UNIT 9: DRUG OF ABUSE Flashcards
Drugs that activate G-protein-coupled receptors (GCPRs)
Class 1
Drugs that bind to ionotropic receptors or ion channels
Class 2
Drugs that bind to biogenic amine transporters
Class 3
Enumeration
Class 1 Drugs
Opioids
Cannabinoids
THC
GHB
LSD
Mescaline
Psilocybin
Enumeration
Class 2 Drugs
Benzodiazepines
Nicotine
Ethanol
Alcohol
Ketamine
PCP
Inhalants
Enumeration
Class 3 Drugs
Cocaine
Amphetamine
Ecstacy (MDMA)
Strong analgesics, narcotic
Opioids
Naturally-occuring alkaloids
Opiates
Enumeration
Opiates
Morphine
Codeine
Thebaine
Papaverine
Enumeration
Opioid receptor subtypes
μ (mu)
δ (delta)
κ (kappa)
This opioid receptor subtype causes inhibition of respiration
μ (mu)
Which opioid receptor subtype has a strong affinity to Dynorphins
κ (kappa)
This opioid receptor subtype causes psychotomimetic effects and slowed gastrointestinal transit
κ (kappa)
Natural painkillers in the body with varying affinity to the three types of opioid receptors
Endogenous peptides
The following acts as agonists of the κ (kappa) receptor, except one:
Morphine
Sufentanil
Butorphanol
Nalbuphine
Buprenorphine
Pentazocine
Buprenorphine
Antagonist
Opium is derived from
Scientific name
Papaver somniferum
The principal active ingredient of opium
Morphine
The only antagonist of the μ (mu) receptor
Nalbuphine
Powerful narcotic that causes histamine release
Opium
Smack
H
Ska
Junk
Heroin
Street drug of abuse of opioids
Heroin
An addictive drug as a white or brown powder, IV injected
Heroin
Half-life of Heroin
3-5 hours
Withdrawal time of Heroin
5-10 hours after
Oxycodone is synthesized from ____ and derived from ____
Thebaine, Codeine
Enumeration
Opioids
Opium
Heroin
Oxycodone
Meperidine
Serious interaction with MAOs, can result in MPTP which can cause parkinsonism
Meperidine
Opioid receptors block ____ channels in the dorsal horn
Ca+ channels
Postsynaptically, opioids can inhibit the pain stimulus by enhancing the ____ conductance
K+ conductance
The mechanism of action of opioids involve preventing the release of what neurotransmitters?
Glutamate, Neuropeptides
True or False
The principal effects of opioid analgesics with affinity for mu receptors are on the PNS
False
CNS
Effect of opioids that develops a moderate degree of tolerance
Bradycardia
Slow heart rate
Adverse effects of opioid analgesics can be reversed by
Naloxone
Which drug group results in this interaction with opioids:
Increased CNS depression, particularly respiratory depression
Sedative-hypnotics
Which drug group results in this interaction with opioids:
Increased sedation, Accenuation of cardiovascular effects
Antipsychotic agents
Which drug group results in this interaction with opioids:
High incidence of hyperpyrexic coma and reported hypertension
Monoamine oxidase inhibitors
Which drug group is relatively contraindicated to all opioid analgesics?
Monoamine oxidase inhibitors
Enumeration
Sedative-hypnotics
Alcohol
Barbituates
Benzodiazepines
Gamma-hydroxybutyric acid (GHB)
True or False
Sedative-hypnotics can be short or long-acting
True
Used to be called “Physical Dependence”
Dependence
Used to be called “Psychological Dependence”
Addiction
Hallmark of addiction
Compulsive
Repetitive exposure induces widespread adaptive changes in the brain. What effect of DOA is this?
Altered perception
A combination of signs that defines dependence
Withdrawal Syndrome
Consists of compulsive, relapsing drug use despite negative consequences, at times triggered by cravings that occur in response to contextual cues
Addiction
True or False
Dependence is not always a correlate of drug abuse—it can also occur with many classes of nonpsychoactive drugs
True
Dependence or Addiction
Physical
Dependence
Dependence or Addiction
Tolerance
Dependence
Dependence or Addiction
Psychological
Addiction
Dependence or Addiction
Withdrawal Syndrome
Dependence
Dependence or Addiction
Compulsion
Addiction
Dependence or Addiction
Relapsing
Addiction
Dependence or Addiction
Non-psychoactive drugs
Dependence
Dependence or Addiction
Craving
Addiction
The prime target of addictive drugs
Mesolimbic Dopamine System
True or False
Each addictive drug activates the mesolimbic system via its specific molecular target, engaging distinct cellular mechanisms to increase dopamine levels.
