20) Drugs of Abuse Flashcards
Physical (physiologic) versus psychological dependence (old/new terms)
- Physical (physiologic) = dependence
- Psychological = addiction
Addiction (definition)
- Compulsivedrug usingbehavior
- Personalsatisfaction
- Formerly psychological dependence
Dependence (definition)
- Signsandsymptoms (frequentlyoppositeofthosecausedbyadrug) when chronic use stops/dose lowers
- Formerlyphysical/physiologicdependence
Tolerance (definition)
- Adecreasedresponsetoadrug
- Necessitateslargerdosestoachievethesameeffect
Dopamine hypothesis of addiction
- Dopamine involved with reward
- Excessive stimulation may cause reinforcement such that the rewarded behavior may become compulsive (common feature of addiction)
- Most addictive drugs involve dopamine effects in the CNS
Neuropharmacologic classification of addictive drugs by primary target (names)
- DA, dopamine
- GABA, γ-aminobutyric acid
- GHB, γ-hydroxybutyric acid
- GPCRs, G-protein-coupled receptors
- THC, Δ9-tetrahydrocannabinol
Schedule I drug criteria
- No medical use
- High addiction potential
Schedule I drug examples
- Flunitrazepam
- Heroin
- LSD
- Mescaline
- PCP
- MDA, MDMA
- STP
Schedule II drug criteria
- Medical usage
- High addiction potential
Schedule II drug examples
- Amphetamines
- Cocaine
- Methylphenidate
- Short acting barbiturates
- Strong opioids
Schedule III drug criteria
- Medical use
- Moderate abuse potential
Schedule III drug examples
- Anabolic steroids
- Barbiturates
- Dronabinol
- Ketamine
- Moderate opioid agonists
Schedule IV drug criteria
- Medical use
- Low abuse potential
Schedule IV drug examples
- Benzodiazepines
- Chloral hydrate
- Mild stimulants (phentermine, sibutramine, etc.)
- Most hypnotics (zaleplon, zolpidem, etc.)
- Weak opioids
Sedativedrug effects/actions
- Decreases activity
- Moderates excitement
- Calms recipient
Hypnotic drug effects/actions
- Produces drowsiness
- Facilitates onset/maintenance of sleep state resembling natural sleep
The sedative-hypnotics include
- Ethanol
- Barbiturates
- Benzodiazepines
Benzodiazepines are commonly prescribed drugs for
- Anxiety
- They are schedule IV
Benzodiazepines and barbiturates MOA/activity
- Indirect GABA-A agonists
- Increase frequency of Cl- channels –> increase hyperpolarization of the membrane
Primary actions of sedative-hypnotics
- Facilitate effects of GABA
- Also enhance brain dopaminergic pathways (possibly related to the development of addiction)
Sedatives and hypnotics effects
- CNS depressants
- Effects are enhanced by concomitant use of ethanol and/or opioid analgesics
Acute overdoses on sedatives and hypnotics commonly result in death via
- Depression of medullary respiratory and cardiovascular centers
Flunitrazepam(Rohypnol/date rape drug)
- Potent, rapid-onset benzodiazepine
- Marked amnestic properties
Flunitrazepam (Rohypnol) added to alcoholic beverages
- Chloral hydrateorf-hydroxybutyrate(GHB; sodium oxybate)
- Sufficient dosage renders the victim incapable of resisting rape
Types of benzodiazepines and half lives
- Short (less than 12 h)
- Intermediate (12-24 h)
- Long (more than 24 h)
- Benzodoazepine-like drugs (more selective to GABA)
Short acting benzodiazepines
- Midazolam
- Triazolam (Halcion)
- Alprazolam (Xanax)
- Oxazepam
Short acting benzodiazepines indications
- Procedural sedation
- Anesthesia induction
- Sleep-onset insomnia
- Very high potential for dependence
Intermediate benzodiazepines indications
- Sleep onset and sleep maintenance
- Anxiety disorders
- High to very high potential for dependence
Intermediate benzodiazepines
- Temazepam (Restoril)
Long acting benzodiazepines
- Lorazepam (Ativan; some classify it as intermediate because it has the shorted of the long acting)
- Diazepam (Valium)
- Clonazepam (Klonopin)
- Chlordiazepoxide (Librium)
- Tetrazepam
Long acting benzodiazepines indications
- Anxiety and panic attacks
- Stress disorders
- Night
- Seizures
- Muscles relaxation
- Epilepsy
- Alcohol withdrawal symptoms
- High potential for dependence
Benzodiazepine-like drugs
- Zolpidem (Ambien) (4h)
