Stimulants - Dr. Ishmael Flashcards
Define substance dependence (addiction):
The continues, compulsive obsession with obtaining, consuming, and experiencing the effects of self-administered drugs.
What does continues recovery need?
Behavioral, social, psychologic and psychologic changes.
What do many dependence-producing drugs enhance? Where do they enhance it? Is there a common pathway for addiction?
They enhance dopamine in the nucleus accumbens (projections from ventral segmental area). Yes, it has guided the field.
What can change gene expression at the molecular level?
Chronic drug use can cause gene expression changes within certain reinforcement related, dopaminergic brain regions.
What do drugs that block dopamine receptors cause?
Usually cause dysphoric effects that produce unpleasant feelings.
What happens when you enhance dopamine?
You produce euphoria
Why does the convergence of the reward pathways (both natural and drug-induced) on the mesolimbic dopaminergic neurons make it difficult for addicts to break the cycle?
Because the reward pathway is situated in the part of the brain where emotions and new memories are made/stored. You have to remove yourself from certain people and experiences to prevent relapse.
Where does tolerance shift the dose/response curve?
It shifts it to the right.
What is reverse tolerance, and how does the dose/response curve shift on this?
It is the same things as drug sensitization, where some responses/side effects become stronger than anticipated. This can occur with cocaine, amphetamines, marijuana, alcohol. It usually occurs after tolerance. The curve shifts to the left instead.
What is the most common response to repeated use of the same drug?
Tolerance. Where increasing amounts of the drug are needed to produce the same effect. and avoid withdrawal.
What is physicical dependence?
A new normal where the drug is required for normal function and avoid withdrawal. Habituation.
How does an animal model demonstrate habituation or physical dependence?
They will start to choose the drug over water when given the choice.
What is withdrawal syndrome?
Where a drug of dependence is removed from a physically dependent person.
What is detoxification?
The process of a person physically dependent on a drug withdrawing from it.
Does anything that binds to the NMDA receptor have abuse liability?
Before memantine, we thought so.
What binds to use-dependent sites of NMDA?
Dextromethorphan, PCP, and ketamine
What families of drugs are considered addictive/abusable?
1) Methylxanthines
2) Nicotine
3) Alcohol
4) Marijuana
5) Stimulants
6) Opiates
7) Hallucinogenic and dissociative drugs
8) Anabolic steroids
What category does caffeine, theophylline, theobromine fall under?
Methylxanthines, an adenosine receptor antagonist.
What subunit combination of nicotinic acetylcholine receptors does the nicotine bind to? Where in the body does it bind?
Two alpha-4 and three beta-2. It binds in the CNS.
Is the nicotine excitatory or depressive? What neurotransmitters contribute to dependence?
Excitatory. Dopamine, glutamate, and GABA contribute to dependence.
What are the pharmacologic treatment strategies?
1) NRT - change behavior, still have agonist
2) Antidepressants (bupropion, nortiptyline, 2nd gen TCAs) - inhibitor of DAT and NET
3) Varenicline - selective alpha-4 beta-2 receptor partial agonist
Why is a partial agonist like varenicline useful?
Because it occupies the binding site normally occupied by nicotine, and therefore blocks nicotine from binding. It also has some action by itself. It is VERY potent. Sufficient dopamine is released to reduce craving and withdrawal - reduced occupancy by nicotine at reinforcing pathways - prevents full activation of the receptor.
What is type of agonist is varenicline?
A partial agonist located in the ventral segmental area.
What type of agonist is bupropion?
It has affinity for DAT and NET