True
Dopamine pathway functions (5)
Reward (motivation)
Pleasure, euphoria
Motor function (fine tuning)
Compulsion
Perseveration
Which class of drugs directly stimulates the dopamine neurons?
Class 2 (Class 1 sa book)
Nicotine
Which class interferes with the reuptake of dopamine or promotes nonvesicular release?
Class 3 (Class 2 sa book)
Cocaine, Amphetamines (respectively)
Which class uses an indirect mechanism, whereby the drugs inhibit γ-aminobutyric acid (GABA) neurons that act as local inhibitory interneurons?
Class 1 (Class 3 sa book)
Opioids, Cannabis
Drugs That Activate G Protein–Coupled Receptors
Opioids
Cannabinoids
γ-Hydroxybutyric acid (GHB)
LSD, mescaline, psilocybin
Drugs That Activate G Protein–Coupled Receptors
Main molecular target of Opioids
μ-OR (Gio)
Drugs That Activate G Protein–Coupled Receptors
Main molecular target of Cannabinoids
CB1R (Gio)
Drugs That Activate G Protein–Coupled Receptors
Main molecular target of γ-Hydroxybutyric acid (GHB)
GABABR (Gio)
Drugs That Activate G Protein–Coupled Receptors
Main molecular target of LSD, mescaline, psilocybin
5-HT2AR (Gq)
Drugs That Bind to Ionotropic Receptors and Ion Channels
Main molecular target of Nicotine
nAChR (α4β2)
Drugs That Bind to Ionotropic Receptors and Ion Channels
Main molecular target of Alcohol
GABAAR, 5-HT3R, nAChR, NMDAR, Kir3 channels
Drugs That Bind to Ionotropic Receptors and Ion Channels
Main molecular target of Benzodiazepines
GABAAR
Drugs That Bind to Ionotropic Receptors and Ion Channels
Main molecular target of Phencyclidine, Ketamine
NMDAR
Drugs That Bind to Transporters of Biogenic Amines
Main molecular target of Cocaine
DAT, SERT, NET
Drugs That Bind to Transporters of Biogenic Amines
Main molecular target of Amphetamine
DAT, NET, SERT, VMAT
Drugs That Bind to Transporters of Biogenic Amines
Main molecular target of Ecstasy
SERT > DAT, NET
Drugs That Activate G Protein–Coupled Receptors
Opioids
Pharmacology
Agonist
Drugs That Activate G Protein–Coupled Receptors
Cannabinoids
Pharmacology
Agonist
Drugs That Activate G Protein–Coupled Receptors
γ-Hydroxybutyric acid (GHB)
Pharmacology
Weak Agonist
Drugs That Activate G Protein–Coupled Receptors
LSD, mescaline, psilocybin
Pharmacology
Partial Agonist
Drugs That Bind to Ionotropic Receptors and Ion Channels
Nicotine
Pharmacology
Agonist
Drugs That Bind to Ionotropic Receptors and Ion Channels
Benzodiazepines
Pharmacology
Positive Modulator
Drugs That Bind to Ionotropic Receptors and Ion Channels
Phencyclidine
Pharmacology
Antagonist
Drugs That Bind to Ionotropic Receptors and Ion Channels
Ketamine
Pharmacology
Antagonist
Drugs That Bind to Transporters of Biogenic Amines
Cocaine
Pharmacology
Inhibitor
Drugs That Bind to Transporters of Biogenic Amines
Ecstasy
Pharmacology
Reverses transport
Drugs That Bind to Transporters of Biogenic Amines
Amphetamine
Pharmacology
Reverses transport
Drugs That Activate G Protein–Coupled Receptors
Disinhibition
Effect on Dopamine (DA) Neurons
Opioids
Cannabinoids
γ-Hydroxybutyric acid (GHB)
Drugs That Bind to Ionotropic Receptors and Ion Channels
Nicotine
Effect on Dopamine (DA) Neurons
Excitation
Drugs That Bind to Ionotropic Receptors and Ion Channels
Alcohol
Effect on Dopamine (DA) Neurons
Excitation, Disinhibition
Drugs That Bind to Ionotropic Receptors and Ion Channels
Benzodiazepines
Effect on Dopamine (DA) Neurons
Disinhibition
Drugs That Bind to Transporters of Biogenic Amines
Cocaine
Effect on Dopamine (DA) Neurons
Blocks DA uptake
Drugs That Bind to Transporters of Biogenic Amines
Amphetamine
Effect on Dopamine (DA) Neurons
Blocks DA uptake
Synaptic depletion
