psychostimulants 2 Flashcards
Dexedrine names
Chemical - (S)-1-phenylpropan-2-amine
Generic-dextroamphetamine
Trade- Dexedrine
Benzedrine
dextrolevoamphetamine
- Racemic
- Least potent
dexedrine
dextroamphetamine
Active isomer
Desoxyn
methamphetamine
-most potent in CNS
Amphetamine administration
All Forms
-oral
Methamphetamine
- Intranasal
- Intravenous
- Inhalation
Amphetamine weak base absorbtion
- increasing GI Absorbtion with Increasing PH
- Rapid Absorbtion by inhalation
Amphetamine onset and duration of action
Oral:
Onset in 30 minutes, duration 6 hours
Inhalation:
Onset in seconds, Duration 15 minutes
Amphetamine distribution
crosses the blood brain barrier
amphetamine metabolism
Via liver
First order
Amphetamine Elimination
- Increased excretion at lower renal pH
- Antacids Decrease Excretion, Increase Duration
Amphetamine Half-Life
- 6-36 hours Depending on Renal pH
- Metabolites Persist up to 3-5 days After Last Administration, much longer in heavy users
Amphetamine action at synapse
- Enhances release of catecholamines
- Blocks reuptake of catecholamines
- inhibits monamine oxidase (MAO)
- Agonist at Catecholamine Receptors
Amphetamine synapse stimulation
1) enters Neuron via Reuptake
2) Forces DA/NE from Vesicles
3) Inhibits MAO to Reduce DA/NE Breakdown
4) Reverses Transport of DA/NE into Synapse
MicroDialysis
Measurement of Transmitters and their Metabolites in specific Brain regions of behaving rats
-Amphetamine increases Extracellular NE and Da in Prefrontal Cortex
Amphetamine therapeutic usis
approved:
Narcolepsy
ADHD
off label:
Obesity
Depression
Attention Deficit Hyperactivity Disorder (ADHD)
subtypes
- ADHD - Predominantly inattentive
- ADHD - Hyperactive / Impulsive
- ADHD - Combined
Attention ADHD: possible disfunctions
Frontal lobe
-Executive Functions and Working Memory
Executive functions (Right Prefrontal Cortex)
- attention
- planning
- impulse control
- mental flexibility
- monitoring actions
- PreFrontalCortex lesions (Right)
- Distractibility
- Disorganization
- Impulsivity
- Perseveration
- Forgetfulness
Prefrontal Cortex inhibition
confers inhibition on other brain regions -Motor and premotor cortices -Basal Ganglia: Striatum (caudate) Subthalamic nucleus
Cerebellum via pons
psychostimulants effects on add
reset the balance of noradrenergic and dopaminergic neurotransmission in the prefrontal cortex
NE - alpha2A receptors
DA - D1 receptors
Too little alpha2A/D1 ratio leads to drowsiness
-to high ratio leads to stress, misguided attention/responses, Mental Inflexibility, stimulus bound
Attention Deficit Hyperactivity Disorder treatment formulations:
Amphetamines
Dexedrine- dextroamphetamine (1-3)
Adderall - amphetamine salts(1-3)
Attention Deficit Hyperactivity Disorder treatment formulations:
methylphenidates
Ritaline - Methylphenidate(2)
Concerta - Methylphenidate ER (1)
Daytrana - methylphenidate ER(1)
Attention Deficit Hyperactivity Disorder treatment formulations:
Strattera
Atomoxetine
- non-stimulant
- noradrenertic reuptake blocker
- Somewhat less effective than psychostimulants
- lower risk of abuse
Attention Deficit Hyperactivity Disorder treatment formulations:
vyvanse
Vyvanse - lisdexamfetamine (1)
- Prodrug
- Converted to D-amphetamine
- Longer duration of action
- Lower risk of abuse
ADHD psychostimulant therapeutic effects
- improve attention span and focus
- increase ability to follow directions
- decrease distractibility
- decrease impulsivity, stubbornness, aggression
Psychostimulant ADHD side effects
- increased heart rate and blood pressure
- Dizziness, headache
- Insomnia
- Poor appetite, weight loss
- Suppressed growth
- abuse potential
ephedrine
amphetamine-like
(ma huang)
stimulant, anti-asthma
fenfluramine
serotonergic
weight control
phenylephrine
alpha1 agonist
decongestant
Bath salts
cathinone (Khat extract)
synthetic cathinones
amphetamine-like structure
Amphetamine-like effects
Drug Tolerance
reduced effect of a drug after repeated administration
increased dose restores original effect
Tolerance Varies with drug
Tolerance varies with drug effect
mechanisms of tolerance
metabolic tolerance (dispositional)
Celllular Tolerance (Pharmacodynamic)
Behavioral Tolerance
Contextual Tolerance (Situational)
Metabolic tolerance
increase in metabolism
Cellular Tolerance
Pharmacodynamic
Behavioral tolerance
functioning in presence of drug
Contextual Tolerance
Context in which drug is taken induces tolerance
psychostimulant tolerance
Rapidly forming
Slowly or not Forming
Reverse Tolerance (sensitization)
psychostimulant Rapidly Forming Tolerance
Appetite suppression
Euphoria
Cardiovascular Effects
Lethal Effects
Psychostimulant Slowly or Not Forming Tolerance
Effect on Narcolepsy
Effects on ADHD
psychostimulant Reverse Tolerance
Seizures
Locomotion
Drug dependence
physical dependence
psychological dependence
physical dependence
withdrawal syndrome
opposite of acute effects
psychological dependence
Reinforcing effect of Drug
“Drug Craving”
Psychostimulant physical Dependence
Fatigue and exhaustion
Prolonged sleep
Depression or Crash
Intense Hunger
Psychostimulant psychological dependence
Extremely powerful
intense craving
anhedonia (inability to feel pleasure)
self administration
Cocaine ratings
Withdrawal: 3.5 to 4
Reinforcement: 1
1 is most serious, 6 is least serious
models of drug dependence
physical dependence
positive reinforcement
incentive sensitization
physical dependence model (Wikler)
physical withdrawal maintains dependence.
initial drug use - repeated drug use - physical dependence - Attempts at abstinence - Withdrawal symptoms - relapse
Then goes back up to attempts at abstinence
Positive Reinforcement Model (Koob)
Reinforcement maintains dependence
initial drug use - positive reinforcement - repeated drug use - Attempts at abstinence - Compulsive desire to re-experience drug-induced euphoria - relapse
then goes back up to attempts at abstinence
Positive reinforcement
Dopamine activity is what is reinforcing
Cocaine Mesolimbic Pathway (DA)
Cocaine blocks DA reuptake amphetamine Stimulates DA release
Nucleus accumbens
incensitive sensitivation model summary
brain becomes sensitized to effects of drugs
increased dopamine activity increases salience of rewarding stimuli
alters brain structure
incentive sensitivation model
initial drug use - positive reinforcement - repeated drug use - Sensitization of drug "wanting" but not drug "liking" -Attempts at abstinence - Compulsive desire for the drug due to a sensitized incentive salience system - relapse
then goes back to attempts at abstinence
brain changing model
repeated drug administration - transcription factors - gene expression - Dendritic remodeling in Nucleus Accumbens - Drug Addiction
neurotoxicity in striatum
amphetamine use leads to neurotoxicity of Dopamine transporter neuronws in striatum
-less afferents to striatum
meth mouth
dry mouth
clenching
poor dental hygiene
