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Lecture Five


**What are the four main reasons for taking a psychostimulant? To keep you awake. To increase your energy. To make you attentive (increase attention span). To induce euphoria (high).
**If you want to increase the OVERALL excitability in the CNS what two ways can you do this? Decrease inhibition by targeting the GABA system (decreases the GABAnergic tone) or Increase excitation by targeting the Glutamate system (increases Glutamergic tone)
**What is the major problem with increasing OVERALL excitability in CNS (by targeting GABA or Glutamate systems)? Can cause EXCITATOXICITY! Which can manifest as seizures and be fatal.
**What is the mode of action for psychostimulants? increases behavioural activity
**What is DAT? Dopamine transporter
**What is Norepinephrine (NE) made from? Dopamine
What does NE stand for? Norephinephrine
**What is the synthesis for Norepinephrine? NE is derived from dopamine --> NE --> EPI (Epinephrine)
**What is serotonin synthesised/derived from? Tryptophan (high in protein- milk, cheese).
**What is the clearance for serotonin (5-HT)? Pre-synaptic transporter (SERT)
Describe the oscillating relationship in the history of psychostimulants. (possibly **)
** What is Cocaine derived from? Erythroxylon coca plant
**In the 1880s cocaine was used as what....? local anaesthetic (makes things go numb - used medically sometimes)
**Freud started prescribing as 'magical euphoria for...? Depression as it makes you feel better.
**What are the three types of formulation for cocaine? Coca leaf, Cocaine acid, Cocaine base (crack)
** What are the different ROA for cocaine? chewing, intranasal, intravenous and inhalational
**Do the average doses of cocaine differ for the different ROAs of cocaine? Yes the average does is lower for chewing and intranasal and higher for intravenous and inhalational
**Does the initial onset time and duration for the different ROAs of cocaine differ? Yes
**Which ROA of cocaine is has the longest duration? chewing (45-90 minutes)
**What are the 3 modes of action for cocaine? Local anaesthetic (makes muceous membrane numb), vasoconstrictor (less blood if cut as less blood supply), psychostimulant (increases behaviour)
**What are the two mechanism of actions for cocaine? 1) primarily an antagonist for the dopamine transporter (DAT) (SO MORE DOPAMINE IN SYNAPSE). 2) also has minor antagonist activities at the norepinephrine transporter (NET) and serotonin transporter (SERT) (SO BLOCKS)
**What is cocaines primary mechanism of action? Primarily blocks DAT , also NET and SERT (SO COCAINE CAUSES MORE DOPAMINE TO STAY IN SYNAPSE)
**How does cocaine cause more dopamine to stay in synapse? By being an antagonist for the dopamine transporter (DAT) and therefore blocking this transporter so dopamine stays in synapse.
**What is the site of action for cocaine? Dopaminergic "reward pathways"
**The psychostimulant mode of action has various components. Describe them.. 0-30min: Euphoria. 30-120min: restlessness, agitation, appetite suppression. 120+ min: anxiety, and neg. reinforcement happens as want drug again. Then CRASH !
**Remember Cocaine also a vasoconstrictive property, which causes _____________ effects of dose-dependent increases in heart rate and ______ pressure (constricting blood vessels SOMATIC, blood
**What usually happens as you increase the FREQUENCY of cocaine use? You will develop TOLERANCE
**What usually happens as the REGULARITY of cocaine use increases? You will develop DEPENDENCE of cocaine
**What are the first two reasons you would NOT use cocaine while pregnant?? 1) It is a vasoconstrictor so effects amount of blood flow (carrying Oxygen & nutrients) to foetus. 2) increases DA so can induce uterine contractions (as DA receptors on uterus) --> spontaneous abortion, still birth or live premature birth.
**What are the third and fourth reasons you would NOT use cocaine while pregnant?? 3) it can cross the placenta barrier and damage developing foetal organs 4) it can be indirectly psychosocially harmful as mothers are not sensitive to babies so babies do not develop good social skills - cocaine use can severely affect infant development
*Amphetamines are _______________ synthesized? chemically
**First Amphetamines were used _________for a variety of conditions. Then they were used in ____ to increase alertness and combat fatigue. Then Amphetamines experienced Direct to ___________ _________ for Fatigue, euphoriant, anorectic which lead to abuse therapeutically, WWII, DTCA. Then it was banned.
