CNS Stimulants

Question 1

Classes of CNS stimulants

Answer 1

1. Catecholamine releasers
2. Catecholamine reuptake blockers
3. Stimulant antidepressants
4. Methylxanthines
5. Nicotinic agents

Question 2

Therapeutic uses of CNS sitmulants

Answer 2

1. ADHD
2. Narcolepsy
3. Obesity
4. Smoking cessation
5. Alcohol use disorder? (varenicline)

Question 3

Historical prototype of catecholamine releasers

Answer 3

D-ephedrine

Question 4

Catecholamine releasers

Answer 4

1. Amphetamine (Adderal)
2. Methamphetamine (Desoxyn)
3. Methylphenidate (Ritalin SR, Concerta, Metadate)
4. Ephedrine

Question 5

MOA of catecholamine releasers in CNS

Answer 5

1. Binds to presynaptive membrane and induces release from vesicles
2. Causes release of DA from vesicles into the intracellular space in terminal
3. Blocks MAO, blocking degradation of DA and causing buildup inside cytoplasm in terminal
4. Induces reverse transport through the DAT to “release” DA into EC space

Question 6

Reuptake blockers

Answer 6

1. Cocaine
2. Modafinil (Provigil)
3. Sibutramine (Meridia)

Question 7

MOA of reuptake blockers

Answer 7

pure block of re-uptake, prolonging lifetime of catecholamine in the synapse and promoting its action on postsynaptic cell

Question 8

Cocaine

Answer 8

abuse potential; short/intense action; NaV activity (locak anesthetic)

Question 9

Modafinil (Provigil)

Answer 9

monoamine reuptake blocker; MOA unclear; less abuse potential than cocaine

Question 10

What are bath salts?

Answer 10

Synthetic cathinones

Question 11

Intoxication from synthetic cathinones

Answer 11

psychosis, hallucinations, agitation, tachycardia, hypertension, hyperthermia, and combative or violent behaviors

Question 12

What is MDPV?

Answer 12

reuptake blocker for DAT and NET; 10-50X cocaine potency

Question 13

Cathinones that are releasers have variable selectivity for

Answer 13

DAT, SERT, and NET

Question 14

Stimulant antidepressants

Answer 14

1. Atomoxetine (Strattera)

2. Bupropion (Zyban, Welbutrin)

Question 15

Atomoxetine (Strattera)

Answer 15

Net activity; alternative to classical stimulants; refractory ADHD, ADD, and adult ADD

Question 16

Bupropion (Zyban, Welbutrin)

Answer 16

Adjunct for depression/anxiety; smoking cessation; lowers seizure threshold

Question 17

MOA of stimulant antidepressants

Answer 17

mixture of antidepressants properties (block NET or SERT) plus some mild CNS activating properties via block of DA reuptake

Question 18

When are stimulant antidepressants used

Answer 18

used as alternative to classical stimulants, likely in situations refractory to first-line drugs

Question 19

How is bupropion often used?

Answer 19

often used as an adjunct mood enhancer along with an SSRI, has NET and DAT blocking activity

Question 20

Methylxanthines

Answer 20

1. Caffeine
2. Theophylline
3. Theobromine

Question 21

Caffeine

Answer 21

short-acting; diuretic; mild DA and NE stimulant

Question 22

Theophylline

Answer 22

found in tea; bronchodilation, used in asthma

Question 23

Where does caffeine act as an antagonist?

Answer 23

at adenosine receptors; in the brain the A2a receptor seems to be most important for the wakefullness-promoting properties of caffeine

Question 24

Describe A2a receptors

Answer 24

Gs-coupled and have high expression in the area of the brain called the striatum, involved in arousal and drug addiction

Question 25

What does specific knock out of A2a receptors in the striatum do?

