Drugs of Abuse

Question 1

Drugs that activate G protein coupled receptors

Answer 1

• opioids
• cannabinoids
• hydroxybutyric acid (GHB)
• LSD, mescaline, psilocybin

Question 2

main receptor target of opioids

Answer 2

OR (Gio)

Agonist

Question 3

Drugs that bind to Inotropic Receptors and ion channels

Answer 3

• nicotine
• alcohol
• benzodiazepines
• phencyclidine, ketamine

Question 4

drugs that bind to transporters of biogenic amines

Answer 4

• ampheatmines

* ecstacy

Question 5

Symptoms of opioid withdrawal

Answer 5

➢ Intense dysphoria, nausea vomiting, muscle aches, Lacrimation, rhinorrhea
➢ Yawning and sweating
➢ Chills, goose flesh (“cold turkey”)
➢ Tremors, muscle jerks (“kicking the habit”)

Question 6

treatment of opioid withdrawal

Answer 6

➢ 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)

Question 7

CNS effects of Cannabinoids

Answer 7

• 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

Question 8

cannabinoids MOA

Answer 8

• 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)

Question 9

Rimonabant

Answer 9

CB1 receptor agonist

Question 10

g-HydroxyButyrate (GHB)

Answer 10

➢ 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”

Question 11

psilocybin

Answer 11

hallucinogen

Question 12

Dronabinol

Answer 12

Therapeutic Used THC analog

used to treat –
• Nausea & vomiting in patients receiving cancer chemotherapy

Question 13

mescalin

Answer 13

hallucinogen

Question 14

Rimonabant

Answer 14

CB1 receptor agonist

Question 15

LSD has activity at

Answer 15

agonist activity at 5-HT2A receptors

Question 16

Smoking’s effects on pregnancy

Answer 16

• ↑ abortions, ↓ birth weight, ↑ neonatal morbidity & mortality
• delayed physical & mental development in children.

Question 17

Nicotine MOA

Answer 17

nACh-R: Activation in VTA → release of DA

Question 18

Treatment for smoking

Answer 18

➢ 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

Question 19

Ketamine and Phencyclidine (PCP)

Answer 19

➢ 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

Question 20

Effects of cocaine and amphetamines

Answer 20

• 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.

Question 21

Varenicline

Answer 21

partial agonist at a4b2 nACh-R for smoking cessation

Question 22

MOA Cocaine and Amphetamines

Answer 22

➢ 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.

Question 23

Reward center is a set of DAergic cells from the ventral tegmental area (VTA) to the nucleus accumbens.

Answer 23

cocaine and amphetamines

Question 24

Cocaine overdose symptoms

Answer 24

cardiac toxicity, irregular breathing and apnea, itching (cocaine ‘bugs’), tachycardia, impotence, paranoid delusions & severe hypertension → stroke or myocardial infarction.

Question 25

amphetamine overdose symptoms

Answer 25

tachycardia, hypertension, mydriasis, loss of appetite

Question 26

MDMA (ecstacy) toxicity

Answer 26

➢ 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.

Question 27

cardiac toxicity, irregular breathing and apnea, itching (cocaine ‘bugs’), tachycardia, impotence, paranoid delusions & severe hypertension → stroke or myocardial infarction.

Answer 27

cocaine overdose

Question 28

Withdrawl signs of both amphetamine and cocaine

Answer 28

increased appetite, exhaution, increased sleep time and mental depression