Exam 2: Psychostimulants

Question 1

What is a monoamine?

Answer 1

Catecholamines AND indoleamines

Question 2

What is a catecholamine?

Answer 2

Dopamine, Norepinephrine, Epinephrine

Question 3

Catecholamine synthesis enzymes

Answer 3

TH (+OH)
AADC (-COOH)
DBH (-H –> - OH)
PNTM (add -CH3)

Question 4

How and why are catecholamines stored in vesicles?

Answer 4

VMAT2 transporter
ion trapping- proton pump acidifies vesicles ionizing catecholamines,
which are WEAK BASES. low pH in vesicle = ion trapping

Question 5

how does reserpine affect vesicular storage of catecholamines

Answer 5

Reserpine= inhibits vesicularization of monoamines.

Frees monoamines degraded by enzyme (MAO). Depletes monoamines

Induces sedation, low bp

Question 6

What are the subtypes of noradrenergic receptors?

Answer 6

1) alpha 1
2) alpha 2
3) Beta 1

Question 7

What role do receptor subtypes (noradrenergic) play in mediating effects of catecholamines (e.i. autonomic activity)

Answer 7

1) alpha 1- increase phosphoinositide, muscle contraction, activating
2) alpha 2- inhibiting, low cAMP
3) beta 1- activating, increase cAMP

Question 8

What is the difference between reuptake transporters and autoreceptors?

Answer 8

Reuptake= brings NE and DA back into the cell for degradation/reuptake into vesicles

Autoreceptor: binds to cause decrease in vesicular release

Question 9

Norepinephrine/Epinephrine degradation

Answer 9

COMT and MAO, doesn’t matter the order, leads o Vanillylmadnelic Acid (VMA)

Question 10

Norepinehprine: alpha 2 vs. beta 1

Answer 10

Beta 1: Gs, increase cAMP

alpha 2: Gi, low cAMP

Question 11

NE and heart rate stuff

Answer 11

Beta 1 vs. Ach’s M2 to increase heart rate with adenyl cyclase

Question 12

Autonomic control of bladder

Answer 12

Beta 2 (NE)- relax bladder
M3 - contracts bladder
Alpha 1- contracts sphincter
M1- relax sphincter

Question 13

Autoreceptors

Answer 13

D2 - DOPAMINE
Alpha 2= NE

1) Bind DA/NE
2) Close Ca2+ channels
3) Reduce vesicular transmitter release

Question 14

Free base vs. Hydrochloride cocaine

Answer 14

Free base: unionized, LS, Base, vaporizes.

Hydrochloride: Ionized, WS, Salt, purified, degraded before vape

Question 15

Cocaine is an (acid/base)

Answer 15

Base

Question 16

Cocaine HCL (stable salt)–> Free base or crack?

Answer 16

Free base: mix with ammonia, extra with ether, then evaporate

Crack: Mix with baking soda, heat, filter and wash

Question 17

Cocaine HCL (stable salt)–> Free base or crack?

Answer 17

Free base: mix with ammonia, extra with ether, then evaporate

Crack: Mix with baking soda, heat, filter and wash

Question 18

Kinetics of cocaine? (- admin, other card)

2) Absorption
3) Distribute
4) Metabolize
5) Excretion

Answer 18

2) Weak base, increase absorption by increase pH

3) Cross BBB
4) via liver, 1st order
metabolites: benzoylecgonine & cocaethylene

5) after ~4 hr. metabolites may persist up to 3-5 days.

Question 19

What is the primary pharmacodynamic mechanism by which cocaine is proposed to
affect neuronal activity? (Binding/action)

Answer 19

Blocks REUPTAKE of DAT

Blocks UPTAKE of SERT/NET

Blocks local sodium channels

Question 20

What evidence implicates dopamine in cocaine craving as experienced by heavy users?

Answer 20

Cocaine blocks DA reuptake in mesolimbic pathway.

Cocaine rats: want paired compartment, unless DAT KO.

Also, increased dendrite spines in NA

Question 21

Mechanisms of toxic/lethal effects of cocaine admin?

Answer 21

increases heart rate/bp by decreasing NE reuptake

Also constricts coronary artery, reduces oxygen to heart.

Question 22

What is the only approved therapeutic use of cocaine?

