drug classes in substance abuse Flashcards
classes that act through g protein coupled receptors?
opioids
cannabinoids
caffeine
LSD/mescaline
opiates act through…
the mu opioid receptor
GABA release inhibited and dopamine inreased
results in neuronal hyperpolarization –> disinhibition of dopamine release
cannabinoids act on…
cannabinoid receptors (CB1 and CB2)
similar to opioid receptors but located on different neurons
hyperpolarization –> disinhibition of dopamine release and inhibit Ca entry –> reduced transmitter release
LSD and mescaline act on…
partial agonist at serotonin 5HT2 receptor
acts through G protein (Gq) to increase IP3 –> causes depolarization and hallucinations
caffeine acts through…
antagonist at adenosine receptors (A1 and A2)
displaces adenosine at receptors so you dont get tired!
at A1 –> antagonism increases Gi/o activity
at A2 –> antagonism reduces Gs activity
classes that act through ion channel linked receptors?
nicotine
benzodiazepines
alcohol
ketamine/pcp
nicotine acts through
nicotinic acetylcholine receptor (nACH-R)
alpha4 beta2 subunit in brain is very sensitive to nicotine
increase in cation conductance –> depolarization allows dopamine release
benzodiazepines act through….
GABA-A-receptor at an allosteric site (not the same site as GABA)
potentiates the effect of GABA –> hyperpolarization of that ion channel
increased DA
alcohol acts through…
GABA-A receptor at allosteric site and potentiates GABA –> hyperpolarization (sedation)
and
blocks NMDA-receptor –> inhibits Glutamate effect –> euphoria and dopamine release
ketamine and PCP act through..
blocks NMDA receptors –> inhibits Glutamate effect –> disorientation, hallucinations, euphoria, dopamine release
drug classes that act through monoamine transporters?
cocaine
amphetamines
MDMA
cocaine acts through….
inhibits DAT, NET and SERT
increases extracellular DA, NE, and 5HT = high/euphoria
amphetamines act through…
blocks VMAT (displaces DA, NE and 5HT) –> increases extracellular DA, NE,, and 5HT
a high/euphoria and neurotoxicity
MDMA acts through… (ecstasy)
blocks SERT and displaces 5HT
increased extracellular 5HT and depletion = euphoria and neurotoxicity (serotonin)
chronic use of amphetamines/stimulants results in…
loss of stimulatory effects
depression/anxiety/hunger/weight gain
d/t down regulated monoamine receptors and depletion of monoamine vesicular stores (less transmitter and fewer receptors)
cocaine can produce what bad effect in overdose?
seizures, coma, intracranial hemorrhage
amphetamine overdose can cause?
psychotic episodes, paranoia, aggression, and skin/tooth/gum disease
cocaine and amphetamine withdrawal symptoms
relatively mild dysphoria, depression, hunger, and drug craving
MDMA
ecstasy/molly
lasts 3-6 hrs
sympathetic effects (tachycardia, NP, and alertness) dehydration and HTN
mildly hallucinogenic
OD –> hyperthermia/muscle breakdown, MI, stroke, neurotoxic
nicotine
stimulant that acts on the nicotinic receptors (nACh) in brain at alpha4beta2 subunit
increases cation currents and increases extracellular DA levels
from smoke gets to brain very quickly
sympathetic effects on BP and HR
carcinogenic due to combustion products
marijuana (THC)
peripheral effects: tachycardia, but little change in BP, dry mouth, hunger, flushing (vasodilation)
central effects: euphoria/high, distortion of visual/auditory stimuli, altered time perception, talk more, relaxing, sedation, psychomotor impairment
higher dose(edibles usually) = confusion, delusions, panic, paranoia
what distinguishes THC from LSD?
THC induces a feeling of relaxation/sedation
THC acts through
THC Receptors: CB1(in nervous system), CB2 (in immune cells)
G-protein coupled receptors, regulating Gi and Go - inhibit adenylyl cyclase - open K+ channels; reduce Ca2+ conductances
high concs CB1- receptors in brain
therapeutic uses of THC (marijuana)
- treatment of drug/radiation-induced nausea and vomiting in cancer chemotherapy
- enhancement of appetite
- reduction of intra-ocular pressure in glaucoma
use of CB1 antagonist, rimonabant, to control appetite
pain relief, either as analgesic, or as co-analgesic
chronic mal-effects of smoking marijuana
respiratory problems
suppression of immune system
amotivational syndrome (memory loss and impaired mental performance)
LSD
lysergic acid diethylamide synthetic
**partial agonist at 5HT2 receptors
somatic effects: dizzy, mydriasis, tremor
perceptual effects: blurred vision, altered colors and shapes, hallucinations mood swings, elation or dysphoria, panic, fear, detachment
