substance-related disorders PART 1: stimulants, hallucinogens, cannabinoids - dr krysiak

what is the most important reward pathway?

mesolimbic dopamine system

list the parts of the brain involved in the reward pathway

• ventral tegmental area (VTA)

• nucleus accumbens

• amygdala

• prefrontal cortex

idk if we need to know

what part of the reward pathway is the site of dopaminergic neurons, responds to external stimulus perceived as rewarding or aversive, and connects nucleus accumbens and prefrontal cortex?

a. ventral tegmental area (VTA)

b. nucleus accumbens

c. amygdala

d. prefrontal cortex

a.

idk if we need to know

what part of the reward pathway mediates the rewarding effects of dopamine, where stimulation by dopamine creates a pleasurable effect (positive reinforcement)?

a. ventral tegmental area (VTA)

b. nucleus accumbens

c. amygdala

d. prefrontal cortex

b.

idk if we need to know

what part of the reward pathway helps establish associations between environmental cues and if they are rewarding or aversive?

a. ventral tegmental area (VTA)

b. nucleus accumbens

c. amygdala

d. prefrontal cortex

c.

idk if we need to know

what part of the reward system provides executive control of decision and whether to seek a reward or not?

a. ventral tegmental area (VTA)

b. nucleus accumbens

c. amygdala

d. prefrontal cortex

d.

what do opiates and cocaine bind to that activates the reward pathway?

• VTA

• nucleus accumbens

what is defined as: problematic pattern of substance use leading to clinically significant impairment or distress as manifested by 2 of 11 criteria occurring in the preceding 12-month period

substance use disorder

which of the following is when you use a drug or medication improperly (larger doses, more frequent dosing)?

a. drug abuse

b. drug dependence

c. drug tolerance

a.

which of the following is a state in which an organism functions normally only in the presence of a drug with physical disturbance when the drug is removed?

a. drug abuse

b. drug dependence

c. drug tolerance

b.

which of the following is a state in which an organism responds with a lessened effect to the same dose of a drug and higher doses are required to elicit the previous effects?

a. drug abuse

b. drug dependence

c. drug tolerance

c.

what addictive drug is the most behaviorally reinforcing and blocks reuptake of DA and NE?

cocaine

which route of cocaine is absorbed more rapidly?

what is the duration of effect of both?

absorption: smoking > nasal

duration of effect:

• nasal: 15-30 minutes

• smoking: 5-10 minutes

what happens when you combine cocaine with alcohol?

cocaine metabolized to cocaethylene

-longer duration of action

-incr. potency

higher risk of death and injury

how do we treat cocaine intoxication?

• IM benzo for agitation

• lorazepam 2-4 mg IM Q30 min to Q6H PRN

• short term, low dose antipsychotics for psychotic symptoms

what effects does cocaine have on the heart?

• dose dependent incr. in HR and BP

  • effects intensified by EtOH

• coronary vasospasm

• incr. platelet count

• acceleration of atherosclerosis (ACS)

• results in MI

if someone has cocaine associated ACS, what beta blockers do we not use?

which is directly contraindicated?

note: use of beta blockers at discharge is very controversial

do NOT use cardiac selective beta blockers

directly CI: propranolol

is pharm tx ordinarily indicated for cocaine use?

not ordinarily

no meds have clear efficacy

list possible tx for severe cocaine dependence

• desipramine

• fluoxetine & bupropion

• dopamine agonists (amantadine)

none of them really have good efficacy

what is the MOA of methamphetamine?

• inhibits monoamine oxidase

  • prevents degradation of NE and DA

• blocks reuptake of monoamines (DA, NE, and 5-HT)

list effects of methamphetamine

• highly neurotoxic

  • incr. oxidative stress and excitotoxic effects

  • glial inflammation and mitochondrial dysfunction

• cardiopulmonary manifestations

  • pulmonary HTN and ACS

what addictive substance has physical danger in synthesis of drug?

methamphetamine — easily synthesized from pseudoephedrine

think about meth labs

what addictive drug may induce caries (cavities)?

methamphetamine

meth mouth

what is a major risk associated with methamphetamine intoxication?

RISK TO HARM SELF AND HEALTH CARE PROFESSIONALS

• severe paranoia and psychosis

• aggressive and violent behavior

• self mutilation

how do we treat methamphetamine intoxication (same as amphetamine analogs)?

• supportive care: de-escalation

• VERY high doses of sedatives required

  • benzos

what do we avoid when treating methamphetamine intoxication?

butyrophenones (haloperidol)

what effects does methamphetamine intoxication have?

• seizures

• ACS

• aortic dissection

what are the symptoms of methamphetamine withdrawal?

“crash”

• severe fatigue

• insomnia

• depressed mood

• anhedonia

• impaired concentration

• suicidality

• anxiety

• intense cravings

begins as the drug is wearing off, can peak over 5 days

how do we treat methamphetamine withdrawal acutely?

NO MEDS approved for mgmt

supportive care: nutrition, hydration, sleep

what maintenance therapy is recommended for methamphetamine withdrawal?

• behavioral therapy

• methylphenidate

• dextroamphetamine

• bupropion

• topiramate

• naltrexone

list the amphetamine analogs

• methylenedioxymethaphetamine (MDMA)

  • ecstasy (pill/tablet)

  • molly (powder)

what is seen in mild-moderate intoxication from amphetamine analogs?

• profound positive feelings and empathy for others

• eliminates anxiety and induces extreme relaxation

• suppresses the need to eat, drink, or sleep

what is seen in heavy intoxication from amphetamine analogs?

• depression

• anxiety and paranoia

• irrationality and psychosis

list complications of long-term use of amphetamine analogs

• neurotoxic to serotonin neurons

• decr. cognitive performance

what are synthetic cathinones (bath salts) used for?

what is their base compound?

what can the fresh plant be used for?

• used for amphetamine/cocaine like effects

• base compound: evergreen shrub, catha edulis (Khat)

• fresh plant can be used for stimulant effect

what does acute intoxication with synthetic cathinones (bath salts) cause?

• sympathomimetic symptoms

  • tachycardia

  • hypertension

  • hyperthermia

what do hallucinogenic compounds stimulate?

presynaptic and postsynaptic serotonin receptors

list the hallucinogenic compounds

• lysergic acid diethylamide (LSD)

• psilocybin (shrooms)

• ketamine (special K)

• phencyclidine (angel dust)

how do you treat hallucinogenic compound intoxication?

• calm reaassurance

• reorientation

• supportive care

• benzodiazepines for anxiety or agitation

what do we need to avoid when treating hallucinogenic compound intoxication?

phenothiazines

-reduce seizure threshold

what is the most commonly used illicit drug in the USA?

marijuana

what is the active ingredient of marijuana?

delta-9-tetraahydrocannabinol (THC)

when are effects of marijuana seen after smoking and how long do they last?

orally consumed?

• smoking

  • effects begin shortly after

  • last 1-3 hours

• orally consumed

  • effects begin within 30 minutes - 1 hour

  • last up to 4 hours

when does marijuana have the most adverse effects?

developing brain

how does intoxication with synthetic cannabinoids compare to THC?

• more potent

• longer half-life

• additional sympathomimetic symptoms

how do we treat intoxication from synthetic cannabinoids?

• benzodiazepines for agitation and seizures

  • lorazepam 1-2 mg PRN

• antiemetics for N/V

  • ondansetron 4-8 mg IV PRN