4. Principles of Drug Abuse

Question 1

What is drug abuse?

Answer 1

• Use of a drug outside of its medically intended (therapeutic) purpose

Question 2

At what point does ‘drug use’ become ‘drug abuse’?

Answer 2

• it depends on…
  
  • individual
  • the drug itself
  • reason for taking it
• there is a spectrum of psychoactive substance use:
  
  • Beneficial: use that has positive health, spiritual and/or social impacts
    
    • ex. medicinal use as prescribed, moderate consumption of alcohol
  • Non-problematic: recreational, casual or other use that has negligible health or social effect
  • Problematic: use at an early age or use that begins to have negative impacts for individuals, family/friends or society
    
    • ex. use by minors, impaired driving, binge consumption
  • Chronic Dependent: use that has become habitual and cmpulsice despite negative health and social effects

Question 3

What is a drug of abuse?

Answer 3

• Difficult to characterize in absolute terms
  
  • because they still have therapeutic effects
• Commonly, a drug characterized as (more) likely to be associated with problematic use
  
  • Limited therapeutic benefit, but not always!
• Context-dependent characterization
  
  • ex. Opioid use for pain, or pleasure?
    
    • ex. prescription drugs

Question 4

What are 3 important things to note about the relationship between Drug Abuse and Drug of Abuse?

Answer 4

• Using a Drug of Abuse need not imply Drug Abuse
• Many Drugs of Abuse have therapeutic benefits
• Drug Abuse is not exclusive to Drugs of Abuse

Question 5

What are the Consequences of drug use?
- hint kinda: Aside from specific pharmacodynamic drug effects, two other processes can occur in the presence of a drug (or, to be more inclusive, substance)

Answer 5

• Dependence (“physical dependence”) –> body attempts to produce homeostasis = wants to stay in equilibrium –> tries to revert back to normal. But if the drug is there because you’re chronically taking it, the body will engage in long-term physiological processes to offset these changes
  
  • Progressive physical adaptation to drug use
    
    • Tolerance
    • Dependence
    • Withdrawal
  • Progression and extent depends on drug and conditions of use
• Substance Use Disorder (“addiction” or “psychological dependence”)

Question 6

What is tolerance?

Answer 6

• refers to a reduction in the perceived or demonstrated response of a drug//Reduced response to a drug…
  
  • …following repeated administration
    
    • Acquired tolerance
      
      • acquired: due to drug exposure
  • …compared to the general population
    
    • Innate tolerance
      
      • Innate: is internal to you and usually dependent of genetics
• Acquired tolerance is generally reversible, though dependent on removal of drugs and restoration of underlying biology/physiology

*refer to slide 5 for acquired and innate response graph

Question 7

What are the 2 types of Tolerance?

Answer 7

• PK tolerance
• PD tolerance

Question 8

What is PK tolerance?

Answer 8

• Alterations in ADME processes, reducing drug plasma concentration

Question 9

What is PD tolerance?

Answer 9

• the changes in the cell in terms of adaptation of the drug being present
• no change in plasma [ ] b/c drug isn’t being metabolized to any greater degree
• Adaptive changes within the systems affected by the drug
  
  • ex: Altered receptor expression
    
    • Agonists –> overstimulation –> dec receptor internalization
      
      • (cell feedback aiming to quiet signal)
    • Antagonists –> dec stimulation –> inc receptor expression
      
      • (cell feedback seeking expected/regular signal)

Question 10

How can you become more tolerant?

Answer 10

• Significant source of drug complications, because:
  
  • A higher dose is required to achieve the desired effect –> potential reduction in specificity
  • Not all of a drug’s effects experience tolerance equally
    
    • tolerance is stimulate dependency
• the reason why you’re becoming tolerant is b/c your body has changed b/c of the drug and the body’s attempt to equilibrate those changes

*refer to slide 9 for visual version

Question 11

What is dependence?

Answer 11

• State of altered homeostatic mechanisms or equilibria in chronic – or repeated – presence of drug
  
  • Body works “harder” to (partially) compensate/counterbalance pharmacodynamics effects
• Most easily diagnosed by removing the drug in question and looking for an effect
• If the body expects drug to be there = dependent
  
  • equilibrium shifted with new homeostasis = imbalance
  • b/c body expects drug to be there = the new normal

*refer to slide 11 for an example

Question 12

What is withdrawal syndrome and what are its 2 major elements?

