Drugs of Abuse (Week 5) Flashcards
Abuse
Self-administration of any drug in a culturally disapproved manner that causes adverse consequences.
Addiction
A behavioral patter of drug abuse characterized by overhwhelming involvement with the use of a drug(compulsive use), the securing of its supply, and a high tendency to relapse after discontinuation.
Compulsivity
-Repetitive actions inappropriate to the situation that persist, have no obvious relationship to the overall goal and that often result in undesirable consequences: behavior that results in perseveration in responding in the face of adverse consequences;perseveration in responding in the face of incorrect responses in choice situations or persistent reinitiation of habitual acts.
dependence
physiological adaptation produced by repeated administration of drugs such as alcohol, heroin, benzos. When abruptly discontinued they are associated with physical drug withdrawal distinct from the motivational changes of acute withdrawal and protracted abstinence which is part of addiction.
tolerance
After repeated administration a given dose of a drug produces a decreased effect or a larger dose must be administered to obtain the prior effects.
Withdrawal
psychological and physiological reactions to abrupt cessation of a dependence producing drug.
Common neurotransmitters involved in dependenceo
dopamine, serotonin, acetylcholine, endorphins, GABA, Glutamate
Most important neurotransmitters involved in addiction
Dopamine and glutamate
Which type of addiction most involves dopamine?
amphetamines, cocaine, ETOH
Which type of drug most affects serotonin?
LSD, ETOH, DMT, Psilocybin
Which drug most affects endorphins
opiates, ETOH
Which Drugs most affect GABA?
Benzodiazepines and ETOH
Which drugs most affect acetylcholine?
NIcotine and ETOH
Which drug affects Anandamide
Cannabis
Where do drugs leading to addiction increase dopamine?
ventral striatum
Where is the pleasure center?
Mesolimbic pathway
Cocaine adverse effects:
-rhabdomyelosis from hypermetabolic state.
-vasoconstriction that may outlast use.
-Tactile hallucinations associated with withdrawal.
-transient psychosis with intoxication
-Neuroadaptation: prevention of dopamine reuptake.
What medication can be used to treat cocaine dependence?
Disulfuram 250 mg daily to reduce cravings
Amphetamines
-Similar intoxication to cocaine but generally longer
-no vasconstriction effect
-chronic use results in neurotoxicity (possibly from glutamate and axonal degeneration).
-can see permanent amphetamine psychosis with continued use.
-no known substances to reduce cravings. naltrexone and buprenorphine are being studied.
-Amphetamines inhibit reuptake of DA,NE, SE. Greatest effect by increased release of DA.
How is cocaine dependence treated?
psychotherapy, support, education, relapse prevention skills.
nicotine
Tolerance is rapid
-withdrawal symptoms: dysphoria, irritability, anxiety, decreased concentration, insomnia, increased appetite, weight gain, cravings
-nicotine intoxication: abdominal pain, dizziness, headache, N/V, palpitations, self limited.
Cross-tolerance or cross dependence
The ability of one drug to suppress the manifestations of physical dependence produced by another drug and to maintain the physically dependent state.
Habit
Responses triggered by environmental stimuli regardless of the current desirability of the consequences. Conditioned response to stimulus that has been reinforced/strengthened by positive or negative reinforcement.
Positive reinforcement
Reward
Negative reinforcement
omission of aversive event.
Impulsivity
Acting prematurely without foresight. Actions poorly conceived, prematurely expressed, unduly risky, inappropropriate to situation, result in undesirable consequences; Predisposition to rapid unplanned responses to internal and external stimuli without regard for negative consequences.
-may be measured in 2 domains: inability to inhibit behavior to change the course of action or stop a response once it is initated. Choice of small immediate reward over larger delayed reward.
Rebound
Exaggerated expression of original condition sometimes experienced by patients immediately after cessation of effective treatment.
Reinforcement
tendency of pleasure producing experience or drug to lead to repeated self-administration.
Relapse
Reoccurence once effective medical treatment is discontinued, of the original condition from which the patient suffered.
Where does nicotine act?
Nicotinic cholinergic receptors.
Varenicline
Alpha-4-Beta-2 Nicotine acetylcholine receptor partial agonist, nicotine receptor partial agonist, not metabolized. Doses titrated over 1 week.
Varenicline black box warning
Worsening depression, agitation, suicidal ideation.
How does bupropion help nicotine addiction
NDRI that boosts dopamine release. During abstinence nicotine receptors are no longer receiving dopamine. Bupropion helps provide some dopamine to help with cravings. Use 150 bId to help with cravings.
