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ACTIVELEARNINGDRUGSOFABUSE.16APRIL,9:4511
AMROOM545GENERALANDSPECIFICINSTRUCTIONS
The purpose of this activity is to illustrate the effects
of drugs of abuse discussed in class and drugs used
to treat addictions.
You are not responsible for detailsof the cases
presented. The cases are to illustrate actions and
adverse effects of drugs presented in class.
You are responsible for knowing how the addictive
drugs increase dopamine in the Nucleus accumbens.
You are responsible for associating the adverse
effects in these cases with the drug that induced it.
This is a compulsory team activity. The exam
questions will be based on this material and the
material from class on Tuesday.
1.

You have been assigned to a team group (CPR)

2.

Each person in your team has been assigned to read

an article about a drug of abuse and report to the
group, so that the RaspayGanacards can be
completed. You mustprepareby reading the article and
completing the questions beforearriving at the class.

3.

Some cases are more difficult than others. Such is

life. You can trade, if both agree.

4.

You can meet with the other students who have the
same articles to prepare. We could not program time
for this, but I will be available on Tuesday and

Wednesday afternoon.
5.

In the class time on Thursday you will haveonly5

minutesto present the selected portions of the article.
Important sections of each article are highlighted in
yellow.

6.

Start each presentation with the following briefreview

a.

This case is about ....x drug

b.

X drug is/is not addictive.

c.

Its mechanism of action is ....

d.

(if addictive) it increases dopamine in the Nucleu

Accumbens by....
7.

Each team should identify a time-keeper to keep the

group on schedule. If you use more than 5-6 minutes
per topic, the group will not be able to finish during
the assigned time.

9.

The ANSWERS will be posted .

10. Resources:
a.

I will be available in the area of the Amphitheater II

on Tuesday afternoon from 1-2 pm

b.

Email: susan.corey@upr.edu

c.

Office: A-336/337

d.

Your textbook, either Golan or Katzung

8.
Ifyouareabsent,thewholeteamwillbemissingyourinput.Ifyou
mustbeabsent,pleasereadthe
article,preparetheanswers,andarrangeforacolleaguetopresent
thematerialtotheteam.

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SPECIFICINSTRUCTIONSFOREACHTOPIC
READTHEARTICLE(S),PRESENTTHECASE
HIGHLIGHTED,ANDPRESENTYOURANSWERSTOTHE
QUESTIONSONTHEFOLLOWINGPAGES.
EACHSTUDENTISRESPONSIBLEFORONETOPIC.
GROUPSTHATHAVEONLY6STUDENTSWILLNEEDTO
DIVIDETHEREMAININGTOPIC
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1.OPIOIDS:Opioidwithdrawal,naturalandprecipitated2articles:
(1)EffectofinappropriateNaltrexoneuseinaheroinmisuser
(Precipitatedwithdrawal)
(2)UnintentionalrapidopioiddetoxificationDiscussant:Presentthe
answerstothesequestions
Information:Naltrexoneisusuallyadministeredonceperday.Can
blockheroineffectsforupto48hours.Itshalflifeis4h,soitis
administeredinahighdosetoenableonceperdaydosing.]

*1. You have two cases. In one, the patient had a lower
dose, but the time course is known. In the second, the
dose is higher, so the full syndrome is worse. Present
both briefly.
[* You do not have to turn in the description of the
cases].2. How does precipitated withdrawal compare
with usual (passive) withdrawal? Much more violent,
shorter extent3. How do you change a patient from
Methadone Maintenance to buprenorphine?
Patient must be completely (or nearly completely)
opioid- free before changing to a partial agonist, since a
partial agonist can act like an antagonist and precipitate
withdrawal. Clonidine may be administered to suppress
withdrawal symptoms during detox.
Takeaway:Understandwhyitisnecessarytoavoidprecipitated
withdrawal

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2.OPIOIDS:WithdrawalfrommethadoneandWithdrawalfrom
buprenorphine
2articles:1)Usingacceptanceandcommitmenttherapyduring
methadonedosereduction:rationale,treatmentdescription,andacase
report
2)CourseandTreatmentofBuprenorphine/NaloxoneWithdrawal:An
AnalysisofCaseReportsDiscussant:Presenttheanswerstothese
questions
1.Article#1:Present the highlighted material about a trial
method for withdrawal from methadone. Buprenorphine
is a partial mu agonist and methadone is a full mu
agonist2. How long do patients usually stay in

