Drugs of Abuse Flashcards
depressant that enhances GABA binding to GABAa receptor and inhibits glutamate binding to NMDA receptor, and facilitates release of endogenous opioids in VTA
acute effect: CNS depression
toxicity: potentially life-threatening respiratory depression
mild withdrawal: sympathetically driven tremors, tachycardia, hypertension, sweating
severe withdrawal: potential life-threatening seizures due to down-regulation of GABAa receptors and upregulation of NMDA receptors
profound addiction and physiological dependence
ethanol
depressants that enhance GABA binding to GABAa receptor
acute effect: CNS depression
toxicity: potentially life-threatening respiratory depression when used in combination with other depressants
moderate use withdrawal includes anxiety, paresthesia, sleep disturbance
severe withdrawal: potential life-threatening seizures due to down-regulation of GABAa receptors
profound addiction and physiological dependence
benzodiazepines
depressants that enhance GABA binding and directly activate GABAa receptors
toxicity: potentially life-threatening respiratory depression when used in combination with other depressants
severe withdrawal: potential life-threatening seizures due to down-regulation of GABAa receptors
profound addiction and physiological dependence
barbiturates
activation of mu opioid receptors in medullary respiratory center, spinal/supraspinal sites mediating analgesia, enteric nerves, and reward pathway
histamine release results in vasodilation, bronchoconstriction, hypotension
potentially life-threatening respiratory depression
withdrawal is uncomfortable but not life-threatening
hyperalgesia, diarrhea, dilated pupils, hypertension, sweating, dysphoria, craving
profound addiction and physiological dependence
heroin (opioids)
activation of central and peripheral nicotinic acetylcholine receptors
activation of nicotinic acetylcholine receptors in the reward pathway
stimulant effects - increased arousal, concentration
depressant effects - decreased anxiety
withdrawal: irritability, anxiety, dysphoria, difficulty concentrating, restlessness, increased appetite or weight gain
profound addiction and physiological dependence
nicotine
activation of cannabinoid receptors in the brain, spinal cord, and reward pathway
depressant-like effects including relaxation
psychedelic-like effects
sympathomimetic effects
increased appetite
tolerance to acute effects develops rapidly
withdrawal tends to be mild including restlessness, irritability, depression, insomnia
addiction and physiological dependence considered less prominent compared to opioids and ethanol
THC (Cannabinoids)
stimulants that enhance synaptic release of dopamine and norepinephrine
acute effects: CNS arousal, alertness, euphoria, sympathomimetic effects (increased HR and BP)
overdose leads to cardiac arrhythmia, MI, stroke, seizures
seizures rarer and due to decrease in seizure threshold by unknown mechanism
chronic use can lead to hallucinations, violent behavior, psychosis
tolerance to euphoric effects develops rapidly
reverse tolerance can be seen with continued use - increased risk of cardiac arrhythmia, cerebral vasoconstriction leading to stroke
withdrawal mild in most patients - dysphoria, sleepiness, bradycardia, craving, depression
with major depression or suicidal ideation treat with antidepressants
addiction can be profound
physiological dependence considered less prominent than with alcohol or opioids
amphetamine and methamphetamine
stimulants that block reuptake of dopamine, norepinephrine, and serotonin
acute effects: CNS arousal, alertness, euphoria, sympathomimetic effects (increased HR and BP)
overdose leads to cardiac arrhythmia, MI, stroke, seizures
seizures due to blocking GABAa receptors
chronic use can lead to hallucinations, violent behavior, psychosis
tolerance to euphoric effects develops rapidly
reverse tolerance can be seen with continued use - increased risk of cardiac arrhythmia, cerebral vasoconstriction leading to stroke
withdrawal mild in most patients - dysphoria, sleepiness, bradycardia, craving, depression
with major depression or suicidal ideation treat with antidepressants
addiction can be profound
physiological dependence considered less prominent than with alcohol or opioids
cocaine
psychedelics related to serotonin
agonists at 5HT, dopamine, and adrenergic receptors
weak effect in reward pathway
peripheral sympathomimetic effect, altered perception, hallucinations (primarily visual, not all drugs/doses), altered mood
tolerance is minimal in most cases
withdrawal can include craving, confusion, anxiety, and depression
addiction and physiological dependence thought to be minimal in most individuals
LSD and psilocybin
psychedelics related to dopamine and amphetamines
induce 5HT and dopamine release
agonists at 5HT, dopamine, and adrenergic receptors
