Drug of Abuse
No medical indication
Euphoria
Altered perception
“Compulsive”
Dependence
Physical
Tolerance
Withdrawal Syndrome
Non-psychoactive drugs
you need the drug to function
Addiction
Psychological
Compulsion
Relapsing
Craving
you don’t need the drug to function
Mesolimbic Dopamine System
Reward (motivation)
Pleasure, euphoria
mPFC - Motor function (fine tuning)
Compulsion
Preservation
Drugs of abuse are associated with the increase of dopamine
Class 1: GPCRs
Opioids, THC, GHB
Class 2: Channels
Benzodiazepines, Nicotine,, Ethanol
ionic channels
Class 3: Transporters
Cocaine, Amphetamine, Ecstasy
protein transporters for reuptake, storage, recycling
Schedule I
Heroin, Lysergic acid diethylamide
High potential for abuse, no known medical use and lacks accepted safety for use
Schedule II
morphine, cocaine, methadone, methamphetamine, phencyclidine
Potential for abuse with proven and accepted medical use but with severe restrictions, because abuse may cause severe psycho/physio dependence
Schedule III
Anabolic steroids, codeine and hydrocodone, with aspirin or Tylenol
Less potential for abuse than schedule I or II
moderate or low physical dependence or high psychological dependence
Schedule IV
Valium and Xanax
a low potential for abuse relative to the drugs or other substances in Schedule III
limited physical dependence or psychological dependence
Schedule V
Cough syrups and codeine
low potential for abuse relative to the drugs or other substances in Schedule IV
Pharmacokinetic Tolerance
Reduction of concentration that reaches the binding sites/receptors
Shorter duration of action
Pharmacodynamic Tolerance
drug receptor interaction
binds somewhere instead of target receptor
β-arrestin
binds to G-protein coupled receptors, decreasing its response to the presence of the drug
Desensitization
receptor becomes immune or nonreactive to the drug present in it
Receptor internalization
receptors are taken down from the cell membrane
hide receptors to modulate
imbalance of neurotransmitters
if you immediately withdraw the endogenous sources, there will be ___
Post Acute Withdrawal Syndrome (PAWS)
Irritability and emotional outbursts, anxiety, low energy, trouble sleeping, memory problems, dizziness, increased accident proneness, and delayed reflexes
Addiction
High motivation to obtain and use the drug
Psychological compulsion to use and feel the effect of the drug besides the negative consequences
Non-Addictive
non-psychotropic
does not affect neurotransmission
Alter perception; no reward/euphoria
hallucinogens
take it just to feel their effects but it is not addictive and compulsion to use
cortical: cerebral cortex and thalamic system
instead of targeting the hypothalamus, the dopaminergic which is the primary mechanism for addiction, it targets ___
Opioids
Cannabinoids
GHB
LSD, Mescaline, Psilocybin
Drugs that Activate G-protein coupled receptors
Nicotine
Benzodiazepines
Alcohol
Ketamine & PCP
Inhalants
Drugs that Bind to Ionotropic receptors
Cocaine
Amphetamines
Ecstasy (MDMA)
Drugs that Bind to Transporters of Biogenic Amines
Opioids
Strong analgesics, painkillers
Opiates
morphine, codeine, thebaine, papaverine
Narcotic
sleep inducing
µ (mu)
Supraspinal and spinal analgesia
sedation
inhibition of respiration
slowed gastrointestinal transit
modulation of hormone and neurotransmitter release
δ (delta)
Supraspinal and spinal analgesia
modulation of hormone and neurotransmitter release
κ (kappa)
Supraspinal and spinal analgesia
psychomimetic effects
slowed gastrointestinal transit
Endorphins > enkephalins < dynorphins
µ (mu)
Endorphins > enkephalins and dynorphins
δ (delta)
Endorphins > > enkephalins and dynorphins
κ (kappa)
Opium
Papaver somniferum
insomnia, hallucination, nightmares
histamine release
plant-derived
powerful narcotic
morphine
painkiller principal active ingredient
Heroin (Smack, H, ska, junk)
diamorphine
white or brown powder
3-5 hrs
T1/2
5-10 hrs after
Withdrawal
thebaine
synthesized from ___
codeine
derived from ___
Meperidine (pethidine; Demerol)
serious interaction with MAO’s
attempts to illicitly produce meperidine has resulted in MPTP which can cause parkinsonism
methyl-phenyl-tetrahydropyridine
MPTP
Periphery
opioids bind to the MOR preventing the transmission of pain signal which is perceived by our sensory receptors
receptors that block Ca channels
reaching the presynaptic terminal in our dorsal horn
prevent the release of neurotransmitter that transmit the pain signals to the postsynaptic
enhancing K+ conductance
