Drugs Of Abuse DSA Flashcards
Define abstinence syndrome
Signs and symptoms that occur on withdrawal of drug in a dependent person
Define addiction
Compulsive drug-using behavior in which person uses drug for personal satisfaction, often in face of known risks to health
Formerly psychological dependence
Define controlled substance. What are the 4 schedules?
Drug deemed to have abuse liability that is listed on governmental schedules of controlled substances
I: no medical use, high addiction potential (flunitrazepam, heroin, LSD, mescaline, PCP, MDA, MDMA, STP)
II: medical use, high addiction potential (amphetamines, cocaine, methylphenidate, short acting barbiturates, strong opioids)
III: medical use, moderate abuse potential (anabolic steroids, barbiturates, dronabinol, ketamine, moderate opioid agonists)
IV: medical use, low abuse potential (benzodiazepines, chloracne hydrate, mild stimulants (phentemine, sibutramine), most hypnotics (zaleplon, zolpidem), weak opioids
Define dependence
State characterized by signs and symptoms, frequently opposite of those caused by drug, when it is withdrawn from chronic use or when dose is abruptly lowered
Formerly physical or physiologic dependence
Describe designer drug
Synthetic derivative of drug, with slightly modified structure but no major change in pharmacodynamic action
Circumvention of Schedules of Controlled Drugs is motivation
Define tolerance
Decreased response to drug, necessitating larger doses to achieve same effect
Can result from increased disposition of drug (metabolic tolerance), ability to compensate for effects of drug (behavioral tolerance), or changes in receptor or effector systems involved in drug actions (functional tolerance)
Dose response curve shifts to right
Define sensitization
Increase in response with repetition of same dose of drug (dose-response curve shifts to left)
define withdrawal
Adaptive changes that become fully apparent once drug exposure is terminated
Generally due to readaptation of CNS to absence of drug of dependence
Evidence of physical dependence
Describe dopamine hypothesis of addiction (DA reward pathway)
Dependence-producing drugs activate mesolimbic DA system, releasing DA
Pleasure-related (hedonic) effect results from activation of this pathway, rather than from subjective appreciation of diverse other effects (such as alertness or disinhibition) that drugs produce
Summarize drugs that activate G-protein coupled receptors
Opioids: targets mu receptor, agonist, disinhibition of DA neurons, highly addictive 4/5
Cannabinoids: CB1R, agonist, disinhibition of DA, 2/5
GHB: GABA receptor, weak agonist, disinhibition of DA
LSD, mescaline, psilocybin: 5HT, partial agonist, 1/5
Summarize drugs that bind to ionotropic receptors and ion channels
Nicotine: nAChR, agonist, excitation of DA, 4/5
Alcohol: GABA/5HT/nAChR/NMDAR, excitation(disinhibition?), 3/5
Benzodiazopines: GABA receptor, positive modulator, disinhibition of DA, 3/5
Phencyclidie, ketamine: NMDAR, antagonist, 1/5
Summarize drugs that bind to transporter of biogenic amines
Cocaine: DAT/SERT/NET, inhibitor, blocks DA uptake, 5/5
Amphetamine: DAT/NET/SERT/VMAT, reverses transport, blocks DA uptake/synaptic depletion, 5/5
Ecstasy: SERT>DAT, NET, reverses transport, blocks DA uptake/synaptic depletion
Describe nonaddictive drugs of abuse. Examples?
Primarily target cortical and thalamic circuits rather than mesolimbic dopamine system and therefore alter perception without causing sensations of reward and euphoria
Examples: LSD, mescaline, psilocybin, PCP, ketamine
Describe lysergic acid diethylamine (LSD), mescaline, psilocybin
Nonaddictive
Repetitive exposure leads to rapid tolerance (tachyphylaxis)
Long term: LSD can cause flashbacks of altered perception years after consumption
Describe phencyclidine (PCP, angel dust) and ketamine (special K)
General anesthetics (ketamine still used) Psychedelic effects last 1 hr and also cause increases BP, impaired memory function, disorientation, nystagmus, and visual alterations Long term: PCP may lead to irreversible schizophrenia-like psychosis
Describe opioids
Activates G-coupled receptors and cause disinhibition of DA neurons
mu, kappa, and delta receptors are G protein-coupled receptors that inhibit adenylyl cyclase when activated
In VTA, mu opioids cause inhibition of GABAergic inhibitory interneurons, which leads to disinhibition of DA neurons
Mu receptors cause euphoria when activated and are implicated in reward effects of opiates (morphine, heroin, codeine, oxycodone, meperidine)
Withdrawal symptoms include intense dysphoria, N/V, muscle aches, lacrimation, rhinorrhea, mydriasis, piloerection, sweating, diarrhea, yawning, fever
Treatment: naloxone, methadone, buprenorphine
Describe naloxone
MOA: pure opioid antagonist that reverses effects of dose of opiates within minutes
Provokes acute withdrawal syndrome in situations where dependent has opiates in his system
Describe methadone, buprenorphine
Long-acting opioids used for substitution therapy (half-life 25-52 hrs)
Tolerance and physical dependence develop more slowly in comparison to other opioids (morphine)
Given with supervised intake
Abrupt discontinuation precipitates withdrawal syndrome
Describe MOA of cannabinoids
Activates G-coupled receptors and cause disinhibition of DA neurons
Cannabis saliva (hemp): tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN). Hashish partially purified
Endogenous cannabinoids that act as neurotransmitters include 2-arachidonyl glycerol and anandamide, both of which bind to CB1 receptors
THC causes disinhibition of DA neurons by presynaptic inhibition of GABA neurons in VTA
What are the effects of cannabinoids?
Euphoria, relaxation, feeling of well-being, grandiosity, altered perception of passage of time
Medical therapy use: increased appetite, attenuation of nausea, decreased intraocular pressure, relief of chornic pain
Chronic exposure leads to dependence with mild and short-lived withdrawal syndrome (restlessness, irritability, mild agitation, insomnia, nausea, cramping)
What is dronabinol?
FDA-approved THC analog used for anorexia and weight loss in AIDS pts and cancer-chemo-induced N/V
What is nabilone?
THC analog used for treatment of refractory N/V associated with cancer chemo and as adjunct in chronic pain management
Describe gamma-hydroxybutyric acid (GHB)
Activates G-coupled receptors and cause disinhibition of DA neurons
Produced during metabolism of GABA
Activates GABAb receptor with low affinity and produces euphoria, enhanced sensory perceptions, feelings of social closeness, and amnesia before causing sedation and coma
Liquid ecstasy or date rape drug (odorless, readily dissolved, max plasma conc at 20-30 min after ingestion, elimination 30 min)
Recreational use only inhibits GABA neurons but at higher doses, hyperpolarizes DA neurons and inhibits DA release
GHB targets GABAb receptors on both GABA/DA neurons but GABA neurons more sensitive and lead to disinhibition of DA neurons when activated
Describe nicotine
MOA: selective agonist of nicotinic acetylcholine receptor (nAChR)
Neuronal nAChRs are expressed on DA neurons in VTA. Activation fulfills DA requirement of addictive drugs
Withdrawal is mild compared with opioid withdrawal and involves irritability and sleeplessness
Treatment: nicotine (gum, lozenge, inhalers, transdermal applications), bupropion, varenicline
