(7) psychostimulants Flashcards
What are psychostimulants?
- “sympathomimetics”: mimics activity in SNS
- elevate mood
- increased energy & stamina
- commonly used for medicinal purposes
- commonly abused
What is ephedra?
- naturally derived, found almost everywhere
- contains ephedrine & pseudoephedrine
- used as decongestant (Sudafed)
- also used for weight loss, increased energy, etc.
- banned from USA in 2004 (but not Canada)
What are amphetamines?
- laboratory synthesis
- useful in congestion, narcolepsy, weight loss, ADHD, “performance enhancement”
- aka Benzedrine, Adderall, Vyvanse, “speed”, d-amphetamine:
- aside: optical isomers (D & L), aka enantiomers, racemic mixtures
- racemic mixture: pill/inhaler has D & L - amphetamine
- aside: optical isomers (D & L), aka enantiomers, racemic mixtures
What is methamphetamine?
- semi-synthetic: synthesised from ephedrine/pseudoephedrine
- aka Desoxyn, “crystal meth”
- similar history to amphetamine (e.g. WWII)
- still sometimes used for ADHD, congestion
- primarily street drug
- v. high addiction potential
- stimulant psychosis frequent w/ high doses: show positive symptoms of schizophrenia
What is methylphenidate?
- laboratory synthesis
- aka Ritalin, Concerta, “kiddie coke”
- similar effect to amphetamine
- but effects weaker & shorter-lasting: only until noon
- often preferred as childhood ADHD prescription
What is cathinone?
- derived from khat plant
- e.g. khat (Catha edulis), bath salts (synthetic)
- khat relatively benign but treated like menace
- bath salts less benign
- similar mechanism to other psychostimulants
- synthesised from cathinone:
- Mephedrone
- Methylone
- Methylenedioxypyrovalerone
What are synthetic cathinones?
- v. potent, level similar to methamphetamine
- strong effects
- changes to monoamine systems
- experience psychosis
What is cocaine?
- derived from coca plant
- coca used for ages
- also anaesthetic, analgesic & blood vessel constrictor
- cocaine prep: base → salt → base
- salt: insufflated, injected
- free base: inhaled (i.e. crack cocaine)
What patten can be discerned by examing drug type and addictive potential?
ephedra, khat, coca:
- used for thousands of years w/ almost no consequences
- ingested: lower bio availability
semi-synthetics & synthetics (methamphetamine, synthetic cathinones, cocaine):
- associated w/ potentially adverse outcomes
- inhaled/insufflated: higher bio availability
What are the basic pharmacokinetic properties of psychostimulants, including time to peak effect, active metabolites, polydrug use and elimination rates?
route of administration: more directly to blood stream, more intense & faster peak effect
biotransformation: when drugs metabolised, can produce active metabolites
- active metabolites extend time of drug effect
- metabolites that result from polydrug use, e.g. cocaethylene, ethylphenidate
elimination/half-lives:
- amphetamines: 10-11 hours
- methylphenidate: 2 hours
- cathinones: 1.5 hours
- cocaine: 1 hour
What are the pharmacodynamic actions of amphetamine and cocaine?
amphetamine:
- affects vesicles
- go into vesicles & displace DA
- push DA from vesicles into axon terminal
- reverse DA transporters, more DA released
cocaine:
- reuptake inhibitor: blocks DA transporter
- vesicular transporter: pack more DA than usual into vesicles
Do psychostimulants only increase dopamine neurotransmission? What is DAT, NET and SERT?
- no, usually affect multiple monoamine systems
- DAT, NET, SERT all very similar
- DAT: dopamine transporter
- NET: norepinephrine transporter
- SERT: serotonin transporter
What are the pharmacological effects of psychostimulants? (objective-physiological)
- increased HR
- blood-vessel constriction (high BP)
- airway relaxation
- pupil dilation
- dry mouth (reduced salivation)
- inhibited digestion
- increased body temp
- tooth decay w/ chronic use
What are the pharmacological effects of psychostimulants? (objective-behavioural)
- psychosis, including hallucinations
- increased motor activity
What are the pharmacological effects of psychostimulants? (subjective)
- increased energy, alertness
- improved sense of well-being (low dose)
- euphoria (higher dose)
- anxiousness
- agitation
What are the behavioural effects of psychostimulants?
