LECTURE 21 Flashcards
What are the four level of substance use on the spectrum of psychoactive substance use?
beneficial use
casual/ non problematic use
problematic use
chronic dependence
What are the four main factors that cause SUD?
1: positive reinforcement, activation of brain reward system, take drug to feel good, through dopamine pathway in mesolimbic system
2: Physical dependence, negative reinforcement, develop tolerance and withdrawal, feel bad when not taking the drug
3: genetic
4: behavioral/ envrionmental cue, psychosocial, not physcial
1 and 2 are drug specific factors
What are the three initial causes of drug misuse? Give examples
1: exposure to recreational drug (street drug), due to envrionmental/scoail cues (weed/ alcohol), develop craving for drugs (coke, nicotine)
2: Drug are intially prescribed as therapeutic agents, such as opioids for pain mangement or benzodiazepines fo sleep aids
3: Management stress/ trauma/ self-medicating, such as usig coke for depression
What are the three main things of drugs that play a role in SUD?
The route of administration, length of use, as well as drug PK
eg; high lipophilicity–> faster onset–> stronger craving
what is physical VS psychosocial dependence?
What is associated with the cycle of craving and relapse
physical: physcial changes occur when withdrawal, such as headache/ not feeling well
psychosocial: such as leaving kids to buy drug
It is associated with reward pathway and euphoria, as well as envrionmental ues, such as needles can cause srong craving
What is SUD?
Substance use disorder is the pattern of drug use, which is non-medical, leading to impariment or distress, causing physcial or social harm
What does the reward system do? What are the four natural rewards?
It regulate and control behavior by inducing pleasurable effects
Food, thirst, fighting and sex (procreation), which are all essential for men kind to live
What is opioid mechanism of action and effect on neuron? What about cocaine?
Opioid: mimic neurotransmitter, disinhibition of GABA, increase DA release
Coke: Increase neurotransmitter, Blocks DA uptake
What is cocaine mechanism of action?
When DA is releases, cocaine blocks the DAT, reducing uptake, and causing DA accumulation. The build up and flood of DA cause intense euphoria
What is the mechanism of misuse of opioid? What about mechanism of action?
Through dependence: tolerance and withdrawal
Opioid bind and inhibit GABA, so no GABA is released, and DA release will increase die to disinhibition, and cause euphoria reward
What is tolerance?
Tolerance is a symptom of dependence
Drug tolerance lead to “physiological dependent state”, which screwed the normal homeostatic balance
How is tolerance acquired? What does it lead to?
Tolerance is the reduction in response to a drug upon chronic administration
It can lead to increased dose requirement, additional therapy, physiological dependence and withdrawal symptoms
What happen when repeat exposure to opioids?
Opioid receptor activation causes cellular inhibition, so excitability is reduced.
Increase dose is required for effect
What is cellular (PD) tolerance?
Due to repeated exposure to drug, adaptation occur and the cell responds to drug differently
Higher dose is needed at the site of action to reach the same response, so response dose is right shifted
What is metabolic tolerance?
Repeated exposure might induce drug metabolizing activity, so so less drug can actually make it to the site of action, equivalent to “taking less drug”
Larger dose is needed to maintain the therapeutic effect for same length of time, meaning need to take more drug so it can actually reach site of action
It is not related to physical dependence
Does not alter dose response curve
What is withdrawal?
Withdrawal syndrome is a measurement of drug dependence, which appear upon stopping drug use
It can be worse than the original syndrome
How is drug dependence connected to drug misuse?
When physical dependence is developed, individual misuse drug relief withdrawal and tolerance
eg: use higher dose to counter tolerance
continue to use drug to avoid withdrawal, even if it’s not required no more
Why is tolerance effect of opioid dangerous?
Different tolerance effects are developed at different rate
For example, euphoria may develop tolerance sooner than respiratory depression, so OD can occur as not enough respiratory tolerance was developed
How does physiological dependence cause SUD?
A drug may cause craving for the drug’s rewarding effect
What are the reasons behind the increase in opioid OD death?
1:Craving for euphoria (DA release)
2: Different tolerances occur at different rate, result in dose escalation
3:Avoidance of withdrawal syndrome
4: Polypharmacy
5: high potency opioid, such as fentanyl and carfentanil
What drug is used to counter opioid OD? How does it work?
Narcan ask Naloxone
It is injected through IV to treat acute opioid OD
It is a competitive antagonist, which bind to mu opioid receptor, blocking opioid from binding
Why multi-dose of naloxone is needed sometimes?
The opioid might be too strong/ potent
Naloxone last shorter in time comparing to some drug such as fentanyl
What is the difference between pharmacological VS physiological additive/ synergistic DDI?
Give examples
Pharmacological: target the same receptor
eg: alcohol and diazepines both target GABA-A receptor
Physiological: target the same system
eg: opioid and anti histamine drug are both CNS depressant
What is adulterant? What are the three types of adulterant?
It’s substance that are found in street drug
1: inert substances/ diluents
such as baking soda, sugar, levamisole, xylazine, phenacetin, caffeine
They are added to lower cost of drug
2: Contaminants
By product or cross contamination from manufacture
3: Pharmacologically active adulterant
Such as carfentanil, xylazine, phenactein and caffein
added to make drug user feel more high
