Drugs of Abuse Flashcards
What are some of the criteria for substance abuse disorders?
- Tolerance
- Withdrawal
- Usage of large amounts
- Normal activities are given up
- Continued use despite knowledge of problems
Withdrawal
Signs that emerge when the use of the drug is stopped which will go away when the drug is resumed
Tolerance
Decreased effect with repeated use of drug and increased need for larger doses for the same effect
What pathway is activated by all drugs of dependence?
Ventral Tegemental Area of nucleus accumbens which results in the release of dopamine
Besides lack of the agonist, what is another mechanism that can cause withdrawal?
Antagonism of the receptor that the drug normally binds to
What are the psychostimulants?
Cocaine and amphetamines
Cocaine Uses
Powerful CNS stimulant and appetite suppressant as well as a topical anesthetic.
Cocaine MOA
Inhibits the action of dopamine transporters in the presynaptic terminals - the levels of DOPA in the presynaptic cleft will increase
Amphetamines MOA
Inhibit the action of VMAT2 so DOPA cannot be placed in the vesicles leading to a high level of “free” DOPA that can reverse the DOPA transporter - increased DOPA in the presynaptic cleft
What are the effects of psychostimulants?
- Increased energy
- Decreased fatigue
- Decreased appetite
What is the fastest mechanism to feel “high” from cocaine?
IV
Where is cocaine metabolized?
Hepatic metabolism
What is the problem of combining cocaine with ethanol?
Forms cocaethylene which leads to a longer duration of action and an increased cardiotoxic effect
What is a unique risk of psychostimulant abuse?
Increased risk of rare autoimmune disorders like lupus and Stevens Johnson
Cocaine OD Signs
- Cardiac Arrhythmia
- Tachycardia
- Dilated pupils
- HTN
What is the treatment for cocaine withdrawal?
- Bromocriptine
- Lorazapam
Opioid MOA
Inhibition of GABA interneurons leading to the disinhibition of the mesolimbic DOPA system - increased DOPA in the nucleus accumbens is ultimate result
Opioid OD Signs
- Unconsciousness
- Respiratory depression
- Pulmonary edema
Is there cross tolerance to opioids?
Yes. Tolerance to one will cause tolerance to another opoid.
What is the metabolism of heroin?
Heroin -> 6-monoacetylmorphine -> morphine
Opioid Withdrawal Symptoms
- Lacrimation
- Rhinorrhea
- Yawning
- Piloerection
- Involuntary movement
What is the treatment for opioid addiction and withdrawal?
Methadone or busprenophine
What is the treatment for opioid OD?
Naloxone
What is the treatment for opioid dependence?
Naltrexone
Naloxone MOA
mu-opioid competitive antagonist with very high affinity and short half life to displace heroin - heroin is longer acting though and symptoms can return so monitoring is required
Naltrexone MOA
mu-opioid competitive antagonist with long half life that makes heroin administration no longer rewarding
Methadone MOA
mu-opioid agonist with long half life that prevents withdrawal symptoms
Buprenorphine MOA
Partial mu-opioid agonist that has less potential for respiratory depression
What is suboxone?
4:1 mix of buprenorphine and naloxone
Cannabinoid MOA
THC inhibits GABA interneurons via CB1 which leads to increased DOPA in the nucleus accumbens
What are the symptoms of cannabinoid use?
- Increased appetite
- Redness of the eyes
- Relaxation
- Decreased pressure in the eyes
Cannabinoid SE
- Panic
- Amotivational syndrome
- Personality changes
Type B Alcohol Dependence
Earlier onset at less than 25 yrs and is more severe
Type A Alcohol Dependence
Later onset of greater than 25 yrs and has a slower disease progression
What is the effect of alcohol on neural circuits?
Increases the effects of GABA and inhibition of glutamate - chronic use leads to reduction of the GABA receptors and upregulation of glutamate receptors
What is the result of sudden reduction in alcohol intake from a chronic user?
Abrupt increase in glutamate action due to the release from inhibition
What drugs are used to treat alcohol withdrawal?
Benzodiazepine
Alcohol Withdrawal Symptoms
- Seizures
- Alcoholic hallucinations
- Delirium tremens
- Hyperarousal
Delirium Tremens
Uncontrollable tremors of the extremities with autonomic instability
Besides alcohol withdrawal, what else can cause delirium tremens?
Benzodiazepine withdrawal
What are the treatments for alcohol dependence?
- Disulfiram
- Naltrexone
- Acamprosate
Disulfiram Indications
Alcohol Aversion Therapy
Acamprosate MOA
Restores balance between excitation and inhibition - but true mechanism is unknown
Disulfiram MOA
Inhibits aldehyde dehydrogenase that results in nausea and vomiting if alcohol is taken - decreases desire to drink
What mutation is protective against alcohol dependence?
Often in Asians due to ALDH2*2 mutation
Acamprosate Contraindications
Severe Renal Disease
What is the treatment for benzodiazepine withdrawal?
Diazepam - has a long half-life and it will be tapered off over time
What is used for treatment of nicotine addiction?
Varenicitine - partial agonist that binds nicotine ACh receptors which relieves cravings and binds with greater activity than nicotine which decreases the reward from smoking
What is the molecular target of the hallucinogens?
Serotonin receptors - 5HT2A
Do hallucinogens cause addiction?
No