- Zaleplon (Sonata) (1h)
- Eszopiclone
- Lunesta (6h)
Benzodiazepine-like drugs indications
- Sleep disorders
- High potential for dependence
Benzodiazepine side effects
- Drowsiness, sleepiness, ordizziness
- Increased appetite
- Next-day hangover effect
- Anterograde amnesia
- Drug tolerance
- Paradoxical excitability (increase irritability in elderly)
Benzodiazepine contraindications
- Myasthenia gravis
- Narrow angle glaucoma
Benzodiazepine overdose symptoms
- CNS depression
- Respiratory depression
- Hypotension
- Ataxia
Benzodiazepine overdose antidote
- Flumazenil
Benzodiazepine withdrawal symptoms
- Sweating
- Nausea, vomiting, andanorexia
- Hypertension
- Seizures
- Tremors
- Memory impairment
- Psychosis, hallucinations
- Depressive moods
Types of barbiturates and their half lives
- Ultra short (15min - 3h)
- Short (3-6h)
- Intermediate (6-12h)
- Long (12-24h)
Ultra-short acting barbiturates
- Methohexital
- Thiopental
Ultra-short acting barbiturates indications
- General anesthesia
- Status epilepticus
- Decrease increase pressure for brain edema
- Sedation
Short acting barbiturates
- Pentobarbital
- Secobarbital
Short acting barbiturates indications
- Short term insomnia
- Pre-anesthetic anesthesia
Intermediate acting barbiturates
- Amobarbital
- Butalbital
- NOT USED (no indications)
Long acting barbiturates
- Phenobarbital
- Primidone
Long acting barbiturates indications
Phenobarbital
- Seizures
- Ethanol withdrawal
- Pre-anesthetic sedation
Primidone
- Seizures
- Tremors
Barbiturate side effects
- Hypotension
- Respiratory depressionand/orapnea
- Laryngospasm,bronchospasm(due tohistaminerelease)
- Painful injection
- Dependence
- Cytochrome P450induction
Barbiturate overdose symptoms
- Impaired consciousness
- Coma
- Respiratory failure
- Cardiovascular depression
Barbiturate overdose antidote
- Sodium bicarbonate(NaHCO3)
Barbiturates contraindications
- Myasthenia gravis
- Asrgma
Primary targets underlying the actions of the opioid analgesics
- µ, κ, and δ receptors
Opioids have other actions including
- Disinhibition in dopaminergic pathways in the CNS
The most abused drugs in the opioid group
- Heroin
- Morphine
- Codeine
- Oxycodone
- Meperidineandfentanyl (among health professionals)
Opioid overdose is managed with
- Parenteral naloxone or nalmefene
- Ventilatory support
When opioids binds to opioid receptors, it stimulates
- Potassium (K) conductance
- Prevents AP and inhibits calcium conductance
- Prevents release of NTs glutamate and substance P
Stimulants
- Caffeine and nicotine
- Amphetamines
- Cocaine
Action of cocaine in the CNS
- Blocks uptake of dopamine, noradrenaline, and serotonin
- Blocking thedopamine transporter (DAT) by increasing dopamine concentrations in the nucleus accumbens has been implicated in the rewarding effects of cocaine
Action of amphetamines
- Substrate of the DAT
- Competitively inhibits DA transport
- In the cell, interferes with the vesicular monoamine transporter (VMAT) and impedes the filling of synaptic vesicles
- Thus vesicles are depleted and cytoplasmic DA increases
- Leads to a reversal of DAT direction, strongly increasing nonvesicular release of DA, and further increasing extracellular DA concentrations
Caffeine and nicotine overdose effects
- Excessive CNS stimulation with tremor, insomnia, and nervousness
- Cardiac stimulation and arrhythmias
- Respiratory paralysis (nicotine)
Caffeine withdrawal symptoms
- Lethargy
- Irritability
- Headache
Nicotine withdrawal symptoms
- Anxiety
- Mental discomfort
Amphetamines (Adderall) MOA
- Alter transporters of CNS amines including dopamine, norepinephrine, and serotonin, and increase their release
Amphetamine overdose effetcs
- Agitation
- Restlessness
- Tachycardia
- Hyperthermia
- Hyperreflexia
- Possibly seizures
Amphetamine withdrawal symptoms
- Increased appetite
- Sleepiness, exhaustion
- Mental depression
- Treatment: anti-depressant
- Chronic high-dose abuse leads to a psychotic state (with delusions and paranoia); necrotizing arteritis, leading to cerebral hemorrhage and renal failure.
