Drugs of Abuse Flashcards
Abuse
Excessive self-administration of any substance for nonmedical purposes
Addiction
Use of substance that alter perception & cause a sensation of reward & euphoria
- Impaired control over drug use
- Compulsive use
- Continued use despite harm
- Craving
Dependence
State of adaptation manifested by drug class specific withdrawal syndromes
Withdrawal syndrome
physiological & behavioral changes directly related to sudden cessation or reduction in use of drug to which the body has become adapted to.
Causes of Withdrawal syndrome
- Abrupt cessation
- Rapid dose reduction
- Antagonist administration
Tolerance
State of adaptation in which exposure to drug induces changes that result in a diminution of 1/more of the drug effects over time
- Can occur to both the desired & undesired effects of drugs
- May develop at different rates for different effects
Mechanism of Addiction
Activation of the Mesolimbic Dopamine pathway
Classes of Drugs of abuse based on how Dopamine levels are increased
- Inc DA release indirectly by inhibiting GABA neurons that act as local inhibitory interneurons
- Opioids, cannabinoids, Benzos & ethanol - Directly stimulate dopaminergic neurons
- Nicotine & ethanol - Block or reverse DAT
- Cocaine, amphetamines & MDMA
Classes of Drugs of Abuse
- CNS depressants
- Psychostimulants
- Nicotine
- Opioids
- Marijuana
- Psychedelic agents
- Inhalants
- Anabolic steroids
CNS Depressants (Classes/ names)
- Ethanol
- Benzos
- Barbituates
Why is ethanol classified as a CNS depressant?
its initial effects are perceived as stimulation due to the suppression of inhibitory systems BUT it eventually produces Sedation & Sleep
MOA of Ethanol
Affects:
- GABAa receptors
- Kir3/ GIRK channels
- Adenosine reuptake
- Glycine receptors
- NMDA receptors
- 5HT3 receptors (vomiting)
How does Alcohol/Ethanol increase DA?
Ethanol causes release of Endorphins from the Endorphinergic neurons –> Activates u-receptors –> Inhibits GABAergic interneurons –> Inc DA release
Drugs used to treat Alcohol addiction
- Disulfiram
- Naltrexone
- Acamprosate
- Topiramate (NOT FDA approved)
Disulfiram
Inhibits Aldehyde dehydrogenase
- Creates an aversion to drinking because if ethanol is consumed w/ disulfiram the aldehyde accumulates –> Nausea, headache, flushing & hypotension
Naltrexone
Opioid antagonist- blocks activation of u-receptors –> Dec DA release
- Reduce the craving for alcohol & dec. relapse to heavy drinking
Acamprosate
Unclear mechanism - Blocks Hyper-glutamatergic state in alcoholic brain
NMDA receptor antagonist - Prevent relapse drinking
Topiramate
- Inc GABA function
- Antagonize Glutamate receptors
May reduce cravings
NOT FDA approved
Alcohol Withdrawal Syndrome
- Tremor
- Nausea
- Sweating
- Agitation
- Anxiety
- Hallucinations
- Generalized seizures (24-48hrs)
- Delirium tremens (48-72hrs) - 5-15% mortality
Treatment of Alcohol Withdrawal
Long-term Benzos - Diazepam & Chlordiazepoxide (DOC)
Intermediate-acting Benzos - Lorazepam & Oxazepam (DOC in elderly & pts. w/ liver failure)
Benzodiazepine Withdrawal Syndrome
- Tremors
- Anxiety
- Perceptual disturbances
- Dysphoria
- Psychosis
- Seizures
(Life-threatening)
Benzo Withdrawal Syndrome Management
If pt. is on a short-acting benzo –> Switch to long-acting (DIAZEPAM) –> Gradually reduce dose
Barbiturates Abuse
Similar to that of Benzos
Psychostimulants (Class/ names_
- Methylxanthines
- Caffeine, Theophylline & Theobromine - Cocaine
- Amphetamines
Methylxanthine MOA
Blocks presynaptic Adenosine receptors –> Inc. NE release
Normally, activation of Adenosine receptors inhibits NE release
CNS Effects of Methylxanthines
100-200 mg - Dec fatigue - Inc mental alertness 1.5g - Anxiety - Tremors 2-5g - Spinal cord stimulation
Methylxanthines Tolerance & Withdrawal
Tolerance- rapidly develop
Withdrawal - Fatigue & sedation
Addiction- Rare
Cocaine DEA classification
Schedule 2 (due to its abuse potential)
MOA of Cocaine
Inhibits DA, NE & 5TH reuptake (prolonged dopaminergic effect –> Intense euphoria)
Cocaine CNS Actiosn
- Stimulated cortex & brainstem
- Inc mental awareness
- Feeling of well-being & Euphoria
- Paranoia (repeated doses)
- Tremor & convulsions –> Resp. & Vasomotor depression (High doses)
Cocaine SNS Actions
- Tachycardia
- HTN
- Mydriasis
- Diaphoresis
These are due to the adrenergic stimulation by NE
Cocaine addiction Treatment
- Antidepressants
- Dopamine agonists
Cocaine Withdrawal Syndrome
- Dysphoria
- Depression
- Sleepiness
- Fatigue
- Cocaine craving
- Bradycardia
Withdrawal is generally mild and symptoms are treated are they appear.
