Psychostimulants Flashcards
general drugs for ADHD
- Amphetamines/Amphetamine-like agents (methylphenidate) (IR or XR)
- Atomoxetine (NSRI)
- Guanfacine and Clonidine (alpha-2 agonists)
amphetamines MOA
(ADHD)
Monoamine agonists –> stimulate monoamine NTs (promote release of biogenic amines from storage sites)
Prevents storage of dopamine in vesicles in the axon terminal.
High levels of dopamine.
Transporters push domamine into synaptic cleft due to high concentration.
main concerns for amphetamines
(ADHD) STIMULANT EFFECTS -increased CNS (insomnia) -GI (suppressed appetite, fullness, nausea) -stimulated CV (NE release)
PSYCHOSIS
- hallucinations/delusions with high doses
- bc inc dopamine in mesolimbic path
PSYCHOLOGICAL DEPENDENCE
-Schedule II
WITHDRAWAL
- depressed mood, fatigue
- start w/ low dose and work up
Why are there cardiovascular concerns with amphetamines?
(ADHD)
Stimulants –> stimulate NE release.
NE most readily stimulates Alpha-1 receptors –> increased vasoconstriction, increased peripheral resistance –> increased BP
management of overdose of amphetamines
(ADHD)
Control cardiovascular hemodynamics
-alpha blockers, nitrates
Sedatives
-benzodiazepines
Activated Charcoal
-ties up any drug still available to prevent further absorption
Change pH of urine to much lower than pKa of drug (urine trapping since amphetamines are basic)
names of amphetamines/-like agents
(ADHD) Amphetamine (Benzedrine) -dextroamphetamine (dexedrine) -amphetamine + detroamphetamine (Adderall, most common) -lisdexfetamine (Vyvanse)
Methylphenidate (Ritalin)
- dexmethylphenidate (focalin)
- have fewer cardiovascular effects (NE effects are confined to brain)
black box label warnings for Adderall, amphetamines
- high potential for abuse
- lead to drug dependence (limbic path path stimulated)
- serious cardiovascular effects
schedule II drugs
High potential for abuse, currently accepted medical use
- restricted quantities
- highly controlled (need signature/DEA#, telephone for emergencies only, etc.)
atomoxetine (strattera) use and MOA
ADHD
Selective inhibitor of NE transport (NSRI)
NONSTIMULANT
Blocks NE reuptake so it is available in synapse for longer in prefrontal cortex.
similar mech to anti-depressants.
atomoxetine metabolism, schedule #
(ADHD) Hepatic metabolism (CYP2D6)
Schedule VI drug (non-stimulant)
atomoxetine concerns
- CNS (insomnia)
- GI (appetite suppression)
- Cardiovascular (inc bp)
- others:
- –dry mouth, urinary retention (anti-muscarinic)
- –priapism (prolonged, painful erection due to vasoconstriction)
- –drug interactions (if they block 2D6 then lead to toxicity bc inhibits clearance)
black box label warning for atomoxetine
Increased risk of suicidal ideation.
- unclear why
- confounding
- overall very small risk
Guanfacine, Clonidine use/MOA
ADHD
MOA: alpha-2 receptor agonists (sympatholytic) –> prevents release of NTs
(recall alpha-2 receptors - when stimulated - suppress release of transmitter)
(MOA for ADHD unclear)
side effects of Guanfacine, Clonidine
(ADHD)
Sedation
Dry mouth
Hypotension
what schedule # is Guanfacine and Clonidine?
(ADHD)
Schedule VI drugs
drugs for treatment of sleepiness, narcolepsy, cataplexy
Caffeine
Modafinil
Gammahydroxybutyrate
caffeine is an analog to ________
caffeine is an analog to ADENOSINE (an endogenously produced nucleoside that normally INHIBITS transmitter release)
caffeine mechanism
(sleepiness)
MOA: adenosine receptor antagonist (same shape, but does not cause same effect, just blocks site)
- ultimately inhibiting an inhibitor –> inc transmitter release
Adenosine binding to PRESYNAPTIC receptor:
- closes Ca++ channels
- decreased NT release
Adenosine binding to POSTSYNAPTIC receptor:
- open K+ channel
- hyperpolarizes cell
- decreased response to stimuli
If BLOCKED:
- increased NT release
- increased response to stimuli
pharmacological effects of caffeine
(sleepiness) Effects: -increased arousal and alertness -anorexia -cardiac and smooth muscles effects (inc BP, HR) -diuresis
concerns with caffeine
- CNS (seizures)
- suppressed GI
- cardiovascular overstimulation
- tolerance/withdrawal (rebound effect, cranial vasodilation –> HA)
- be cognizant of guarana (natural caffeine) and presence in supplements
metabolic byproducts of caffeine
All contain xanthine.
