Stimulants - Dr. Ishmael

Question 1

Define substance dependence (addiction):

Answer 1

The continues, compulsive obsession with obtaining, consuming, and experiencing the effects of self-administered drugs.

Question 2

What does continues recovery need?

Answer 2

Behavioral, social, psychologic and psychologic changes.

Question 3

What do many dependence-producing drugs enhance? Where do they enhance it? Is there a common pathway for addiction?

Answer 3

They enhance dopamine in the nucleus accumbens (projections from ventral segmental area). Yes, it has guided the field.

Question 4

What can change gene expression at the molecular level?

Answer 4

Chronic drug use can cause gene expression changes within certain reinforcement related, dopaminergic brain regions.

Question 5

What do drugs that block dopamine receptors cause?

Answer 5

Usually cause dysphoric effects that produce unpleasant feelings.

Question 6

What happens when you enhance dopamine?

Answer 6

You produce euphoria

Question 7

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?

Answer 7

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.

Question 8

Where does tolerance shift the dose/response curve?

Answer 8

It shifts it to the right.

Question 9

What is reverse tolerance, and how does the dose/response curve shift on this?

Answer 9

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.

Question 10

What is the most common response to repeated use of the same drug?

Answer 10

Tolerance. Where increasing amounts of the drug are needed to produce the same effect. and avoid withdrawal.

Question 11

What is physicical dependence?

Answer 11

A new normal where the drug is required for normal function and avoid withdrawal. Habituation.

Question 12

How does an animal model demonstrate habituation or physical dependence?

Answer 12

They will start to choose the drug over water when given the choice.

Question 13

What is withdrawal syndrome?

Answer 13

Where a drug of dependence is removed from a physically dependent person.

Question 14

What is detoxification?

Answer 14

The process of a person physically dependent on a drug withdrawing from it.

Question 15

Does anything that binds to the NMDA receptor have abuse liability?

Answer 15

Before memantine, we thought so.

Question 16

What binds to use-dependent sites of NMDA?

Answer 16

Dextromethorphan, PCP, and ketamine

Question 17

What families of drugs are considered addictive/abusable?

Answer 17

1) Methylxanthines
2) Nicotine
3) Alcohol
4) Marijuana
5) Stimulants
6) Opiates
7) Hallucinogenic and dissociative drugs
8) Anabolic steroids

Question 18

What category does caffeine, theophylline, theobromine fall under?

Answer 18

Methylxanthines, an adenosine receptor antagonist.

Question 19

What subunit combination of nicotinic acetylcholine receptors does the nicotine bind to? Where in the body does it bind?

Answer 19

Two alpha-4 and three beta-2. It binds in the CNS.

Question 20

Is the nicotine excitatory or depressive? What neurotransmitters contribute to dependence?

Answer 20

Excitatory. Dopamine, glutamate, and GABA contribute to dependence.

Question 21

What are the pharmacologic treatment strategies?

Answer 21

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

Question 22

Why is a partial agonist like varenicline useful?

Answer 22

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.

Question 23

What is type of agonist is varenicline?

Answer 23

A partial agonist located in the ventral segmental area.

Question 24

What type of agonist is bupropion?

Answer 24

It has affinity for DAT and NET

Question 25

What type of agonist is nortiptyline?

Answer 25

NET < SERT««< DAT (much higher affinity for NET over DAT)

Question 26

Does alcohol have an affect on the CNS?

Answer 26

Yes, a marked effect. Slurred speech, motor incoordination, impaired judgement, increased pain threshold, etc.

Question 27

What is the Mellanby Effect?

Answer 27

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.

Question 28

What plays a part in the physiological effects of alcohol manifesting?

Answer 28

Food in the stomach, metabolizing enzymes, whether the person is a habitual drinker.

Question 29

What is the metabolite of alcohol? What do these symptoms look like?

Answer 29

Acetaldehyde. It produces unpleasant/dysphoric effects like flushing, headaches hypotension, vomiting (hangover symptoms).

Question 30

What does disulfiram do?

Answer 30

It inhibits aldehyde dehydrogenase.

Question 31

What would a person with an inactive form of aldehyde dehydrogenase feel if they consumed alcohol?

Answer 31

They would experience a disulfiram-like reaction after consuming alcohol.

Question 32

What do withdrawals after habitual drinking look like?

Answer 32

• Tremors, increased blood pressure, rapid breathing, sweating, nausea
• Alcohol hallucinations
• Seizures
• Delirium tremens (temporary confusion, changes in vital signs peaking several days after last drink).

Question 33

What can lessen the symptoms of alcohol withdrawal?

Answer 33

Benzodiazepines. (lorazepam, chlordiazepoxide)

Question 34

How long do the acute effects of marijuana last?

Answer 34

2-4 hours

Question 35

Compare smoking and orally consuming marijuana:

Answer 35

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.

Question 36

Is marijuana associated with a withdrawal symptom?

Answer 36

No, it is thought to be relatively safe due to the dose. It does work via the same reward pathway.

Question 37

What medical conditions qualify for medical marijuana use?

Answer 37

Agitation related to Alzheimer's
Cachexia
Cancer
Glaucoma
HIV/AIDs
Nausea
PTSD
Severe pain
Seizures
Persistant muscle spasms (MS included)

Question 38

How do the goals differ in recreational and medical marijuana use?

Answer 38

Symptom relief vs pleasure.

Question 39

How is the bioavailability different in smoking vs using edible marijuana?

Answer 39

Smoking allows for predictable and rapid titration. Edibles have poorer bioavailability, and have the potential for overdosing/feeling enhanced effects later than intended.

Question 40

How do plant-derived cannabinoids regulate neurotransmitter release?

Answer 40

In the nucleus accumbens, the drug binds to the CB1 receptor, which decreases calcium intake into the cell. This inhibits neurotransmitter release.

Question 41

What is cannabis use disorder?

Answer 41

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.

Question 42

What is cocaine?

Answer 42

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.

Question 43

What does cocaine bind to and block?

Answer 43

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.

Question 44

What do amphetamines do?

Answer 44

They increase alertness

Question 45

What is the mechanism of cocaine?

Answer 45

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.

Question 46

What is the mechanism of amphetamine?

Answer 46

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.

Question 47

What do ADHD medications aim to accomplish?

Answer 47

They reduce hyperactivity, impulsiveness, and improve ability to focus.

Question 48

How does the mechanism of atomoxetine differ from that of the amphetamines and methylphenidate?

Answer 48

Atomoxetine targets NET, and acts as an inhibitor instead of a stimulant. It has low abuse liability, but severe side effects. It has a warning for severe liver toxicity and suicidal ideation. Huge affinity for NET.