Lecture 11 - Drug Abuse Flashcards
Define
Tolerance
Decreased drug effect after repeated administration and larger doses are required to produce the same effect
Define
Pharmacokinetic (Metabolic) Tolerance
Caused by increased expression of drug-metabolizing enzymes, dose must be increased
Define
Pharmacodynamic Tolerance
Caused by neuronal adaptations resulting in reduced response to the same concentration of drug at its site of action in the nervous system (ex the decrease in the number of drug receptors)
Define
Depenence
- Tolerance
- Emergence of withdrawal syndrome upon drug discontinuation
- Drug-seeking behaviors
Define
Physical dependence
result from long-term use and the body relies on an external source of the drug of abuse to prevent unpleasant withdrawal symptoms
Define
Psychological dependence
The continued craving for drug and proclivity to return to out-of-control drug use even after actue withdrawal symptoms have abated
Define
Drug adddiction
A primary condition manifesting as uncontrollable cravings and conpulsive drug use despite doing harm to oneself or others
Behaviors motivated by the brain’s reward system
- Courtship behavior
- Nest building
- Sexual behavior
- Parental behavior
- Social behavior
- Food-seeking behavior
- Feeding, drinking
Major drug classes of abuse + examples
- Opiods - Heroin
- Benzodiazepines - Lorazepam
- Barbiturates - Phenolbarbital
- Alcohol - Ethanol
- Nicotine - Tobacco
- Psychostimulants - Amphetimines
- Caffeine - Coffee
- Cannabinoids - Cannabis
- Phencyclidine - PCP
- Phenylethylamines - MDMA
- Psychedelic agents - LSD
- Inhalants - Nitrous oxide
What are the four central dopamine pathways?
- Nigro-striatal pathway - movement
- Mesolimbic pathway - reward and motivation
- Mesocortical pathway - cognition, schizophrenia
- Tubulo-infundibular pathway - endocrine secretion
Where does the mesolimbic dopamine pathway begin?
Ventral tegmental area
What parts of the brain are affected by the mesolimbic dopamine pathway?
- Prefrontal cortex - executive function, cognitive control
- Orbitofrontal cortex - judgement, decision making
- Amygdala - stress/anxiety
- Hippocampus - context/memory
- Locus ceruleus - arousal/novelty
- Nuclues accumbens
Define
Narcotics
Drugs, such as heroin, morphine, or opium, that in moderate doses dulls the senses, relieves pain, and induces profound sleep but in excessive doses causes stupor, coma, or death
Define
Psychomimetics
Drugs that tend to induce hallucinations, delusions, or other symptoms of a psychosis such as LSD, PCP, or ketamine
Define
Designer Drug
A structural or functional analog of a controlled substance that have been designed to mimic the pharmacological effects of the original drugs while avoiding classification as illegal and/or detection in standard drig tests
List some psychomotor stimulants and their effects
- Amphetamine, methylphenidate, cocaine
- Increase the amount of NE and DA in the brain
Cocaine - Mechanism of action
- Binds tightly at the dopamine transporter forming a complex which causes dopamine to accumulate in the synaptic cleft
- Inhibits voltage-gated ion channel and 5-HT3 receptor
Cocaine - Pharmacokinetics
- Absorbed in intestinal tract
- Intensity and duration of effects vary according to the route of administration
Cocaine - Treatments
- Diazepam - sedative and to control seizures
- Antipsychotic drugs - antagonize DA and NE
- Methadone - slow-acting agonist, suppresses withdrawal symptoms
- Buprenorphine - high-potency partial agonist, suppresses withdrawal symptoms
- Naltrexone - Competitive antagonist of opioid receptors, reduces sensations from opioid use
Amphetamine - Mechanism of action
- Indirectly inhibits dopamine transporter and increases synaptic dopamine levels
- Modulates VMAT
Methylphenidate - Mechanism of action
Binds to and blocks DA and NE transporters
Alcohol addiction treatments
- Naltrexone / Nalmefane (longer duration) - suppresses pleasure of drinking
- Acamprosate - reduces long-lasting withdrawal symptoms (insomnia, anxiety, etc), may act as a NMDA receptor antagonist or a positive allosteric modulator of GABAa receptors
- Disulfiram (diazepam) - interferes with the metabolism of alcohol –> inhibits acetaldehyde dehydrogenase which causes acetaldehyde to build up in the body leading to adverse effects (nausea, headache, etc)
Tobacco addiction treatments
- Nicotine replacement therapies - patches, sprays, gum, lozenges
- Bupropion - weakly increases synaptic dopamine, nicotine receptor partial agonist, atypical antidepressant (Contraindication: seizure)
- Varenicline - nicotine receptor partial agonist
Varenicline - Mechanism of action
Targets nicotine receptors in the brain, partially stimulating them to reduce withdrawal symptoms while also blocking nicotine from attaching to the receptors fully (decreases rewarding effects of smoking if a person relapses)
Varenicline - Administration
Taken orally, started 1 to 2 weeks before planned quit date, standard treatment duration is 12 weeks
Cytisine - Usage in smoking cessation
An alkaloid found in several plant species (ex Golden Rain tree), used in Eastern Europe but not approved by FDA
Cytisine - Mechanism of action
Binds nicotine receptors in the brain to reduce withdrawal and cravings, believed to be a partial agonist of the nicotinic acetylcholine receptor