**not addictive; dont ruin lifestyles/no compulsive use!!
phencyclidine/PCP and ketamine
Glu NMDA receptor antagonists
channel blockers and reduce CA conductance
effects: intoxication, staggered gait, blank stare, muscle rigidity, analgesia (dont respond to pain), hypersalivation, sweating, bizarre/aggressive behavior, paranoia, convulsions
chronic effects: memory deficits, speech impairment
ethanol metabolism (major pathway)
step 1 by alcohol dehydrogenase (ADH) and step 2 by aldehyde dehydrogenase
1) ethanol + NAD –> acetaldehyde + NADH + H
2) acetaldehyde + NAD –> acetic acid + NADH acetic acid –> calories
ethanol metabolism (minor pathway)
by p450 enzyme (CYP2e
1) ethanol + NADPH –> acetaldehyde + NADP + H
then aldehyde dehydrogenase= acetaldehyde + NAD –> acetic acid + NADH
fomepizole
inhibits ADH (alcohol dehydrogenase) by competing for NAD+
more food in stomach DOES….what to alcohol absorption?
SLOWS it downs
legal alcohol limit is
.8 mg/ml
methanol metabolism
also metabolized by alcohol dehydrogenase and aldehyde dehydrogenase but it creates fairly toxic products–> formaledhyde and formic acid
effects of ethanol on the liver -increases 3 things? -decreases 2 things?
increases NADH:NAD ratio (from heavy demand for NAD) increases rate of FA synthesis (since NADH is high)
increases plasma free FAs (d/t increases sympathetic activity)
decreases fatty acid oxidation (d/t lack of NAD) and decreases release of TGs from the liver results in accumulation of TGs
ethanol: effect on gastric acid, sympathetic tone, and ADH
increases gastric acid secretion
increased sympathetic tone and vasodilation, increased heat loss
inhibits ADH secretiion –> diuresis!
ethanol effects on CNS at .4-1 mg/ml 1-2 mg/ml 2-4 mg/ml 4-5 mg.ml
.4-1 mg/ml = mild euphoria, increased rxn time, impaired judgement, increased risk of accident
1-2 mg/ml = impaired gait, ataxia, loss of balance, slurred speech, analgesia, confusion, disinhibition, sedation
2-4 mg/ml = emesis, slow mental process, severe sedation, anesthesia, coma, respiratory depression
4-5 mg.ml = deep coma, death from respiratory depression at this range
1 mg/ml ethanol =
0.1%
what to give in order to retard methanol metabolism
ethanol or fomepizole (they compete for alcohol dehydrogenase and prevent bad methanol products from forming)
benefits of alcohol?
elevates high density lipoproteins (HDL) which bind cholesterol reduction of plasma cholesterol
reduced risk of coronary heart disease, CV disease
improved cognition in elderly- Benefit seen with 1 - 15 g/day; 15 - 30 g/day did not increase effects ***antioxidants might play an important role
resveratrol
from wine an antioxidant, anti-carcinogenic
decreases neuronal death following stroke; reduced platelet aggregation; decreased inflammatory responses • induction of apoptosis (protection against carcinoma) • CYP enzyme induction
Problems: Conc in wine is low - effective dose seems to be liters per day (not a good idea!) Bioavailability is low - poor absorption, very rapid metabolism in vivo
SYNDROMES OF malnutrition due to chronic alcoholsim
peripheral neuropathy
pellagra (niacin deficiency) = GI disturbance, erythema, desquamation, CNS effects
amblyopia = partial loss of vision
Wernicke’s encephalopathy (thiamine deficiency) = disturbed eye movements, ataxia, tremor
Korsakoff’s psychosis (vitamin deficiency; other ?) severe memory loss, confusion
fetal alcohol syndrome
low birth weight, poor growth, low IQ, impaired immune function, characteristic facial features
alcoholic fatty liver
–fat accumulation (inhibition of tricarboxylic acid cycle; reduced oxidation of fat)
–accumulation of acetaldehyde (breakdown reduced because of reduced availability of NAD+)
- increased lipid peroxidation
- membrane damage
- depletion of glutathione, vitamins, trace metals
–induction of CYP2E1
- increased metabolism of many drugs; activation of carcinogens
- result is necrosis and fibrosis: cirrhosis
ethanol induces _____
CYP2E1
this activates procarcinogens
and
increases metabolism of drugs like acetaminophen
alcohol withdrawal
day 1
day 2
day 3
1 - tremor and shakes; mild hallucinations (nondisorienting)
2 - tremors and hallucinations continue; tonic-clonic convulsions (potentially lethal)
3 - delirium tremens (DTs), autonomic symptoms (sweating, nausea, vomiting, disrrhea, fever)
**symptoms peak at 3-4 days then get better days 4-7
synthetic canthinones
bath salts
release DA and 5HT
can cause severe rhabdomyolysis
