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Caffeine base
purinergic
adenosine A1
normally inhibitory, stops adenylyl cyclase. Found in reward and hippocampus
adenosine A2
normally excitatory, starts adenylyl cyclase, found in DA rich regions on GABA neurons
caffeine reward
adenosine A1 receptor on DA neuron’s disinhibiting them
Paraxanthine
Caffeine metabolite, increases blood glycerol and fatty acids via lipolysis
Theobromine
Caffeine metabolite, dilates vessels (periphery) and increases urine
theophylline
caffeine metabolite, inhibits PDE increasing cAMP is the increased breathing mechanism
Nootropics
cognitive enhancers (BDNF linked to LTP in hippocampus)
-caffeine
-taurine
-nicotine
-ritalin
-afinil family
-l-theane
- ginko and ginseng
-amphetamines
Nicotine base
Alkaloid, want it in free base form so burn it
Diacetyl
butter flavour destories lungs
vit E acetate
in vapes causes allergic reactions
nicotine metabolism
CYP2A6, CYP2B6, monooxygenases
Nicotine binding sites
An acetylcholine receptor agonist, binds tightly. notably to alpha 4 beta 2 which is located on GABA interneurons which is quickly desensitized disinhibiting dopamine release. alpha 7 controls Glu release
Nicotine tolerance
vomiting and dizziness go away quick but no tolerance to heart or vessel effects. Sensitization due to higher expression on alpha 4 beta 2 (most in PFC)
Bupropion
nAChR antagonist as a Treatment for nicotine withdrawal has higher affinity. also inhibits NAT and NET to act as antidepressant
Varenicline
partial nAChR agonist to reduce craving
Hypnotics
cause sleep and drowsiness (Zopiclone, Zolpidem)
Z-Drugs
orexin antagonists, melatonin agonists, anti histamines
Sedatives
anxiolytic, sedation, anesthesia, anti convulsant
Sedative charaterization
based on duration of length. short is used for preanesthetic or insomnia. long acting for anticonvulsants, muscle relaxants and anxiolytics
Sedative metabolism
CYP450 creates active metabolites
-chordiazepoxide, diazepam, midazolam
Benzodiazepines
sedative, Binds GABA between alpha and gamma to increase frequency of opening when GABA is present. Rapid tolerance
Barbiturates
sedative, bind GABA between alpha and beta to increase duration of opening (can activate when GABA not present)
Gamma-hydroxybutyric acid
precurose of Glu, gly and GABA. at low doses only binds Glu receptors and acts as stimulant
at high dose binds GABA for sedative like effect (alcohol)
Flumazenil
Overdose treatment for sedatives/ GABA antagonist
Sedative reward
From disinhibition of GABA interneurons on DA terminals
CB1 expression
basically everywhere but mainly in CNS
CB2 expression
on immune cells, spleen and tonsils
Cannabis effects
-pleasure
-analgesia from CB1 activation
-heart rate increase
-increased energy metabolism and appetite/thirst via CB1
-decreasing sex drive and hormones
Cannabis 5HT effect
anti-emetic effect from inhibition of 5HT release in medulla all around. But THC and CBD also bind and inhibit 5HT3 directly.
cannabis binding targets
CB1 and 2 but also TRPV1 and 2 (Na/Ca) channels and 5HT2
cannabis reward
from presynaptic (on axon) activation of CB1 on GABA interneurons
Cannabis acute adverse effect
high THC in hippocampus can reduce memory and learning
-blood shot eyes from CB1 activation and dilation of vessels in the eyes
The munchies
From presynaptic inhibition of Glu neuron’s projecting to nasal GABA interneurons that inhibit nasal mitral cells. The disinhibition sensitizes the mitral cells to smells increasing food drive and pleasure from eating.
Cannabis long term effects
miscarriage rates go up
lung damage (smoke)
low sex hormones otherwise effecting fertility (male and female)
Bath salts structure
highly changing but bases around the cathinone nucleus (phenethylamine with a ketone) and then some stuff added to it.
-a pyrolodine ring can increase potency (more lipophilic)
-long chains increase potency
Bath salts effects
stimulants
-some of the serotonin effects increase heat leading to hyperthermia and maybe rhabdomyolysis and kidney failure
-euphoria
-locomotor activity from increased DA in striatum
Bath salts reward/ mechanism
two types
-without pyridine ring acts like amphetamine
entering the terminal via SERT and displacing DA and NE while reversing DAT via TAAR
- with pyridine ring is too big so acts like cocaine and blocks DAT
DAT/SERT ratio
the higher this ratio the more it favours DA and it is more addictive. based on IC50 (concentration to prevent 50% of reuptake) so the higher the concentration the less favoured that receptor is.
Bathsalts adverse effects
cause violence and homicidal behaviour, self mutilation and excited delirium syndrome
death from surge of NE, DA and 5HT
-hyper thermal and serotonin syndrome leading to water intoxication
MDPV
bathsalt with very very high abuse potential
Type 1 anabolic steroids
have esters to be hydrolyzed into testosterone
-but also into estrogen my aromatase
Type 2 anabolic steroids
19-Nor-testosterone. These have less androgenic effects (secondary sex characteristics) and 80% less aromatization to estrogen
Type 3 anabolic steroids
extra ring of the A ring
- long lasting and not turned into estrogen and has increased anabolic effects
anabolic steroid admin
different dose schedules
-pyramiding (up and down)
-Stacking (many types at once)
-cycling (to stay around testing)
anabolic steroid action
Binds to andro receptor and forms a complex which acts as a transcription factor increasing stem cell development to muscle
anabolic steroid metabolism
5 alpha reductase converts testosterone to DHT. the introduction of more steroids stops their natural production as it is a negative feedback loop.
steroid reward
Can come from natural endorphins inhibiting GABA in VTA. also some direct steroid modulation of GABA to increase DA neuron firing
anabolic steroid effects
the TF produces more anabolic genes (IGF-1) and decreases atrophic genes (MuRF1). this increases myonuclei and muscle fibre size.
steroid withdrawal
depression, mood swings, fatigue, body dissatisfaction
steroid dependance
mostly psychological from wanting to avoid negative effects so 30% become dependant
steroid long term risks
Many other genes activated for a pleiotropic effect
-increased BP, cholesterol and heart defects
-reduced 5HTR expression in PFC, hypo and hippocampus
Steroid rage
anterior hypothalamus is aggression centre and D2 activation there leads to aggression. steroid dose can increase D2 expression there.
steroids also enhance arginine vasopressin (which increases aggression) and decreases 5HT which calms
arginine vasopressin
a molecule that increases aggression. activated and increased by sterioids leading to rage
Steroid abuse
from the DA release but also from BDNF in hippocampus being prevented from stimulating growth leading to depressed behaviours
Chemical heptenation
a small molecule that binds to macromolecule like protein to produce an immune effects (used in lateral flow assays.
