Lecture 13 - Addiction & Drugs of Abuse Flashcards
What are the 5 characteristics of addiction?
- ABCDE
1) Inability to consistently abstain
2) Impairment in behavioural control
3) Craving
4) Diminished recognition of significant problem’s w/ one’s behaviours and interpersonal relationships
5) Dysfunctional emotional response
What is the diagnostic criteria for opioid use disorder?
Problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least 2 of the 11 criteria, occurring w/in a 12 month period
What is the criteria for mild, moderate, or severe opioid use disorder?
- Mild = presence of 2-3 symptoms
- Moderate = presence of 4-5 symptoms
- Severe = present of 6 or more symptoms
What are the 11 symptoms of opioid use disorder?
1) Taken in larger amounts or over a longer period than was intended
2) Persistent desire or unsuccessful efforts to cut down or control opioid use
3) Lots of time spent in activities necessary to obtain or use the opioid and recover from the effects
4) Craving
5) Failure to fulfill major obligations
6) Continued use despite problems caused or exacerbated by the effects of opioids
7) Important activities given up or reduced b/c of opioid use
8) Recurrent use in situations where it is physically hazardous
9) Continued use despite knowledge of a persistent or recurrent physical/psychological problem
10) Tolerance
11) Withdrawal
What is the definition of tolerance?
1) Need for markedly increased amounts of opioids to achieve intoxication or desired effect
2) Markedly diminished effect w/ continued use of the same amount of opioid
When is the criteria for tolerance not met?
When the px is taking opioids solely under appropriate medical supervision
When is the criteria for withdrawal not met?
When the px is taking opioids solely under appropriate medical supervision
What is the purpose of harm reduction?
Attempts to decrease harmful consequences of illicit drug use to the individual, family, community, & society
What are the goals of the harm reduction program?
Reduce illicit opioid use, needle sharing, criminal activity, and mortality associated w/ addiction
What are the pharmacological options for opioid use disorder?
- Methadone
- Buprenorphine/naloxone or buprenoprhine alone
Is methadone structurally related to opiates?
No
Is methadone an agonist or antagonist and for which receptor?
- Agonist for Mu(u) opioid receptor
- NMDA antagonist
What are the uses of methadone?
Analgesia and withdrawal management in opioid dependent individuals
What is the duration of action for methadone and what does this mean for dosing?
- Long duration
- Once daily dosing
Can methadone cause tolerance?
Not normally
How long does it take to reach peak plasma level for methadone, and why is it good to know this?
- 2-4 hours
- When a patient is overdosing, it will likely be when it is peaking and you will see symptoms during this time period
How long does it take to reach steady state w/ methadone?
5-7 days
What is the half-life of methadone?
22 hours, but can be 15-40 hours
With therapeutic doses of methadone, how long can withdrawal symptoms be suppressed for?
24-36 hours
What is methadone metabolized by?
CYP 3A4
Methadone is a weak inhibitor of which CYP enzyme?
2D6
How is methadone excreted?
As an unchanged drug and as metabolites in urine and feces
Amount of methadone excreted in urine _____ as pH decreases
Increases
What are common persistent adverse effects of methadone?
- Constipation
- Dental (dry mouth)
- Insomnia
- Neuroendocrine
- Sexual changes
- Sweating
What are common adverse effects of methadone that a px can develop tolerance to?
- Drowsiness
- Nausea
- Psychoactive effects
- Weight gain
What effect does methadone have on QT interval?
With high doses, can prolong QT interval
What is considered a QT interval that is too long?
- Males = 450
- Females = 470
What should be done when methadone is given with a drug that is a CYP 3A4 inducer or inhibitor?
Monitor for signs of toxicity or withdrawal and adjust dose accordingly
What is the starting dose of methadone?
10-30 mg; 10-20 mg if patient is high risk
When and by how much should methadone dosing be increased?
Increase by 5-10 mg every 3-5 days as tolerated
Why should prescriptions w/ automatic methadone dosing increases be avoided?
If a px misses a dose, they may not be tolerant to the previous dose so an increase will harm them
What is the usual therapeutic dose of methadone?
50-120 mg
What are some withdrawal signs and symptoms?
- Agitation
- Sweating
- Intense anxiety/depression
- Insomnia
- Cravings
- Tachycardia
- Chills
- Muscle aches
- Abdominal cramping/diarrhea
What are some overdose signs and symptoms?
- Sedation
- Lack of coordination
- Respiratory depression
- Cardiac arrest
- Sweating
- Pinpoint pupils
- Death
When should you consider split dosing?
- Rapid metabolizers
- Pregnancy
What are signs that a patient is a rapid metabolizer?
- Drowsy in afternoon but withdrawal in evening
- Measure methadone peak and trough (over 2 = rapid metabolizer)
How is methadone dosing usually split?
Heavier in the morning and a smaller take-home dose
How does pregnancy affect methadone metabolism?
- Metabolism changes in 3rd trimester
- May require dose increase and/or split dosing
____ is standard of care for pregnant women dependent on opioids
Methadone
What effects can opioid withdrawal have during pregnancy?