Drugs That Bind to Transporters of Biogenic Amines
Ecstasy
Effect on Dopamine (DA) Neurons
Blocks DA uptake
Synaptic depletion
Serious side effect of Tolerance
Respiratory Depression
True or False
Tolerance to opioids may be due to an increase of the concentration of a drug or a longer duration of action in a target system (pharmacokinetic tolerance)
False
Reduction of concentration, not increase; shorter duration of action
Regulation Schedules
High potential for abuse
No known medical use
Lacks accepted safety for use
Eg, Heroin, Lysergic acid diethylamide
Schedule I
Regulation Schedules
Potential for abuse
Proven and accepted medical use with severe restrictions
Abuse may cause severe psycho/physio dependence
Eg, Morphine, Cocaine, Methadone, Methampetamine, Phencyclidine
Schedule II
Regulation Schedules
Less potential for abuse
With accepted medical use
Abuse may cause moderate or low physical dependence or high psychological dependence
Eg, Anabolic steroids, Codeine and hydrocodone with aspirin or Tylenol
Schedule III
Regulation Schedules
Low potential for abuse
Abuse may lead to limited physical or psychological dependence
Eg, Valium and Xanax
Schedule IV
Regulation Schedules
Low potential for abuse relative to drugs in Schedule IV
Eg, Cough syrups and Codeine
Schedule V
Pharmacokinetic or Pharmacodynamic Tolerance
Reduction of Concentration
Pharmacokinetic Tolerance
Pharmacokinetic or Pharmacodynamic Tolerance
Shorter duration of action
Pharmacokinetic Tolerance
Pharmacokinetic or Pharmacodynamic Tolerance
Recruitment of adaptor protein (B-arrestin)
Pharmacodynamic Tolerance
Pharmacokinetic or Pharmacodynamic Tolerance
Desensitization and receptor internalization
Pharmacodynamic Tolerance
Adaptive changes that become fully apparent once drug exposure is terminated
Withdrawal
Observed to varying degrees after chronic exposure to most drugs of abuse
Withdrawal
Symptom of withdrawal that involves physical stimulations
Illusions
Symptom of withdrawal that has no external stimulus
Hallucinations
Signs or Symptoms of Withdrawal
Elevated blood pressure
Increased heart rate (tachycardia)
Elevated body temperature (hypertermia)
Sweating
Tremulousness
Dilated pupils
Disorientation
Hyper arousal
Grand mal seizure
Signs of Withdrawal
Signs or Symptoms of Withdrawal
Anxiety
Insomnia
Illusions
Hallucinations
Paranoid ideas
Nausea
Irritability
Symptoms of Withdrawal
Refers to the high motivation to obtain and use a drug despite negative consequences
Addiction
A recalcitrant, chronic, and stubbornly relapsing disease that is very difficult to treat
Addiction
Three conditions that trigger relapse
Re-exposure
Stress
Context Recall
True or False
All drugs of abuse lead to addiction
False
Some drugs of abuse do not lead to addiction
Alters perception but does not provide feelings of reward/euphoria
Non-addictive Drug of Abuse
Target of Non-addictive Drug of Abuse in the body
Cortical and Thalamic system
Enumeration
Non-addictive Drugs of Abuse
Hallucinogens
Dissociative anesthetics
LSD
PCP/Ketamine
Dextromethorphan
Receptor subtype with affinity of endorphins = enkephalins
μ (mu)
Receptor subtype with strong affinity for enkephalins
δ (delta)
True or False
The principal effects of opioid analgesics with affinity for μ (mu) receptors are on the CNS
True
Important principal effects of opioid analgesics with affinity for μ (mu) receptors on the CNS (4)
Analgesia
Euphoria
Sedation
Respiratory Depression
Effect of opioids with Minimal or None degree of tolerance
Miosis
Constipation
Convulsions
Effect of opioids with high degree of tolerance
Analgesia
Euphoria, dysphoria
Mental clouding