DEA Classification of Amphetamine
Schedule 2
MOA of Amphetamines
Taken into neurons by Biogenic Amine Transporters –> Interferes w/ VMAT –> Deplete synaptic vessels –> Inc in cytoplasmic levels of DA & other transmitter amines –>Reversal of DAT –> DA release into synapse
- Inc catecholamine levels
- Weak MAOI
- Direct catecholaminergic agonists in brain
Actions of Amphetamines
CNS (DA release)
- Behavioral effects similar to cocaine
- Inc alertness & insomnia
- Depressed appetite
- Psychosis & convulsion (high does)
SNS
- Activate receptors through NE release
Uses of Amphetamines
Amphetamine + Methylphenidate
- Attention Deficit Syndrome
- Narcolepsy
Amphetamine Withdrawal Symptoms & Treatment
- Inc appetite
- Sleepiness
- Exhaustion
- Mental depression
Tx = Antidepressants
MOA of Nicotine
Full Nicotine receptor agonists
Ventral tegmental area (VTA) nicotinic receptors are expressed on DA neurons
Nicotine excites neurons –> DA release
Actions of Nicotine
CNS
LOW DOSE - Ganglionic stimulation by depolarization
- Euphoria & relaxation
- Improves attention, learning, problem solving & reaction time
- Restlessness
HIGH DOSE - Ganglionic blockade
- Central Resp. paralysis
- Severe hypotension (medullary paralysis)
- Appetite suppressant
Treatment of Nicotine Addiction
- Nicotine replacement therapy
- Transdermal patch, gum, nasal spray, vapor inhaler or lozenge for buccal absorption - Sustained-release Bupropion
- MOA unclear - Varenicline
- Partial Nicotinic receptor agonist in the CNS
- Dec reward of smoking
Nicotine Withdrawal Syndrome
- Irritability
- Sleeplessness
- Anxiety
- Dec concentration
- Inc appetite/ weight gain
Withdrawal is mild but relapse is very common
Opioids (names)
- Heroin
- Morphine
- Codeine
- Oxycodone
Opioid Intoxication
- Euphoria
- Resp & CNS depression
- Dec gag reflex
- “Pinpoint pupils”
- Seizures
- Dec GI motility
Opioid Withdrawal Syndrome
- Dysphoria
- Lacrimation
- Rhinorrhea
- Yawning
- Stomach cramps, nausea & diarrhea
- Dilated pupils
- Sweating
- Piloerection
Unpleasant but not life-threatening
Opioid Tolerance & Dependence
Strong tolerance & dependence
addiction to heroin (& other short-acting opioids) produces behavioral disruptions & is usually incompatible w/ a productive life
MOA for Treating Opioid Withdrawal Syndrome
- Detoxification w/ Opioid agonists
- METHADONE or BUPRENORPHINE
- Illicit agent replaced w/ long-acting opioid and then the dose is slowly reduced - Detoxification w/ Opioid antagonist
- NALTREXONE (antagonist w/ high affinity for u-receptor)
- Used after detox in pts. that really wants to remain opioid-free
- Will NOT satisfy craving or relieve withdrawal symptoms
Marijuana (smoking)
61 different cannabinoids release
- Δ9-tetrahydrocannabinol
MOA of Marijuana
Cannabinoid receptors = CB1 (GABAergic neurons in VTA of Brain) & CB2 (Immune cells)
- G-protein-linked receptors coupled to Gi
THC binds to CB1 –> Dec GABA –> No inhibition of dopaminergic neurons –> Inc DA release
Actions of Marijuana
- Euphoria –> Drowsiness & Relaxation
- Conjunctival injection
- Affects short-term memory & mental activity
- Impaired judgement
- Perception of slowed time
- Social withdrawal
- Impairs highly skilled motor activity
- Stimulate appetite
- Xerostomia
- Visual hallucination & delusion
