(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
