Flashcards in Stimulants - Dr. Ishmael Deck (48):
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?
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
What type of agonist is nortiptyline?
NET < SERT<<<<< DAT (much higher affinity for NET over DAT)
Does alcohol have an affect on the CNS?
Yes, a marked effect. Slurred speech, motor incoordination, impaired judgement, increased pain threshold, etc.
What is the Mellanby Effect?
As the blood alcohol level in a person rises, so does the symptoms associated with the alcohol. At the blood alcohol level peak, the symptoms/physiological effects almost stop completely.
What plays a part in the physiological effects of alcohol manifesting?
Food in the stomach, metabolizing enzymes, whether the person is a habitual drinker.
What is the metabolite of alcohol? What do these symptoms look like?
Acetaldehyde. It produces unpleasant/dysphoric effects like flushing, headaches hypotension, vomiting (hangover symptoms).
What does disulfiram do?
It inhibits aldehyde dehydrogenase.
What would a person with an inactive form of aldehyde dehydrogenase feel if they consumed alcohol?
They would experience a disulfiram-like reaction after consuming alcohol.
What do withdrawals after habitual drinking look like?
- Tremors, increased blood pressure, rapid breathing, sweating, nausea
- Alcohol hallucinations
- Delirium tremens (temporary confusion, changes in vital signs peaking several days after last drink).
What can lessen the symptoms of alcohol withdrawal?
Benzodiazepines. (lorazepam, chlordiazepoxide)
How long do the acute effects of marijuana last?
Compare smoking and orally consuming marijuana:
The onset is slower with edibles. This can be dangerous because people may take more than intended because they do not feel the effects of a smaller dose right away.
Is marijuana associated with a withdrawal symptom?
No, it is thought to be relatively safe due to the dose. It does work via the same reward pathway.
What medical conditions qualify for medical marijuana use?
Agitation related to Alzheimer's
Persistant muscle spasms (MS included)
How do the goals differ in recreational and medical marijuana use?
Symptom relief vs pleasure.
How is the bioavailability different in smoking vs using edible marijuana?
Smoking allows for predictable and rapid titration. Edibles have poorer bioavailability, and have the potential for overdosing/feeling enhanced effects later than intended.
How do plant-derived cannabinoids regulate neurotransmitter release?
In the nucleus accumbens, the drug binds to the CB1 receptor, which decreases calcium intake into the cell. This inhibits neurotransmitter release.
What is cannabis use disorder?
1) Substance abuse leading to significant impairment
2) Other activities reduced in favor of drug
3) Transition from use to dependence (7-10%) in regular users is less than other drugs
4) Tolerance, withdrawal. Behavior persists in spite of problems.
What is cocaine?
A stimulant first used for its sodium channel blocker effects - an anesthetic. Also used as a vasoconstrictor of the upper respiratory tract, ear, nose, and throat. Use-dependent Na channel blocker.
What does cocaine bind to and block?
It is nonspecific. Binds to the dopamine transporter (5HT and NE transporters as well). It enhances dopamine levels especially in the nucleus accumbens. It is a peripheral sympathomimetic; blocks cardiac sodium channels. Usually fatal on overdose.
What do amphetamines do?
They increase alertness
What is the mechanism of cocaine?
It is a non transported inhibitor. It stays outside of cells and increases the function of available dopamine. This is in contrast to amphetamine action.
What is the mechanism of amphetamine?
It is a substrate for DAT like cocaine, but is actually transported inside through the DAT. Once inside, it acts on the vesicles which become leaky; it destroys the pH gradient, and causes reverse transport. Leaky dopamine is effluxed through the DAT because the transporter is working in the wrong way.
What do ADHD medications aim to accomplish?
They reduce hyperactivity, impulsiveness, and improve ability to focus.