Postsynaptically
inhibitory (GABAergic) interneuron
pain-inhibitory neuron is indirectly activated by opioids (exogenous or endogenous), which inhibit ___
results in enhanced inhibition of nociceptive processing in the dorsal horn of the spinal cord
Sedative-hypnotics
Increased central nervous system depression, particularly respiratory depression
Antipsychotic agents
Increases sedation
Variable effects on respiratory depression
Accentuation of cardiovascular effects (antimuscarinic and α-blocking actions)
Monoamine oxidase inhibitors
Relative contraindication to all opioid analgesics because of the high incidence of hyperpyrexic coma
hypertension
Sedative-hypnotics
alcohol, barbiturates, benzodiazepines, gamma-hydroxybutyric acid (GHB)
can be short- to long- acting
the longer the duration the less the withdrawal
Benzodiazepines
increase GABA activity, used for anxiety and insomnia
Barbiturates
enhance GABA activity, used for anesthesia and seizures
Z-drugs
bind to GABA receptors, used for insomnia
Alprazolam
Rapid oral absorption
Chlordiazepoxide & Diazepam
Active metabolites; erratic bioavailability from IM injection
Chlorazepate
Prodrug; hydrolyzed to active form in stomach
Eszopiclone
Minor active metabolites
Flurazepam
Active metabolites with long T1/2
Lorazepam, Oxazepam, Zolpidem
No active metabolites
Temazepam
Slow oral absorption
Triazolam
Rapid onset; slow duration of action
Zaleplon
Metabolized via aldehyde dehydrogenase
Benzodiazepines
rare occurrence of physiologic dependence
Enhance the activity of GABA neurotransmitter
Therapeutic Dose Dependence
weight loss, change in perception, paresthesia, headache
Flunitrazepam: anterograde amnesia
date rape
Rohypnol
roofies
Barbiturates
GABA-A receptors
Short - acting drugs due to the risk of dependence and overdose
Unpredictable
Alcohol
GABA-A and NMDA
euphoria
Gamma Hydroxybutyric Acid
GABA-B
found in the body & in fermented drinks
Georgia homeboy
euphoric, sedative, anabolic
chlordiazepoxide or phenobarbital
Short acting and Long acting drugs
disulfiram, naltrexone
alcohol
Marijuana
Cannabis sativa
cannabinoid receptors (CB1)
antiemetic - prevents vomitting
2-3 inhalations
Amotivational syndrome
tetrahydrocannabinol
addictive component
Hallucinogens
substances that cause hallucinations
Lysergic Acid Diethylamide (LSD)
Claviceps purpurea
synthetic agent related to ergot alkaloids
one of the most potent drugs
5-HT1a & 5-HT1c agonists
Mescaline
Lophophora williamsii
Psilocybin
Psilocybe mushroom (shrooms)
Ketamine
anesthetic primarily in race horses
“special K” “vitamin K”
dream-like states, fatal respiratory problems
Phencyclidine
phenylcyclohexylamine derivative
veterinary anesthetic
antagonize NMDA
Olney’s lesions
long t1/2
Scopolamine
Hyoscyamus niger
block central muscarinic receptors
Cocaine
Erythroxylon coca
inhibit reuptake of dopamine and NE
feeling of bugs under skin, paranoia and schizophrenia like state
1hr, repeated 30 min
t1/2
Amphetamines
alpha-methyl-phenethylamine
increase catecholaminergic neurotransmitters
dopamine not be metabolized thus released
antiobesity drugs
treats narcolepsy and ADHD
Ecstasy
Methylene-dioxymethamphetamine (MDMA)
intimacy and empathy
“raves” designer drug
Stimulants
reverse the effects of fatigue on both mental and physical tasks
Nicotine (Nicotiana tobacum)
tobacco products
nicotinic cholinergic receptor agonist
strong psychological and physiological dependence
Caffeine (1,3,7-trimethylxanthine)
coffee, tea, some soft drinks, and many non-prescription medicines
xanthine alkaloid from Coffea arabica
adenosine receptors
Inhalants
psychoactive effects
alcohol-like intoxications, hallucinations
anesthetic gases
difficulty in concentrating, dreaminess, euphoria, numbness, tingling
N2O= 35% used; 100% death
ether & chloroform
industrial solvents
gasoline, toluene, benzene, trichloro-ethylene
5-15 min
euphoria, “drunk” feeling, disorientation slow passage of time
organic nitrites
amyl nitrite, isobutyl nitrite
dizziness, rapid heart rate, lowered BP, “speeding,” flushing of skin
enhance, prolong erection
Anabolic Steroids
Synthetic substances that mimic the effects of testosterone in the body.
cyclopentanoperhydrophenanthrene ring
bone growth, appetite, puberty, muscle growth
change in libido, irritability, violence, mood swings, forgetfulness, confusion
fatigue, depressed mood, craving for steroids
hypertrophied muscles, acne, oily skin, hirsutism in females, gynecomastia in males, needle punctures
high LDL; low HDL
elevated liver function