- low doses increase purposeful behaviour
- higher doses increase purposeless behaviour: stereotypy, punding
What is stereotypy?
stereotyped behaviour of species
What is punding?
nail biting, teeth grinding, skin scratching
What are the subjective effects of psychostimulants?
- similar across most: drug-discrimination studies - amphetamine (high) & cocaine (sober)
- lower doses: increased sense of alertness, of energy & of well-being
- higher doses: rush/euphoria
What factors confer an increased risk of psychostimulant addiction?
- route of administration & polydrug use are predictors
- women more likely
- genetic differences: predisposed to feeling effects
- drug metabolism
- positive effects
- negative effects: polymorphism - decreases ability to convert dopamine into norepinephrine
- addiction directly related to dopamine release onto nucleus accumbens
What are the primary phases of recovery?
- detoxification: abstaining from drug & adaptations in system going away
- relapse
What are the numerous treatment types for relapse and why are they unsuccessful?
- disulfiram
- modafinil
- tricyclic antidepressants
- anticonvulsant drugs
- vaccine?
- not changing environment, individual’s cues & circumstances
What is disulfiram?
- reduces positive effects of psychostimulant use
- prevents DA from turning into NE → creates unpleasant feeling
- low compliance: stop using drug before stop using psychostimulant
What is modafinil?
- psychostimulant, safer
- drug replacement therapy: give safer alternative
What are tricyclic antidepressants?
- reduce cravings & depression associated w/ detox & withdrawal
- low efficacy
What are anticonvulsant drugs?
- drugs for epilepsy (prone to seizures, convulsions)
- decrease brain function, increase GABA function
What does a vaccine do?
- create antibodies
- bind to & destroy drug before reach targets in brain
- high antibody: no big difference to low antibody & placebo
If people with ADHD are hyperactive, why do stimulants improve their symptoms?
- ADHD: extreme inattention, hyperactivity, impulsivity
- psychostimulants (amphetamine, methylphenidate) improve symptoms
- hypothesis: ADHD driven by low DAfunction
- low & high levels of arousal: poor performance
- ADHD: at far left, v. low levels of arousal
How is the Yerks-Dodson curve seen in PFC monoamines?
- PFC functioning related to levels of DA & NE in PFC: more stress/arousal, more cathecholamines released into PFC
- inadequate amount: inappropriate network connections
- appropriate amount:
- neurons organise themselves into smart networks of activity
- pay attention to 1 aspect of task/environment/cognition & attention
- too much: neurons stop firing, networks disconnected
What are cathecholamines?
dopamines & norepinephrine
What are long-term effects of psychostimulant use in ADHD?
- difficult to study/capture
- but most fears haven’t been borne out
- “normalising effect” on brain devleopment in ADHD:
- ADHD has developmental effects on brain that medication attenuates
- jury’s not out
- no effects on weight/cardiovascular/etc.
What is drug diversion?
pressure to sell prescription drug for performance enhancement
What are nootropics and the pattern with all known nootropics?
- nootropic: smart drug, cognitive enhancer
- no support for other putative nootropics: racetams, ginseng, ginkgo biloba, omega-3 fatty acids, vitamins, etc.
- leads to interesting ethical questions
- common drugs that are nootropics (modestly): amphetamine, methylphenidate, modafinil, caffeine, nicotine
- pattern: all psychostimulants
What are the adverse effects of psychostimulants?
- cardiovascular dysfunction:
- high doses: cocaine is Na+ channel blocker
- increased SNS output
- pulmonary dysfunction
- “meth mouth”
- psychostimulant-induced psychosis: formication
- some evidence for neuron damage
- developmental? “crack” babies:
- control for other factors, no long lasting effect
- stable, healthy, secure home: don’t see negative effects
- hard socioeconomic conditions: demonstrate cognitive/developmental related impairments later
What is “meth mouth”?
less likely to brush teeth, damage to gums, less salivation, sugary foods
What is formication?
feeling of bugs crawling under skin
What are “crack” babies?
babies exposed to cocaine when in mother’s body
