CNS Stimulants

Question 1

List the amphetamines (3)

Answer 1

i) DL-amphetamine (Adderall, Speed)
ii) Dextroamphetamine (More potent D-isomer of amphetamine, Dexedrine)
iii) Methamphetamine (Crystal meth)

Question 2

Amphetamines release monoamines, primarily __________and _________, from nerve terminals in the brain

Answer 2

norepinephrine, dopamine

Question 3

i) NET =

Answer 3

norepinephrine transporter

Question 4

ii) DAT =

Answer 4

dopamine active transporter

Question 5

__________ Enter the sympathetic nerve ending and displace stored NE and DA
i) “Displacer” effect – NE and DA released

Answer 5

Amphetamines

Question 6

_____________At high concentration – Inhibit monoamine oxidase (MAO)
[MAOs break down DA and NE]

Answer 6

Amphetamines

Question 7

The main central effects of amphetamine-like drugs are

Answer 7

Locomotor stimulation, Euphoria and excitement, Especially intense with IV injection, Insomnia, Increased stamina, Anorexia

Question 8

c) Amphetamine Peripheral sympathomimetic effects – rise in _____________, inhibition of ______________

Answer 8

blood pressure, gastrointestinal motility

Question 9

Amphetamine stimulant effect lasts for a few hours, followed by ______ and ______

Answer 9

depression and anxiety

Question 10

i) If amphetamines taken repeatedly over a few days
ii) Resembles an acute schizophrenic attack – hallucinations, paranoia and aggressive behavior
iii) Repetitive stereotyped behavior may develop

Answer 10

Amphetamine psychosis

Question 11

develops rapidly to euphoric and anorexic effects of amphetamines, but more slowly to the other effects.

Answer 11

Tolerance

Question 12

No clear-cut physical withdrawal syndrome

Answer 12

6) Amphetamines

Question 13

a) Readily absorbed from the gastrointestinal tract
b) Can be snorted or injected
c) Smoked in crystal form (crystal meth)
d) Freely penetrate the blood–brain barrier
e) Mainly excreted unchanged in the urine
f) The plasma half-life of amphetamines varies from 5 to 30 hours, depending on urine flow

Answer 13

7) Amphetamines PharmacokinetiCs

Question 14

a) Profound and sustained elevation of extracellular NE and DA
b) Inhibits the NET and DAT transporters
i) (Also inhibits SERT, but with much lower potency)
c) NOT a substrate for NET/DAT transporters –> does not enter the nerve terminals to facilitate NE and DA release
d) Orally active, absorbed from the intestine and colon

Answer 14

Methylphenidate (Ritalin)

Question 15

Methylphenidate (Ritalin) Clinical use:

Answer 15

e) Clinical use: attention deficit/hyperactivity disorder (ADHD)

Question 16

a) Increases extracellular DA levels in striatum and nucleus accumbens
i) Likely inhibits DA reuptake by binding to DAT
b) Other effects:
i) enhanced release of 5-HT, glutamate and histamine
ii) inhibition of GABA release
c) Well absorbed from the gut, metabolized in the liver and has a half-life of 10–14 h.

Answer 16

9) Modafinil

Question 17

d) Used in treatment of narcolepsy
e) Promoted as a ‘wakefulness promoting agent’ rather than a classic amphetamine-like stimulant
f) Reported to ‘brighten mood’
g) Claimed to enhance cognitive performance
h) Effective treatment for ADHD in adults
i) No euphoria when administered by mouth

Answer 17

9) Modafinil

Question 18

a) 3,4-methylenedioxymethamphetamine, or MDMA
b) Widely used as a party drug
c) Euphoria, loss of inhibitions, and energy surge that it induces
d) Stimulant + mild hallucinogenic effects

Answer 18

Psychotomimetic

Question 19

e) ______________- affect thought, perception and mood

i) Thoughts and perceptions become distorted and dream-like, rather than being merely sharpened or dulled

Answer 19

Psychotomimetic

Question 20

e) Psychotomimetic

f) Feelings of empathy and emotional closeness to others (empathogen)

Answer 20

10) MDMA (Ecstasy)

Question 21

a) An amphetamine derivative
b) Inhibits monoamine transporters, principally the 5-HT transporter
c) Also releases 5-HT
d)  large increase in free 5-HT in certain brain regions
i) Similar changes occur in with DA and NE
e) Followed by monoamine depletion

Answer 21

11) MDMA Pharmacological Effects

Question 22

j) Sudden illness and death can occur even after small doses of MDMA. This can be due to several factors:

Answer 22

Acute hyperthermia
Excess water intake and water retention
heart failure

Question 23

d) The stimulant effects have not proved to be clinically useful
i) But have led it to becoming a widespread drug of abuse.

Answer 23

12) Cocaine

Question 24

Cocaine Pharmacological Effects

Answer 24

a) Binds to and inhibits the transporters NET, DAT and SERT
i) marked psychomotor stimulant effect
ii) enhances the peripheral effects of sympathetic nerve activity
b) Euphoria, chattiness, increased motor activity, magnification of pleasure
c) Users feel alert, energetic and physically strong and believe they have enhanced mental capabilities

Question 25

d) Effects similar to amphetamines | i) less tendency to produce stereotyped behavior, delusions, hallucinations and paranoia

Answer 25

13) Cocaine Pharmacological Effects

Question 26

13) Cocaine Pharmacological Effects: e) Euphoric effects involve inhibition of both ___ and ____ reuptake

Answer 26

DA and 5-HT

Question 27

Cocaine peripheral sympathomimetic actions

Answer 27

tachycardia vasoconstriction increase in blood pressure

Question 28

g) Body temperature may increase, owing to the increased motor activity coupled with reduced heat loss.