peripheral sympathomimetic effect, altered perception, hallucinations (primarily visual, not all drugs/doses), altered mood
tolerance is minimal in most cases
withdrawal can include craving, confusion, anxiety, and depression
addiction and physiological dependence thought to be minimal in most individuals
MDMA/ecstacy
dissociatives that inhibit NMDA receptors (in and outside of reward pathway)
developed as general anesthetic agents
acute effects: analgesia, anesthesia, dissociation, sympathomimetic (increased HR and BP)
toxicities include hallucinations, delusions, psychosis, violent behavior
at higher doses - seizures, coma, death
withdrawal symptoms can include craving, confusion, and depression
addiction and physiological dependence is considered less prominent compared to opioids and ethanol
PCP and ketamine
alcohol aversion therapy
prevent relapse in recovering alcoholics
inhibits acetaldehyde dehydrogenase leading to accumulation of acetaldehyde upon alcohol consumption which causes flushing, nausea, headache, vomiting, adn hypotension
hepatotoxic at high doses
can lead to marked respiratory depression, cardiovascular collapse, convulsion, closely monitor patient
effectiveness is limited by failures in adherence
disulfram
FDA approved anti-craving medications for alcohol addiction, can also be used as anti-epileptic meds
anti-craving mechanism is unknown
known to increase activity of GABAa receptors and inhibit glutamatergic NMDA receptor activity
combination with disulfram is more effective than either alone
not used to treat alcohol withdrawal
acamprosate and topiramate
Narcan challenge test before treatment when recovering alcoholic is suspected of using opioids
used in opioid overdose
inhibits mu opioid receptors in ventral tegmental area of the brain - short acting antagonist
cardiac arrhythmias, hepatotoxicity, pulmonary edema, opioid withdrawal
duration/severity of withdrawal symptoms is less severe
Naloxone
anti-craving therapy for alcohol addiction, prevent relapse in recovering alcoholics
limited success in treating opioid dependence by preventing high, does not alleviate craving
inhibits mu opioid receptors in ventral tegmental region of the brain - long acting antagonist
hepatotoxic at high dose
combination with disulfram does not offer substantial advantage for recovering alcoholics
inhibits opioid analgesia
Naltrexone
used for both drug maintenance therapy and detoxification of opioid addiction
strong opioid analgesic drug
high efficacy agonist at mu opioid receptor
suppresses symptoms of craving and withdrawal due to slow absorption and long half-life
produces plasma opioid levels that remain stable over time and therefore mitigate cravings and withdrawal symptoms
stable concentration bypasses alternating highs and withdrawals seen in heroin use
cardiac arrest/arrhythmias due to prolonged QT syndrome, respiratory arrest, constipation, nausea, risk of death when combined with other CNS depressants
administered orally on a daily basis, has significant abuse liability
methadone
used for both drug maintenance therapy and detoxification of opioid addiction
similar to methadone but longer acting
QT prolongation longer than with methadone
ECG monitoring is recommended
administered orally 2-3 times per week
LAAM
used for both drug maintenance therapy and detoxification of opioid addiction
partial agonist at mu opioid receptor and antagonist at kappa opioid receptor - long acting
respiratory depression, hypotension, dizziness, sedation, bradyarrhythmia, tachyarrhythmia
overdose is difficult due to partial agonist property
available in combination with naloxone to prevent elicit drug use (Suboxone)
Buprenorphine
smoking cessation aid, reduces craving, prevents withdrawal
multiple forms available - gum, patches, nasal spray
different kinetics than smoking
slower absorption and longer lasting nicotine plasma levels - less rewarding
alleviates craving and is associated with less frequent withdrawal symptoms
limited success (15-20%)
Nicotine replacement therapy (NRT)
smoking cessation aid, reduces craving, prevents withdrawal
antidepressants (efficacy not related to depression)
mechanism unknown
non-competitive antagonist of nicotinic acetylcholine receptors in reward pathway
weak inhibitor of dopamine, norepinephrine, and 5HT reuptake in reward pathway
black box warning - suicidal thoughts, erratic/aggressive behavior, exacerbation of underlying psychiatric illness
can be combined with NRT to improve results
exercise caution in patients with preexisting psychiatric illnesses
Bupropion
smoking cessation aid, reduces craving, prevents withdrawal
partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) in ventral tegmental area and nucleus accumbens
inhibits nicotine full agonist activation at nAChRs
black-box warning - suicidal thoughts, erratic/aggressive behavior, exacerbation of underlying psychiatric illness
exercise caution in patients with preexisintg psychiatric illnesses
Varenicline