Answer 12

• Imbalance following abrupt cessation of drug until the original “drug-free” homeostatic state can be restored
• 2 major elements
  
  • Rapid removal of the effect of the drug of dependence
    
    • Drug cessation and rapid metabolism/clearance
    • Antagonist administration
  • Hyperarousal of physiological systems due to drug-induced adaptations, now unopposed
• Symptoms vary by drug pharmacodynamics…
  
  • Generally opposite to those normally produced by the drug
    
    • e.g. opioids  dilated pupils, tachycardia, etc.
• …and severity heavily influenced by pharmacokinetics

Question 13

Refer to slides 13-15 for long question practice on PK and drug withdrawal.

Answer 13

other side!

Question 14

What is substance use disorder?

Answer 14

• Progression of dependence beyond biological phenomena into disorder
  
  • More arbitrary in diagnosis compared to tolerance, dependence, and withdrawal
• Condition can prevail long after successfully navigating dependence/withdrawal
  
  • i.e. no more drug in body, but cravings still exist
• Relapses common, even after treatment
  
  • Re-exposure to addictive drug
  • Stress
  • Contextual cues that recall prior drug use
• Does not occur in all people who use a Drug of Abuse
• continued use despite significant substance-related problems

Question 15

What are the 3 general reasons for abuse/SUD?

Answer 15

• Drug-related factors/variables
  
  • Reinforcement
  • Mechanism of Action
  • Pharmacokinetics
• Factors/variables related to the Individual
  
  • Genetics (polymorphisms affecting drug PD/PK)
  • Preexisting Conditions (altered baseline neurophysiology)
• Environmental factors/variables
  
  • how people that use drugs are perceived in their community
  • presence of drug

Question 16

How does reinforcement play a role regarding drugs?

Answer 16

• Stimulus that increases the odds of the associated behaviour being repeated
  
  • Does not necessarily imply the stimulus is enjoyable
• Effectively assayed in animal models…
  
  • ex. Experiment of lab rat pushing buttons to get a drug. Every time they push the drug = gets drug
    
    • if you inc button pushes to get a single dose, reinforcement = see how much they’ll work for it
• …and results generally correlate well to addiction risk in humans

Question 17

How does the Nucleus Accumbens play a role regarding drugs?

Answer 17

• With few exceptions, drugs of abuse associated with increased levels of dopamine in neurons of the nucleus accumbens
  
  • Key element of mesolimbic dopamine system
  • Widely thought of as “reward pathway” of brain
    
    • Reinforcement of association between drug and pleasurable feelings
• Drugs that stimulate the NAc more strongly are more likely to lead to addiction
  
  • Greater feelings of pleasure/reward
• Drugs that stimulate the NAc sooner after time of
  administration are more likely to lead to addiction
  
  • Increased link between the drug and “feelings of pleasure”
• These concepts also apply within the same drug!
  
  • ex. different routes of administration
    –> meaning addiction is more likely if the drug has a high peak and faster Tmax on the graph (can refer to slide 21)

*please refer to slide 20 on how the visual on dopamine inc in NAc

Question 18

How does the PK play a role regarding drugs?

Answer 18

• The preparation of the drug will often dictate plasma concentrations
  
  • These levels, and their rates of onset/metabolism, can vary the propensity for abuse
• ex. case study: cocaine
  
  • please refer to slide 22

Question 19

List the ways from lowest to highest of which methods of transport of drug is more likely to lead to SUD.

Answer 19

• whichever method goes to the brain fastest = higher chance of SUD

1. oral
2. Intravenous injection
3. Inhalation

Question 20

What are the treatment options?

Answer 20

• No universal answer to address all drugs
• What can we do?
  
  • Understand the pharmacology of the drug/drug combination
  • Understand the associated psychosocial issues of the individual
  • Individualize the treatment plan
    
    • Months or years of rehabilitation to affect behavioural patterns
      
      • expect periods of relapse and remission
• Consider substitution of a legally available agonist, with different pharmacodynamics/pharmacokinetics
  
  • Heroin –> methadone
  • Cigarettes –> nicotine patch
  • May be able to combine with behavioural therapy to wean off drug
  • can refer to slide 25 for visual