Answer 25

eliminates the wakefullness property of caffeine

Question 26

Nicotine's action in the DA system

Answer 26

1. Stimulate AP firing | 2. Stimulate DA release (direct and indirect)

Question 27

Nicotinic agents

Answer 27

1. Nicotine 2. Varenicline (Chantix) 3. Bupropion (Zyban)

Question 28

Describe nicotinic acetylcholine receptors

Answer 28

acetylcholine-gated cation channels, where activation promotes cellular depolarization and NT release when receptors on presynaptic terminals are activated

Question 29

Brain or neuronal nicotinic receptors have the same secondary structure as

Answer 29

muscle receptors

Question 30

Brain nicotinic receptors have high affinity for

Answer 30

both nicotine and Ach

Question 31

Most brain nicotinic receptors are expressed

Answer 31

pre-synaptically (in axon terminals) or pre-terminally (on axons) where they regulate NT release

Question 32

Key area with regard to the medical pharmacology of nicotine addiction and nicotinic agents

Answer 32

dopamine pathway from the VTA to the striatum and cortex

Question 33

Essential for ligand binding to the nicotinic receptor binding site

Answer 33

nitrogens that are protonated at physiological pH

Question 34

The likely form of nicotine that binds to receptors

Answer 34

the charged or protonated form of nicotine

Question 35

Which enzyme is nicotine degraded by?

Answer 35

trick question - it has no enzyme that can degrade it like ACh does

Question 36

How does bupropion work as a smoking cessation aid?

Answer 36

It has nAChR antagonist activity at receptors in the DA system and it can block nicotine-stimulated action potential firing and ACh-activated nAChR currents

Question 37

Varenicline

Answer 37

partial agonist at most nAChRs; can directly activate receptors but can also interfere with full action of stronger agonists like nicotine

Question 38

May explain why varenicline has unwanted side effects

Answer 38

It also has activity at a3b4 nAChRs expressed in peripheral sites

Question 39

How does varenicline promote cessation of nicotine intake?

Answer 39

Blocks reinforcing action of nicotine and produces moderate DA release (alleviates craving)

Question 40

Abuse potential of catecholamine releasers

Answer 40

high

Question 41

Abuse potential of reuptake blockers

Answer 41

Cocaine > modafinil, silbutramine

Question 42

Abuse potential of stiulant antidepressants

Answer 42

low

Question 43

Abuse potential of methylxanthines

Answer 43

low

Question 44

Abuse potential of nicotine

Answer 44

high

Question 45

Toxicity of amphetamines

Answer 45

have CV side effects, can exacerbate HTN, HR can slow reflexively at moderate doses, but tachycardia happens in overdose situations, psycological symptoms includes psychosis

Question 46

Toxicity of cocaine

Answer 46

CV (MI, stroke, arrhythmias), CNS (seizure), respiratory depression

Question 47

Toxicity of Nicotinics

Answer 47

GI upset and CNS (odd dreams, suicide ideations, insomnia)

Question 48

ADHD

Answer 48

mainly children with poor attention: poor listening, cannot follow instructions, forgetful, poor academic performance, easily distracted, impossible to sit still, engage in quiet tasks, impulsive in thought or action, impatient

Question 49

Treatment of ADHD

Answer 49

amphetamine (Adderall) or methylphenidate (Ritalin)

Question 50

Adverse effects of ADHD

Answer 50

insomnia, abdominal pain, anorexia/weight loss (growth suppression in children)

Question 51

Narcolepsy

Answer 51

refreshing "sleep attacks" with cataplexy; REM sleep intrusions

Question 52

What is cataplexy

Answer 52

sudden loss of muscle tone (bilateral) often with intense emotional engagement

Question 53

Treatment of Narcolepsy

Answer 53

1. TCAs and MAOIs 2. Methylphenidate (Ritalin), amphetamine 3. Modafinil (Provigil)

Question 54

Problems of using CNS stimulants to control obesity

Answer 54

1. Weight can be re-gained after discontinuation 2. Exacerbated HTN, problem in population who would take this for obesity 3. Tolerance to anorexic effect 4. Abuse and habituation

Question 55

CNS stimulants used for obesity treatment

Answer 55

1. Amphetamine 2. Benzphetamine 3. Phentermine

Question 56

Treatment for nicotine addiction

Answer 56

1. Varenicline (Chantix) 2. Bupropion (Zyban) - puts people in a better mood 3. Nicotine (patch, gum)