Drugs of Abuse Flashcards
Drugs that activate G protein coupled receptors
- opioids
- cannabinoids
- hydroxybutyric acid (GHB)
- LSD, mescaline, psilocybin
main receptor target of opioids
OR (Gio)
Agonist
Drugs that bind to Inotropic Receptors and ion channels
- nicotine
- alcohol
- benzodiazepines
- phencyclidine, ketamine
drugs that bind to transporters of biogenic amines
- ampheatmines
* ecstacy
Symptoms of opioid withdrawal
➢ Intense dysphoria, nausea vomiting, muscle aches, Lacrimation, rhinorrhea
➢ Yawning and sweating
➢ Chills, goose flesh (“cold turkey”)
➢ Tremors, muscle jerks (“kicking the habit”)
treatment of opioid withdrawal
➢ Treatment of withdrawal: substituting with Methadone or buprenorphine…followed by its slow dose reduction
➢ Clonidine is also found to be effective for withdrawal
➢ Use of opioid antagonist (naloxone, naltrexone) in an abuser may precipitate withdrawal (precipitated withdrawal)
CNS effects of Cannabinoids
- A feeling of being “High”
- euphoria
- uncontrollable laughter
- increased appetite
- altered sense of time
- difficulty concentrating
- decreased memory
- Vasodilation and tachycardia
- Habitual users show Reddened conjunctiva
cannabinoids MOA
• THC is an agonist at CB1 & CB2 (cannabinoid) receptors
• CB receptors are in many areas of the CNS
➢ Therapeutic Used THC analog is Dronabinol
➢ used to treat –
• Nausea & vomiting in patients receiving cancer chemotherapy
➢ Rimonabant CB1 receptor agonist
➢ FDA approved use to treat obesity, smoking cessation (offlabel use)
Rimonabant
CB1 receptor agonist
g-HydroxyButyrate (GHB)
➢ Site of action: weak agonist on GABAB receptor
➢ Lactone (GBL) may be found in nail polish remover
➢ Effects – used as hypnotic:
• Euphoria
• Enhanced sensory perception
• Feeling of social closeness
• Amnesia, general anesthesia, coma, death
➢ Pharmaceutical properties: rapid onset, short half-life
• –tmax = 20-30 min; t1/2 = 60 min
• Odorless liquid
➢ “Club drug” “date rape drug”
psilocybin
hallucinogen
Dronabinol
Therapeutic Used THC analog
used to treat –
• Nausea & vomiting in patients receiving cancer chemotherapy
mescalin
hallucinogen
Rimonabant
CB1 receptor agonist
LSD has activity at
agonist activity at 5-HT2A receptors
Smoking’s effects on pregnancy
- ↑ abortions, ↓ birth weight, ↑ neonatal morbidity & mortality
- delayed physical & mental development in children.
Nicotine MOA
nACh-R: Activation in VTA → release of DA
Treatment for smoking
➢ Clonidine (off label) – a2 adrenergic agonist; reduces anxiety, irritability and craving during withdrawal.
➢ Varenicline – partial agonist at a4b2 nACh-R for smoking cessation
➢ Bupropion – antidepressant & nACh-R antagonist
Ketamine and Phencyclidine (PCP)
➢ Ketamine (dissociative anesthetic) is structurally related to PCP, is also abused
• A “pyschomimetic”.
➢ Phencyclidine may be smoked (by mixing the powder with tobacco), “snorted,” taken orally, or injected intravenously.
➢ Also called as “Angel dust”, “Hog” “Special K”
➢ Mechanism: NMDA antagonist
➢ The most dangerous hallucinogen
Effects • Euphoria (can be addictive) • Physiological effects (diagnostic) • hyperreflexia, hypersalivation, nystagmus, marked hypertension , seizures (fatal) • Dissociation -->loss of contact with reality (self, senses) -->inability to communicate -->aggression, panic, violence
Effects of cocaine and amphetamines
- Elevate mood, induce euphoria, increase alertness and reduce fatigue
- Coke high lasts 30-60 min; Meth lasts 12-24 hr.
- Smoked or injected, the “rush” is intensely pleasurable for a period of sec to min, followed by a longer period of milder euphoria mixed with increased anxiety and a strong desire to obtain more of the drug.
- Repeated use over short times → toxic paranoid psychosis which is clinically indistinguishable from the florid early signs of schizophrenia.
Varenicline
partial agonist at a4b2 nACh-R for smoking cessation
MOA Cocaine and Amphetamines
➢ Cocaine acts by blocking the presynaptic DA transporter (DAT) (Also NET and SERT)
➢ Amphetamine blocks DAT, but also causes DAT to run backwards, releasing DA from the terminal cytoplasm
➢ MOA may also involve NET & SERT. Mice lacking DAT can still be made addicted to these drugs.
Reward center is a set of DAergic cells from the ventral tegmental area (VTA) to the nucleus accumbens.
cocaine and amphetamines
Cocaine overdose symptoms
cardiac toxicity, irregular breathing and apnea, itching (cocaine ‘bugs’), tachycardia, impotence, paranoid delusions & severe hypertension → stroke or myocardial infarction.
amphetamine overdose symptoms
tachycardia, hypertension, mydriasis, loss of appetite
MDMA (ecstacy) toxicity
➢ A common “club drug” used for increased energy
& pleasurable feelings such as peacefulness & empathy
➢ Causes euphoria, facilitate interpersonal communication, heightens sexuality
➢ Hyperthermia is a potentially fatal side effect of use of high doses of ecstasy – serotonin syndrome (or toxidrome).
MOA
➢ Ecstasy causes a massive release of serotonin. It has preferential affinity for SERT.
cardiac toxicity, irregular breathing and apnea, itching (cocaine ‘bugs’), tachycardia, impotence, paranoid delusions & severe hypertension → stroke or myocardial infarction.
cocaine overdose
Withdrawl signs of both amphetamine and cocaine
increased appetite, exhaution, increased sleep time and mental depression
