UNIT 9: DRUG OF ABUSE Flashcards by lab rat

Drugs that activate G-protein-coupled receptors (GCPRs)

Class 1

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Drugs that bind to ionotropic receptors or ion channels

Class 2

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Drugs that bind to biogenic amine transporters

Class 3

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Enumeration

Class 1 Drugs

Opioids
Cannabinoids
THC
GHB
LSD
Mescaline
Psilocybin

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Enumeration

Class 2 Drugs

Benzodiazepines
Nicotine
Ethanol
Alcohol
Ketamine
PCP
Inhalants

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Enumeration

Class 3 Drugs

Cocaine
Amphetamine
Ecstacy (MDMA)

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Strong analgesics, narcotic

Opioids

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Naturally-occuring alkaloids

Opiates

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Enumeration

Opiates

Morphine
Codeine
Thebaine
Papaverine

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Enumeration

Opioid receptor subtypes

μ (mu)
δ (delta)
κ (kappa)

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This opioid receptor subtype causes inhibition of respiration

μ (mu)

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Which opioid receptor subtype has a strong affinity to Dynorphins

κ (kappa)

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This opioid receptor subtype causes psychotomimetic effects and slowed gastrointestinal transit

κ (kappa)

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Natural painkillers in the body with varying affinity to the three types of opioid receptors

Endogenous peptides

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The following acts as agonists of the κ (kappa) receptor, except one:

Morphine
Sufentanil
Butorphanol
Nalbuphine
Buprenorphine
Pentazocine

Buprenorphine

Antagonist

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Opium is derived from

Scientific name

Papaver somniferum

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The principal active ingredient of opium

Morphine

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The only antagonist of the μ (mu) receptor

Nalbuphine

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Powerful narcotic that causes histamine release

Opium

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Smack
H
Ska
Junk

Heroin

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Street drug of abuse of opioids

Heroin

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An addictive drug as a white or brown powder, IV injected

Heroin

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Half-life of Heroin

3-5 hours

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Withdrawal time of Heroin

5-10 hours after

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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

UNIT 9: DRUG OF ABUSE Flashcards

(249 cards)