Drugs Of Abuse DSA

Question 1

Define abstinence syndrome

Answer 1

Signs and symptoms that occur on withdrawal of drug in a dependent person

Question 2

Define addiction

Answer 2

Compulsive drug-using behavior in which person uses drug for personal satisfaction, often in face of known risks to health
Formerly psychological dependence

Question 3

Define controlled substance. What are the 4 schedules?

Answer 3

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

Question 4

Define dependence

Answer 4

State characterized by signs and symptoms, frequently opposite of those caused by drug, when it is withdrawn from chronic use or when dose is abruptly lowered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

Question 5

Describe designer drug

Answer 5

Synthetic derivative of drug, with slightly modified structure but no major change in pharmacodynamic action
Circumvention of Schedules of Controlled Drugs is motivation

Question 6

Define tolerance

Answer 6

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

Question 7

Define sensitization

Answer 7

Increase in response with repetition of same dose of drug (dose-response curve shifts to left)

Question 8

define withdrawal

Answer 8

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

Question 9

Describe dopamine hypothesis of addiction (DA reward pathway)

Answer 9

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

Question 10

Summarize drugs that activate G-protein coupled receptors

Answer 10

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

Question 11

Summarize drugs that bind to ionotropic receptors and ion channels

Answer 11

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

Question 12

Summarize drugs that bind to transporter of biogenic amines

Answer 12

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

Question 13

Describe nonaddictive drugs of abuse. Examples?

Answer 13

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

Question 14

Describe lysergic acid diethylamine (LSD), mescaline, psilocybin

Answer 14

Nonaddictive
Repetitive exposure leads to rapid tolerance (tachyphylaxis)
Long term: LSD can cause flashbacks of altered perception years after consumption

Question 15

Describe phencyclidine (PCP, angel dust) and ketamine (special K)

Answer 15

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

Question 16

Describe opioids

Answer 16

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

Question 17

Describe naloxone

Answer 17

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

Question 18

Describe methadone, buprenorphine

Answer 18

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

Question 19

Describe MOA of cannabinoids

Answer 19

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

Question 20

What are the effects of cannabinoids?

Answer 20

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)

Question 21

What is dronabinol?

Answer 21

FDA-approved THC analog used for anorexia and weight loss in AIDS pts and cancer-chemo-induced N/V

Question 22

What is nabilone?

Answer 22

THC analog used for treatment of refractory N/V associated with cancer chemo and as adjunct in chronic pain management

Question 23

Describe gamma-hydroxybutyric acid (GHB)

Answer 23

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

Question 24

Describe nicotine

Answer 24

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

Question 25

Describe bupropion

Answer 25

Antidepressant with unknown MOA

Used alone or in combo with nicotine-replacement therapy and/or behavioral therapy

Question 26

Describe varenicline

Answer 26

Partial neuronal nAChR agonist approved for treating smoking cessation
Prevents nicotine stimulation of mesolimbic dopamine system associated with nicotine addiction

Question 27

Describe inhalants that mediate ionotropic receptors

Answer 27

Recreational exposure to chemical vapors like nitrates, ketones, aliphatic and aromatic hydrocarbons
Unknown mech. Some increase excitability of VTA and interact with ionotropic receptors and ion channels
Most inhalants produce euphoria
Overdose management is supportive care

Question 28

Describe MOA of cocaine

Answer 28

In peripheral nervous system, inhibits voltage-gated sodium channels and can be used as local anesthetic
Blocks DAT and increases DA concentrations in nucleus accumbens (rewarding effects)
Blocks NET and activates sympathetic nervous system, which leads to acute increase in arterial pressure, tachycardia, ventricular arrhythmias, and pupil dilation

Question 29

Describe effects of cocaine

Answer 29

Typical acute symptoms include loss of appetite, hyperactivity, lack of sleep
Overdose may lead to hyperthermia, coma, death
Exposure increases risk of intracranial hemorrhage, ischemic stroke, myocardial infarction, seizures
Withdrawal syndrome not as strong as with opioids
Reverse tolerance can occur (sensitization to small doses)
Susceptible pts may become dependent/addicted after a few exposures
No antidote. Supportive with agents to control HR (b-adrenergic receptor antagonist propranolol) and seizures (sedative-hypnotic diazepam)

Question 30

Describe amphetamines

Answer 30

MOA: causes release of endogenous biogenic amines by reversing action of biogenic amine transporters at plasma membrane

• amphetamines are taken up into cell by DAT
• amphetamines block intracellular VMAT and deplete synaptic vesicles of their neurotransmitter content, which causes levels of DA and other amines (serotonin, NE) to increase in cytoplasm
• increasing levels of amines in cytoplasm cause DAT, SERT, and NET to work in reverse and release amines into synapse

Neurotoxic (dependent on NMDA receptor and affects mainly serotonin and DA neurons
Withdrawal symptoms: dysphoria, drowsiness (insomnia in some), and general irritability and depression

Question 31

Describe ecstasy (MDMA, methylenedioxymethamphetamine)

Answer 31

MOA: similar to amphetamines (reverses action of biogenic amine transporters)
Preferential affinity for SERT and increases extracellular concentration of serotonin
Heavy users of MDMA report long-term cognitive impairment due to continued serotonin depletion
Acute toxic effects include hyperthermia, dehydration, serotonin syndrome (mental status change, autonomic hyperactivity, neuromuscular abnormalities), and seizures
Withdrawal consists of mood offset characterized by depression lasting up to several weeks, possible increased aggression

Question 32

What are overdose effects and withdrawal symptoms of amphetamines, methylphenidate, cocaine?

Answer 32

OVerdose: agitation, HTN, tachycardia, delusions, hallucinations, hyperthermia, seizures, death

Withdrawal: apathy, irritability, increased, sleep time, disorientation, depression

Question 33

What are overdose effects and withdrawal symptoms of barbiturates, benzodiazepines, ethanol?

Answer 33

Overdose: slurred speech, drunken behavior, dilated pupils, weak and rapid pulse, clammy skin, shallow respiration, coma, death

Withdrawal: anxiety, insomnia, delirium, tremors, seizures, death

Question 34

What are overdose effects and withdrawal symptoms of heroin, other strong opioids?

Answer 34

Overdose: constricted pupils, clammy skin, nausea, drowsiness, respiratory depression, coma, death

Withdrawal: nausea, chills, cramps, lacrimation, rhinorrhea, yawning, hyperpnea, tremor