DRUGS OF ABUSE (1/2)

Controlled Substance Act (1970): Regulates the manufacture, distribution, & dispensing of drugs that have potential for abuse

FEDERAL SCHEDULES OF CONTROLLED SUBSTANCES

SCHEDULE I SCHEDULE II
-No accepted medical use in US -High abuse potential -Heroin, LSD, Marijuana, Mescaline -Substances w/ therapeutic ability -High abuse potential -Analgesics, Morphine, Fentanyl, Meperidine, Methadone, Oxycodone, Amphetamines, Cocaine, Pentobarbital -Substances w/ less abuse potential than those in I&II -Moderate abuse potential (Buprenorphine) -Mixtures of limited, specified quantities of codeine, for example, w/ uncontrolled active ingredients (Tylenol 3) -Substances w/ less abuse potential than those in III -Limited abuse potential -Dextropropoxyphene, Pentazocine, Diazepam, Pemoline, Benzodiazepams (sedatives) -Substances w/ less abuse potential than those in IV -Subject to state & local regulation, Rx may not be required -Antidiarrheal & cough-suppressant preparations w/ limited, specified quantities of, for example, Codeine or Dihydrocodeine

SCHEDULE III

SCHEDULE IV

SCHEDULE V

1. Addiction primary, chronic, neurobiologic disease w/ genetic, psychosocial & environmental factors influencing its development & manifestations; characterized by impaired
over drug use, compulsive use, continued use despite harm & craving

2. Physical Dependence state of adaptation manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing
blood level of drug, and/or administration of antagonist

3. Tolerance state of adaptation in which exposure to a drug induces changes that result in a diminution of 1+ of drugs effect over time 4. Variables Influencing Likelihood of Abuse: - Drug: availability, cost, purity, potency, mode of administration - User: risk taker, metabolism, experience, background - Environment: social settings, education, peer groups/friends
5. Detoxification of Heroin Addicts: - Methadone used for detoxification/maintenance b/c cross-dependence exists; replaces heroin on mu receptor, longer duration, thus addict doesnt experience heroin w/d or when dose - LAAM longer duration than methadone, severe cardiac-related adverse events (QT interval prolongation, cardiac arrest) - Buprenorphine partial agonist at mu receptor, lower ceiling so chance of respiratory depression, sublingual administration = rapid absorption, combo w/ Naltrexone - Naltrexone Opioid adjunct for heroin dependency and alcoholism - Clonidine adrenergic agonist

DRUGS OF ABUSE (2/2)

DRUG
MARIJUANA

PD/PK
-THC, delta-9-tetrahydrocannabinol = active ingredient bind to CB1 receptors in the brain -Anandamide endogenous ligand for CB receptors -Rapid onset -Inhibits reuptake of DA, 5-HT, NE -Local anesthetic by inhibition of voltage-gated NA channels -Euphoria, CV effects, Mydriasis, Hyperthermia, Neuroendocrine Effects -Nasal, IV, inhaled (hydrochloride free base form) -Very Rapid Onset, Short Duration -Peak plasma levels 35-90m Intranasal, 5m IV/Inhaled -Duration 20-40m IV/Inhaled, 1h nasal -Metabolized by esterases in serum & liver forming metabolites (benzoylecgonine, ecgonine) -Cocaethylene active/toxic metabolite when coabused w/ EtOH, longer life -Excreted in urine -Releases DA/NE -Alertness, euphoria, feelings of enhanced well-being, moderate exhilaration - BP, tachycardia, mydriasis, sweating, constipation -Oral, IV, inhaled -Rapid Onset, Long Duration -Methamphetamine derivative, similar PD, potency, longer acting, neurotoxic -Modulates central 5-HT systems (agonist) -Oral, perentreral -Rapid Onset dizzy, weak, numb, nauseated, mydriasis, BP, tachycardia, tremor, ataxia -Long Duration perceptual & psychic effects, euphoria, elation, ecstasy, anxiety, panic, depression, rage -Effects similar to EtOH: drowsiness, impaired motor coordination, ataxia, loss of inhibitions, slurred speech, and some amnesia, euphoria, sense of well being, headache, nausea, insomnia

