Addiction Flashcards
Opioids:
Tolerance?
W/drawal?
Lethality of w/drawal syndrome?
Opioids readily produce tolerance (including to apnea).
Withdrawal symptoms are most unpleasant but are NOT considered to be lethal.
Their Sx may start 6-12 hrs after last dose of short-acting Fentanyl or 3-4 days after last dose of Methadone.
Opioids - Sx of w/drawal?
Drug craving, hyperalgesia, nausea, abdominal cramps, insomnia, anxiety
Heroine - describe the time course of its effects
Intense euphoria lasting only a few minutes followed by hours of sedation.
B/c of its lipid solubility it has a much faster onset than Morphine.
How would heroine overdose kill someone?
Apnea (temporary cessation of breathing during sleep/sedation)
- usually tolerance develops to this, however overdose would be if they take impure heroine
What does “cross-tolerance” refer to?
When one substance may substitute for another in preventing the withdrawal syndrome of the
first substance
What types of drugs are included in CNS depressants?
Ethanol, Benzodiazepines, Barbiturates, & obsolete nighttime sedatives such as methaqualone
CNS Depressants - is the w/drawal syndrome fatal?
Yes, b/c it includes status epilepticus. Additional Sx include craving, irritability, insomnia, tachycardia, hypertension, and hallucinations.
Tolerance develops at different rates to the sedating and apneic doses in which type of drugs?
CNS depressants
NOT opioids
Most specialists substitute a CNS depressant with a longer half-life than the abused substance during
the detoxification period.
For example, ethanol detoxification may include the administration of a __(a1)__, while detoxification from __(a2)__ abuse may be achieved by giving __(b)__ and tapering the dose over a period of weeks to months.
a1) benzodiazepine such as oxazepam
a2) Diazepam
b) phenobarbitol
**get that Benzos treat Ethanol addiction & Barbiturates treat Benzo addiction —> as long as half-life of treatment is longer than that of the substance they were addicted to
What is “Tachyphylaxis” & in what drug does this occur in?
The rapid development of tolerance, is common and is manifested as lessening of the effects after
each dose within a single drug-using session.
Happens w/ cocaine
Describe the w/drawal syndrome following prolonged cocaine use.
It is physiologically mild and consists of drug craving, sleepiness, dysphoria, depression, and bradycardia, and lasts a week or two after prolonged cocaine use.
Cocaine Addiction - Tx?
Management of cocaine addiction is largely supportive and psychotherapeutic; there is no known medication with efficacy in preventing cocaine use.
CNS stimulants are used appropriately in the Tx of what?
ADHD & Narcolepsy
Which of the CNS stimulants may cause hallucinations?
MDMA
Δ-9-THC is also called dronabinol (Marinol®) and is available in tablet form for the treatment of what?
Severe nausea & vomiting ass’d w/ cancer chemotherapy
What is N-arachidonylethanolamine (AKA anandamide)?
What are its receptors & where are they located?
It is an endogenous ligand that binds the same receptor as Δ-9-THC (Dronabinol).
These are G-protein coupled receptors present in high densities in the cerebral cortex, hippocampus, striatum, and cerebellum.
Binding to the receptors decreases GABA release, thus inhibiting its activity.
T or F?
Tolerance to the effects of a marijuana high develops rapidly after a few doses.
True
Describe the w/drawal symptoms of marijuana use.
Withdrawal symptoms are mild and consist of insomnia, restlessness, irritability, and nausea.
LSD, mescaline, and psilocybin affect many different receptor types, but their hallucinogenic effects may be due primarily to _____ at _____ receptors.
agonism at 5-HT2 receptors
This is noteworthy because the newer, atypical antipsychotic medications are primarily
antagonists at this same receptor.
Phencyclidine (used as a veterinary anesthetic) and Ketamine are _____ at the _____ receptor.
antagonists at the NMDA receptor
Describe the timeframe for the effects of serotinergic psychedelics.
The effects of the serotonergic psychedelic substances usually begin within an hour of oral ingestion and usually last for about 8 hr.
What symptoms may the serotinergic psychedelics cause other than hallucinations?
In addition to hallucinations, these medications often cause mood changes (euphoria or depression), and alterations in color and shape perception.
