Substance Abuse Flashcards
Physical dependence
withdrawal signs occur upon discontinuation; can be physically dependent but not addicted
Psychological dependence
Addiction; compulsive drug use; drug seeking, craving, despite negative consequences
Tolerance
higher doses are required to elicit the same effect, functional changes in receptors or drug metabolism; reflects adaptive changes the body has made to compensate for the drug’s presence
Withdrawal
signs of symptoms occurring as a result of drug discontinuation
All abused drugs active which dopamine pathway?
all abused drugs activate the mesolimbic DA pathway, causing release of DA in forebrain structures such as the NAc and PFC
How is dopamine usually used in the brain?
dopamine is normally used as a learning signal in the brain (signaling the difference between expected and actual reward)
Addiction to drugs is what type of learning?
maladaptive learning, often stronger than “natural rewards”
Precipitated withdrawal
pharmacologically-induced onset of withdrawal; often worse than normal withdrawal because some or all the receptors are blocked at once
Example of precipitated withdrawal
buprenorphine can induced precipitated withdrawal to opioids such as heroin
Conditioned withdrawal
withdrawal (and possible drug seeking) brought on or exacerbated by environmental cues
What did the controlled substance ace of 1970 establish?
established schedules for controlled substances
Alcohol used recreationally for
anxiolytic and euphoria
Other uses of alcohol besides recreationally
disinfectant, analgesic, organic solvents
How do you define alcoholism?
If it interferes with daily life, if you continue to do it even though it negatively impacts your life
Differences in distribution of alcohol between men and women
Men have 58% body water whereas women have 48% , so men can dilute it more and therefore drink more
What type of kinetics is alcohol eliminated by?
eliminated with zero order kinetics (constant rate)
Acute tolerance of alcohol
intoxication greater when BAC is ascending versus descending
Chronic tolerance of alcohol
greater concentrations needed to achieve desired effect
Fomepizol inhibits
Alcohol dehydrogenase (ADH)
Disulfiram inhibits
Aldehyde dehydrogenase (ALDH)
Fomepizol is used to treat
methanol, ethylene glycol poisoning
Disulfiram is used for
used for motivated drinkers; sensitizes a person to ethanol; disuades ethanol use during abstinence
Describe alcohol metabolism
- Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase
- Acetaldehyde is metabolized to acetate by aldehyde dehydrogenase
CNS targets of alcohol
- GABA(A) receptor potentiator (hyperpolarizes neuronal membrane, inhibits firing)
- NMDA receptor antagonist (inhibits excitatory aa receptor)
What contributes to the CNS depression, cognitive deficits and memory impairment seen with alcohol?
NMDA receptor antagonism
Effects of the CNS targets of alcohol
- Mild CNS stimulation (disinhibition)
- CNS depression
- Cognitive impairment
- Motor impairment
- Coma, death
Acute organ toxicity from alcohol
- CNS: sedation, ataxia, intoxication
2. Cardiovascular: vasodilation, CV depression
Chronic organ toxicity from alcohol
- CNS: tolerance, physical dependence, nerve injury
- CV: prevent coronary disease, cardiomyopathy, arrhythmias, hypertension
- Liver/GI: liver disease (cirrhosis)
- Cancer: mouth, pharynx, larynx, esophagus, liver
Drug interactions with alcohol
- Synergy with CNS depressants
- Inhibits metabolism of phenothiazines, TCAs, sedative-hypnotics
- Disulfiram
- Acetaminophen (promotes liver damage by NAPQI)
Contraindications for alcohol use
- Liver disease
- Peptic ulcers: ethanol is a secretagogue
- Epilepsy: ethanol changes neuronal excitability
Treatment of ethanol intoxication
support respiration, prevent aspiration when at 300-500 mg/dl
Treatment of Methanol and ethylene glycol toxicity
fomepizole or ethanol, hemodialysis
General treatment of alcoholism
- Detoxification (ethanol abstinence syndrome)
2. Psycho-social and drug therapy
Treatment of ethanol abstinence syndrome
- prevent seizures, delirium, arrhythmias
- maintain potassium, magnesium, phosphate balance
- Thiamine to prevent Wernicke-Korsakoff syndrome
- Substitute benzodiazepine for alcohol initially, then taper
- Antidepressants for mood
Naltrexone
mu, kappa opioid antagonist; attenuates alcohol’s action
Acamprosate
GABA system activator; NMDA antagonist; substitutes for some of alcohol’s actions
Ondansetron
5HT3 antagonism for emesis
Topiramate
anticonvulsant
Vaclofen
GABA(b) antagonism
Varenicline
nAChR partial agonist
Endogenous cannabinoids
2-arachidonyl glycerol (2-AG) and anandamide
Endogenous cannabinoids involved with which processes in the body?