Alcohol intoxication symptoms
Mood lability, impaired judgement, ataxia, nystagmus, slurred speech, decreased concentration, anterograde memory loss(blackouts).
Alcohol early withdrawal
anxiety, irritability, tremor, decreased consciousness, insomnia, nausea, vomiting.
DT’s
confusion, alternating level of consciousness, hallucinations, hypertension, tachycardia, sweating, vascular collapse, seizures (about 72 hours from stopping). Seizures 48-72 hours within stopping.
Medications to treat ETOH withdrawal
-benzodiazepine (GABA agonist)-cross tolerant with alcohol, reduces the risk of seizures and increases comfort.
-carbamazepine 200 mg TID or valproic acid 250 mg BID or TID>65 y.o. for at least 3 weeks.
Disulfuram
MOA: inhivits aldehyde dehydrogenase and dopamine beta hydrxoxylase.
-check LFT’s and history of Hep.C due to hepatotoxicity.
-dermatologic rashes and itching.
-Can cause neurologic polyneuropathy/paresthesia, that slowly increase over time. Increased risk with increased doses.
-Causes vasodilation, flushing, n/v, hypotension/HTN, coma/death.
-Psychiatric side effects: psychosis, depression confusion,anxiety.
Naltrexone
Opioid antagonist thought to block mu receptors reducing intoxication euphoria and cravings.
-hepatotoxicity at high doses, monitor liver function tests.
-Acts on reward circuits.
-Can help reduce heavy drinking and promote abstinence.
-Available in monthly injection or orally.
Acamprosate(campral) 666 mg TID.
Unknown mechanism of action but thought to stabilize neuron excitation and inhibition.
May interact with GABA and Glutamate receptor (reduces glutamate release).
Cleared renally.
Benzodiazepene withdrawal
-Convert short acting benzo to longer half life drug and slowly taper.
-Decrease dose every 1-2 weeks.
-May consider carbamazepine or valproic acid if doing rapid taper.
Acute alcohol withdrawal interventions
-force fluids and sleep.
-auditory and visual hallucinations will usually self limit
-magnesium sulfate for convulsions.
-IV or IM benzos. (librium, valium, lorazepam.
Methadone
Opiate substitution therapy: mu agonist
cross-tolerant drug. synthetic narcotic blocks the high of opioids.
-Start at 20-40 mg and titrate up until cravings resolve or no longer using ilicit opiates.
-average dose 80-100 mg daily
-must be enrolled in certified opiate substitution program.
Suboxone (buprenorphine/ naloxone)
May cause N/V, constipation. Target dose 16 mg/day. Place dose under tongue until dissolved, do not swallow.
Buprenorphine
-partial mu agonist/antagonist.
-low doses act as an agonist w/ pain control
-at higher doses no increased effect, less risk of overdose. May behave like antagonist at higher doses (can trigger withdrawal).
Helpful for highly motivated people who do not need high doses.
MDMA
-designer club drug(related to amphetamine).
-enhanced empathy, personal insight, euphoria, increased energy.
-3-6 hour duration.
-can cause parkinson’s in animals. hyperthermia, dehydration, seizures, coma. CV/renal failure, coma, death.
MDMA intoxication
Illusions,hyperacusis, sensitivity of touch, taste/smell altered. Synesthesia, “oneness with the world, tearfulness, euphoria, panic, paranoia, impaired judgment.
Tolerance: develops quickly and unpleasant side effect with continued use(teeth grinding) so dependence less likely.
MDMA pharmacology
Affects serotonin, DA, NE but primarily 5HT2 receptor agonists.
Cannabis
-most commonly used drug in world
-THC levels reach peak 10-30 minutes, lipid soluble, long half life of 50 hours.
Cannabis effects
-increased confidence and euphoria
-relaxation, increased libido, transient depression/anxiety/paranoia.
-tachycardia, dry mouth, conjunctival injection.
-slowed reaction time/motor speed.
-impaired cognition.
-psychosis
-Dependence can lead to amotivational syndrome.
Phencyclidine (PCP, angel dust)
-dissociative anesthetic
similar to ketamine, used in anesthesia, especially w/ kids.
-Intoxication: severe dissociative reactions, paranoid delusions, hallucinations, agitation, violence, decreased awareness of pain.
PCP intoxication treatment
-Antipsychotics or benzodiazepenes if required.
-acidify urine with IV ammonium chloride if severe toxicity/coma
-Difficult to tolerate withdrawal.
PCP neuroadaptation
Opiate receptor effect and allosteric modulator of the glutamate NMDA receptor.
