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)
Stimulate monoamine neurotransmitters (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 -suppressed GI -stimulated cardiovascular
PSYCHOSIS
-hallucinations/delusions with high doses
PSYCHOLOGICAL DEPENDENCE
WITHDRAWAL
-depressed mood, fatigue
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 blood pressure
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
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
black box label warnings for Adderall, amphetamines
- high potential for abuse
- lead to drug dependence
- serious cardiovascular effects
schedule II drugs
High potential for abuse, currently accepted medical use
- restricted quantities
- highly controlled
atomoxetine (strattera) use and MOA
ADHD
Selective inhibitor of NE transport (NSRI)
NONSTIMULANT
Blocks NE reuptake so it is available in synapse for longer.
atomoxetine metabolism, schedule #
(ADHD) Hepatic metabolism (CYP2D6)
Schedule VI drug (non-stimulant)
atomoxetine concerns
- CNS
- GI
- Cardiovascular
- others:
- –dry mouth, urinary retention (anti-muscarinic)
- –priapism (prolonged, painful erection due to vasoconstriction)
- –drug interactions (if they block 2D6 then lead to toxicity)
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 –> prevents release of NTs (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
caffeine mechanism
(sleepiness)
MOA: adenosine receptor antagonist (same shape, but does not cause same effect, just blocks site)
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 -diuresis
concerns with caffeine
- CNS (seizures)
- suppressed GI
- cardiovascular overstimulation
- tolerance/withdrawal
- be cognizant of guarana (natural caffeine) and presence in supplements
metabolic byproducts of caffeine
All contain xanthine.
Paraxanthine is a prescription drug itself.
- bronchodilator
- narrow therapeutic window
- increased adverse effects
mechanism of Modafinil (provigil)
Blocks dopamine transporter (dopamine available in synapse longer).
Increases synaptic dopamine (DSRI).
Not entirely clear how it relates to sleep
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
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)
- exhibits GABA and dopamine-like effects
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
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
burpropion + Naltrexone use, MOA
Anorexiant
DA and NE reuptake inhibitor.
Opioid receptor antagonist.
fenfluramine and dexfenfluramine: old use, current use, MOA
Previous: anorexiant
Currently: off market
- serotonin modulation
- carried over to cardiac valves –> pulmonary hypertension
sibutramine: old use, current use, MOA
Previous: anorexiant
Currently: off market
NE, 5HT transport inhibition
-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, hypertension, dyslipidemia)
other agents used as anorexiants
OTC decongestants
GLP-1 analogs (non-stimulants)
Absorption inhibitors (non-stimulants)
