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Flashcards in Drugs of abuse Deck (17):
1

Psychomotor stimulant

Amphetamine (methylphenidate, fenfluramine, methamphetamine, MDMA – ecstasy)
Cocaine

2

Amphetamine (methylphenidate, fenfluramine, methamphetamine, MDMA – ecstasy)

Psychomotor stimulant
•Presynaptic action, releases DA, NE and 5HT; predominant effect from DA
•Methylphenidate → ADHD treatment
•Fenfluramine → appetite suppressant, no abuse liability
•Methamphetamine → neurotoxicity if long-term
•MDMA – 5HT system effects
•Locomotor stimulation, excitement and euphoria, insomnia, lack of appetite, incr blood pressure and GI motility
•AE: Anxiety, irritability, restlessness
•Can induce panic, paranoia, stereotype amphetamine psychosis (repeated use)
•Tolerance develops to euphoria and anorectic (appetite suppressant); slow to locomotor and stereotyped behaviors
•Dependence related to unpleasant after effects and euphoria
•No clear withdrawal syndrome

3

Cocaine

Psychomotor stimulant
•Binds to and inhibits DA and NE reuptake → incr DA at pre and post-synaptic R
•Nasal inhalation, IV
•Reinforcing effects: mild to intense euphoria (nucl accumb)
•Short duration of action (t1/2 10-30m)
•Local anesthetic
•AE: Marked psychomotor stim, respiratory effects and vasoconstriction, incr bp, tachycardia + tremors, incr vigilance and attn., higher dose → paranoid psychotic rxn, convulsions, craving
•No clear withdrawal syndrome
•No clear tolerance or physical dependence
•Effects on CNS after chronic admin can last (CNS plasticity)
•Prenatal exposure → premature birth, lack of prenatal care, malnutrition, cognitive and motor deficits, lower IQ, impaired language development, deficits in attn., impaired auditory processing

4

Methylxanthines

Tea, coffee, cocoa

5

Tea, coffee, cocoa

Methylxanthines
•Mild stim effects by caffeine and theophylline
•Mild CNS stim, diuresis, stim of cardiac muscles, relaxation of smooth muscle
•AE: Slight tolerance, withdrawal (headache)

6

Nicotine, tobacco

•nAChR action, widely expressed in brain (cortex, VTA, hippocampus) – ligand-gated cation channels pre and post-synapt, several subunits (a4b2 – drug target)
•chronic nicotine → desensitization, incr in # of nAChRs
•Skeletal muscle relaxation, incr learning
•Parkinsons – twice as common in non-smokers
•AE: Tachycardia
•Cancer – lung, URT, esophagus, pancreas, bladder
•CHD, PVD, COPD
•Fetus – reduction in birth weight, spontaneous abortion, premature delivery
•Schizo – high incidence of smoking
•Tx: buproprion, varenicline (nAChR partial agonist, prevents relapse, black box for suicide)

7

Psychedelics

Indoleamines (LSD, DMT, Psilocybin)
Phenethylamines (mescaline, DOM, MDMA)
Salvinorin A

8

Indoleamines (LSD, DMT, Psilocybin)
Phenethylamines (mescaline, DOM, MDMA)
Salvinorin A

Psychedelics
•Targets cortical and thalamic circuits
•Partial agonists at 5HT2A and 5HT2C-R’s
•Produce perceptual distortions (hallucinogenic), thought disturbances (psychotomimetic), feelings of enhanced insight and self-knowledge of a spiritual nature (psychedelic)
•Salvinorin A – kappa opioid receptor agonist
•AE: MDMA: hyperthermia, damage to skeletal muscle, renal failure
•Excess water intake and retention through secretion of ADH → thirst, overhydration, water intoxication (hyponatremia)
•Prolonged after effects – depression, irritability, aggression

9

Hallucinogens

PCP, ketamine, dizocilpine
Marijuana
Dronabinol (marinol)
Levonantradol
Gamma-hydroxybutyric Acid (GHB)