- Enhancement of sensory activity
- Toxic psychosis (HIGH DOSE)
Withdrawal syndrome of Marijuana
- Irritability
- Anxiety
- Depression
- Insomnia
- Restlessness
- Dec appetite
Tolerance & Dependence of Marijuana
Mild
FDA-approved Cannabinoids for medical use (names)
- Nabilone (Synthetic THC derivative)
- Dronabinol (Synthetic form of THC)
- Cannabidiol (CBD)
Medical uses of Marijuana
Dronabinol & Nabilone
- Nausea & vomiting associated w/ cancer chemotherapy in pts. who failed to respond to conventional antiemetic treatments
- Anorexia associated w/ weight loss in pts. w/ AIDS (DRONABINOL ONLY)
CBD
- seizures associated w/ Lennox-Gastaut syndrome, Dravet syndrome or Tuberous sclerosis complex
Psychedelic agents (names)
LSD-like drugs
- LSD
- Mescaline
- Psilocybin
- Phencyclidine
- MDMA
Psychedelic agents (names)
LSD-like drugs
- LSD
- Mescaline
- Psilocybin
- Phencyclidine
- MDMA
What features are affected by Psychedelics?
- Thought
- Perception
- Mood
Does NOT cause marked psychomotor stimulation or depression
MOA of LSD
5HT2 receptor agonist –> Hallucinogenic effects
CFs of LSD use
Combination of Somatic (Sympathomimetic effects) & Psychomimetic symptoms
- Mydriasis
- HTN
- Tachycardia
- Flushing
- Sweating
- Tremors
- Piloerection
- Perceptual distortion
- Depersonalization
- Anxiety & Paranoia
- Flashbacks
LSD Dependence & Withdrawal
NO addiction or withdrawal
Adverse effects of LSD
“Bad trips”
Severe agitation – Tx is Diazepam
MOA of Phencyclidine (PCP)
Dissociative anesthetic
Blocks NE & DA reuptake
- Cholinergic & Anticholinergic effects
- Nicotinic effects
- Opioid receptor actions
Non-competitive antagonist of NMDA receptors
- Dissociative properties
CFs of PCP
- Violent or bizarre behavior
- Psychosis
- Delirium
- Seizures
- Impulsivity
- Tachycardia
- HTN
- Diaphoresis
- Miosis
- Anesthesia
- Analgesia
- NYSTAGMUS (important diagnostic clue)
PCP treatment
NO antidote
Extreme violence & seizures
- Sedation w/ parenteral Benzos
MDMA “Ecstasy” MOA
Causes release of Biogenic amines —> Inc 5HT conc in synaptic cleft
MDMA CFs
Feelings of empathy & intimacy - Euphoria - Hallucinations - Disinhibition - Hyperactivity - Inc thirst - Social withdrawal - Distorted sensory & time perception - Mydriasis - Bruxism - teeth grinding/clenching NO Intellectual impairment
Life-threatening effects of MDMA
- HTN
- Tachycardia
- Hyperthermia
- Hyponatremia
- Serotonin syndrome
Withdrawal Syndrome of MDMA
- Depression (lasting several weeks)
- Fatigue
- Appetite changes
- Difficulty concentrating
- Anxiety
Inhalants (Classes/ Names)
- Nitrous Oxide
- Volatile organic solvents
- Gasoline, paint thinners, lighter fluid, glue & degreasers - Organic nitrates
- Amyl nitrate & Butyl nitrate
Nitrous oxide
34% N2O + O2
- Euphoria
- Analgesics –>
- Loss of consciousness
100% N20
- Asphyxia –>
- Death
Volatile Organic Solvents
- Sense of exhilaration & light-headedness
- Implicated in cancer, cardiotoxicity, neuropathies & hepatotoxicity
(Gasoline, lighter fluid, glue, paint thinner & degreaser)
Organic Nitrites
Amyl nitrite & Butyl nitrite
- Enhance Erection
NOT addictive
Anabolic Steroids
Inc muscle mass
Opioid overdose treatment
Naloxone
Overdose usually results in death
Naloxone vs Naltrexone
Naloxone
- Overdose
Naltrexone
- Withdrawal treatment
