CNS Stimulants

Question 1

amphetamines mechanism

Answer 1

Release monoamines, primarily NE and DO from nerve terminals in brain

Question 2

amphetamines are substrates for

Answer 2

neuronal monoamine uptake transporters NET and DA (not SERT)

–> competitive inhibition of DA and NE reuptake

Question 3

amphetamines mechanism once in nerve terminal

Answer 3

enter sympathetic nerve ending and displace stored NE and DE from vesicles –> cytoplasm
– release NE and DA out of DAT and NET in reverse

Question 4

Effects of amphetamines

Answer 4

locomotor stimulation, euphoria and excitement, insomnia, increased stamina (mental and physical fatigue reduced), anorexia ( food intake returns to normal with continued administration)

Question 5

AE amphetamines

Answer 5

Anxiety, irritability, restlessness
high dose- panic, paranoia
psychotic symptoms, anxiety, depression, cognitive impairment

Question 6

peripheral effects amphetamines

Answer 6

sympathomimetic - rise in BP, inhibit GI motility

Question 7

Locomotor and rewarding effects of amphetamines driven by

Answer 7

DA release
inhibited by destruction of DA containing nucleus accumben
inhibited by D2 receptor antagonists

Question 8

amphetamine psychosis

Answer 8

acute schizophrenic attack - hallucinations, paranoia, aggressive behavior
repetitive stereotyped behavior

antipsychotics = effective tx

Question 9

when amphetamine drug stopped

Answer 9

period of deep sleep
upon waking, feel lethargic, depressed, anxious, hungry

result of DA and NE depletion? recovery?

Question 10

amphetamines tolerance

Answer 10

devleops rapidly to euphoric and anorexic effects, but slowly to other

Question 11

amph dependence

Answer 11

strong psychological: insistent memory of euphoria
no clear-cut physical withdrawal syndrome
increase dose –> then uncontrolled binges –> high risk of acute toxicity

Question 12

PK amph

Answer 12

GI absorb
snorted or injected
smoked in crystal form
freely penetrate BBB
mainly excrete in urine (unchanged)
5-30 hrs, depending on urine flow and pH

Question 13

methylphenidate name

Answer 13

ritalin (amph like)

Question 14

ritalin mechanism

Answer 14

elevation of ec NE and DA

inhibits NET and DAT transporters (not a substrate of transporters - does not enter nerve terminal)

Question 15

PK ritalin

Answer 15

orally active, absorbed in intestine and colon
presystemic metabolism - only 20% enter systemic
slow absorption
half life 2-4 hrs

Question 16

clinical use ritalin

Answer 16

ADHD

Question 17

modafinil mechanism

Answer 17

increase Ec DA levels in striatum and nucleus accumbens

likely inhibits DA reuptake by binding DAT

Question 18

other effects madafinil

Answer 18

enhanced release of 5-HT, glutamate, histamine

inhibition of GABA release

Question 19

PK modafinil

Answer 19

gut absorb, metabolized in liver, half life 10-14 hrs

Question 20

uses modafinil

Answer 20

ADHD (adults, kids get rash), narcolepsy
shift work sleep disorder
excessive daytime sleepiness from sleep apnea

“wakefulness promoting agent”, enhance cognitive performance,

Question 21

MDMA

Answer 21

ecstasy

3,4-methylenedioxymethamphetamine, or MDMA

Question 22

MDMA effects

Answer 22

euphoria, loss of inhibitions, energy surge
stimulant + mild hallucinogenic effects
psychomimetic -affect thought, perception and mood (dream like)

Question 23

Potential use of MDMA

Answer 23

feelings of empathy and emotional closeness to others (empathogen) – useful in PTSD? depression?

Question 24

MDMA mechanism

Answer 24

inhibits monoamine transporters, principally the 5-HT transporter
Also releases 5-HT –> large increase in free 5-HT in certain brain regions (psychotomimetic)
similar changes occur in DA and NE (initial euphoria and later rebound dysphoria)
Followed by period of monoamine depletion

Question 25

AE MDMA

Answer 25

sudden illness and death can occur even after small doses of MDMA acute hyperthermia --> damage to skeletal muscle and consequent renal failure excess water intake and water retention (MDMA --> release ADH) heart failure in undiagnosed heart conditions

Question 26

after effects mdma

Answer 26

depression, anxiety, irritability, increased aggression | evidence of long-term deleterious effects on memory and cognitive function in heavy mdma users

Question 27

cocaine mechanism

Answer 27

binds to and inhibits transporters NET, DAT, SERT (reuptake)

Question 28

cocaine effects

Answer 28

euphoria, chattiness, increased motor activity, magnification of pleasure

Question 29

cocaine vs amphetamines

Answer 29

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

Question 30

peripheral sympathomimetic actions cocaine

Answer 30

tachycardia vasoconstriction increase in blood pressure body temperature may increase --> motor activity coupled with reduced heat loss

Question 31

overdose cocaine

Answer 31

tremors and convulsions | respiratory and vasomotor depression

Question 32

cocaine dependence

Answer 32

strong psych dependence - crave euphoria and stimulatory effects inc. dose, binges

Question 33

tolerance cocaine

Answer 33

debatable

Question 34

withdrawal cocaine

Answer 34

no clear-cut withdrawal syndrome | depression, dysphoria, fatigue

Question 35

PK

Answer 35

``` readily absorbed many routes nasal inhalation crack cocaine - smoked ~30 min affect metabolized in liver used as local anesthetic ```

Question 36

AE cocaine

Answer 36

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

Question 37

cocaine in utero

Answer 37

brain size reduce, neuro and limb malformations increased, incidence of ischemic/hemorrhagic brain lesions and SIDS

Question 38

methylxanthines

Answer 38

tea, coffee, cocoa mild central stimulant effects caffeine and theophylline

Question 39

methylxanthines effects

Answer 39

CNS stimulation Diuresis stimulation of cardiac muscle relaxation of smooth muscle, bronchial muscle

Question 40

MX effects on cardiac and smooth muscle resembe

Answer 40

beta-adrenoceptor stimulation inhibit phosphodiesterase --> increase intracellular cAMP --> effects that mimic mediators that stimulate Adenylyl cyclase

Question 41

stimulant mech MX

Answer 41

antagonize many effects of adenosine - acting on both A1 and A2 adenosine receptors (A2 more important)

Question 42

diuretic mech mx

Answer 42

The diuretic effect probably results from vasodilatation of the afferent glomerular arteriole, causing an increased glomerular filtration rate.

Question 43

clinical uses MX

Answer 43

aspirin ergotamine in migraine alertness respiratory stimulants in treatment of apnea in premature babies theophylline - bronchodilator in asthma attacks