Pharm: Drugs of Abuse

Question 0

What is a general pharmacokinetic characteristic of addictive drugs?

Answer 0

Rapid rise in plasma concentration followed by a rapid fall due to short half-lives and rapid clearance from the site of action.
(rapid peaks and troughs)

Question 1

What is the main cause of opioid-related deaths?

Answer 1

Respiratory arrest

Question 2

Why do Barbiturates have worse withdrawal than Benzodiazepines?

Answer 2

Barbiturates are less specific and have a wider distribution.

Question 3

Accepted treatment for alcohol withdrawal.

Answer 3

Benzodiazepines

-diazepam and clonazepam

Question 4

What characteristic of nicotine contributes to its high addiction potential?

Answer 4

It affects the mesolimbic system and has a short half-life.

Question 5

What is the MOA of cocaine and amphetamines and what are the two primary targets of these drugs?

Answer 5

MOA: blocks NE, DA, and 5HT re-uptake transporters.

Targets

1. Locus Ceruleus
2. Nucleus Accumbens

Question 6

What is the MOA of marijuana?

Answer 6

Partial agonist at Type-1 cannabinoid receptors. Release of cannabinoids is normally moderated by release of DA from VTA neurons and inhibited by GABAergic neurons. Binding of the CB1 receptor stimulates DA release and inhibits GABA release leading to a “feed forward” response in the reward center.

Question 7

What is the MOA of phencyclidine?

Answer 7

PCP: blocks NMDA receptors leading to anesthesia, delirium, hallucinations, intense paranoia, and amnesia.

Question 8

What is the MOA of methylenedioxymethamphetamine?

Answer 8

MDMA (ecstacy): stimulates 5HT release and inhibits its re-uptake. Acts as a stimulant much like cocaine but MDMA induces hallucinations.

Question 9

What is the MOA of caffeine?

Answer 9

Blocks adenosine receptors on pre-synaptic DA and NE neurons increasing the amount of DA and NE in the synapse acting like a stimulant.

Question 10

Name the drug that blocks the sympathetic hyperactivity associated with the worst withdrawal symptoms.

Answer 10

Clonidine

Question 11

What is the 1st pharmacotherapy approach for substance abuse and what is an example?

Answer 11

Chronic administration of an agent that causes adverse effects when the drug is abused.

Ex. Disulfuram: inhibits aldehyde dehydrogenase so when alcoholics consume drinks, they cannot metabolize the toxic metabolite acetaldehyde and they get sick.

Question 12

What is the 2nd pharmacotherapy approach for substance abuse and what is one example?

Answer 12

Block the affects of the drug being abused. Usually only works with motivated patients.

Naltrexone: blocks opioid binding sites to prevent the “high” but not the cravings or withdrawal.

Question 13

What is the 3rd pharmacotherapy approach for substance abuse?

Answer 13

Utilize long acting agonists for medication maintenance. Basically “weening” them off the abused drug.

Question 14

Methadone

Answer 14

MOA: long acting opioid agonist with cross-tolerance to other opioids, which prevents the high, cravings, and withdrawal.

Indications: opioid addiction

Question 15

Buprenorphine

Answer 15

MOA: partial agonist at the mu-opioid receptor. So it actually has antagonistic effects in the presence of the abused drug and will also not have as dramatic of an effect on its own.

Indications: opioid addiction

Question 16

Suboxone

Answer 16

MOA: Combo of Buprenorphine and Naloxone.

• naloxone is destroyed in 1st pass when taken orally, so it won’t have any antagonistic effects.
• however, if an addict wanted to get high off the buprenorphine they would take it IV to get a more potent effect, however, if the naloxone is not sent thru the liver it will have antagonistic effects.
• the result would be an addict getting sick rather than high

Indications: opioid addiction

Question 17

Varenicline

Answer 17

MOA: nicotinic receptor partial agonist that will act as an antagonist in the presence of nicotine.

Indications: smoking cessation

Contraindicated in pts. with psychiatric disorders.

Question 18

What is the 4th pharmacotherapy approach for substance abuse?

Answer 18

Utilize medications to prevent long term dyshporia and dysfunctional reward mechanisms. Prevent the brain from neural remodeling associated with addiction.

Question 19

Acomprosate

Answer 19

MOA: down-regulates glutamate hyperactivity (seen in alcoholics)

Indications: alcohol withdrawal by preventing symptoms of delirium tremens

Question 20

Topiramate

Answer 20

MOA: AMPA/Kainate receptor blockers

Indications: alcoholism

Question 21

Bupropion

Answer 21

MOA: DA and NE re-uptake inhibitor in mesolimbic pathway buffering nicotine withdrawal

Indication: smoking cessation

Contraindications: seizure patients

Question 22

What is the last pharmacotherapy approach for substance abuse?

Answer 22

Treat co-morbidities associated with substance abuse.