Lecture 44: Stimulants

Question 1

On and off label indications for stimulants (6)

Answer 1

Exogenous obesity, ADHD, narcolepsy, fatigue, cessation of tobacco use, local anesthesia

Question 2

Broadly, cocaine and amphetamine do what?

Answer 2

Increase synaptic levels of DA, NE, and 5HT

Question 3

What is the mechanism of cocaine?

Answer 3

Inhibits DA reuptake

Question 4

What is the dual effect of amphetamines? How does this increase DA in the synapse?

Answer 4

Compete w/ DA for reuptake and for vesicular packaging; leads to nonvesicular release of DA

Question 5

What is the only FDA-approved use of cocaine?

Answer 5

Topical anesthetic

Question 6

What are the peripheral effects of cocaine and the underlying mechanism

Answer 6

Potent vasoconstrictor because it increases NE at sympathetic synapses

Question 7

Cocaine is eliminated where? (2) One important metabolite is useful for what function?

Answer 7

Plasma and hepatic esterases; metabolite can be detected in urine for up to a week after binge use

Question 8

Name the four key amphetamines in order of increasing half-lives. Where are they eliminated?

Answer 8

Methylphenidate, amphetamine, methamphetamine, phentermine; kidney

Question 9

Broadly, amphetamines are prescribe for two things…

Answer 9

ADHD and narcolepsy

Question 10

Which two amphetamine can also be prescribed for exogenous obesity?

Answer 10

Methamphetamine and phentermine

Question 11

Off-label, methylphenidate has been used…

Answer 11

To treat depression in medically ill older adults

Question 12

The D amphetamine isomer is active where? What about L? Relevance for methamphetamine? How about amphetamine?

Answer 12

D = CNS, L = ANS; D-meth = prescribed form, L-meth = decongestant; amph = mix (75% D)

Question 13

What are the cardio effects of amphetamines as they compare to cocaine?

Answer 13

Increase BP but variable effect on HR (can even see reflex bradycardia)

Question 14

Describe two phases of amphetamine withdrawal

Answer 14

“Crash” (anxiety, craving) then withdrawal (fatigue)

Question 15

Modafinil is prescribed for (3)…off label (2)…

Answer 15

Narcolepsy, shift disorder, sleep apnea; ADHD, fatigue in MS

Question 16

How is Modafinil similar and different compared to the amphetamines?

Answer 16

Stimulant, but structurally unrelated (mechanism not well understood), low risk of addiction

Question 17

Caffeine is a what at what receptor?

Answer 17

Adenosine receptor antagonist

Question 18

Nicotine is a what at what receptor?

Answer 18

Full agnoist at nAChRs

Question 19

CNS effects

Answer 19

Arousal, relaxation, enhanced mood, attention

Question 20

PNS effects

Answer 20

Increase BP, HR, CO, vasoconstriction

Question 21

At very high doses, what does nicotine cause?

Answer 21

Hypotension and bradycardia

Question 22

What are synthetic cathinones derived from? Where are they found (on the streets) and what is their mechanism similar to?

Answer 22

Khat; bath salts; amphetamines

Question 23

Hallucinogens do what at what receptor? (2 categories, name relevant drugs)

Answer 23

LSD, MDMA: partial agonist at 5HT2A receptor; PCP: NMDA glutamate receptor antagonist

Question 24

Are there tolerance or withdrawal symptoms for LSD/MDMA?

Answer 24

Tolerance, yes; withdrawal, no

Question 25

PCP comes with a high risk of…

Answer 25

Addiction

Question 26

Besides hallucinations, PCP intoxication can cause…What are some peripheral symptoms?

Answer 26

Hostile behavior, numbness, nystagmus; tachycardia, hypertension, sweating

Question 27

Toxic effects of PCP present as…(3)

Answer 27

Anesthesia, coma, cataonia

Question 28

Cannabinoids are all what at what receptors? These are normally activated how?

Answer 28

Agonists at cannabinoid receptors (mainly CB1); endocannabinoids are synthesized from cell bodies and diffuse retrograde onto afferent nerve terminals

Question 29

What is the most potent cannbindoid in marijuana?

Answer 29

THC

Question 30

Why can cannabinoids be detected in the urine for other a month?

Answer 30

Despite quick hepatoic metabolism, very lipid soluble and store in tissues

Question 31

Are there tolerance or withdrawal symptoms for marijuana?

Answer 31

Tolerance yes, withdrawal has been difficult to observe

Question 32

What is dronabinol prescribed for?

Answer 32

Anorexia in AIDS and antiemetic for patients who are undergoing chemotherapy

Question 33

Acutely, inhalants can cause? (4)

Answer 33

Euphoria, ataxia, hallucinations, seizures

Question 34

What are some of the toxicities of inhalants? (2 CNS and 4 affected organs)

Answer 34

Cerebellar degeneration, cognitive decline, kidney/heart/lung and bone marrow malfunction