Sedation
Respiratory depression
Antidiuresis
Nausea and vomiting
Cough suppression
True or False
Nonsteroidal anti-inflammatory analgesic drugs (eg, ibuprofen) have a significant effect on the **emotional aspect **of pain
False
No significant effect
Characteristic effect of opioid analgesics wherein they reduce both sensory and affective (emotional) components of pain
Analgesia
Respiratory depression is caused by (inhibition, excitation) of brainstem respiratory mechanisms
Inhibition
True or False
Respiratory Depression is dose-related
True
True or False
Respiratory Depression is unaffected by the degree of sensory input occuring at the time
False
It is significantly influenced
Adverse effects of opioid analgesics with acute use (10)
Respiratory depression
Nausea/Vomiting
Pruritus
Urticaria
Constipation
Urinary retention
Delirium
Sedation
Myoclonus
Seizures
Adverse effects of opioid analgesics with chronic use (9)
Hypogonadism
Immunosuppression
Increased feeding
Increased growth hormone secretion
Withdrawal effects
Tolerance, dependence
Abuse, addiction
Hyperalgesia
Impairment while driving
An increased sensitivity to feeling pain and an extreme response to pain; adverse effect of opioid analgesics with chronic use
Hyperalgesia
Decreased functional activity of the gonads; adverse effect of opioid analgesics with chronic use
Hypogonadism
Sudden, brief involuntary twitching or jerking of a muscle or group of muscles; adverse effect of opioid analgesics with acute use
Myoclonus
Sedative-hypnotics
Rare occurence of physiologic dependence but has therapeutic dose dependence
Benzodiazepines
Benzodiazepines
Used for date rape
Flunitrazepam
Trade name of flunitrazepam
Rohypnol, “roofies”
Flunitrazepam is what schedule?
Schedule IV
Main effect of flunitrazepam
Anterograde amnesia
Loss of the ability to create new memories after the event that caused the amnesia
Anterograde amnesia
The feeling of tingling, numbness or “pins and needles”; withdrawal effect of benzodiazepines
Paresthesia
Target of Barbituates
GABA-A receptors
Nonselective antagonist of opioid receptors
Naloxone
Opioid Receptor Antagonists
Naloxone
Naltrexone
Antagonist of opioid receptors
Naltrexone
Opioid Receptor Antagonists
Blocks effects of illicit opioids
Naltrexone
Opioid Receptor Antagonists
Reverses the acute effects of opioids
Naloxone
Opioid Receptor Antagonists
Can precipitate severe abstinence syndrome
Naloxone
Opioid Receptor Antagonists
Used for opioid overdose
Naloxone
Opioid Receptor Antagonists
Used for treatment of alcoholism and opioid addiction
Naltrexone
Opioid Receptor Antagonists
Effect is much shorter than morphine (1-2 h)
Several injections are required
Naloxone
Opioid Receptor Antagonists
Half-life of 10 h (oral) or
5-10 days (depot injection)
Naltrexone
Synthetic Opioids
Methadone
Levomethadone
Morphine sulphate
Synthetic Opioids
Slow-acting agonist of μ-opioid receptor
Methadone
Synthetic Opioids
“Enantiopure” methadone containing only the left-enantiomer of the molecule
Levomethadone
Synthetic Opioids
A salt containing morphine sulfate pentahydrate
Morphine sulphate
Synthetic Opioids
Has acute effects similar to morphine
Methadone
Synthetic Opioids
Similar to morphine and methadone, but at half the dose of the latter
Levomethadone
Synthetic Opioids
Slow-release version with a longer action than morphine
Morphine sulphate
Synthetic Opioids
Used in substitution therapy for opioid addicts
Methadone
Synthetic Opioids
High oral bioavailability
Half-life highly variable among individuals (range 4-130 h)
Methadone
Synthetic Opioids
