Drugs of Abuse Flashcards
Which NT plays a major role in motivation and behavioral reinforcment?
Dopamine (DA)
Describe the mechanism behind addiction as a “chronic relapsing disease of maladaptive learning.”
Repeated or sustained exposure to many drugs involved in substance use disorders leads to synaptic adaptations in one or more of the above pathways; these adaptations resemble learning in many ways; at a cellular level the basic learning functions, long-term potentiation (LTP) or long term depression (LTD), are known to occur at DA and other synapses in the NAc, VTA and other reward structures. Many signaling pathways appear to be involved.
Definition - Tolerance
Tolerance occurs when a standard dose of drug, repeatedly administered, produces progressively less effect, or when an increasing dose of drug is required to produce the same intensity of effect after repeated administration.
Definition – Cross Tolerance
Tolerance to the effects of other drugs acting by the same mechanism (usually through the same type of receptors).
Definition – Physical Dependence
Occurs when sustained or repeated administration of a drug leads to a condition in which normal physiological function requires continued presence of the drug. Removal of the drug results in a temporary disturbance of function, known as the “withdrawal” or “abstinence” syndrome, that is characteristic for each drug class. Withdrawal syndromes can be suppressed by re- administration of the active drug or a related drug (e.g. methadone can suppress heroin withdrawal); cross-dependence.
Definition – Conditioned Withdrawal Syndrome
Return to an environment in which drugs have previously been used may induce intense craving and symptoms of withdrawal.
Definition – Addiction
Describes the overall pattern of drug use by an individual - characterized by an over- whelming involvement with the use of a drug, the securing of its supply, and by a high tendency to relapse after withdrawal. Addiction may be present in individuals displaying little or no tolerance and physical dependence. Such conditions are known as substance use disorders, characterized in their most intense forms by lifestyles dominated by drug seeking and drug using behavior.
List – Drug Classes
- Alcohols
- Cannabinoids
- Opiates
- Stimulants
- CNS Depressants
- Hallucinogens
List – Alcohols
- Ethanol
- Methanol
List – Cannabinoids
- Marijuana (THC)
- Synthetic Cannabinoids (“Spice”)
List – Opiates
- Morphine
- Heroin (Diacetylmorphine)
- Oxycodone (OxyContin)
- Hydrocodone (Vicodin)
- Methadone
- Meperidine
- Fentanyl
List – Stimulants
- Caffeine
- Nicotine
- Cocaine
- Amphetamines (Dexamphetamine, Methamphetamine)
- Phenylethylamine (PEA)
- Phenylpropanoamine (PPA)
- Methylene-dioxyamphetamine (MDMA, “Ecstasy”)
- Synthetic Canthinones (“Bath Salts”)
List – CNS Depressants
- Barbiturates
- Benzodiazepines
List – Hallucinogens
- LSD (Lysergic Acid Diethylamide)
- PCP (Phencyclidine)
- Mescaline, Psylocibin
- Salvinorum A (kappa opioid receptor agonist)
Cocaine (Stimulant)
Method of Administration & Effects
Euphoria –> depression –> mild dysphoria –> craving.
- Intranasal (power form, ‘cocaine’) - inc HR, inc BP
- IV, smoking (free base form, ‘crack’) - v. intense effects with v. short duration; leads to binge use
- Oral (power form, ‘cocaine’) - prolonged intense stimulation with high risk CV & CNS toxicity
Cocaine (Stimulant)
Method of Action
- blocks DAT, NET, SERT
- blocks reuptake of DA, NE, 5HT
- increased DA, NE, 5HT at the synapse
note - also used as local anesthetic (blocks Na+ channels)
How are cocaine and amphetamines similar? different?
- Same - effects; different - mechanism of action.
- Cocaine has a much shorter duration of action than amphetamines, and its actions are activity-dependent.
Cocaine (Stimulant)
Chronic Use
- Sensitization –> tolerance. Withdrawal – anhedonia/chronic depression, cravings, increased appetite, lethargy.
- Cardiac arrythmias and damage (enlarged heart).
- Paranoia and psychotic behavior (similar to that seen with amphetamines).
- Sexual dysfunction.
- Damage to the nasal septum from repeated local vasoconstriction (intranasal route).
Amphetamines (Stimulant)
List Various Types
Synthetic benzylethylamine derivatives.
Methamphetamine.
Dexamphetamine (D-isomer) is more active.
Amphetamines (Stimulant)
CNS Effects
CNS stimulation - increased altertness, concentration, delays onset of fatigue. Depression of appetite.
In drug naive users - elation and euphoria; sometimes irritability and anxiety.
Amphetamines (Stimulant)
Mechanism of Action
- Enters pre-synaptic neuron by diffusion, DAT, or NET.
- Inhibits MAO (inactivates NTs) –> increases cytoplasmic concentration of DA, NE, 5-HT.
- Excellent substrate for VMAT (transfers NTs into vesicles) –> displaces DA, NE, 5-HT –> increases cytoplasmic concentration of DA, NE, 5-HT.
- Elevated cytoplasmic concentrations of DA, NE, 5-HT invert the usual concentration gradien, plasma membrane transporter operates in reverse, releasing DA, NE, 5-HT into the synaptic cleft.
- In the CNS, stimulation of DA receptors in nucleus accumbens and caudate-putamen is critical to the
euphoriant and motor effects of amphetamines.
Amphetamines (Stimulant)
Chronic Use
Prescription medications (“speed”), IV amphetamines – severe paranoia and psychotic behavior, violent crime. Other effects – sinus arrhythmias, paroxysmal tachycardia, and heart block.
Methamphetamine (“meth”) – smoked; manufactured from pseudoephedrine-containing starting materials. “Meth heads” or “tweakers” can remain awake for days before crashing; present with psychoses, skin lesions, and dental problems (“meth mouth”).
Note - Relapse rates for recovering addicts are high, and there is good evidence for chronic brain damage in addicts.
Methylene Dioxymethamphetamine (MDMA, Ecstasy, X, Molly)
Mechanism of Action
- Substrate for SERT –> depletes brain 5HT levels.
- DA release.
