BasicPharmacologyofCommonlyMisusedPrescriptionDrugs

LaneWallace,PhD

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Vision

To contribute to student success nationally by achieving a measurable reduction in alcohol and

drug misuse on America’s campuses and promoting recovery efforts.

MissionThe mission of the Higher Education Center for Alcohol and

Drug Misuse Prevention and Recovery, in partnership with the nation’s colleges and universities, is to:

• Promote student success nationally by providing data-driven solutions to alcohol and drug misuse

• Lead the dialogue on collegiate alcohol and drug misuse and recovery in the national agenda

• Ensure the long-term sustainability and effectiveness of the Center’s efforts

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Higher Education Centerfor Alcohol and Drug Misuse Prevention and Recovery

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Lane Wallace received his PhD in Pharmacology from the University of Utah. Dr. Wallace is now a Professor and former Chair of Pharmacology at The Ohio State University. He specializes in neuropharmacology, mechanisms of action for addicting drugs, computational neurobiology of dopamine signaling and neurodegenerative diseases.

Prescription Drugs

Physician visit – Prescription

FDA approval for a specific use

Quality control

Some, manageable, risk

Misusetaken for purpose other than that for which prescription written

taken by person other than for whom the prescription written

Potential Dangers of Misuse“overdose” problems

emergency room visitsdeath

addiction liability

“Generation Rx” culture

Addictioncompulsion to use drugs

loss of control over amount of drug use

continuing use in spite of adverse consequences

Generation Rxexcessive reliance on pharmaceuticals

Polling Question:Do you feel that students frequently misuse

prescription drugs in any of these ways?

A. Taking a drug for a purpose other than that for which the prescription was written

B. Giving one of their prescription medications to someone else

C. Taking a drug prescribed for someone elseD. All of the above

PharmacologyThe interaction of chemicals (drugs) with living biological systems

Receptorchemical with which a drug primarily interacts to produce pharmacological effects

often a proteinoften the target for a hormone or neurotransmitter molecule

Agonist

“runner’s high”

“high”

enkephalin + mu-opioid receptor

morphine + mu-opioid receptor

Antagonist

nothing

naloxone + mu-opioid receptor

Enkephalin + naloxone + mu-opioid receptor

nothing

Drug Classes (Families)

set of drugs with similar effectsall have similar effect on same target can substitute in therapymay differ in

duration of actionamount of drug needed to produce an effect

Polling Question:

Which of these drug classes are prone to misuse?

A. Opioid pain medications (e.g., OxyContin, Vicodin)

B. Stimulants (e.g., Adderall, Ritalin)C. Sedatives (e.g., Xanax, Valium)D. All of the above

DoseDose is the amount of drug a person takes.

The spectrum of effects experienced by a person is a function of the dose of drug.

The intensity of a particular effect experienced by a person is a function of the dose of drug.

Building Temperature

PainHomeostatic system

lessens injuryhelps learn behaviors to prevent injurycan be modulated to adapt to current conditions

Marked variability within individual over timebetween individuals

Physical Paindetectors in tissues

sensitivity is modifiable

first level integration in spinal cordcontrol reflexes

signals sent to brainintegration in brain

determines response

Mu-Opioid receptor is the target for opioid pain-relieving drugs

A Manglik et al, Nature 485:321, 2012

Mu-opioid receptors (targets for morphine) are located in several sites processing pain information

LS Stone and DC Molliver, Mol Interventions 9:234, 2009

Agonists at µ-Opioid Receptorshydrocodone

morphine

propoxyphene

oxycodone (Oxycontin)

tramadol

Opioids for Chronic Pain in USA320 million people in USA100 million with chronic pain

(includes headache, low back pain, cancer pain, arthritis pain, etc.)

5-8 million treated chronically with opioid drugs

~ 2% of total USA population

Prescriptions for opioids have increased over the last two

decades.

Polling Question:

Which of the following are reasons often given by students for first misuse of a

prescription drug?A. Self-medication for pain, anxiety, etc.B. CuriosityC. Seeking a mental feeling or stateD. All of the above

Misuse often characterized by

preference for higher doses of drug

preference for faster onset of drug effectinjectedsnortedsmoked

Oxycodone Extended Release Tablet

Time-release Capsules

~2% of people >12 years old (~5 million people) have mis-used opioids in the last month.

SAMSHA: Results from the 2013 National Survey on Drug Use and Health

Polling Question:

Where do students most frequently obtain prescription medications for misuse:

A. The InternetB. A drug dealerC. From multiple physiciansD. From family members or friends

Where do non-medical opioid users get their drugs?

SAMSHA: Results from the 2013 National Survey on Drug Use and Health

“Doctor Shopping”~ 2% of opioid prescriptions1 in every 143 patientsaverage of 32 opioid prescriptions per person per year from 10 different prescribers

McDonald and Carlson, PLoS One July 17, 2013

Approximately 1 million people in USA are dependent on or abuse pain relievers

SAMSHA: Results from the 2013 National Survey on Drug Use and Health

Death from Opioid OverdoseCombination of drugs

alcohol anti-anxiety/tranquilizers

Switch to more potent drugfail to account for different dose requirement

Stimulant Drugs

Stimulant DrugsEffects

elevation in mood, confidencelessen fatiguedecrease appetitelessen power of distractionsincrease heart rate and blood pressure

Used to treat ADHD

Dopamine transporter is target for stimulant drugs

Wikipedia

Dopamine Signalingcurrent situation is

unexpectedimportant

mobilizes brain for learning

Stimulant Drugs Affect Learning and Memory

Polling Question:

What do we know about the misuse of prescription stimulants among college students?

A. This behavior is on a downward trendB. Students who misuse these medications as

“study aids” typically have higher grade-point averages

C. Students often have inflated perceptions of the misuse of these substances by other students

D. All of the above

~0.5% of people >12 years old (~1.2 million people) have mis-used stimulants in the last month.

SAMSHA: Results from the 2013 National Survey on Drug Use and Health

Anti-anxiety Agentsbenzodiazepine family

alprazolam

clonazepam

diazepam

lorazepam

Depressant Effects as a Function of Dose

Anti-anxiety Agentsuses (all benzodiazepines)

treat anxiety

uses (some benzodiazepines)hypnosis (sleep aid)treat panic attackspre-operative sedationanesthetictreat epilepsymuscle relaxant

Anti-anxiety Agentsimpair short-term memory

sometimes adversesometimes beneficial

dependence / addiction

GABA receptor is target for

anti-anxiety drugs.

Wikipedia

~1% of people >12 years old (~2.5 million people) have mis-used anti-anxieties in the

last month.

SAMSHA: Results from the 2013 National Survey on Drug Use and Health

Factors Predisposing to Addiction

geneticsstresschildhood abusemental illness

depressionobsessive compulsivemanic depressant

motive for using drugs

Conclusions

Opioids, stimulants, anti-anxiety are commonly used therapeutic drugs

A small percent of medical users will develop addiction

A small percent of prescriptions are diverted

ConclusionsPeople misusing drugs often prefer

higher dosesfaster onset of action

Death from overdose often involvescombinations of drugsswitching to a more potent form

ConclusionsLiability for addiction

geneticsstressful life experiencesmotivation for using drugs

Questions?

Thank you!