10

PCP, ketamine, dizocilpine

Hallucinogens
Incr extracellular glut in prefrontal cortex via stim of postsynaptic 5HT2A-R → activation of AMPA and NMDA R
•Dissociative anesthetics
•Noncompetitive blockers of NMDA associated calcium channel
•Ketamine also blocks GABA interneurons → incr glut
•Model for psychotic behavior
•Ketamine for complex regional pain syndrome and for tx resistant depression
•AE: Withdrawal: agitated psychotic state, tx with diazepam or haloperidol
•Emotional withdrawal, concrete thinking, bizarre responses to projective tests, catatonic posturing, hallucinations, hostile or assaultive behavior

11

Gamma-hydroxybutyric Acid (GHB)

Hallucinogens
Incr extracellular glut in prefrontal cortex via stim of postsynaptic 5HT2A-R → activation of AMPA and NMDA R
•Produced in metab of GABA, function unknown
•General anesthetic (not in USA)
•Narcolepsy
•AE: Narrow safety margin, abuse liability
•Euphoria, enhanced sensory perceptions and amnesia, social closeness, sedation

12

Marijuana
Dronabinol (marinol)
Levonantradol

Hallucinogens
Incr extracellular glut in prefrontal cortex via stim of postsynaptic 5HT2A-R → activation of AMPA and NMDA R
•Active ingredient: delta-9 THC
•CB1-R: brain – Gi, cerebral cortex, hippocampus, striatum, hypothal, mesencephalon, cerebellum
•CB2-R: periphery – Gi, testes, spleen, leukocytes, lymphos, cerebellar granule cells
•Endogenous ligand = amandamide
•Used for anorexia in AIDS pts, antiemtic for chemo, analgesic for chronic pain, movement disorders, glaucoma
•Dronabinol → agonist, antinausea and antiemetic
•Levonantradol → analgesic, antispasmodic • Withdrawal: restlessness, irritability, mild agitation, insomnia, nausea, cramping, sleep disturbance
•CB1-R: analgesia, hypothermia, catalepsy, decr locomotor activity, memory disturbances
•CB2-R: impaired immune response

13

CNS depressants

Ethanol
BZD
Barbiturates
Opioids

14

Ethanol

CNS depressants
•Inhibits NMDA-R, enhances inhibition by actions at mod site on GABA-A and at 5HT3-R → decr excita
•Inhibits Ca++ channel opening & activates K+ channel
•Tolerance is pharmacokinetic, pharmacodynamics and behavioral
•Alteration of therapeutic index: tolerance to depr or resp more slowly than sedation
•Tx for addiction: behavioral approaches
•AE: Cross-tolerance to other sedative-hypnotic drugs (BZD, barb)
•Toxicity: liver disease, CVD, endocrine/GI effects, malnutrition, severe depression, Korsakoff’s, fetal toxicity (FAS) → mental retardation
•Withdrawal: craving, tremor, irritability, nausea, sleep disturbance, tachycardia, htn, sweating, perceptual distortions, delirium tremens (tx: oxazepam)

15

BZD

CNS depressants
•Intentional abuse is rare
•Addiction → enormous escalation of dose
•Abuse for “high”, but also to heighten effects of other drugs or reduce unwanted SE
•AE: Tolerance and physical dependence slow to develop
•Withdrawal: usually mild; high dose → seizures, delirium (tx anticonvulsants, Flumazenil for acute toxic OD)

16

Barbiturates

CNS depressants
•Blocks excitatory Ca++ and enhance inhibitory Cl-
•Tx for addiction same as BZDs
•AE: Tolerance: pharmacokinetic, dynamic and behavioral; therapeutic index decr
•Physical dependence: upreg of NMDA-R → withdrawal (like with BZDs, incl seizures)

17

Opioids

CNS depressants
•Pharmacology mediated by mu-receptors
•Inhibit adenylate cyclase
•Tx opioid addiction – methadone and/or buprenorphine
•AE: Tolerance pharmacodynamics, behavioral, pharmacokinetic → 100x incr in dose
•Tolerance to resp depressant, sedative and emetic effects
•Withdrawal: severe – nausea, muscle aches, diarrhea, piloerection (tx with naloxone)