fluid replacement if hypovolemic
- Short acting benzodiazepine (e.g., lorazepam) if convulsing
- Thiamine (IM), glucose (IV), electrolytes, etc.
What kind of receptors does EtOH target?
Ionotropic
NMDA glutamate R - decreases fxn
GABAa R - increases fxn
What is the effect of EtOH’s action on NMDA-glu R?
- N-methyl-D-aspartate (NMDA) glutamate receptors
- Cation channel (Na+ and Ca2+)
- Glutamate is the primary excitatory neurotransmitter in the CNS (memory)
- Alcohol inhibits NMDA receptor channel opening
What is EtOH’s effect on GABAa R?
- Alcohol inhibits NMDA receptor channel opening
- GABAA receptors
- Anion channel (Cl-)
- GABA is the primary inhibitory neurotransmitter in the CNS
- Alcohol enhances GABA’s effects on the GABAA receptor
What are the chronic effects of EtOH in the CNS?
- CNS: changes in GABAA and NMDA receptor expression
- Tolerance and physical dependence
- Degenerative changes – generalized symmetric peripheral nerve injury
- Wernicke-Korsakoff syndrome
What are the chronic effects of EtOH on the liver, CV system?
- Liver: 15-30% of chronic abusers develop severe liver disease
- Alcoholic fatty liver → hepatitis → cirrhosis → liver failure
- CV system: cardiomyopathy, heart failure, arrhythmias, hypertension, stroke, coronary heart disease
In addition to effects on the CNS, liver and CV system; what else does EtOH increase risk of?
- Increased risk of cancer (mouth, pharynx, esophagus, and liver)
- Fetal alcohol syndrome
A 22 y/o presents to the ED after falling and cutting her head at a bar. She and a friend had been there for about an hour and then the patient suddenly became drowsy and fell (she was still conscious when she fell). She can feel pain from the trauma. Her ventilatory rate and depth are depressed, but not to a worrisome degree. Her patellar reflexes are blunted and she is ataxic. She responds slowly to questions but is unable to recall anything that happened after arriving at the bar and sipping her first (and last) adult beverage.
With what was her drink most likely spiked?
•
A.Cocaine
B.Flunitrazepam
C.Oxycodone
D.Phenobarbital
E.Pure (grain) alcohol
flunitrazepam
How does sensitization work with DA and reward pathways?
- DA levels were detected in the extracellular fluid of the nucleus accumbens of rats
- First injection of cocaine produces a modest increase in DA while the last injection 7 days later produces a much larger increase in DA
- Saline has no effect on DA levels, but saline given 3 days after 7 days of cocaine injections produces a significant rise in DA
What is the time course of events during EtOH withdrawal syndrome?
- Earliest signs and symptoms: anxiety, insomnia, tremor, palpitations, nausea, and anorexia
- Hallucinations and seizures are possible in severe syndromes
- Can persist, in a milder form, for several months after alcohol discontinuation
- Delirium tremens typically develops 48–72 hours after alcohol discontinuation
What are the goals for Tx of EtOH withdrawal syndrome?
- Goals: prevention of seizures, delirium, and arrhythmias
- Detoxification involves substituting a long-acting sedative-hypnotic drug for alcohol and then gradually tapering the dose
Which drugs are used for EtOH syndrome?
Benzodiazepines
•Long-acting (diazepam, chlordiazepoxide)- Less frequent dosing and built-in tapering effect
Active metabolites may accumulate (liver disease)
•Short-acting (lorazepam, oxazepam) - Rapidly converted to inactive metabolites (useful in patients with liver disease)
Antipsychotics for hallucinations
•Haloperidol (IM and IV preparations available)
How is naltrexone used for EtOH dependence?
Naltrexone
- Approved for the treatment of alcohol and opiate dependence
- Opioid receptor antagonist
- Reduces alcohol craving and rate of relapse short-term (12-16 weeks)
How is acamprosate used for EtOH dependence?
Acamprosate
- Weak NMDA receptor antagonist and GABAA receptor agonist
- Reduces short-term and long-term (> 6 months) relapse rates
How is disulfiram used for EtOH dependence?
Disulfiram (Antabuse)
- Inhibits aldehyde dehydrogenase
- Causes extreme discomfort in patients who drink alcohol due to accumulation of aldehyde (flushing, throbbing headache, nausea, vomiting, sweating, hypotension, confusion)
- Patient must be highly motivated
What are some non-FDA approved Tx for EtOH dependence?
Topiramate and ondansetron – not FDA approved
How does bupropion work for Tx of nicotine dependence?
- Antidepressant with incompletely understood mechanisms of action
- May reduce cravings by increasing dopaminergic activity in the mesolimbic pathway
- Contraindicated in patients predisposed to seizure
How does varenicline work in Tx of nicotine dependence?
- Partial agonist at neuronal nicotinic receptors
- Serious neuropsychiatric events (including depression, suicidal thoughts, and suicide) have been reported and warrant discontinuation
In addition to bupropion and varenicline, what are therapies can help with nicotine dependence?
- Nicotine replacement therapy
- Acupuncture
- Hypnosis