Cocaine MOA
- Inhibitor of the CNS transporters of dopamine, norepinephrine, and serotonin
- Has marked amphetamine-like effects (“super-speed”); euphoria, self-confidence, and mental alertness
Cocaine overdose effects
- Cardiac toxicity is partly due to blockade of norepinephrine reuptake by cocaine
- Local anesthetic action contributes to the production of seizures
- Vasoconstriction may lead to severe hypertensive episodes, resulting in myocardial infarcts and strokes
Cocaine withdrawal symptoms
- Severe depression of mood is common and strongly reinforces the compulsion to use the drug
Phencyclidine (PCP, “angel dust”) and ketamine (“special K”)
- Hallucinogens known as ‘club drugs’
- Non-competitive antagonists at the glutamate NMDA receptor (excitatory synapse)
- No actions on dopaminergic neurons in the CNS
PCP effects and dangers
- Most dangerous of the hallucinogenic agents
- Psychotic reactions, impaired judgment often leads to reckless behavior
PCP overdose effetcs
- Marked hypertension, and seizures which may be fatal.
Miscellaneous hallucinogenic agents
- Lysergic acid diethylamide(LSD)
- Mescaline
- Psilocybin
Miscellaneous hallucinogenic agents actions
- None of these drugs act on dopaminergic pathways in the CNS
- Do not cause dependence
LSD actions
- Activates the serotonin 5-HT2Areceptor in the prefrontal cortex
- Enhances glutamatergic transmission onto pyramidal neurons
- Excitatory afferents mainly come from the thalamus constitute a link to enhanced perception
Perceptual and psychological effects of LSD
- Somatic effects, particularly nausea, weakness, and paresthesias
- Panic reactions (“bad trips”) may also occur
Marijuana
- Psychoactive constituents in crude extracts of the cannabis plant
- Include the cannabinoid compoundstetrahydrocannabinol (THC),cannabidiol (CBD),and cannabinol (CBN)
- Hashishis a partially purified material that is more potent
Marijuana products disinhibition actions
- Disinhibition of dopamine neurons
- Mainly by presynaptic inhibition of GABA neurons in the brainstem
Two types ofcannabinoid receptors
- CB1 receptor
- CB2receptor
- Both areG protein-coupled receptors
CB1receptor
- Found primarily in the brain
- Also in some peripheral tissues
CB2receptor
- Found primarily in peripheral tissues
- Also expressed inneuroglial cells
THC appears to alter mood and cognition through
- Agonist actions on the CB1receptors leading to Dopamine release
CNS effects of marijuana
- Feeling of being “high,” with euphoria, uncontrollable laughter, changes in perception, and achievement of a dream-like state
- Vasodilation occurs, and the pulse rate is increased
- Habitual users show a reddened conjunctiva
Marijuana and withdrawal
- Withdrawal state has been noted only in heavy users of marijuana
- The dangers of marijuana use concern its impairment of judgment and reflexes
Potential therapeutic effects of marijuana
- Ability to decrease intraocular pressure
- Antiemetic actions
Dronabinol
- A controlled-substance formulation of THC
- Used to combat severe nausea
Rimonabant
- An inverse agonist that acts as an antagonist at cannabinoid receptors
- Approved for use in the treatment of obesity
Anabolic steroids
- Controlled substances based on their potential for abuse
- Effects sought by abusers are increase in muscle mass and strength rather than euphoria
Excessive use of steroids can have adverse effects
Anticipated androgenic adverse effects
- Acne
- Premature closure of the epiphyses
- Masculinization in females are
- Hepatic dysfunction has been reported
- Anabolic steroids may pose an increased risk of myocardial infarction
