Drugs of Abuse

Question 1

Drugs with dependence liability (signif) share what property?

Answer 1

-enhance dopamine activity in the nucleus accumbens

DA neuron cell body in ventral tegmental area, nerve terminal in Nucleus Accumbens

Question 2

drug abuse

Answer 2

Use of a drug for nonmedical reasons that deviates from approved social patterns (alters mood, level of perception, or brain functioning).

Question 3

metabolic tolerance

Answer 3

a change in pharmacokinetics results in lowered drug concentrations at the active site; metabolism the primary mech (eg more rapid enzymatic degradation of the drug)

Question 4

Pharmacodynamic tolerance

Answer 4

lessened response at active site to the same drug concentration; achieved via changes in receptor sensitivity or other adaptive changes

Question 5

learned tolerance

Answer 5

• reduction in the effects of a drug due to learned compensatory mechanisms
• behavioral tolerance: describes skills developed due to repeated experiences in attempting to function despite mild-moderate intoxication

-conditioned tolerance: develops when environmental cues (sights, smells, situations) are consistently paired with drug administration

Question 6

reverse tolerance

Answer 6

sensitization (increased response) to drug following repeated doses

Question 7

cross tolerance

Answer 7

after tolerance develops to one drug, it is also seen to other drugs
-used in detox procedures
Ex: heroin and hydrocodone (both @ mu recep)
Ex: ethanol and BDZ (both at GABA recep)

Question 8

Physical dependece

Answer 8

-repeated drug use alters physiological state such that continued admin is needed to prevent withdrawal sx

Question 9

cross dependence

Answer 9

ability of drug to suppress the withdrawal assoc w/ physical dependence of another drug
Ex: benzos are often used to suppress alcohol withdrawal sx

Question 10

psychological dependence

Answer 10

perceived need for a drug (“CRAVING”)

-related to pathologic learning in reward pathway

Question 11

opioids

Answer 11

Heroin, (oxycodone, hydrocodone)

Action in CNS: interaction w/ endogenous opiate receptors (especiall mu); rush feeling related to histamine release

Major effects leading to abuse: euphoria, analgesia, sedation w/ anxiety reduction

Sx of acute toxicity: coma, respiratory distress, pinpoint pupils
Treatment: naloxone (Narcan)–could precip withdrawal

tolerance develops rapidly to most opioids

physical dependence: develops rapidly

withdrawal: sx are not MEDICALLY dangerous, but bothersome

Question 12

Which route of admin from psychoactive drugs provides most rapid onset of effects in the brain?

Answer 12

inhalation (smoking)

Question 13

MOAs of drugs of abuse

Answer 13

opioids: mu opioid receptors (Gi)
CNS depressants: enhance GABA, inhibit glut
CNS stimulants: block DA reuptake or enhance DA release
Nicotine: agonist @ nicotinic neuronal receptors
Hallucinogens: partial agonist at 5HT2 receptors (DA releaser)
Dissociative anesthetics: antagonist at NMDA-Glu receptors
Cannabinoids: agonist at cannabinoid (CB1-CB2) receptors

Question 14

reinforcing effects of opioids

Answer 14

euphoria, sedation, anxiolytic

Question 15

reinforcing effects of CNS depressants

Answer 15

euphoria, sedation, loss of inhibition

Question 16

reinforcing effects of CNS stimulants

Answer 16

euphoria, decreased fatigue, increased arousal

Question 17

reinforcing effects of nicotine

Answer 17

increased alertness

Question 18

reinforcing effects of hallucinogens

Answer 18

altered sensory perception, enhanced insight

Question 19

reinforcing effects of dissociative anesthetics

Answer 19

euphoria, heightened emotionality

Question 20

reinforcing effects of cannabinoids

Answer 20

euphoria, mellowness, changes in perception

Question 21

examples of stimulants

Answer 21

cocaine
meth
nicotine

cocaine and meth have highest relative risk of addiction

Question 22

ex of drug that blocks reuptake of DA and NE into presyn catecholamine neurons and also blocks Na channels in neuronal membranes

Answer 22

cocaine

Question 23

CNS depressants

-action/acute toxicity

Answer 23

-via GABA activation +/- glu inhibition
-respiratory depression, coma (extremely rare w/ BDZs)
Treatment:
ethanol: supportive plus fluids-electrolytes-thiamine
BDZs: flumazenil
Barbs: supportive

Question 24

CNS stimulants

-action/acute toxicity

Answer 24

-via activation of NE and DA receptors
-tox: SNS overactivity, increased HR/BP/temp, chest pain/MI, psychosis
Treatment: CVS suport, vasodilators for BP, BDZs for agitation/seizures

Question 25

Nicotine | -action/acute toxicity

Answer 25

-rare toxicity -via activation of nicotinic cholinergic receptors Tox: n/v, diarrhea, CVP collapse, convulsions Tx: CVS support, emetics, gastric lavage, charcoal

Question 26

Hallucinogens | -action/acute toxicity

Answer 26

-actions on 5HT receptors -LSD-Psilocybin: "bad trip", severe anxiety Tx: talking down, BDZs for agitation -MDMA: agitation, hyperthermia, ADH release-->hyponatremia

Question 27

Dissociative anesthetics | -action/acute toxicity

Answer 27

Phencyclidine (PCP), Ketamine -via block of NMDA Glu receptors -delirium, increased RR, HR, BP, temp, agitation, violent behavior Tx: supportive for BP-hyperthermia, agitation (BDZs)

Question 28

Cannabinoids action/acute tox

Answer 28

-activation of CB1 receptors | minimal-->possible anxiety, impaired coord-tracking, acute psychosis

Question 29

Tolerance to drugs of abuse

Answer 29

opioids: rapid (but not to constipation) CNS dep: rapid to barbs>ethanol, BDZs (signif to sedation/intox, less to lethal dose) CNS stim: develops to euphoria, anorex/hyperthermia, can see supersensitivity to paranoia Nicotine: develops to subjective effects and nausea hallucinogens: not common dissociative anesthetics: not well studied cannabinoids: rapid to most effects, but disappears rapidly

Question 30

Do tolerance and dependence coexist?

Answer 30

-not necessarily | nor do addiction and physical dependence

Question 31

Dependence on Drugs of abuse

Answer 31

-opioids: develops rapidly (scheduled doses, within 1-2 wks) -CNS dep: w/in WEEKS -CNS stimulants: arguable, lack of physiological effects -Nicotine: moderate devel -Hallucinogens: does not devel Dissoc anesthetics: probably none Cannabinoids: accumulating evidence for dependence

Question 32

Withdrawal

Answer 32

characterized by rebound effects on the phsyiological sx that have been modified by chronic drug use - Effects generally opposite of the acute effects of the drug - Withdrawal sx can be FATAL and may require emergent interventions

Question 33

Withdrawal from opioids

Answer 33

rarely life threatening** insomnia, diarrhea, irritability, cramps, muscle aches, increased BP Tx: clonidine, methadone

Question 34

CNS depressants withdrawal

Answer 34

-significant risk of mortality due to seizures | Tx: substitution with BDZs: loading dose then taper to prevent sz

Question 35

CNS stim withdrawal

Answer 35

sleepiness, fatigue, depression, hyperphagia, craving | Tx: largely behavioral

Question 36

Nicotine withdrawal

Answer 36

-irritability, hostility, anxiety, increased appetite, weight gain Tx: relapse-->nicotine replacement, bupropion, varenicline

Question 37

Hallucinogens withdrawal

Answer 37

not known, "flashbacks in some former users

Question 38

Withdrawal from cannabinoids

Answer 38

not clinically significant (long t1/2) | Tx: usually not needed