memory, appetite, synaptic transmission
How does marijuana cause euphoria?
perhaps via disinhibition of the DA system and other NT systems
MOA of THC
Activates CB1 receptors on VTA GABA neurons; these receptors are coupled to K+ channels, and activation of CB1 receptors increases potassium conductance in these VTA GABA neurons (inhibits GABAergic neurons)
What does THC inhibition of GABAergic neurons do?
because these cells normally provide tonic inhibition to neighboring DA cells, reducing their activity causes activation of DA neurons via a disinhibition mechanism
Nabilone
THC analog for chronic pain
Rimonabant
CB1 inverse agonist, appetite suppressant (withdrawn)
Dronabinol
synthetic THC analog, chemotherapy nausea/vomiting, weight control in AIDS
Perceptual hallucinations
shape, color
Psychotic episodes
depersonalization, hallucinations, distorted time perception
Somatic symptoms of hallucinogens
dizziness, nausea, paresthesias, blurred vision
What are hallucinogens?
a group of drugs that produce perceptual disturbances that can span the range from slightly odd to highly dangerous (psychotic)
Are hallucinogens addictive?
No; tolerance develops but they are typically not addictive
Paresthesias
tickling, tingling, burning, prickling, or numbness of a person’s skin with no apparent long term physical effect
Lysergic acid diethylamide
LSD; 5HT2a partial agonist; psychosis possible, enhanced Glu transmission
MDMA
ectasy; 5HT, NE, DA releaser, 5HT syndrome possible
Mescaline
5HT2A partial agonist
Psilocybin mushrooms
5HT2A agonist; mimics 5HT
Phencylidine
PCP; NMDA, nAChR antagonist, D2 partial agonist
Ketamine
dissociative anesthetic (separation of mind and body); NMDA antagonist
Hallucinogen pharmacology centers on the effects of which system?
serotonin system - with a few having actions at glutamate systems as well
Which hallucinogens target the glutamate system
PCP and ketamine
MOA for opioid dependence
- MOR activation inhibits VGCCs, reducing GABA release onto DA neurons
- MOR activation activates GIRK channels, hyperpolarizing GABa neurons, reducing AP firing
- disinhibition of DA transmission
Opioids
- Heroin
- Morphine
- Oxycodone
- Methadone
- Buprenorphine
- Naltrexone
Methadone
MOR full agonist; NMDA antagonist; chronic pain, opiate cessation
Buprenorphine
potent MOR partial agonist; KOR/DOR antagonist; chronic pain, opiate cessation
Naltrexone
MOR, KOR antagonist, alcohol and opiate cessation
Morphine
MOR agonist, analgesia
Oxycodone
MOR and KOR agent, analgesia, chronic pain
Heroin
schedule I illicit drug
Physical symptoms of opioid withdrawal
tremors, chills, perspiration, tachycardia, flu-like symptoms, vomiting, diarrhea
Psychological symptoms of opioid withdrawal
dysphoria, anxiety, insomnia, depression, cravings
Treatment of opioid withdrawal
- Substitute long-acting, high-affinity/potency often partial agonist (buprenorphine)
- Detoxification
