drugs of abuse Flashcards
addiction vs physical dependence
addiction: impaired control over use, compulsive, craving
physical dependence: adapted state, causing specific withdrawal syndrome.
produced by abrupt cessation, sudden dose reduction, admin antag
addictive drugs activate which pathway?
mesolimbic dopamine system
which receptors does ethanol affect
- GABAA receptors
- Kir3/GIRK channels
- Adenosine reuptake
- Glycine receptors
- NMDA receptors
- 5-HT3 receptors
ethanol withdrawal
tremor, n/v, sweating
seizures 24-48 hours
delirium tremens 48-72 horus
tx ethanol withdrawal
diazepam and chlordiazepoxide (long half life benzo’s)
elderly/liver failure pt = use lorazepam and oxazepam
tx alcohol addiction
1) disulfiram: aldehyde dehydrogenase inhibitor
2) naltrexone: opioid antagonist - dec craving
3) acamprosate - NMDA antagonist - prevents relapse
4) topiramate - (not FDA approved). facilitates for GABA fxn, antagonizes glutamate receptor - reduce cravings
acamprosate
used to tx alcohol addiction
NMDA blocker
topiramate
tx alcohol addiction - not FDA approved
facilitates for GABA fxn, antagonizes glutamate receptor - reduce cravings
benzodiazepine - physical dependence or addiction?
addiction is very rare
physical dependence**
benzodiazepine withdrawal
LIFE THREATENING
tremor, anxiety, perceptual disturbances, dysphoria, psychosis, sz
benzo withdrawal tx
diazepam (replace with long acting) - gradually reduce dose
barbituate withdrawal
resemble benzos
methylxanthines
caffeine
theophylline
theobromine
methylxanthine MOA
block presynaptic adenosine receptors = inc NE release
normally - activation of adenosine receptors inhibit NE release
methylxanthine actions by dose
100-200 mg caffeine = inc alertness
1.5 g = anxiety/tremors
2-5 g = stimulation of spinal cord
methylxanthine tolerance/withdrawal
rapid tolerance develops
withdrawal: fatigue, sedation
rarely addiction occurs
cocaine MOA
inhibits DA, NE, 5 HT reuptake = prolongation of DA effects in limbic system - euphoria
cocaine withdrawal
dysphoria, depression, sleepiness, cocaine craving, bradycardia
withdrawal is mild
no tx needed
cocaine addiction tx
none show efficacy
amphetamines MAO
inc release of catecholamines
weak MAOI
amphetamine tolerance/withdrawl
withdrawal: inc appetitie, sleepiness, exhaustion, depression
marked tolerance
nicotine MOA
VTA (nicotinic receptors on dopamine neurons) = activation by nicotine stimulates dopamine release
nicotine actions - low vs high dose
low: ganglionic stimulation via depolarization - euphoria, relaxation
high: ganglionic blockade - respiratory paralysis, severe hypotension - medullary paralysis
nicotine withdrawal
mild
irritable, sleeplessness
extremely addictive
tx for nicotine addiction
1) replacement therapy
2) sustained release bupropion
3) varenicline - partial agonist at nicotinic receptors
opioids withdrawal
dysphoria
lacrimation
rhinorrhea
yawning
opioid withdrawal tx
1) detoxification using opioid agonist (LONG ACTING) - slowly reduce dose
- methadone, buprenorphine
2) detox using adrenergic agonist
- chronic opioid intake causes withdrawal to cause rebound firing (noradrenergic storm) = clonidine and lofexidine (a2 agonists)
3) detox using opioid antagonists
- naltrexone - doesn’t satisfy craving or relieve withdrawal = used for pt after detox with high motivation to stay clean
marijuana MOA
receptors CB1 (psych effects) and CB2 (on immune cells)
marijuana use
drobainol - anorexia associated with weight loss in pt with AIDS and n/v in chemo
LSD
5HT2 receptor agonists
sympathomimetic effects
mydriasis, HTN, tachy, high body temp, flushing, sweating, tremors, piloerection
LSD addiction/withdrawal
doesn’t cause addiction and there is no withdrawal
LSD agitated state tx
diazepam
phencyclidine
PCP
dissociative anesthetic –> non-comp antagonist at NMDA receptors
blocks reuptake of NE and DA
- -> cholinergic and anticholinergic effects
- -> actions at nicotinic and opioid receptors
phencyclidine presentation
violent bizarre behavior psychosis **nystagmus** miosis
phencyclidine tx
benzodiazepeines for psychotic behavior and seizures
MDMA
empathy and intimacy w/o impairing intellectual capacities
release of biogenic amines (mainly 5HT)
withdrawal: depression, lasting weeks
nitrous oxide
euphoria
analgesia –> LOC
taken as mixture with O2 (not purely N2O)
volatile organic solvents
gasoline, paint thinner, lighter fluid
exhilaration, light headedness
implicated in cancer, cardiotoxicity, neuropathies, hepatotoxicity
organic nitrites
amyl nitrite
butyl nitrite
used to enhance erection
not addictive
