Drugs of Abuse

Question 1

What are some of the criteria for substance abuse disorders?

Answer 1

• Tolerance
• Withdrawal
• Usage of large amounts
• Normal activities are given up
• Continued use despite knowledge of problems

Question 2

Withdrawal

Answer 2

Signs that emerge when the use of the drug is stopped which will go away when the drug is resumed

Question 3

Tolerance

Answer 3

Decreased effect with repeated use of drug and increased need for larger doses for the same effect

Question 4

What pathway is activated by all drugs of dependence?

Answer 4

Ventral Tegemental Area of nucleus accumbens which results in the release of dopamine

Question 5

Besides lack of the agonist, what is another mechanism that can cause withdrawal?

Answer 5

Antagonism of the receptor that the drug normally binds to

Question 6

What are the psychostimulants?

Answer 6

Cocaine and amphetamines

Question 7

Cocaine Uses

Answer 7

Powerful CNS stimulant and appetite suppressant as well as a topical anesthetic.

Question 8

Cocaine MOA

Answer 8

Inhibits the action of dopamine transporters in the presynaptic terminals - the levels of DOPA in the presynaptic cleft will increase

Question 9

Amphetamines MOA

Answer 9

Inhibit the action of VMAT2 so DOPA cannot be placed in the vesicles leading to a high level of “free” DOPA that can reverse the DOPA transporter - increased DOPA in the presynaptic cleft

Question 10

What are the effects of psychostimulants?

Answer 10

• Increased energy
• Decreased fatigue
• Decreased appetite

Question 11

What is the fastest mechanism to feel “high” from cocaine?

Answer 11

IV

Question 12

Where is cocaine metabolized?

Answer 12

Hepatic metabolism

Question 13

What is the problem of combining cocaine with ethanol?

Answer 13

Forms cocaethylene which leads to a longer duration of action and an increased cardiotoxic effect

Question 14

What is a unique risk of psychostimulant abuse?

Answer 14

Increased risk of rare autoimmune disorders like lupus and Stevens Johnson

Question 15

Cocaine OD Signs

Answer 15

• Cardiac Arrhythmia
• Tachycardia
• Dilated pupils
• HTN

Question 16

What is the treatment for cocaine withdrawal?

Answer 16

• Bromocriptine

- Lorazapam

Question 17

Opioid MOA

Answer 17

Inhibition of GABA interneurons leading to the disinhibition of the mesolimbic DOPA system - increased DOPA in the nucleus accumbens is ultimate result

Question 18

Opioid OD Signs

Answer 18

• Unconsciousness
• Respiratory depression
• Pulmonary edema

Question 19

Is there cross tolerance to opioids?

Answer 19

Yes. Tolerance to one will cause tolerance to another opoid.

Question 20

What is the metabolism of heroin?

Answer 20

Heroin -> 6-monoacetylmorphine -> morphine

Question 21

Opioid Withdrawal Symptoms

Answer 21

• Lacrimation
• Rhinorrhea
• Yawning
• Piloerection
• Involuntary movement

Question 22

What is the treatment for opioid addiction and withdrawal?

Answer 22

Methadone or busprenophine

Question 23

What is the treatment for opioid OD?

Answer 23

Naloxone

Question 24

What is the treatment for opioid dependence?

Answer 24

Naltrexone

Question 25

Naloxone MOA

Answer 25

mu-opioid competitive antagonist with very high affinity and short half life to displace heroin - heroin is longer acting though and symptoms can return so monitoring is required

Question 26

Naltrexone MOA

Answer 26

mu-opioid competitive antagonist with long half life that makes heroin administration no longer rewarding

Question 27

Methadone MOA

Answer 27

mu-opioid agonist with long half life that prevents withdrawal symptoms

Question 28

Buprenorphine MOA

Answer 28

Partial mu-opioid agonist that has less potential for respiratory depression

Question 29

What is suboxone?

Answer 29

4:1 mix of buprenorphine and naloxone

Question 30

Cannabinoid MOA

Answer 30

THC inhibits GABA interneurons via CB1 which leads to increased DOPA in the nucleus accumbens

Question 31

What are the symptoms of cannabinoid use?

Answer 31

- Increased appetite - Redness of the eyes - Relaxation - Decreased pressure in the eyes

Question 32

Cannabinoid SE

Answer 32

- Panic - Amotivational syndrome - Personality changes

Question 33

Type B Alcohol Dependence

Answer 33

Earlier onset at less than 25 yrs and is more severe

Question 34

Type A Alcohol Dependence

Answer 34

Later onset of greater than 25 yrs and has a slower disease progression

Question 35

What is the effect of alcohol on neural circuits?

Answer 35

Increases the effects of GABA and inhibition of glutamate - chronic use leads to reduction of the GABA receptors and upregulation of glutamate receptors

Question 36

What is the result of sudden reduction in alcohol intake from a chronic user?

Answer 36

Abrupt increase in glutamate action due to the release from inhibition

Question 37

What drugs are used to treat alcohol withdrawal?

Answer 37

Benzodiazepine

Question 38

Alcohol Withdrawal Symptoms

Answer 38

- Seizures - Alcoholic hallucinations - Delirium tremens - Hyperarousal

Question 39

Delirium Tremens

Answer 39

Uncontrollable tremors of the extremities with autonomic instability

Question 40

Besides alcohol withdrawal, what else can cause delirium tremens?

Answer 40

Benzodiazepine withdrawal

Question 41

What are the treatments for alcohol dependence?

Answer 41

- Disulfiram - Naltrexone - Acamprosate

Question 42

Disulfiram Indications

Answer 42

Alcohol Aversion Therapy

Question 43

Acamprosate MOA

Answer 43

Restores balance between excitation and inhibition - but true mechanism is unknown

Question 44

Disulfiram MOA

Answer 44

Inhibits aldehyde dehydrogenase that results in nausea and vomiting if alcohol is taken - decreases desire to drink

Question 45

What mutation is protective against alcohol dependence?

Answer 45

Often in Asians due to ALDH2*2 mutation

Question 46

Acamprosate Contraindications

Answer 46

Severe Renal Disease

Question 47

What is the treatment for benzodiazepine withdrawal?

Answer 47

Diazepam - has a long half-life and it will be tapered off over time

Question 48

What is used for treatment of nicotine addiction?

Answer 48

Varenicitine - partial agonist that binds nicotine ACh receptors which relieves cravings and binds with greater activity than nicotine which decreases the reward from smoking

Question 49

What is the molecular target of the hallucinogens?

Answer 49

Serotonin receptors - 5HT2A

Question 50

Do hallucinogens cause addiction?

Answer 50

No