Theophylline is a rx drug itself.
- bronchodilator
- narrow therapeutic window
- increased adverse effects (more intense caffeine-like sx)
mechanism of Modafinil (provigil)
Blocks dopamine transporter (dopamine available in synapse longer).
Increases synaptic dopamine (DSRI).
Not entirely clear how it relates to sleep
isomer: armodafinil
Modafinil uses
Excessive sleepiness.
- narcolepsy
- shift work
- obstructive sleep apnea
schedule # for Modafinil?
schedule IV
-potential for abuse, but minor
gammahydroxybutyrate (GHB) is also known as
Sodium oxybate (Xyrem)
(used for cataplexy/narcolepsy)
date rape drug.
use of GHB (gammahydroxybutyrate)
Cataplexy (low muscle tone –> falls).
Narcolepsy.
Promotes profound sleep at night, so less likely to fall asleep the next day.
MOA of gammahydroxybutyrate (GHB)
(narcolepsy, cataplexy)
-potent enhancer of GABA (powerful sedative bc GABA is primary inhibitor)
-exhibits GABA and dopamine-like effects
^ DA/GABA agonism
date rape drug (conscious sedation)
schedule # of GHB
(narcolepsy, cataplexy)
schedule III
bc date rape drug
concerns with GHB (gammahydroxybutyrate)
(narcolepsy/cataplexy)
Fatal overdose due to respiratory depression.
names/types of anorexiants
- phentermine: NE transporter inhibition
- lorcaserin: 5HT(2C) receptor agonist
- bupropion + naltrexone: DA and NE reuptake inhibitor and opioid receptor antagonist
anorexiants are used to
Reduce appetite. Treat obesity.
Moderate weight gain.
Have rebound effect when stop using so beware.
phentermine (lonamin) MOA
anorexiant
NE transporter inhibition
- NE stays in synapse longer, acts as stimulant
- sympathetic NS activated, parasympathetic suppressed
side effects of phentermine
(anorexiant)
- increased BP
- increased arousal
- irritability
due to increased NE
lorcaserin (belviq) use, MOA
anorexiant
5HT(2C) [serotonin] receptor agonist
- more serotonin produced
- change in hypothalamus
- less hungry
-similar receptor being modulated as fen-phen –> possibly future cardiomyopathy issues?
burpropion + Naltrexone use, MOA
Anorexiant
DA and NE reuptake inhibitor.
Opioid receptor antagonist. (prevent reward pathways from being stimulated. No reward when people eat.)
fenfluramine and dexfenfluramine: old use, current use, MOA
(fen-phen)
Previous: anorexiant
Currently: off market
- serotonin modulation
- carried over to cardiac valves –> pulmonary HTN
sibutramine: old use, current use, MOA
Previous: anorexiant, stimulant drug
Currently: off market
NE, 5HT transport inhibition
- more NE in periphery –> CV side effects
main concerns with anorexiants
- CNS
- cardiovascular
- rebound effects on discontinuation
- commonly found undeclared in dietary supplements
candidate for anorexiants if:
- obese and unresponsive to lifestyle modification
- overweight with comorbidities (diabetes, HTN, dyslipidemia)
other agents used as anorexiants
OTC decongestants (in sudafed prods, stim alpha-1-r or promote NE release) GLP-1 analogs (non-stimulants) Absorption inhibitors (non-stimulants)
Methylphenidate (Ritalin) has lesser risk of cardiac side effects, why?
ability of NE to promote methylphenydate release seems to be confined to brain, not periphery or extremities
MA schedule of drugs
schedule I: high abuse potential (no accepted med use (heroin, cocaine used illicitly)
schedule II: high abuse potential, accepted med use (amphetamines)
schedule III-IV: less potential for abuse
schedule VI: all other rx drugs (penicillin)
Phentermine is sometimes used in combo w/ which med?
topiramate (Qsymia)
an anti-convulsant that promotes nausea.
Are lorcaserin and buoprion+naltrexone stimulants?
NOT stimulants.
Rx’d for weight loss via acting in hypothalamus to suppress appetite.
Order of pharmacological tx for ADHD
- stimulants (methylphenidate or amphetamine)
- stimulants (try another subtype)
- atomoxetine (Strattera)
- buproprion
- tricyclic antidepressants
- alpha agonists