Answer 28

13) Cocaine Pharmacological Effects

Question 29

h) Overdose: i) tremors and convulsions ii) respiratory and vasomotor depression

Answer 29

Cocaine

Question 30

c) No clear-cut withdrawal syndrome | i) Depression, dysphoria and fatigue may be experienced following the initial stimulant effect

Answer 30

Cocaine

Question 31

readily absorbed by many routes b) Hydrochloride salt: nasal inhalation or IV i) Intense and immediate euphoria with IV ii) Nasal inhalation less dramatic (1) Atrophy and necrosis of the nasal mucosa and septum.

Answer 31

Cocaine

Question 32

e) Rapidly metabolized in the liver | f) Occasionally used topically as a local anesthetic

Answer 32

Cocaine

Question 33

exposure during pregnancy -- in utero impact i) Brain size is significantly reduced ii) Neurological and limb malformations are increased iii) Incidence of ischemic, hemorrhagic brain lesions, and SIDS, also higher in cocaine-exposed babies

Answer 33

Cocaine

Question 34

b) Serious cardiovascular events i) Cardiac dysrhythmias ii) Aortic dissection iii) Myocardial or cerebral infarction or hemorrhage iv) Progressive myocardial damage can lead to heart failure, even in the absence of a history of acute cardiac effects c) Dependence

Answer 34

Cocaine

Question 35

a) Tea, coffee and cocoa b) Mild central stimulant effects c) Main compounds caffeine and theophylline

Answer 35

17) Methylxanthines

Question 36

a) Methylxanthines have the following major pharmacological actions:

Answer 36

i) CNS stimulation ii) Diuresis iii) Stimulation of cardiac muscle iv) Relaxation of smooth muscle, especially bronchial muscle

Question 37

i) inhibit phosphodiesterase | ii) Block PDE, increase intracellular cAMP  effects that mimic those of mediators that stimulate adenylyl cyclase

Answer 37

methylxanthines

Question 38

c) Antagonize many of the effects of adenosine, acting on both A1 and A2 adenosine receptors

Answer 38

methylxanthines

Question 39

d) The diuretic effect of methylxanthines probably results from vasodilatation of the afferent glomerular arteriole, causing an increased _________________

Answer 39

glomerular filtration rate

Question 40

19) Methylxanthines Clinical use

Answer 40

b) Effective respiratory stimulants in the treatment of apnea of prematurity i) Developmental disorder caused by immaturity of central respiratory control ii) Caffeine is preferred to theophylline because of its long half-life and safety c) Theophylline is used mainly as a bronchodilator in treating severe asthmatic attacks. d) Mutagenic activity in vitro, and large doses are teratogenic in animals

Question 41

CLINICAL USES OF CNS STIMULANTS: b) Attention deficit/hyperactivity disorder (ADHD):

Answer 41

i) Amphetamines ii) Methylphenidate iii) Modafinil

Question 42

20) CLINICAL USES OF CNS STIMULANTS: c) Narcolepsy

Answer 42

modafinil for the excessive sleepiness

Question 43

20) CLINICAL USES OF CNS STIMULANTS:d) Apnea of prematurity

Answer 43

xanthine alkaloids (under expert supervision in hospital) are effective; caffeine is preferred to theophylline

Question 44

rare, disabling sleep disturbance i) Sudden, unpredictable sleep during day ii) Nocturnal insomnia iii) Often accompanied by cataplexy (1) abrupt onset of paralysis of variable extent often triggered by emotion, sometimes with ‘frozen’ posture iv) Amphetamine is helpful but not completely effective v) Modafinil is also effective in reducing the need for sleep

Answer 44

e) Narcolepsy

Question 45

Catecholamine release, inhibition of catecholamine uptake

Answer 45

Amphetamines

Question 46

Dexamphetamine used for ADHD; narcolepsy; otherwise important as drugs of abuse

Answer 46

Amphetamines

Question 47

Inhibition of catecholamine uptake

Answer 47

Methylphenidate

Question 48

ADHD

Answer 48

Methylphenidate

Question 49

Unclear, likely inhibits DA uptake

Answer 49

Modafinil

Question 50

Reduce fatigue, enhance cognition

Answer 50

Modafinil

Question 51

Inhibition of catecholamine uptake; also a local anesthetic

Answer 51

Cocaine

Question 52

Occasionally for nasopharyngeal or opthalmic anesthesia; otherwise important drug of abuse

Answer 52

Cocaine

Question 53

Inhibition of phosphodiesterase, antagonism of adenosine A2 receptors

Answer 53

Methylxanthines | caffeine and theophylline

Question 54

Widely consumed in beverages, some clinical use unrelated to CNS stimulation (cardiac and bronchial actions)

Answer 54

Methylxanthines | caffeine and theophylline

Question 55

5-HT release and blocks reuptake

Answer 55

MDMA

Question 56

Nothing currently, potential in PTSD and depression; important as drug of abuse

Answer 56

MDMA