Behavioral manifestations of excessive steroid use
- Increases in libido
- Aggression (“road rage”)
Signs withdrawal syndrome associate with steroid use
- Fatigue
- Depression of mood
Classes of drugs that treat dependence and addiction
- Opioid antagonists
- Synthetic opioid
- Partial μ-receptor agonist
- N-receptor partial agonist
- Benzodiazepines
- NMDA receptor antagonist
- Cannabinoid receptor antagonist
Opioid antagonists
- Naloxone
- Naltrexone
Synthetic opioids
- Methadone
Partial μ-receptor agonists
- Buprenorphine
N-receptor partial agonists
- Varenicline
Benzodiazepines
- Oxazepam
- Lorazepam
NMDA receptor antagonists
- Acamprosate
Cannabinoid receptor agonists
- Rimonabant
Naloxone MOA/effects/clinical impact
- Antagonists of opioid receptors
- Reverse or block effects of opioids
- Opioid overdose
Naloxone characteristics
- Short half-life (1–2 h)
Naltrexone clinical impact/characteristics
- Treatment of alcoholism
- Half-life like morphine (4h)
Methadone MOA/effects/clinical impact
- Slow-acting agonist at μ opioid receptors
- Acute effects like morphine
- Substitution therapy for opioid addicts
Methadone characteristics
- Variable but longer half-life
- Toxicity: Like morphine regarding acute and chronic effects including withdrawal
Buprenorphine MOA/effects/clinical impact
- Partial agonist at μ opioid receptors
- Attenuates acute effects of morphine and other strong opioids
- Substitution therapy for opioid addicts
Buprenorphine characteristics
- Long half-life (>40 h)
- Formulated with nalorphine to avoid illicit IV use
Varenicline MOA/effetcs/clinical impact
- Partial agonist at AChNreceptor subtype
- Blocks rewarding effects of nicotine
- Smoking cessation
Varenicline characteristics
- Nausea and vomiting
- Psychiatric changes
- Seizures in high dose
Oxazepam and lorazepam MOA/effects/clinical impact
- Modulators of GABA A receptors
- Enhance GABA functions in the CNS
- Attenuate withdrawal symptoms including seizures fromalcoholand other sedative-hypnotics
Oxazepam and lorazepam characteristics
- Half-life 4–15 h
- Lorazepam kinetics not affected by liver dysfunction
Acamprostate MOA/effects/clinical impact
- Antagonist at glutamate NMDA receptors
- May block synaptic plasticity
- Treatment of alcoholism
Acamprostate characteristics
- Allergies, arrhythmias, variable BP effects
- Headaches
- Impotence
- Hallucinations in elderly
Rimonabant MOA/effects/clinical impact
- Inverse agonist at CB1 receptors
- Decrease GABA and glutamate release in CNS
- Treatment of obesity
Rimonabant characteristics
- Major depression
- Increased suicide risk
Amphetamines,methylphenidate, cocaine overdose effects
- Agitation
- Hypertension,tachycardia
- Delusions,hallucinations
- Hyperthermia
- Seizures,death
Common cocaine overdose effects
- Cardiacarrhythmias
- Myocardialinfarction
- Stroke
Amphetamines,methylphenidate, cocaine withdrawal symptoms
- Apathy,irritability
- Increasedsleeptime
- Disorientation
- Depression
Barbiturates,benzodiazepines, ethanol overdose effects
- Slurredspeech,drunkenbehavior
- Dilatedpupils
- Weakandrapid pulse
- Clammyskin
- Shallowrespiration
- Coma,death
Barbiturates,benzodiazepines, ethanol withdrawal symptoms
- Anxiety
- Insomnia
- Delirium, tremors (excited hallucinatory state associated with ethanol)
- Seizures
- Death
Heroin, other strong opioids overdose effects
- Constrictedpupils
- Clammyskin
- Nausea
- Drowsiness
- Respiratory depression
- Coma,death
Heroin, other strong opioids withdrawal symptoms
- Nausea
- Chills,cramps
- Lacrimation,rhinorrhea
- Yawning
- Hyperpnea
- Temor, muscle jerks