Methadone Maintenance?3.Article#2: Present the

highlighted material about withdrawal from
buprenorphine.
Frequently for life, or several decades. Withdrawal is
very difficult because of dysphoria and prolonged 3.
3withdrawal.
3. How is buprenorphine pharmacologically different
from Methadone? [agonist/partial agonist]
4. How does this differ from the natural history of
buprenorphine maintenance?
Withdrawal is easier, taking a few weeks.
5. What is a possible reason for the easier withdrawal
from buprenorphine? (page 3 of article)
The mild withdrawal observed with buprenorphine/naloxone may result from its
mu opioid partial agonist activity as well as the high affinity of buprenorphine for
the mu opioid receptor and slow dissociation from that receptor when stopped
abruptly. Since buprenorphine is a partial agonist, the

tolerance mechanisms are not activated to such a high

degree as with full agonists. Therefore, withdrawal of
buprenorphine does not expose such an up-regulated
autonomic system, and withdrawal is not so traumatic.

Takeaway:Understandthewithdrawalsyndromesofbuprenorphinevs
methadoneand
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3.Cannabis/Marijuana:CannabisDependenceandCannabisPsychosis
2articles
UseofDronabinolforCannabisDependence:TwoCase
ReportsandReview

Twocasesof"cannabisacutepsychosis"followingthe
administrationoforalcannabisA.Cannabisdependencesyndrome*1.
Describe at least Case 1 of cannabis dependence. (* Do
not write the description here) 2. What signs of
marijuana withdrawal were described? What signs of
intoxication were mentioned? Withdrawal: Irritability and
anxiety; depression (case 2); decrease in appetite, sleep
disturbances, relapse. Complaints of decreased energy
and creativity Intoxication: spaced out, disinterested in
his family, 3. What is the rationale for using dronabinol in
these cases? Dronabinol is an agonist = THC. This is
agonist therapy for addiction, in which a safer version of
the drug of abuse is substituted for the original drug of
abuse. 4. What is the difference between dronabinol and
herbal marijuana? Dronabinol is not a complete
substitute, since marijuana contains many related
cannabinoids, some of which are pharmacologically
active. The method of administration is also different,
oral vs smoked. The oral administration has no
euphoriant effect (slower onset). Takeaway:Understandwhy
peopleentertherapyformarijuanaaddictionB.CannabisPsychosis
*1. Describe at least one case of cannabis psychosis,
including both initial signs of intoxication, and later
development of psychosis. (*Do not write the description
here) 2. This article was written in 2005. What relevance
may it have for newer synthetic cannabinoids on the
market.New synthetic cannabinoids are very potent
agonists at the CB1 receptor, more potent than THC. The
increased toxicity of the newer compounds is may be the
reason.

Takeaway:Understandwhatcannabispsychosisis.
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4.Cocaine:Acute toxicityArticle:Neurotoxicandcardiotoxiceffects
ofcocaineandalcohol
Useful informationBlood alcohol in this case: = 0.2 g/dL
= 0.2%. Legal limit = 0.08%
In one study, the median half-life of cocaethylene was
144.3minuteswhereas the median half-life of cocaine was
96.7minutes(p < 0.01)
Discussant:Presenttheanswerstothesequestions
*1. Chest pain is a common reason why cocaine
addicted patients call the emergency department. ...
What cardiac and neurotoxicities were seen in this
patient? When you present the case, it is not necessary
to
describe the detailsof the cardiotoxicity.
Elevated blood pressure, massive cerebral infarct, later
develop prolonged QT and torsades de pointes.
2. How did cocaine cause these toxicities?
Vasospasm due to elevated NBA,DA and 5HT is probably
the initial cause. Cocaine also is a Na chalnnel blocker,
and may have some activity to block K channels.
3. How does alcohol increase the toxicity of cocaine?.
Cocaine is metabolized by hydrolysis of its ester groups.
Benzoylecgonine, produced by demethylation of cocaine,
is the major urinary metabolite and can be found in the
urine for 2 to 5 days after a binge. Cocaine is frequently
used in combination with other drugs that can modify its
metabolism. Cocaine gets transesterified in the presence
of ethy alcohol to its ethyl homologue, cocaethylene. In
vitro bindingstudies demonstrate the pharmacological
profile of cocaethylene to be identical to that of cocaine

