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Flashcards in L15 - Drugs of abuse Deck (22):
1

Substance dependence syndrome

a cluster of symptoms which include
- drug tolerance,
- withdrawal symptoms,
- continued use despite substance-related problems

2

Tolerance

Reduction in response to a drug after repeated administration

3

Acquired tolerance

Pharmacokinetic: related to distrubution and metabolism and therefore concentration of the drug
Pharmacodynamics: related to receptor density or coupling efficiency and therefore response to drug

4

Mesolimbic dopamine reward system

Reinforces rewarding behaviour by releasing dopamine, starts a chain of addiction

5

Physical dependence **

State that developes as a result of tolerance produced by resetting normal homeostatic mechanisms after repeated drug abuse.

Characterised by a withdrawal syndrome upon drug stopping.

6

Withdrawal

The only evidence of physical dependence and acts to reinforce the use of the drug.

Caused by the removal of the drug of dependence and characterised by CNS hyperarousal.

Symptoms tends to be opposite to the effects of the drug

7

Origins of drug abuse:
Agent - the drug

Reinforcement by withdrawal syndromes make the user want the drug.

Reinforcement is related to the drug's abuse potential, and is associated with an increase in neurotransmitter release

8

Origins of drug abuse:
Origin - the user

Individual variability in personality (genetics, development, upbringing).

Individual variability in pharmacokinetics and pharmacodynamics.

Presence of psychiatric disorders.

Predisposition for addiction has polymorphic inheritance

9

Innate tolerance (alcoholics)

Sons of alcoholics are less sensitive to alcohol and have a greater tolerance, makes them more prone to alcoholism themselves

10

Innate tolerance (Asians)

Have elevated mitochondrial alcohol dehydrogenase converting alcohol to acetaldehyde.

Less likely to be alcoholics as acetaldehyde builds up and has unpleasant effects

11

Origins of drug abuse:
Environment - the setting

Societal norms
Peer pressure
Socioeconomic status

12

Opioid withdrawal

Symptoms: cravings, restlessness, irritability

Can lead to autonomic dysfunction with tachycardia, hypertension

13

Dependence vs. physical harm

Increased physical harm = increased dependence.

Greatest dependence and physical harm is fentanyl.

Then heroin, cocaine etc.

14

Alcohol
Mechanism?
Metabolism?
Tolerance?

Unsure of mechanism, may be GABA enhancement or NMDA inhibition.

Mainly hepatic metabolism.
Follows FIRST ORDER rate until enzymes saturate, then ZERO ORDER (exponential to linear decrease in conc).

Tolerance will lead to a decrease in sedation but the lethal dose won't change (will just be a narrow TI)

15

Opioids
Epidemic?
Death?
Abuse potential?
Weaning treatment?

64,000 deaths in 2017.
Epidemic is WORSENING due to cheaper and more available drugs (fentanyl - readily avail).

Death is caused by respiratory depression.

Abuse potential is high due to high lipid solubility so fast acting and because they induce a euphoric high.

Methadone is long acting slow onset opioid used in weaning

16

Heroin

Diamorphine

Rapidly metabolised into morphine

17

Methamphetamine

Increases the release and stops reuptake of catecholamines e.g. dopamine, 5HT
= CNS stimulant

18

Cocaine

Local anaesthetic and vasoconstrictor.
Inhibitor of catecholamine reuptake.

Street form is cut with baking soda to make it more rapidly absorbed.

19

Cannabinoids

Acts on cannabinoid receptors.

Active ingredient is tetrahydrocannabinol

20

Propofol

Anaesthetic induction agent.

Rapid induction and offset with minimal side effects

21

WHO analgesic ladder

Start with a good history and prescribe a healthy lifestyle (exercise, diet).

Start with mild non-opioid and slowly step up.

22

Amphetamines ***

What do they cause?
Side effects?

Anorexia, restlessness, euphoria, wakefulness.

Irritability, aggression, hallucinations, neglect, psychosis, arrhythmia, hypertension, MI, renal failure