CLINICAL INFO -Dronabinol slow acting, synthetic THC used for nausea & vomiting, anti-cancer chemotherapy, stimulates appetite, antiepileptic, analgesic, antiglaucoma, antispasticity
1. Psychological Effects euphoria, arousal, elation, alertness, anxiety, irritability, restlessness, paranoia 2. Addiction & Dependence binging, irritability, restlessness, paranoia, psychological & physical dependence, tolerance, sensitization 3. Withdrawal crash, depression, dysphoria, socially withdrawn, tremor, hyperphagia, hypersomnia, drug-craving, muscle pain, extinction 4. Tx for Dependency behavioral, tricyclics may work -Binging, physical & psychological dependence, tolerance/cross tolerance -Chronic use anxiety, akathesia, volatile mood, headache, cramps, compulsive behavior, psychosis, overt violence -Withdrawal dysphoria, depression, restlessness, hunger, exhaustion, confusion, delusions, memory loss -Effects vary w/ pt, environment, dose -Short-term tolerance -Little or no withdrawal & physical dependence -Psychological & physical dependence -Tolerance to the sedative effects, no tolerance to respiratory depressant effects -Withdrawal seizures, anxiety, agitation, insomnia, confusion, anorexia, nausea/vomiting, tremors, mydriasis, respiratory rate, HR, BP, delirium, hallucinations, confusion, paranoia, convulsions, xerostomia, jaw/teeth pain -Tx Benzodiazepine OD -Relaxation, tranquility, euphoria, disinhibition, numbing, drowsiness, dizziness, nausea, vomiting, weakness, confusion, agitation, hallucination, bradycardia

COCAINE
-Naturally occurring alkaloid -Inhaling produces blood levels, reaches brain faster

AMPHETAMINES

TOXICITY -Long-term use can cause HR, slows thinking, impairs short-term memory, euphoria, relaxation, auditory & visual hallucinations, bronchitis, chronic cough, emphysema 1. CNS psychosis, depression, personality changes, intracerebral hemorrhage, cerebral infarction, seizures, headaches 2. CV tachycardia, vasoconstriction, arrhythmias, MI, fatal cardiac arrest, stroke 3. Nasal Use chronic rhinitis, loss of smell, necrosis, perforation of nasal septum 4. Pulmonary congestion, edema, alveolar hemorrhage, respiratory arrest 5. Others sexual dysfunction, hepatotoxicity, GI effects 6. Excited Delirium psychosis accompanied by agitation & hyperthermia 7. OD death due to cardiac arrhythmias, convulsions, stroke, respiratory failure -No antidote, tx symptoms only -Psychosis, paranoia, compulsive behavior, fatigue, depression, anxiety, akathisia, headaches, volatile moods, violence, stereotypy -Necrotizing arteritis renal failure, cerebral hemorrhages -Decreased growth in children -OD CNS & CV stimulation, coma & convulsions leading to epilepticus, arrythmias, hypertension, hyperthermia, mydriasis, subarachnoid hemorrhage -Tx- acidify urine, symptomatic tx
-Adverse psychological rxns -Panic rxn, acute depression, psychotic rxn -Errors in judgment - 1 cause of death -Hallucinogen persisting perception disorder -OD coma, progressive deterioration of respiration & BP, hypoxia, cyanosis, shock, hypothermia, anuria, death from cerebral anoxia due to respiratory failure -Lethal if combo w/ other CNS depressants -Tx Flumazenil, gastric lavage, maintenance of respiration

LSD
-Fungus from grains -Very Potent -High therapeutic index

BENZODIAZEPINE: ALPRAZOLAM FLUNITRAZEPAM FLUMAZENIL GHB

-Endogenous NT -Anesthetic, sleep aid, body building supplement,

-Benzodiazepine receptor antagonist -Rapidly absorbing/acting hypnotic, short half life -Oral, short duratioin -Indirectly release of DA, endogenous opioids & growth hormones

-Loss of bladder control, amnesia, sleepwalking, seizures, cardiopulmonary depression, coma, persistent vegetative states -Synergy w/ other CNS depressants

recreational intoxicant

-Used to tx cataplexy in pt w/ narcolepsy -Low therapeutic index

-Physical Dependence -Withdrawal anxiety, tremor, insomnia, depression

-OD unconsciousness, vomiting, deaths