EXAM #3: DRUGS OF ABUSE Flashcards
What is the hallmark of drug addiction?
Compulsive drug use
What is the basic definition of physical dependence?
Dependence is when the drug is necessary for normal physiologic function
What is the hallmark of physical dependence with drug cessation?
Withdrawal
Generally, what withdrawal symptoms with drug cessation?
The OPPOSITE effects of the drug
What three factors confer a high degree of relapse in addicts?
1) Re-exposure to the drug
2) Exposure to contextual cues
3) Stress
What brain system are activated by all addictive drugs?
Mesolimbic dopamine system
What is pharmacokinetic tolerance?
Increased drug metabolism resulting in tolerance
What is pharmacodynamic tolerance? What are the mechanisms of pharmacodynamic tolerance?
CNS response to chronic drug use:
- Desensitiziation
- Down-regulation of drug receptors
- Internalization of receptors
What are the psychological manifestations of withdrawal?
- Dysphoria
- Depression
- Anxiety
- Craving
- Psychosis
What region of the brain is involved in the reward pathway?
Ventral Tegmental Area (VTA)
What four areas does the VTA project to?
1) Amygdala
2) Nucleus Accumbens
3) Prefrontal cortex
4) Hippocampus
What are the three drug “targets” in the VTA?
1) Gi GPRCs that inhibit GABA
2) Ionotropic DA receptors
3) DA uptake transporter (inhibition)
What drugs act on Gi GABA GPRCs in the VTA?
1) Opioids
2) THC
3) GHB
What drugs act on DA ionotropic receptors in the VTA?
1) Benzodiazepines
2) Nicotine
3) Ethanol
What drugs block DA transporters in the VTA?
1) Cocaine
2) Amphetamine
3) Ecstasy
What is the RR of addiction to CNS depressants?
3
What type of elimination kinetics does alcohol follow?
Zero-order i.e. a constant amount of alcohol is eliminated per unit of time
Is the half-life of alcohol dependent on dose?
Yes e.g. 5 drinks= 5 hours to eliminate vs. 10 drinks = 10 hours to eliminate
What is the first step in alcohol metabolism?
Alcohol Dehydrogenase (ADH)
What drug is used to treat methonal and ethylene glycol poisoning? What is the MOA of this drug?
Fomepizole–inhibits ADH i.e. Alcohol Dehydrogenase
What is the second step in alcohol metabolism?
Aldehyde Dehydrogenase
What drug blocks Aldehyde Dehydrogenase (ALDH)? What is this drug used for?
Disulfram– causes acetaldehyde to accumulate and causes unpleasant side effects
How many drinks does it take to put the average adult over the legal limit to drive?
2-4 drinks/hour
What general class of drugs should not be combined with alcohol for fear or potentially fatal side effects?
CNS depressants i.e. Barbiturates, Benzodiazepines, Marijuana
What is Wernicke-Korsakoff Syndrome?
Neurological condition associated with B1 deficiency in combination with excessive alcohol consumption
What are the symptoms of Wernicke-Korsakoff Syndrome?
1) Ocular disturbance
2) Changes in mental status
3) Memory impairment
4) Movement difficulties
What is Fetal Alcohol Syndrome (FAS)?
Teratogenic disorder seen in children borne to alcoholic mothers
Note that there is NO safe level of alcohol consumption in pregnancy
What are the symptoms of FAS?
1) Mental retardation
2) Hyperactivity
3) Antisocial behavior
What is the progression of liver pathology seen in chronic alcoholism?
1) Fatty liver
2) Alcoholic hepatitis
3) Liver cirrhosis
4) Liver failure
What is the most common two-drug combination that results in death?
Cocaethylene
What is cocaethylene
Liver metabolizes alcohol and cocaine–product is Cocaethylene
What are the two drugs that are used to treat chronic alcoholism?
1) Disulfiram
2) Naltrexone
What is the mechansim of action of Naltrexone in alcohol abuse?
Blocks reinforcing properties of alcohol
Note that this is an OPAITE antagonist*