Fetal complications or stillbirth
When does opioid overdose most often occur?
When patients are using other sedating drugs
How is opioid overdose treated?
Naloxone for a minimum of 24 hours w/ additional 12 hours of monitoring
Is buprenorphine an agonist or antagonist and at which receptor?
- Partial Mu-opioid agonist
- Very high affinity and slow dissociation from receptor
Is naloxone an agonist or antagonist and at which receptor?
Pure opioid antagonist
How is buprenorphine/naloxone administered?
Sublingual (under tongue)
What will happen when someone is administered buprenorphine?
- Will go into withdrawal
- When going from a full agonist to a partial agonist, px will feel sluggish
When does buprenorphine reach peak levels?
1-4 hours
What is the max dose of buprenorphine in Canada?
24 mg/day
What is buprenorphine metabolized by?
CYP 3A4 and glucuronidation
What occurs when BZDs and buprenorphine are used in combination?
Additive respiratory depression w/ no plateau
Is methadone or buprenorphine considered safer in overdose?
Buprenorphine
What is recreational drug use?
- Use of a pharmacologically active drug for purposes other than its intended medicinal or other purpose
- Use of a substance/drug to get “high” or be in a mentally altered state
What is the difference between drug misuse and drug abuse?
- Drug misuse - taking a drug that you think is for a certain condition when it actually isn’t
- Drug abuse - purposely taking a drug to get euphoric effects
Which system and which receptors are activated during addictive drug use?
- Mesolimbic dopamine system
- Receptors = Gio protein-coupled receptors, ionotropic receptors, and dopamine transporter
What is dependence?
A state at which the user functions normally only when taking the drug
Is physiological or psychological dependence more serious?
Physiological
What is thought to play a role in cravings for opioids?
Affects on the dopaminergic pathways
Do opioids have separate or the same neurochemical pathways for physiological vs. psychological dependence?
Separate
Does tolerance always mean addiction?
No
How long does it take for tolerance to be lost?
10-14 days
What is reverse tolerance?
Sensitization
Which drugs can cause reverse tolerance?
Cocaine and amphetamines
When are impairing effects of a drug greater?
During rise to maximal concentration, as opposed to on the downward slope
What occurs to neurons during functional tolerance?
- Changes in post synapses of CNS (stimulatory and inhibitory pathways)
- Exposure to psychoactive drugs and cause desensitization of receptors or down regulation of receptors/signaling pathways
What is another name for functional tolerance?
Pharmacodynamic tolerance
What is another name for metabolic tolerance?
Pharmacokinetic tolerance
What occurs during metabolic tolerance and what is it similar to?
- Adaptation of metabolic “machinery” to repeated exposure to drug
- Similar to drug resistance mechanisms
What must occur for withdrawal to take place?
Blood or tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance
Is withdrawal a permanent consequence?
No, the body will get used to no drug eventually
What role does laboratory testing play in diagnosis of abuse?
Doesn’t help w/ diagnosis, but gives info about how the px is using the drug (ex: if they took the drug weeks ago, but are still excreting it now); can also determine extent of damage
What is the difference between opiates and opioids and what are examples of each?
- Opiates are naturally occurring or semi-synthetic (ex: morphine, heroin)
- Opioids are completely synthetic (ex: fentanyl)
What determines the potency of opioids?
Binding affinity to Mu, Kappa, and Delta receptors
Most opioids are selective for ___ receptors, except ___
Mu; pentazocine
What are desirable effects of opioids?
- Analgesia
- Euphoria
- Sedation
- Relief of anxiety
- Depress cough reflex
What are common autopsy findings associated w/ opioid overdose?
- Pulmonary congestion and frothing of mouth
- Heavily snoring prior to death
- Blockade of respiratory centres to CO2
What is the general effect of opioid toxicity on the respiratory, CV, and GI centres?
Depresses systems and functions
What are cannabinoids?
All drugs that have similar pharmacological properties as cannabis
Can cannabis produce tolerance?
Yes
___ is the major psychoactive constituent of cannabis
THC
What is the mechanism of action of cannabis?
Cannabinoid receptors CB1 and CB2
What are the CNS effects of cannabis?
- Euphoria
- Lack of concentration, attention, and memory
- Motor function impairment
- Heightened anxious state
- Paranoia
What are the cardiovascular effects of cannabis?
Increased heart rate and decreased blood pressure from vasodilation
What are the respiratory effects of cannabis?
- Decreased respiratory rate
- Bronchodilation
- Lung damage from smoking
What are the drug interactions w/ cannabis?
- Use w/ cocaine and amphetamines may lead to increased hypertension, tachycardia, and possible cardiotoxicity
- Additive effect w/ CNS depressants
What is the onset and bioavailability from smoking cannabis?
- Rapid onset, minutes
- 18-50% bioavailability
THC is ___philic and undergoes _____ circulation
Lipophilic; enterohepatic
What are the acceptable limits of THC blood concentration?
2-5 ng/mL
