Stimulant Misuse

Question 1

Stimulant use trends

Answer 1

-40% of OD deaths
-most federal drug offenses
-17.2 million ppl w rx (access)
-use exceeds opioid use

Question 2

Stimulants effects

Answer 2

-activate CNS
-alertness, excitation, elevated mood

Question 3

Stimulants

Answer 3

-Nicotine
-MDMA (ecstasy)
-meth
-methylphenidate
-cocaine
-amphetamine
-pseudophed
-fenethylline
-bath salts
-cathinones?: bath salts, molly, flakka, scarface, plant food

Question 4

Nicotine and stimulant effect on DA reward system

Answer 4

-nicotine interact w glutamate and DA
-stimulants in pre-synaptic region to inc DA

Question 4

Nicotine MOA

Answer 4

-activates nicotinic acetylcholinergic receptor
-Na enters, K exits = action potential
-pentameric heterogeneity of subunits determines how many molecules of Ach bind to receptor
-at least 12 diff subunits
-variation in receptor composition at dif sites may influence response

Question 5

Ach vs nicotine

Answer 5

-both have charged amino groups and H bond acceptor groups
-nicotine is membrane penetrable at pH (weak base)
-nicotine not degraded by Ach-esterase SIGNIFICANCE
=nicotine last longer and more profound bc it is reuptaken

Question 6

Nicotine Addiction Liability

Answer 6

-1/3 become addicted to tobacco
-highest rate of all substances
-but why doesnt everyone get addicted? - pharmacology alone not sufficient

Question 7

Nicotinic partial agonist therapy

Answer 7

-cause release of DA
-highly addictive
-nicotine replacement therapy ineffective alone (gum, spray)
-varenicline inc quit rate success

Question 8

Stimulant structure

Answer 8

-aromatic ring
-look p similar to DA and NE

Question 9

Pseudophed

Answer 9

-pseudophed makes meth if OH reduced to H w ammonia
-phenylephrine cannot be reduced (nasal effective, not oral)
-OTC is regulated but meth OD is still up

Question 10

Fenethylline

Answer 10

-AKA captagona and Abu Hilalai
-invented 1960s for ADHD
-widespread in Syria and arabian peninsula
-amphetamine + theophyline (similar to caffeine)

Question 11

Cocaine MOA

Answer 11

-antagonists of DAT >/= SERT > NERT
-prevent DA uptake
-inc DA concentration and duration in nucleus accumbens

Question 12

Methamphetamine/XTC/bath salt MOA

Answer 12

-compete for reuptake
-resemble DA, NE
-block DA uptake
-push DA out from vesicles!
-reverse transport (gradient)
-amphetamines are MAOis
-activate Trace amine-associated receptor (TAAR1)
-phosphorylates DAT
-induces reverse transport! function (pumping DA out)

Question 13

Canthiones

Answer 13

-Catha edulis
-derivatives of Khat plant (arabia/africa)
-mild euphoria/excitement
-similar to strong coffee
-synthetics produced in China and southeast Asian countries
-$25-35 per half gram package
-bath salts, plant food, molly, flakka, scarface (nutmeg?)

Question 14

Clinical effect of meth abuse

Answer 14

-delirium, tremor
-anxiety, paranoia, hallucinations, repetitive behavior
-dental decay
-tachycardia, HTN, vasospams
-diaphoresis

Question 15

Brain on Meth

Answer 15

-DA receptor changes (similar to NE and 5-HT on antideppressants)
-receptor downregulation maybe mediates withdrawal sx
-DA downregulation not evidence of broken brain
-recovery of DA receptors shows ability to return to homostasis
-consider: can substitution tx prevent return to homeostasis + full recovery?

Question 16

Do addicitve drugs inc brain dopamine

Answer 16

-not straight-forward
-role of DA far more complex

Question 17

Use of stimulants as cognitive enhancers

Answer 17

-cognitive enhancement/wakefullness turns to addiction, psychosis w inc dose
-not necessarily cognitive benefit
-abuse among college kids crazy

Question 18

Sympathomimetic Toxidrome (MATHS)

Answer 18

-Mydriasis
-Agitation, Arrhytmia, Angina
-Tachycardia
-HTN, Hyperthermia
-Seizure, Sweating

Question 19

Sympathomimetic toxidrome tx

Answer 19

1. benzos for HTN, agitation, sz
2. avoid B-blockers due to unapposed alpha agonism
   -HTN responds to sedation
   -hyperthermia denotes poor prognosis
   -aggression and paranoia often seen