Less toxic compared to racemic methadone, particularly related to cardiac adverse effects (long QT interval)
Levomethadone
Partial μ-opioid receptor agonist
Buprenorphine
Attenutates acute effects of morphine
Buprenorphine
Oral substitution therapy for opioid addicts
Buprenorphine
Has long half-life (40 h)
Formulated together with naloxone to avoid illicit IV injections
Buprenorphine
Partial agonist of nicotinic acetylcholine receptor of the α4β2-type
Varenicline
Occludes “rewarding” effects of **smoking **
Heightened awareness of colors
Varenicline
Natural analog (extracted from laburnum flowers) of varenicline
Cytisine
Used for smoking cessation
Varenicline
Positive modulators of the GABA-A receptors
Oxazepam
Benzodiazepines
Oxazepam
Lorazepam
Diazepam
Chlordiazepoxide
Flurazepam
Desmethyldiazepam
Nitrazepam
Triazolam
Alprazolam
Benziodiazepine used for delirium tremens
Oxazepam
True or False
The pharmacokinetics of oxazepam are not affected by decreased liver function
True
Benzodiazepines
Alternate to oxazepam with similar properties
Lorazepam
Antagonist of N-Methyl-D-Aspartate (NMDA) glutamate receptors
Acamprosate
May interfere with forms of synaptic plasticity that depend on NMDA receptors
Acamprosate
Used for treatment of alcoholism, effective only in combination with counseling
Acamprosate
Toxicity causes hallucinations particularly in elderly patients
Acamprosate
Cannabinoid (CB1) receptor inverse agonist
Rimonabant
Decreases neurotransmitter release at GABAergic and glutamatergic synapses
Rimonabant
Formerly used to treat obesity, smoking cessation (off-label indication)
Rimonabant
Causes major depression, including increased risk of suicide
Rimonabant
What schedule are Amphetamines?
Schedule II
Amphetamines are managed by
Benzodiazepines
Catecholinergic transmitter agonists
Amphetamines
Used to treat narcolepsy and ADHD
Amphetamines
Effects of Amphetamines
Paranoid psychosis
Necrotizing arteritis
Decreased appetite, including stamina, energy, sexual drive
Loss of REM sleep, tremor, restlessnes, anxiety
Fosters **false intimacy **and empathy
“Raves” designer drug
Ecstasy
Serotonin inhibitor (SERT)
Ecstasy
Called Methylene-dioxymethamphetamine (MDMA)
Ecstacy
Reverses the effects of fatigue on both mental and physical tasks
Called “uppers”
Stimulants
Substance of Abuse (3)
Stimulants
Inhalants
Anabolic Steroids
Stimulants
Stimulant found in tobacco products
1 drop is fatal
More addictive than heroin and cocaine
Nicotine
Stimulants
Associated with Sudden Infant Death Syndrome (SIDS)
Nicotine
Nicotine is derived from?
Nicotania tobacum
A selective agonist of the nicotinic acetylcholine receptor (nAChR)
Nicotine
Xanthine alkaloid
Low chance of abuse and addiction
Caffeine
Caffeine is derived from?
Coffea arabica
Adenosine receptor agonist
Caffeine
Enumeration
Inhalants
Anesthetic gasses
Industrial solvents
Aerosol propellants
Organic nitrates
Stimulant that causes psychoactive effects, alcohol-like intoxications, slurred speech, and loss of motor coordination
Inhalants
Anesthetics
Examples of Anesthetics
Nitric Oxide (N2O)
Ether & Chloroform
% use of Nitric Oxide that can lead to death
35%
Inhalants
Examples of Industrial Solvents
Gasoline
Toluene
Benzene
Trichloro-ethylene
Stimulants
Inhalant that causes euphoria, “drunk” feeling, disorientation, and slow passage of time
Industrial solvents
Inhalant that causes dizziness, rapid heart rate, lowered blood pressure, and “speeding” (flushing of skin)
Organic Nitrates
Enumeration
Toxicities of Inhalants (4)
Liver, kidney, peripheral nerve, and brain damage
Bone marrow suppression
Pulmonary disease
Death
What schedule are anabolic steroids?