Sometimes there is intense anxiety and/or dysphoria, the so-called “bad trip.”
Rarely the psychedelic or psychotic effects will last for a few days.
Describe the w/drawal syndrome of the serotinergic psychedelics.
There is no w/drawal syndrome.
A few users of these medications will experience visual hallucinations (“flashbacks”) long after the last usage. This effect is thought to be due to permanent drug-induced changes in the visual cortex.
Describe the effects of Phencyclidine and Ketamine
The effects include emotional w/drawal & bizarre & unusual responses to environmental stimuli.
At higher doses, coma results although ventilation is usually preserved; recall that these are desirable effects for medications developed and used as anesthetic agents.
Recovery is often prolonged & accompanied by hallucinations and delirium.
Describe the effects of the “high” from organic solvents like Toluene & Gasoline.
Inhalation of these vapors causes dizziness & an intoxicated feeling.
What is the major short-term adverse effect of inhaling Toluene or Gasoline?
Generation of cardiac arrhythmias; these
hydrocarbons increase automaticity in cardiac cells.
What are the major long-term adverse effects of inhaling Toluene or Gasoline?
Include potentially irreversible damage to the brain, peripheral nerves, liver & kidney.
There are more people physically & psychologically dependent on _____ in the U.S. than to any other substance.
nicotine
Nicotine:
Does tolerance develop?
What is the w/drawal syndrome like?
Tolerance develops to the effects of nicotine.
The withdrawal syndrome is well characterized: Insomnia, Irritability, Anxiety, Dysphoria, & increased appetite → weight gain
T or F?
Gradually tapering the dose of nicotine delivered is a successful method for eliminating dependence.
True
How should you treat patients w/ physical dependence on Opioids but no pattern of abuse?
Taper their medication gradually (to avoid the w/drawal syndrome) after their need for analgesia has ended
How should you treat patients w/ a pattern of abuse of Opioids?
Detoxification and/or Substitution therapy
Remove opioids & treat w/drawal symptoms w/ a centrally-acting α-adrenergic agonist such as Clonidine (autonomic Sx) & Octreotide (GI symptoms).
Chronic Tx = Psychotherapy + Naltrexone
Naltrexone - MOA?
Orally effective opioid receptor antagonist
- ppl on this do not get “high” if they take opioids
- reduces drug cravings
Naltrexone - Clinical uses?
- Oral chronic Tx for opioid addiction (inhibits “high” if they take opioids & reduces/eliminates cravings)
- 1/month IV treatment for alcoholics to maintain sobriety
What drugs may be used for Substitution therapy in Opioid addicts?
Methadone or Buprenorphine
Daily administration of _____ prevents the opioid withdrawal syndrome.
methadone
Buprenorphine - MOA?
- Extremely tight binding to the μ-receptor
- Partial agonist — therefore has limited analgesic effects
- Like methadone, patient will not get the opioid “high”
- Like Naltrexone, eliminates drug seeking behavior
- Cannot be overcome even by high μ-agonist (opioid) doses if analgesia is needed
What is the appropriate Substitution therapy for addicts that use HIGH-doses of opioids?
Methadone
NOT Buprenorphine b/c this binds too tightly & although it is a partial agonist, it will still produce w/drawal symptoms in patients taking HIGH opioid doses — too big of a drop
Buprenorphine = Schedule ___ drug
Methadone = Schedule ___ drug
Buprenorphine = Schedule III drug (reqs 8-hr course by physician to have up to 30 pts)
Methadone = Schedule II drug
Why is Naloxone (Suboxone) added to oral Buprenorphine pill?
b/c it’s not taken up orally so it has no effect if the pill is taken properly, but if the patient shoots up the drug then it will inhibit any opioid effects of Buprenorphine
Long-term management options for Ethanol-addiction?
Disulfiram = irreversible inhibitor of aldehyde dehydrogenase
Naltrexone = Opioid antagonist & blocks the
activation by alcohol of dopaminergic reward pathways in the brain
Acamprosate = newer drug that appears to
decrease neurotransmitter release at NMDA synapses
How long do the effects of Disulfiram last?
~ 2 weeks
b/c inhibition of aldehyde dehydrogenase is irreversible
How long do the effects of Acamprosate seem to last following a 1-year treatment program?
“Many months”