**Acknowledge that Amphetamine has different formulations, ROAs, does, initial onsets and duration. ..
**How is Amphetamine distributed to the CNS? All cross the BBB (+PLCENTA). Meth is very quick to cross the BBB. so bad if pregnant
**What are the 3 modes of action for Amphetamines? 1) Sympathomimentic (flighter fight effect). 2) Vasoconstrictor and 3) Psychostimulant
**What is the mechanism of action of Amphetamines? It promotes the release of newly synthesized NE and DA. so more norepinephrine and dopamine in synapse?
**What is the site of action for Amphetamines? effects the DA reward system
**Amphetamines mode of action has various components (like cocaine). Describe the three main stages Euphoria, anxiet (leads to reinforcement) and CRASH.
**With initial use of Amphetamines what happens? (similar to cocaine) Tolerance develops (body gets used to it)
**Regular/moderate use of Amphetamines leads to...? Dependence develops
**Describe how Psychostimulants and CNS can co-occur. When you get restless from being high, you take CNS depressant to get back down/ less restless. This co-occurrence is ongoing and an oscilating relationship (up and down).
**ADHD has high co-morbidity. What does this mean? Another diagnosis is presenting at the same time e.g. depression. anxiety, conduct and learning disabilities.
** What are the three pharmaceutical approaches for ADHD? 1) Amphetamine drugs 2) Amphetamine-like drugs (so not actually amphetamine) 3) Alternative non-stimulants. So has potential for abuse and diversion
**Does it make sense to prescribe stimulants to ADHD patients? (who are already hypo.). Yes as they help to bring the child back to normal. They prime the reward pathway and prime the attention pathway.
**Why are stimulants so important to use for ADHD? Because when they are at normal hypo, this means you can do CBT to actually TREAT the ADHD.
**Do you think Amphetamines as pills would be reinforcing? Yes, but wouldn't be as bad as cocaine as oral makes it less reinforcing. But there is still a risk of substance abuse and addiction.
Methylphenidate is ? Ritalin
**Ritalin's mode of action mimic what? And how? Cocaine and amphetamine because Ritalin blocks the presynaptic DA transporter (like cocaine) and can slightly increase the release of DA and NE (like amphetamine)
**What is Ritalin's MOA? It blocks presynaptic DA transporters and can slightly increase the release of DA and NE
**Why were alternative non-stimulant drugs (amphetamine-like drugs) created? For when ADHD person is treatment resistant to methylphenidate (Ritalin) or when stimulant abuse is of concern. So created these alternative non-stimulants for ADHD.
**Are Purinergic Stimulants psychostimulants? Yes
**What is a prime example of a purinergic stimulant? Caffeine
**Caffeine is found in several plants . What are they? Coffee, cocoa, guarana, mate, kola
**What is the MOA of Caffeine? (purinergic stimulants) Is primarily an antagonist for the adenosine receptor (so blocks the adenosine receptor)
**But caffeine also has another MOA. So what are the two MOAs for caffeine? 1) Vasoconstrictor (in eyecreams to constrict vessels in skin under eyes) 2) Psychostimulant
**What is the mechanism of action of caffeine? It is an antagonist for the adenosine receptors
**The depressant system of adenosine: An adenosine receptor agonist would cause __________ ___________. While an adenosine receptor antagonist would cause stimulant effect sedative depressant
**The ROA for caffeine is...? All oral
What is the absorption for caffeine? Rapid absorption from the GI tract
What is the distribution for caffeine? Caffeine crosses the BBB, and crosses the placental barrier.
What is the metabolism for caffeine? The half-life in plasma is 3-9hours
What is the clearance of caffeine? Urine and lactation (which is why you shouldn't drink coffee when breastfeeding)
Can you develop tolerance with caffeine? Yes, it develops RAPIDLY
**Can you develop dependence with caffeine? Yes, mild dependence as you can get withdrawal symptoms e.g. headaches.
** Do people get addicted to caffeine? No, but there are financial consequences ($5 per coffee) but does cause dependence, but no actual addiction
**Are there are safety/side effects of caffeine use in kids? The effects on brain development is not well understood. The effects on sleep are well understood. The effects on nutrition are beginning to be noted.
**What is the long term prognosis for caffeine use in kids? ??? ???? ask natu
Created by: alice476