43/44: Drugs of Abuse Flashcards
define drug abuse
consumption of drugs without medical approval or supervision to achieve strong feelings of euphoria and reward ; use of a drug in a manner detrimental to the health and well-being of the drug user, other individuals or society as a whole
hallmark of drug addiction
compulsive drug use
when drug is necessary for normal physiological functioning =
physical dependence
pharmacokinetic v. pharmacodynamic tolerance
pharmacokinetic: increased drug metabolism results in decrease in the amount of available drug or duration of drug action at the target site
pharmacodynamic: CNS responds and adapts to presence of drug –> desensitization, down-regulation and/or internalization of receptors
compulsive drug use to induce pleasure and/or an escape from reality despite negative consequences
addiction
CNS mechanisms of psychological dependence
increased synaptic plasticity and DA release in the mesolimbic reward pathways
t or f: all drugs of abuse are addictive
false
all addictive drugs activate…
mesolimbic dopamine system –> reward pathway
DA neurons from the ventral tegmentum project to…
amygdala
nculeus accumbens
prefrontal cortex
hippocampus
all part of reward pathway
RR for CNS depressants and sedative/hypnotics
3
ETOH is a depressant –> ________. Why do we use it?
produces sedation and sleep
low doses of ETOH cause suppression of inhibitory systems and mild euphoria, which facilitates social interactions by reducing behavioral inhibitions and self-consciousness
basis for breathalyzer test
10% ETOH metabolized in GI tract and excreted through kidney and lungs
elimination of ETOH from the blood follows
zero-order kinetics
rate of elimination is independent of time and concentration of ETOH (constant amount eliminated per unit time )
one drink/hr approx
converts ETOH into acetaldehyde
alcohol dehyrogenase
part of alcohol metabolism
converts acetaldehyde to acetic acid
aldehyde dehydrogenase
MOA and use of disulfiram
inhibits ALDH and is used to encourag alcoholic to abstain from ETOH abuse
high acetaldehyde levels cause unpleasant rxns
BAC is determined by the __ of ETOH ingestion
rate
0.08 by 2-4 drinks/hr
12 oz beer = one drink = ___ liquor = ______ wine
1.5 oz liquor
5 oz wine
ETOH MOA
1) potentiates effects of GABA at GABAa receptors (hyperpolarization)
2) inhibits glutamate-activated NMDA receptors –> ETOH related memory loss
describe wernicke-korsakoff syndrome
aka wet brain or alcoholic encephalopathy
neurological condition associated with thiamine deficiency B1 in combination with excessive ETOH intake
observe: ocular disturbances, changes in mental state, memory impairment, and movement difficulties
describe fetal alcohol syndrome
ETOH is powerful teratogen –> mental retardation, hyperactivity and antisocial behavior
no safe level of alcohol intake for preggers
long-term ETOH consumption affect the following organs
- liver cirrhosis
- cardiovascular HTN, arrhythmias, etc
- inhibits ADH in kidney
- gastritis, cancer in GI tract, ulcers
most common two-drug combination that results in drug-related death
cocaethylene = cocaine + ETOH
produced in liver –> intensifies cocaine’s euphoric effects
what should be given to avoid wernicke-kosakoff syndrome
thiamine
why give naltrexone for chronic alcoholism?
opioid antagonist that blocks reinforcing properties of ETOH and reduces the rate of relapse
flunitrazepam =
date rape drug, benzodiazepine
“roofie”
tastesless when dissolve din a beverage, retrograde amnesia
benzodiazepine receptor antagonist useful in treatment of overdose and in reversing the effects of long-acting benzodiazepines used in anesthesia
flumazenil
MOA benzodiazepines and barbiturates
positive modulators of GABAa chloride channels —> increase inhibition
how do benzodiazepines and barbiturates work in the reward pathway?
activation of GABAa receptors on interneurons leads to decreased activity and reduced release of GABA –> disinhibiton of VTA DA neurons and activation of mesolimbic reward pathway
MOA GHB
disinhibiton of DA neurons in VTA via GABAb receptors
GHB causes…
euphoria enhanced sensory perceptoion sedation felling of social closeness amnesia "date rape drug"
RR of addiction for psychostimulants
5
“speedballing”
IV heroin and cocaine mixed together
reward effects of cocaine
increased DA release in the nucleus accumbers
cocaine produces these effects:
intense euphoric effect
increased energy and libido
also linked to cardiovascular toxicity!
strongest psychological dependence of any drug
cocaine
why might you prefer meth over cocaine?
price
and effects last 6-24 hrs compared to 20-30min with cocaine
amphetamines lead to…
euphoria
increased arousal
reduced sleep
common name for methylphenidate
ritalin
“ecstasy” =
MDMA
evokes feeling of intimacy and empathy
MOA MDMA
interferes with 5HT transporters to release 5HT from presynaptic terminals
toxicity of MDMA **
hyperthermia and dehydration
chronic abuse of psychostimulants can lead to ….
toxic psychosis that is indistinguishable from paranoid schizophrenia
must be treated with antipsychotic agents (haloperidol or chlorpromazine)
RR of addiction for psychedelics/hallucinogens
1
lysergic acid diethylamide
LSD
psilocybin =
magic mushroom
ketamine =
special K
phencyclidine =
PCP or angel dust
MOA for LSD and psilocybin
release glutamate in cortex via thalmic excitation
taget 5HT2a receptors
is LSD addictive?
no
does not stimulate mesolimbic doapmine release —> no dependence or addiction and no withdrawal syndrome
what type of anesthetic is ketamine?
dissociative (look awake but the pt doesn’t remember anything)
MOA ketamine and PCP
block NMDA type glutamate receptors; decrease activity of cortex and limbic system
RR of addiction for opioids
4
opiates =
morphine
codeine
heroin
MOA of opioids
1) inhibition of GABAergic neurons vi aactivation of mu-opiod receptors leads to disinhibition of the VTA DA neurons causing euphoria
2) inhibition of VTA DA neurons via activation of kapp-opioid receptors (inhibitory) causes dysphoria
used for emergency overdose of opioids
naloxone
mu opioid receptor competitive antagonist that reverse the effects of morphine or heroin within minutes
opioid abstinence syndrome
cessatiion of long-term opiate use leads to withdrawal with dysphoria, nausea and vomiting, lacrimation, flu-like, etc.
subsides within 5 days
used to treat opioid withdrawal and opioid addiction
methadone
long-acting opioid agonist that has easier withdrawal symptoms
mu opioid receptor antagonist used primarily for maintenance therapy
naltrexone
RR of addiction for cannabinoids
2
synthetic THC approved for treatment of chronic pain
dronabinol
MOA THC
disinhibits DA neurons in the VTA via pre-synaptic cannabinoid receptors –> euphoria, relaxation and sense of well-being
MOA nicotine
activation of nicotinic acetylcholine receptors on VTA projection neurons result in DA release in nucleus accumbens and PFC
MOA varenicline
high affinity nACHR agonist that competes for binding with nicotine
which is more addictive: shcedule I or V?
schedule I