Answer 22

Local anesthetic, block Na+ channels for surgeries and reduce blood flow to site

(e.i. procaine and lidocaine)

Question 23

What are the different chemical forms of amphetamine? Parent compound?

Answer 23

??

Question 24

Desired effects associated with amphetamine/cocaine admin?

Answer 24

Arousal, alert, wake, energy, concentrate, no distraction, confidence, euphoria, physical performance

Question 25

How does renal pH affect 1/2 life of amphetamine?

Answer 25

??

Question 26

Amphetamines and vesicular storage: primary mechanism

Answer 26

Enters vesicle by VMAT2 Increases pH in vesicle reduces ionization/ion trapping, so molecules leak out

Question 27

Mechanisms behind toxic/lethal effects of amphetamine admin?

Answer 27

increases heart rate/bp by increasing NE release

Question 28

What are approved/off label therapeutic applications of amphetamine?

Answer 28

FDA: narcolepsy/ADHD Off-Label: Obesity/Depression

Question 29

How are stimulant/non-stimulants proposed to manage ADHD symptoms?

Answer 29

Improve attention/focus, no distraction, etc. Increase DA/NE from VTA/LC to PFC regions for inhibition of motor, basal ganglia, and cerebellum.

Question 30

What are some important features/consequences of psychostimlant tolerance?

Answer 30

Slow tolerance in ADHD/narcolepsy Tolerance to therapeutic effects fast for other disorders. Reverse tolerance possible for some effects (brain seizures).

Question 31

Psychostimulant dependence.

Answer 31

Withdrawal: fatigue, sleep, depression, hunger Positive reinforcement: craving, anhedonia

Question 32

Effect of drugs of abuse on synaptic dopamine levels: 11C-raclopride

Answer 32

1) baseline density 2) density after drug abuse 3) (1-2), decrease in 11C-R binding= A) Decrease in D2/D3 receptors B) increase in synaptic dopamine

Question 33

Cocaine adminstration

Answer 33

Internasal: onset min, duration 60 min Inhalation: onset sec, duration 15 min

Question 34

Adminstration: Coco Leaves

Answer 34

Buccal

Question 35

Admin: Cocaine HCL or Speed

Answer 35

intranasal/intravenous

Question 36

Admine: Cocaine base or Ice

Answer 36

inhalation

Question 37

What amphetamine is racemic and less potent?

Answer 37

dextrolevoamphetamine (Benzedrine)

Question 38

What amphetamine is an active isomer?

Answer 38

dextroamphetamine (Dexedrine)

Question 39

What amphetamine is more potent in CNS?

Answer 39

dextromethamphetamine (Desoxyn)

Question 40

Amphetamine adminstration (uppers)

Answer 40

Uppers: Oral

Question 41

Amphetamine onset and duration of action: Oral vs. inhalation

Answer 41

Oral: Onset in 30 Minutes, Variable Duration | – Inhalation: Onset in Seconds, Duration of 15 Minute

Question 42

Amphetamine elimination

Answer 42

Half-life between 6-36 hours depending on renal pH Metabolites persist up to 3-5 days after last administration in urine and saliva, 90 days in hair Detection is affected by amount and duration of use, route of administration, metabolism, hydration, body size, percent body fat, age

Question 43

Cocaine is ___ than amphetamine

Answer 43

larger

Question 44

Amphetamine stimulates what?

Answer 44

``` Release DA/NE 1) enter by reuptake 2) leaky vesicles (primary) 3) inhibits MAO 4) High Concentration of DA and NE in Cytoplasm Reverses the Transport of DA and NE into Synapse ```

Question 45

sympathomimic effects

Answer 45

dilation airway/pupils inhibit digestions urinary retention increase body temp

Question 46

Toxic effects

Answer 46

``` Headache • Dizziness • Confusion • Agitation • Fatigue • Insomnia • Seizures • Cardiac Arrest • Stimulant Psychosis • Dental Disease (Amphetamine) • Neurotoxicity (Amphetamine) ```

Question 47

stimulant psychosis

Answer 47

paranoia, hallucination, delusion, stereotypy

Question 48

reverse tolerance for amphetamines can occur for

Answer 48

brain seizures

Question 49

cocaine vs. amphetamine in mesolimbic pathway

Answer 49

cocaine- blocks DA reuptake | amphetamine- stimulates DA release