at monoamine transport binding sites in the human

brain.
Takeaway:Understandtheacutecardiovasculartoxicityofcocaine.
Thesametoxicitycanoccurathighdosesofsimilardrugs(cocaine
typeandamphetaminetype)
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5.ALCOHOLANDNICOTINE:Twoarticlesabouttreatmentof
dependence1):Medicationtreatmentofdifferenttypesofalcoholism
(I was not able to add yellow highlights to this article.
The parts to be presented are detailed below)
2)Psychopharmacologyofsmokingcessationinpatientswithmental
illnessA.Alcoholdependence:PresentCase#2
*1. Present case #2 (page 2/631; 635). (Do not write
details of the case)
2. What treatment was recommended?
Naltrexone (depot)
2. Why is chlordiazepoxide treatment used before
starting naltrexone (page 635, left column)
To suppress alcohol withdrawal seizures
3. What other pharmacologic options for treatment of
alcoholism are mentioned (page 636)?
Disulfiram, acamprosate, ondansetron, topiramate
4. What is the hypothesis for the usefulness of
naltrexone in alcoholism?
It is thought that alcohol must be acting at least in part

through opioid interneurons. By blocking opioid

receptors with naltrexone you are blocking the ability of
alcohol to increase dopamine in the nucleus accumbens.
Takeaway:Identifydrugsusedfortreatmentofalcoholism.
Understandthereasonforselectingnaltrexoneinthiscase
B.Nicotinedependence:
Bupropion
*1. Present the case2. What is the mechanism of action
of bupropion?Antagonist at central nicotine
channels. May also increase synaptic dopamine in the
nucleus accumbens, providing some reward.
3. What is the concern about smoking, and cessation of
smoking, while taking psychiatric drugs such as
clozapine?Smoking induces CYP1A2, which metabolizes
clozapine, causing a shorter halflife and requiring a
higher dose of clozapine. When smoking is reduced, it is
necessary to lower the dose of clozapine.
Takeaway:Understandwhysmokingisaconcernforpsychiatrists.
Understandthenicotinewithdrawalsyndrome.Identifydrugsusedto
treatnicotineaddiction

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6.PCPandAddictiontoGasolinehuffing
Two articles
1.

Seizuredisorderandsubstanceabuse

2.

GasolineAbuseina10YearOldChildwithMentalRetardation:A
CaseReport

Discussant:PresenttheanswerstothesequestionsA.
PCP/Phencylidine
*1. Present the case, including the duration of the
toxicity (*Do not write the presentation here)
2. What is the mechanism of action of PCP? NMDA
antagonist
3. The half life of PCP = 3 days. How long will be required
to eliminate more than 95% of the drug?
T12About3days.95%elimination=5halflives=15days
B.Inhalants:Gasolineinhalation
*1. Describe the case
2. What was the pattern of abuse?
He exhibited regular administration of the drug,
tolerance and increasing frequency of use. He showed a
withdrawal syndrome.
3. Describe the apparent withdrawal syndrome
restlessness, irritability, inattention, sleep disturbance, and
craving (difficulty in preventing child to remain away from
substance use) were observed in this child.

Takeaway:UnderstandwhyPCPremainsasignificantdrugfor
EmergencyMedicine.Understandwhyinhalantaddictionlookslike
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7.LSD,DaturaintoxicationJimsonweedpoisoningTherearetwo
articles
1.LSD-associated Alice in Wonderland Syndrome

(AIWS): A Hallucinogen Persisting Perception Disorder

(HPPD) Case Report
2. Teenagers with Jimson weed (Daturastramonium)
poisoning Case1:LSDassociatedAliceinWonderlandSyndrome
1. What is the mechanism of action of LSD?
LSD is primarily a non-selective 5-HT agonist. LSD may
exert its hallucinogenic effect by interacting with 5-HT
2A receptors as a partial agonist and modulating the
NMDA receptor-mediated sensory, perceptual, affective
and cognitive processes. LSD mimics 5-HT at 5-HT 1A
receptors, producing a marked slowing of the firing rate
of serotonergic neurons
*2. Describe adverse event in this article
Case2:Datura1. What common plant in Puerto Rico also
contains daturastrammonium?
Campana
2. What is the mechanism of action of datura
strammonium?
Anti-muscarinic (like atropine)*3. Describe the cases.
[The alcohol level of the second person corresponds to .
067%] (*Do not write the description here)
4. How would you differentiate cocaine or amphetamine
intoxication from Daturaintoxications?Blood pressure and
pulse is high with cocaine. The heart rate is elevated
with atropine poisoning, but the blood pressure is
regulated, and is normal or low.
5. According to the article, what is the preferred choice
for anticholinergic poisoning, and why is it not
physostigmine?Supportive therapy is used.
Physostigmine is an anticholinesterase, and could

increase Ach to compete with datura, but it is hard to

control, and might cause cholinergic toxicity
Takeaway:RecognizethetoxicityofacommonhallucinogeninPR.
Differentiateanticholinergicandsympathetictoxicity