Svensson Pharmacology of Psychostimulant Misuse Flashcards
Are we in an opioid crisis right now?
No, we are in a drug abuse crisis where stimulants play a major role
Nicotine mechanism of action
-Nicotine activates nicotinic acetylcholinergic receptor
-Na+ enter cell, K+ exits the cell -> action potential
-Heterogenicity of subunits determines how many molecules of Ach bind to receptor
-Variation in receptor composition at different sites may influence physiological response
Acetylcholine vs nicotine
-Similarities between nicotine and ACh are charged amino groups and hydrogen bond acceptor groups
-Nicotine is membrane penetrable at physiological pH (weak base)
-Nicotine is not degraded by acetylcholinesterase
Substances from most addictive to least addictive
Tobacco > heroin > alcohol > cocaine = cannabis
Why do a minority of people become addicted if the pharmacology of the drug drives addiction?
Data suggests that it is not just pharmacology that drives addiction but that context is important
How does varenicline work?
-It is a partial agonist that increases quit rate success
-Stopping nicotine use causes a lack of dopamine which leads to withdrawal symptoms
-Varenicline partially activates the dopamine receptors to cause them to release a little bit of dopamine, but not too much so that way people do not get the euphoric effects
Commonly abused psychostimulants
-MDMA (ecstasy)
-Methamphetamine (crystal meth)
-Methylphenidate (Ritalin)
-Cocaine
What molecule are psychostimulants structurally similar to?
Norepinephrine and dopamine
Why is pseudoephedrine kept behind the counter?
To prevent people from using it to make meth
Why have regulations on pseudoephedrine not worked?
The use of methamphetamine is continually escalating due to people finding different ways to manufacture it
What is fenethylline?
-Also known as Captagon and Abu Hilalai
-Widespread use in Arabian peninsula
-A combination of caffeine and amphetamines
What receptors does cocaine antagonize?
-Dopamine transporter (DAT)
-Serotonin transporter (SERT)
-Norepinephrine transporter (NERT)
What is the order of selectivity cocaine has towards the receptors it antagonizes?
DAT>/=SERT>NERT
Cocaine mechanism of action
-Prevents DA reuptake
-Increases DA concentration
-Increase duration of DA action
Methamphetamine/XTC/Bath salts mechanism of action
-Amphetamines/XTC/bath salts compete for reuptake
-Resembles endogenous dopamine and norepinephrine
-Block DA reuptake
-Push out DA from vesicles
-Increase extra-vesicular DA
-Reverse transport (gradient)
-Amphetamines are MAOis
-Activate trace amine-associated receptor (TAAR1)
-Phosphorylates DAT
-Induces reverse transport function