Schedule III
True or False
Anabolic steroids causes hirsutism in males and gynecomastia in females
False
Hirsutism - females; Gynecomastia - males
Melatonin receptor agonists
Ramelteon
Tasimelteon
Orexin antagonists that improve sleep duration
Suvorexant
Lemborexant
A slow-onset anxiolytic agent
Buspirone
Cannabinoids
Marijuana is derived from?
Cannabis sativa
Cannabinoids
The addictive component of marijuana
Tetrahydrocannabinol (THC)
Enumeration
Cannabinoids in Cannabis sativa with proven therapeutic effects (3)
Cannabinol
Tetrahydrocannabinol (THC)
Cannabidiol
What schedule is Marijuana?
Schedule I
The following are effects of?
Antiemetic (prevents nausea and vomiting)
Tolerance
Uncertain effects on fetus
Amotivational syndrome
Diseases related to smoking
Marijuana
Cannabinoids
Bodily effects of Cannabis on the eyes
Reddening
Decreased intra-ocular presure
Bodily effects of Cannabis on the mouth
Dryness
Bodily effects of Cannabis on the skin
Sensation of heat or cold
Bodily effects of Cannabis on the heart
Increased heart rate
Bodily effects of Cannabis on the muscles
Relaxation
Enumeration
FDA approved cannabinoids
Dronabinol
Nabilone
Nabiximol
FDA approved cannabinoid used for Chemotherapy Px
Nabilone
Enumeration
Hallucinogens
Lysergic Acid Diethylamide (LSD)
Phencyclidine (PCP)
Ketamine
Scopolamine
Hallucinogens
LSD is derived from?
Claviceps purpurea
Hallucinogens
Mescaline is derived from?
Lophophora williamsii
Hallucinogens
Psilocybin is derived from?
Psilocybe mushroom
Hallucinogens
Synthetic agent related to ergot alkaloids
LSD
Hallucinogens
LSD is an agonist of what serotonin receptors?
5-HT1a
5-HT1c
Hallucinogens
One of the most potent drugs (1ug/kg)
LSD
Hallucinogen responsible for waxing and waning effects
LSD
True or False
LSD is fatal
False
Absence of known fatalities (non-fatal)
The following are effects of what hallucinogen?
Uterine contractions
Elevated sugar levels
Goosebumps
Pupil dilation
Rise in body temperature
LSD
The following are effects of what hallucinogen?
Mydriasis
Muscle relaxation
Dizziness
Psilocybin
Hallucinogen that is restricted but allowed occasionally to North American Indians as herbal medication
Mescaline
Hallucinogens
“Special K” or “Vitamin K”
Ketamine
Hallucinogens
Ketamine route of administration
Intravenous administration
The following are effects of what hallucinogen?
Dream-like states
Delirium
Amnesia
High blood pressure
Depression
Fatal respiratory problems
Ketamine
Veterinary anesthetic
Self-administered by animals
Called “Angeldust”
Phencyclidine
Hallucinogens
NMDA antagonist
Phencyclidine
The following are effects of what hallucinogen?
Olney’s lesions
Violent and suicidal tendencies
“Bad-trips”
Phencyclidine
Hallucinogens
Scopolamine is derived from?
Hyoscyamus niger
Central muscarinic receptor blocker
Scopolamine
Known as “Devil’s breath”
Causes anterograde amnesia
Scopolamine
Cocaine is derived from?
Erthroxylon coca
Affects the dopaminergic reuptake transmitter
Inhibits reuptake of dopamine and NE
Cocaine
Cocaine half-life
1 hour
Repeated every 30 mins
The following are effects of what drug?
Feeling of bugs under skin
Paranoia and schizophrenia-like state
Exhaustion by lack of sleep and food
Cocaine
Enumeration
Drugs that interfere with dopamine reuptake
Cocaine
Amphetamine
Ecstasy (MDMA)
Drugs that disinhibit dopamine neurons
Opioids
Cannabinoids
Gamma-Hydroxybutyric Acid (GHB)
Benzodiazepines
Drugs with multiple mechanisms of action
Alcohol
Inhalants
